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WHO DRUG

INFORMATION V O L U M E 2 1• N U M B E R 2 • 2 0 0 7

P R O P O S E D I N N L I S T 9 7 I N T E R N A T I O N A L N O N P R O P R I E T A R Y N A M E S F O R P H A R M A C E U T I C A L S U B S T A N C E S

W O R L D H E A L T H O R G A N I Z A T I O N • G E N E V A

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WHO Drug Information Vol 21, No. 2, 2007

WHO Drug Information

Contents

World Health Organization

Safety and Efficacy IssuesEntecavir: not for use in HIV/HBV

co-infection 87Deferasirox: acute renal failure and

cytopenias 87Safety of oseltamivir 87Fluticasone: reports of behavioural

changes 88Quetiapine: pancreatitis and thrombo-

cytopenia 88Aprotinin: hypersensitivity reactions and

renal dysfunction 89Metoclopramide in children: extra-

pyramidal symptoms 90Drug-eluting stents: to be used with

caution 90Darbepoetin alfa and epoetin alfa: update

for non-myeloid malignancies 91Ayurvedic and Chinese medicines:

heavy metals 91ADHD drugs: cardiovascular and psychi-

atric events 92Clozapine can impair motility of the entire

GI tract 93

Essential Medicines15th Model List of Essential Medicines 94Model List of Essential Medicines, 15th

Edition, revised March 2007 95

Regulatory Action and NewsTegaserod: marketing suspension 112Pergolide: voluntary withdrawal of

products 112Aliskiren approved for hypertension 113Lapatinib approved for breast cancer 114Adalimumab approved for Crohn disease114Rapid test for meningitis cleared for

marketing 114

Eculizumab approved for paroxysmalnocturnal haemoglobinuria 115

Access to MedicinesNeglected tropical diseases 116Open access database for neglected

medicines development 116

Consultation DocumentInternational PharmacopoeiaArtemether and lumefantrine capsules 118Magnesium sulfate injection 123Zinc sulfate 124Paediatric zinc sulfate tablets 125Paediatric zinc sulfate oral solution 127

Recent Publications,Information and EventsInformed consent for research in resource-

poor settings 129Lessons learned in home management

of malaria 129Developing drug information centres

in India 130First-in-man clinical trials for high risk

products 130Pakistan Pharmacists Society

discussion forum 130New quality assurance compendium 130Pharmacological management of human

H5N1 infection 131

Proposed InternationalNonproprietary Names: List 97 133

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WHO Drug Information Vol 21, No. 2, 2007World Health Organization

Announcement

The 13th International Conferenceof Drug Regulatory Authorities (ICDRA)will be hosted by the Swiss Agency forTherapeutic Products (Swissmedic) incollaboration with the World Health

Organization

The ICDRA will take placein Berne, Switzerland

from 16 to 19 September 2008

Updated information will be provided regularly at:http://www.icdra.ch

or

http://www.who.int/medicines/icdra/en/index/html

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Safety and Efficacy Issues

Entecavir : not for use inHIV/HBV co-infectionEuropean Union — The Committee forMedicinal Products for Human Use(CHMP) reminds healthcare professionalsthat entecavir (Baraclude®) has not beenevaluated for the treatment of patientswith chronic hepatitis B virus (HBV) infec-tion who are co-infected with the humanimmunodeficiency virus (HIV) and are notreceiving highly active antiretroviraltherapy (HAART).

Based on new data, the EMEA adviseshealthcare professionals that:

• Baraclude® has not been evaluated inHIV/HBV co-infected patients notsimultaneously receiving effective HIVtreatment.

• When considering therapy with ente-cavir in an HIV/HBV co-infected patientnot receiving HAART, there appears tobe a risk of developing HIV resistance.

• Until reassuring data become available,Baraclude® should only be consideredin this setting under exceptional circum-stances.

Reference: European Medicines Agency,Public Statement, EMEA/79902/20075. March2007.

Deferasirox: acute renalfailure and cytopeniasCanada — The manufacturer of defera-sirox (Exjade®) has updated the safetyinformation regarding reports of acuterenal failure and peripheral blood cyto-penias.

Deferasirox is indicated in the manage-ment of chronic iron overload in patientswith transfusion-dependent anaemiasaged 6 years or older. It is also indicatedin the management of chronic iron over-load in patients with transfusion-depend-ent anaemias aged two to five whocannot be adequately treated withdeferoxamine.

Therapy should be initiated and main-tained by physicians experienced in thetreatment of chronic iron overload due toblood transfusions.

Cases of acute renal failure (some withfatal outcome) have been reportedfollowing the post-marketing use ofdeferasirox. For the fatal cases, it isimpossible to completely exclude acontributory role of deferasirox to therenal impairment The fact that there wasan improvement after stopping thetreatment in most of the cases with non-fatal acute renal failure is suggestive of acontributory role. Deferasirox has notbeen studied in patients with renal impair-ment.

Reference: Communication from NovartisPharmaceuticals Canada Inc. on Medeffect athttp://www.hc-sc.gc.ca

Safety of oseltamivirEuropean Union — The EuropeanMedicines Agency (EMEA) has docu-mented new reports of neuropsychiatricadverse events occurring with the use ofoseltamivir (Tamiflu®) originating fromJapan. These cases have been detectedthrough routine safety monitoring.

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WHO Drug Information Vol 21, No. 2, 2007Safety and Efficacy Issues

The Agency’s Committee for MedicinalProducts for Human Use (CHMP) hasmonitored closely all adverse drugreactions reported in connection with theuse of oseltamivir since it was introducedin the European Union in 2003.

The CHMP recommended an update ofthe product information on neuropsychi-atric side effects: “Convulsion, depressedlevel of consciousness, abnormal behav-iour, hallucinations and delirium havebeen reported during Tamiflu® adminis-tration, leading in rare cases to accidentalinjury. Patients, especially children andadolescents should be closely monitoredand their healthcare professional shouldbe contacted immediately if the patientshows any signs of unusual behaviour.”

The EMEA and CHMP will continue toclosely monitor any emerging safetyinformation on Tamiflu®, including neuro-psychiatric disorders. If any concernsemerge, further action will be taken. Withthese measures in place, the CHMPmaintains its opinion that the benefits ofTamiflu® outweigh its risks when theproduct is used according to the adoptedrecommendations.

Reference: EMEA Press Release, 23 March2007. Doc. Ref. EMEA/134566/2007. http://www.emea.europa.eu

Fluticasone: reports ofbehavioural changesNetherlands — The Netherlands Phar-macovigilance Centre, Lareb, has re-ceived 17 reports of behavioural changesin children associated with the use ofinhaled fluticasone propionate orsalmeterol/fluticasone propionate (4). In11 cases, symptoms disappeared whenfluticasone propionate was withdrawn. Apositive rechallenge was observed in onecase. Six patients who had receivedfluticasone propionate also receivedsalbutamol. However, in all but one case,

the reporter did not see a causal relation-ship between the adverse drug reactionand salbutamol. Psychiatric effects havealso been reported in association with theuse of oral corticosteroids and inhaledbudesonide, which raises the possibilityof a group effect.

Reference: Fluticasone inhalation andbehavioural changes in children. Lareb,Netherlands Pharmacovigilance Centre,January 2007 (www.lareb.nl).

Quetiapine: pancreatitisand thrombocytopeniaCanada — Quetiapine (Seroquel®) is anatypical antipsychotic drug indicated forthe management of symptoms of schizo-phrenia and the acute management ofmanic episodes associated with bipolardisorder (1). In Canada, quetiapine hasbeen marketed since December 1997.

From 1997 to 2006, Health Canada hasreceived 615 domestic reports of adversereactions suspected of being associatedwith the use of quetiapine. Nine reportsinvolved cases of pancreatitis and 11involved cases of thrombocytopenia.Neither of these ARs is mentioned in theCanadian product monograph (1).

PancreatitisThe 9 reported cases of pancreatitisinvolved patients aged 24–71 years. In 5cases, quetiapine was the only suspectdrug; in the other cases, reported co-suspect drugs included medications thathave been associated with pancreatitis:clozapine, divalproex sodium, fenofibrateand minocycline (2, 3).

Acute pancreatitis typically presents asan acute inflammation of the pancreasthat may or may not involve the surround-ing tissues (2). Gallstones and heavyalcohol use are the most common causes(2). The severity of drug-induced pan-creatitis is variable; the majority of pa-

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tients recover without any long-termmorbidity, but 5% –15% of patientsexperience life-threatening complications(4). People at risk of drug-induced pan-creatitis include elderly patients takingmultiple medications, patients who areHIV positive, patients who have cancerand patients receiving immunomodulatoryagents (5).

ThrombocytopeniaThe 11 reported cases of thrombocytope-nia involved patients aged 28–84 years.In 6 cases, quetiapine was the onlysuspect drug. In 5 cases, reported co-suspect drugs included medications thathave been associated with thrombocyto-penia: citalopram, clozapine, olanzapine,pantoprazole, rofecoxib and zuclopen-thixol (6–12).

Thrombocytopenia is usually defined as aplatelet count of less than 150 x 109/L ora 50% decrease in the platelet count frombaseline (6). Some reports define drug-induced thrombocytopenia as a plateletcount of less than 100 x 109/L (6). Al-though relatively rare, drug-inducedthrombocytopenia may be associatedwith risks of morbidity and mortality (6).Perhaps because of its low incidenceand idiosyncratic nature, drug-inducedthrombocytopenia has often gone unrec-ognized during early clinical trials of drugsand was first reported after marketing (6).

Extracted from Canadian Adverse ReactionNewsletter, Volume 17, Number 2, 2007

References

1. Seroquel (quetiapine fumarate tablets)[product monograph]. Mississauga (ON):AstraZeneca Canada Inc.; 2006.

2. Eltookhy A, Pearson NL. Drug-inducedpancreatitis. Can Pharmacists J, 2006;139(6):58–60.

3. Gropper D, Jackson CW. Pancreatitisassociated with quetiapine use. J ClinPsychopharmacol, 2004;24(3):343–5.

4. Kale-Pradhan PB, Conroy JL. Pancreatitis.In: Drug-induced diseases: prevention,detection, and management. Bethesda (MD):American Society of Health-System Pharma-cists, Inc.; 2005. p. 537–47.

5. Adverse Drug Reactions Advisory Commit-tee (ADRAC). Drug induced pancreatitis. AustAdv Drug Reactions Bull, 2006;25(6):22.

6. Skirvin JA. Thrombocytopenia. In: TisdaleJE, Miller DA, editors. Drug-induced diseases:prevention, detection, and management.Bethesda (MD): American Society of Health-System Pharmacists, Inc.; 2005. p. 649–59.

7. Kentos A, Robin V, Lambermont M, et al.Probable rofecoxib-induced thrombocytope-nia. Rheumatology, 2003;42(5):699–700.

8. Hirshberg B, Gural A, Caraco Y. Zuclo-penthixol-associated neutropenia and throm-bocytopenia. Ann Pharmacother, 2000;34(6):740–2.

9. Huynh M, Chee K, Lau DH. Thromboticthrombocytopenic purpura associated withquetiapine. Ann Pharmacother, 2005;39(7–8):1346-8.

10. Watson TD, Stark JE, Vesta KS.Pantoprazole-induced thrombocytopenia. AnnPharmacother, 2006;40(4):758–61.

11. Celexa (citalopram hydrobromide tablets)[product monograph]. Montreal: LundbeckCanada Inc.; 2006.

12. Clozaril (clozapine tablets) [productmonograph]. Dorval (QC): Novartis Pharma-ceuticals Canada Inc.; 2006.

Aprotinin: hypersensitivityreactions and renaldysfunctionCanada — Health Canada has informedhospitals and pharmacies of an associa-tion of aprotinin (Trasylol®) with hyper-sensitivity reactions and renal dysfunc-tion. Aprotinin is indicated for prophylacticuse to reduce perioperative blood lossand the need for blood transfusion in

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those patients undergoing cardiopulmo-nary bypass in the course of coronaryartery bypass graft (CABG) surgery whoare at increased risk for blood loss andblood transfusion requirement.

The authorized indication for Trasylol® isrestricted to those patients undergoingcardiopulmonary bypass in the course ofcoronary artery bypass graft (CABG)surgery who are at increased risk forblood loss and blood transfusion.

Trasylol® administration may cause fataland nonfatal anaphylactic or anaphylac-toid reactions. Fatal reactions haveoccurred with an initial (test) dose as wellas with any of the components of thedose regimen. Fatal reactions have alsooccurred in situations where the initial(test) dose was tolerated. As a result,Trasylol® should only be administered inoperative settings where cardiopulmonarybypass can be rapidly initiated.

The risk for anaphylactic or anaphylactoidreactions is increased among patientswith prior aprotinin exposure, and ahistory of any prior aprotinin exposuremust be sought prior to Trasylol® admin-istration. The risk for a fatal reactionappears to be greater upon re-exposure.As a result, administration of Trasylol® topatients with a known or suspectedprevious aprotinin exposure during thelast 12 months is contraindicated.

Trasylol® administration increases therisk of renal dysfunction and may in-crease the need for dialysis in theperioperative period. This risk may beespecially increased for patients with pre-existing renal impairment or those whoreceive aminoglycoside antibiotics ordrugs that alter renal function.

Reference: Information Update 2007-36, 31March 2007: Communication from Bayer Inc.on http://.www.hc-sc.gc.ca

Metoclopramide in children:extrapyramidal symptomsNetherlands — Following an increase inthe number of registered cases of ex-trapyramidal symptoms in childrenreceiving metoclopramide, the MedicinesEvaluation Board has restricted the use ofmetoclopramide in this population totreatment of severe nausea and vomitingof known origin, and only if treatment withother products is ineffective or is notpossible.

The MEB considers there are betteralternatives to metoclopramide. Forexample, domperidone is a better choicein treating post-operative nausea inchildren. Domperidone is also the drug ofchoice in treating migraine in childrenbecause the risk of extrapyramidal effectsis lower than with metoclopramide.Similarly, 5-HT3 receptor antagonists(e.g. ondansetron) are the drugs ofchoice in nausea due to strongly emeto-genic chemotherapy because of betterefficacy and fewer adverse events.

Reference: News and Publications. TheMedicines Evaluation Board, the Netherlands,21 February 2007. http://www.cbg-meb.nl/uk/nieuws

Drug-eluting stents:to be used with cautionSweden — The Swedish Medical Prod-ucts Agency (MPA), in conjunction withthe National Board of Health and Welfareand the Swedish Society of Cardiology,has recommended utmost restraint in theuse of drug-eluting stents. The recom-mendation was based on the results ofclinical studies, including the SwedishCoronary and Angioplasty Registry(SCAAR) study that showed increasedrisk of thrombosis associated with the useof drug-eluting stents. The results of theSCAAR study and four other randomizedstudies showed that drug-eluting stents

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have no advantages in terms of myocar-dial infarction or mortality, compared withbare-metal stents; in addition, the SCAARstudy data indicated a small, long-termincreased risk of these events. Accordingto the MPA, drug-eluting stents must onlybe used in patients for whom no othertreatment alternative exists or in patientswho are at greatly increased risk ofrestenosis and for whom the effect ofrestenosis is expected to be severe.

Reference: Swedish Medical ProductsAgency, 13 February 2007. http://www.lake-medelesverket.se.

Darbepoetin alfa and epoetinalfa: update for non-myeloidmalignanciesCanada — The manufacturers of theerythropoiesis-stimulating agents (ESAs),have updated safety information basedon completed or ongoing clinical studiesregarding treatment with darbepoetin alfa(Aranesp®) and epoetin alfa (Eprex®).

Darbepoetin alfa is indicated for thetreatment of anaemia associated withchronic renal failure, and for the treatmentof anaemia in patients with non-myeloidmalignancies, where anaemia is due tothe effect of concomitantly administeredchemotherapy.

Epoetin alfa (Eprex®) is indicated for thetreatment of anaemia associated withchronic renal failure, the treatment ofanaemia in patients with non-myeloidmalignancies, where anaemia is due tothe effect of concomitantly administeredchemotherapy, the treatment of anaemiain zidovudine-treated/HIV-infected pa-tients, and for the treatment of patientsundergoing major elective surgery tofacilitate autologous blood collection, andto reduce allogeneic blood exposure.

Epoetin alfa is no longer indicated in thetreatment of anaemia in patients withnon-myeloid malignancies, where anae-

mia is due to the disease itself. Therefore,none of the ESAs are indicated in thispatient population. Recent clinical studieshave provided new safety informationregarding the use of ESAs, including risksof tumour progression and seriouscardiovascular events.

ESAs increased the risk of death and ofserious cardiovascular adverse events inpatients with cancer or renal failure, whentreated to a target haemoglobin level ofgreater than 120 g/L.

An increased risk of death was seen incancer patients with active malignantdisease, who were not being treated witheither radiation or chemotherapy and whowere treated with ESAs to a targethaemoglobin level of 120 g/L. ESAs arenot indicated in this patient population.

ESAs shortened the time to tumourprogression in patients with advancedhead and neck cancer receiving radiationtherapy; in addition, ESAs decreasedoverall survival and increased deaths at4 months, attributed to disease progres-sion in patients with metastatic breastcancer receiving chemotherapy, whenthese groups of patients were treated to atarget haemoglobin level of greater than120 g/L.

Reference: Communication from AmgenCanada, Inc. 16 April 2007 on http://www.hc-sc.gc.ca

Ayurvedic and Chinesemedicines: heavy metalsAustralia — The Therapeutic GoodsAdministration (TGA) has released astatement about the safety of Ayurvedicmedicines in Australia, in response torecent research into the toxic content ofheavy metals found in some Ayurvedicmedicines (1).

There are several possible explanationsfor the presence of heavy metals intraditional herbal remedies (2). Salts of

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heavy metals (for example those of lead,mercury and arsenic) are used as princi-pal ingredients in some traditional Indianand (to a lesser extent) Chinese herbalremedies (4). In addition, cross-contami-nation of ingredients can occur betweenthese types of products and products notintended to contain metal salts if manu-facturing conditions are not controlled.

The possibility of contamination andadulteration should be considered for anyherb or herbal medicine purchased over-seas or imported for personal use, orobtained over the internet.

Extracted from Australian Adverse DrugReactions Bulletin, Volume 26, Number 1,2007

References

1. Safety of Ayurvedic medicine in Australia.www.tga.gov.au/cm/ayurvedic.htm

2. Ernst E. Contamination of herbal medicines.The Pharmaceutical Journal 2005; 275; 167

3. Pharmacopoeia of the People’s Republic ofChina. Beijing, China: People’s MedicalPublishing House 2005.

ADHD drugs: cardiovascularand psychiatric eventsUnited States of America — The Foodand Drug Administration (FDA) hasdirected the manufacturers of all drugproducts approved for the treatment ofAttention Deficit Hyperactivity Disorder(ADHD) to develop Patient MedicationGuides concerning risks of possiblecardiovascular and psychiatric events.

An FDA review of reports of seriouscardiovascular adverse events in patientstaking usual doses of ADHD productsrevealed reports of sudden death inpatients with underlying serious heartproblems or defects, and reports of strokeand heart attack in adults with certain riskfactors.

Another FDA review of ADHD medicinesrevealed a slight increased risk (about 1per 1000) for drug-related psychiatricadverse events, such as hearing voices,becoming suspicious for no reason, orbecoming manic, even in patients whodid not have previous psychiatric prob-lems.

The medicines that are the focus of therevised labelling and new Patient Medi-cation Guides include the following:

Adderall® (mixed salts of a single entityamphetamine product) Tablets

Adderall® XR (mixed salts of a single entityamphetamine product) Extended-ReleaseCapsules

Concerta® (methylphenidate hydrochloride)Extended-Release Tablets

Daytrana® (methylphenidate) TransdermalSystem

Desoxyn® (methamphetamine HCl) Tablets

Dexedrine® (dextroamphetamine sulfate)

Spansule® Capsules and Tablets

Focalin® (dexmethylphenidate hydrochlo-ride) Tablets

Focalin® XR (dexmethylphenidate hydro-chloride) Extended-Release Capsules

Metadate® CD (methylphenidate hydrochlo-ride) Extended-Release Capsules

Methylin® (methylphenidate hydrochloride)Oral Solution

Methylin® (methylphenidate hydrochloride)Chewable Tablets

Ritalin® (methylphenidate hydrochloride)Tablets

Ritalin® SR (methylphenidate hydrochlo-ride) Sustained-Release Tablets

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Ritalin® LA (methylphenidate hydrochloride)Extended-Release Capsules

Strattera® (atomoxetine HCl) Capsules

Reference: FDA News, P07-26, 21 February2007 with draft Patient Medication Guides foreach product at http://www.fda.gov/cder/drug/infopage/ADHD/default.htm.

Clozapine can impair motilityof the entire GI tractNew Zealand — Clozapine (Clozaril®,Clopine®) is an atypical antipsychotic thatis effective for treatment-resistant schizo-phrenia. It causes agranulocytosis in upto 1% of patients (1) and regular monitor-ing of neutrophil counts is mandatorythroughout treatment. In New Zealandone death from agranulocytosis has beenreported. In contrast, four deaths fromcomplications of severe constipation havebeen reported to the Intensive MedicinesMonitoring Programme. Health profes-sionals are reminded that the gastro-intestinal (GI) effects of clozapine arepotentially serious.

Constipation is often regarded as afrequent, minor side effect of clozapine.However, review of New Zealand reportsshows that clozapine-induced constipa-

Spontaneous monitoring systems are useful in detecting signals of relatively rare, serious and unexpected adversedrug reactions. A signal is defined as "reported information on a possible causal relationship between an adverse eventand a drug, the relationship being unknown or incompletely documented previously. Usually, more than a single reportis required to generate a signal, depending upon the seriousness of the event and the quality of the information". Allsignals must be validated before any regulatory decision can be made.

tion may be associated with seriouseffects such as intestinal obstruction,bowel perforation and toxic megacolon.

In addition to reports of constipationassociated with clozapine, there havebeen three reports of paralytic ileus and afurther three reports of oesophagealdysmotility. These case reports suggestthat clozapine may reduce GI motilitythroughout the gut, resulting in complica-tions higher in the GI tract.

Many anticholinergic drugs can cause GIdysmotility, but clozapine has a muchmore potent effect through its interactionwith multiple receptors (including anti-cholinergic and serotonergic receptors)affecting GI activity. This action is exacer-bated by co-prescription of anticholinergicagents such as benztropine and tricyclicantidepressants.

References

1. Alvir JMJ, Lieberman JA, Safferman AZ, etal. Clozapine-induced agranulocytosis. NewEngland Journal of Medicine 1993;329:162-167

2. PM Ellis. Clozapine: Fatal ‘constipation’more common than fatal agranulocytosis.Prescriber Update. March 2007. http://www.medsafe.govt.nz

Safety and Efficacy Issues

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Essential Medicines

15th Model Listof Essential MedicinesModel List updatedThe WHO Model List of Essential Medi-cines allows countries to select medicinesof public health priority, address problemsof cost and availability and provides guid-ance to pharmaceutical manufacturers onmedicine needs.

During its 2007 meeting in Geneva, theWHO Expert Committee on EssentialMedicines made a number of importantupdates to the Model List of EssentialMedicines (set out on the followingpages). These included the addition offive fixed-dose-combinations to treat HIV/AIDS in adults, two of which are availablein generic form, and antimalarials recom-mended by WHO.

Five oral liquid formulations were in-cluded for children — three for epilepsy,one for children born prematurely, andone new medicine for HIV/AIDS. Threeother epilepsy medicines were included inthe form of chewable, dispersable tabletswhich are also effective in children.

A medicines list for childrenFollowing recommendations from theExpert Committee, work will begin tocreate a list if essential medicines specifi-cally tailored to children’s needs. A groupof experts will meet in July 2007 to beginwork on a list of medicines to addressdiseases of high mortality and morbidityin children.

Children suffer from the same illnessesas adults but they are more seriously

affected by certain conditions such asrespiratory tract infections, malaria anddiarrhoeal diseases — particularly indeveloping countries. An estimated 10.6million children under five die every year,many from treatable conditions. In 2005,2.3 million children under 15 years wereHIV positive.

In spite of the huge need, there are fewformulations appropriate for children orthat can be easily consumed by a child.At present, children must often takecrushed adult tablets, with little evidenceto guide the efficacy and safety of thedose. When medicines do exist in theright dosage they are usually in syrupform, which may pose supply, storageand pricing problems in developingcountries.

The challenge for children becomes moreacute when they are affected by a condi-tion requiring combination therapy, suchas HIV/AIDS and malaria. In these cases,fixed dose combination tablets are re-quired. While production of adult fixed-dose-combinations is increasing, theseare lacking for children. In addition, anti-retrovirals for children are currently threetimes more expensive than the adultversions.

WHO will also work with partners toadvocate innovation and research intochildren’s medicines, manufacture of newdosage forms and new formulas, andmechanisms to relay information aboutchildren’s medicines to countries quicklyand effectively.

Reference: WHO News Release. WHO/17. 13April 2007 http://www.who.int

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WHO Model List of Essential Medicines15th Edition, revised March 2007

The core list presents a list of minimum medicine needs for a basic health care system, listingthe most efficacious, safe and cost-effective medicines for priority conditions. Priority condi-tions are selected on the basis of current and estimated future public health relevance, andpotential for safe and cost-effective treatment.

The complementary list presents essential medicines for priority diseases, for which special-ized diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist trainingare needed. In case of doubt medicines may also be listed as complementary on the basis ofconsistent higher costs or less attractive cost-effectiveness in a variety of settings.

The square box symbol (■ ) is primarily intended to indicate similar clinical performance withina pharmacological class. The listed medicine should be the example of the class for whichthere is the best evidence for effectiveness and safety. In some cases, this may be the firstmedicine that is licensed for marketing; in other instances, subsequently licensed compoundsmay be safer or more effective. Where there is no difference in terms of efficacy and safetydata, the listed medicine should be the one that is generally available at the lowest price,based on international drug price information sources. Therapeutic equivalence is only indi-cated on the basis of reviews of efficacy and safety and when consistent with WHO clinicalguidelines. National lists should not use a similar symbol and should be specific in their finalselection, which would depend on local availability and price. Medicines are listed in alphabeti-cal order, within sections.

The presence of an entry on the Essential Medicines List carries no assurance as to pharma-ceutical quality. It is the responsibility of each local regulatory authority to ensure that eachbrand is of appropriate pharmaceutical quality (including stability) and that, when relevant,different brands are interchangeable.

Dosage forms of medicines are listed in alphabetical order and there is no implication of pref-erence for one form over another. Standard treatment guidelines should be consulted for infor-mation on appropriate dosage forms.

Entries of the type oral liquid are intended to permit any solution, suspension or other form ofliquid. Granules for reconstitution as an oral liquid may substitute for oral liquids, and typicallycarry benefits in the form of better stability and lower transport costs. If more than one type oforal liquid is available on the same market (e.g. solution, suspension, granules for reconstitu-tion), they may be interchanged and in such cases should be bioequivalent. It is preferable thatoral liquids do not contain sugar, and that solutions for children do not contain alcohol.

Entries of the type tablet are intended to allow various forms of immediate-release tablet suchas uncoated, film-coated, crushable, chewable, dispersible etc. Enteric coating, on the otherhand, modifies drug release, and enteric-coated products are a modified release dosage form.Crushable, chewable and dispersible tablets may be easier to administer to paediatric popula-tions and to the elderly.

Explanatory Notes

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1. Anaesthetics

1.1 General anaesthetics and oxygen

■ halothane inhalation

ketamine injection: 50 mg(as hydrochloride)/

ml in 10-ml vial

nitrous oxide inhalation

oxygen inhalation (medicinal gas)

■ thiopental powder for injection: 0.5 g,1.0 g (sodium salt) in ampoule

1.2 Local anaesthetics

■ bupivacaine Injection: 0.25%; 0.5%(hydrochloride) in via.

Injection for spinal anaesthesia:0.5% (hydrochloride) in 4-ml ampoule

to be mixed with 7.5% glucose solution

■ lidocaine Injection: 1%; 2%(hydrochloride) in vial

Injection for spinal anaesthesia:5% (hydrochloride) in 2-ml ampoule

to be mixed with 7.5% glucose solution

Topical forms: 2–4% (hydrochloride)

lidocaine + epinephrine Dental cartridge: (adrenaline) 2% (hydrochloride) +

epinephrine 1:80 000

Injection: 1%; 2% (hydrochloride) +epinephrine 1:200 000 in vial

Complementary List

ephedrine Injection: 30 mg (hydro-chloride)/ml in 1-ml ampoule

(For use in spinal anaesthesiaduring delivery, to prevent

hypotension)

1.3 Preoperative medication and sedationfor short-term procedures

atropine Injection: 1 mg (sulfate)in 1-ml ampoule

■ diazepam Injection: 5 mg/ml in 2-ml ampoule

Tablet: 5 mg

morphine Injection: 10 mg (sulfate orhydrochloride) in 1-ml ampoule

promethazine Oral liquid: 5 mg(hydrochloride)/5 ml

2. Analgesics, antipyretics, non-steroidal anti-inflammatorymedicines (NSAIMs), medi-cines used to treat gout anddisease modifying agents inrheumatoid disorders(DMARDs)2.1 Nonopioids and nonsteroidal anti-inflammatory medicines (NSAIMs)

acetylsalicylic acid Suppository: 50–150 mg

Tablet: 100–500 mg

ibuprofen Tablet: 200 mg; 400 mg

paracetamol* Oral liquid: 125 mg/5 m

Suppository: 100 mg

Tablet: 100–500 mg

* Not recommended for anti-inflammatory use dueto lack of proven benefit to that effect.

2.2 Opioid analgesics

codeine Tablet: 30 mg (phosphate)

morphine Injection: 10 mg (morphinehydrochloride or morphine

sulfate) in 1-ml ampoule

Oral liquid: 10 mg (morphinehydrochloride or morphine

sulfate)/5 ml

Tablet: 10 mg (morphine sulfate)

Tablet (prolonged release): 10 mg;30 mg; 60 mg (morphine sulfate)

2.3 Medicines used to treat gout

allopurinol Tablet: 100 mg

2.4 Disease modifying agents used inrheumatoid disorders (DMARDs)

chloroquine Tablet: 100 mg; 150 mg(as phosphate or sulfate).

Complementary List

azathioprine Tablet: 50 mg

methotrexate Tablet: 2.5 mg (as sodium salt)

penicillamine Capsule or tablet: 250 mg

sulfasalazine Tablet: 500 mg

15th Model List of Essential Medicines

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3. Antiallergics and medi-cines used in anaphylaxis■ chlorphenamine Injection: 10 mg (hydrogen

maleate) in 1-ml ampoule

Tablet: 4 mg (hydrogen maleate)

dexamethasone Injection: 4 mg dexamethasonephosphate (as disodium salt)

in 1-ml ampoule

epinephrine (adrenaline) Injection: 1 mg (ashydrochloride or hydrogen

tartrate) in 1-ml ampoule

hydrocortisone Powder for injection: 100 mg(as sodium succinate) in vial

■ prednisolone* Tablet: 5 mg; 25 mg

* There is no evidence for complete clinical simil-arity between prednisolone and dexamethasone athigh doses.

4. Antidotes and other sub-stancess used in poisonings

4.1 Non-specificcharcoal, activated Powder

4.2 Specific

acetylcysteine Injection: 200 mg/ml in10-ml ampoule

atropine Injection: 1 mg (sulfate) in1-ml ampoule

calcium gluconate Injection: 100 mg/ml in10-ml ampoule

deferoxamine Powder for injection: 500 mg(mesilate) in vial

dimercaprol Injection in oil: 50 mg/mlin 2-ml ampoule

DL-methionine Tablet: 250 mg

methylthioninium chloride Injection: 10 mg/ml in(methylene blue) 10-ml ampoule

naloxone Injection: 400 micrograms(hydrochloride) in 1-ml ampoule

penicillamine Capsule or tablet: 250 mg

potassium ferric hexacyano- Powder for oralferrate(II) -2H20 (Prussian blue) administration

sodium calcium edetate Injection: 200 mg/mlin 5-ml ampoule

sodium nitrite Injection: 30 mg/mlin 10-ml ampoule

sodium thiosulfate Injection: 250 mg/mlin 50-ml ampoule

5. Anticonvulsants/anti-epilepticscarbamazepine Oral liquid: 100 mg/5 ml

Tablet (chewable):100 mg; 200 mg

Tablet (scored): 100 mg; 200 mg

■ diazepam Injection: 5 mg/ml in 2-mlampoule (intravenous or rectal)

magnesium sulfate* Injection: 500 mg/ml in2-ml ampoule; 500 mg/ml in

10-ml ampoule

* For use in eclampsia and severe pre-eclampsia andnot for other convulsant disorders.

phenobarbital Injection: 200 mg/ml(phenobarbital sodium)

Oral liquid: 15 mg/5 ml (phenobarbital)or 5 ml (phenobarbital sodium)

Tablet: 15-100 mg (phenobarbital)

phenytoin Capsule: 25 mg; 50 mg;100 mg (sodium salt)

Injection: 50 mg/mlin 5-ml vial (sodium salt)

Oral liquid: 25-30 mg/5 ml.*

Tablet: 25 mg; 50 mg;100 mg (sodium salt)

Tablet (chewable): 50 mg

* The presence of both 25 mg/5 ml and 30 mg/5 mlstrengths on the same market would cause confu-sion in prescribing and dispensing and should beavoided.

valproic acid Oral liquid: 200 mg/5 ml

Tablet (crushable): 100 mg

Tablet (enteric-coated): 200 mg;500 mg (sodium valproate)

Complementary List

ethosuximide Capsule: 250 mg

Oral liquid: 250 mg/5 ml


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6. Anti-infective medicines6.1 Anthelminthics

6.1.1 Intestinal anthelminthics

albendazole Tablet (chewable): 400 mg

levamisole Tablet: 50 mg; 150 mg(as hydrochloride)

■ mebendazole Tablet (chewable): 100 mg;500 mg

niclosamide* Tablet (chewable): 500 mg

* Niclosamide is listed for use when praziquanteltreatment fails.

praziquantel Tablet: 150 mg; 600 mg

pyrantel Oral liquid: 50 mg (as embonate)/ml

Tablet (chewable): 250 mg(as embonate)

6.1.2 Antifilarials

ivermectin Tablet (scored): 3 mg; 6 mg

Complementary List

diethylcarbamazine Tablet: 50 mg; 100 mg(dihydrogen citrate)

suramin sodium Powder for injection: 1 g in vial

6.1.3 Antischistosomals and antitrematodemedicine

praziquantel Tablet: 600 mg

triclabendazole Tablet: 250 mg

Complementary List

oxamniquine* Capsule: 250 mg


* Oxamniquine is listed for use when praziquanteltreatment fails.

6.2 Antibacterials

6.2.1 Beta Lactam medicines

amoxicillin Capsule or tablet: 250 mg;500 mg (anhydrous)

Powder for oral liquid: 125 mg(anhydrous)/5 ml

amoxicillin + Tablet: 500 mg + 125 mgclavulanic acid

ampicillin Powder for injection: 500 mg;1 g (as sodium salt) in vial

benzathine benzylpenicillin Powder for injection:1.44 g benzylpenicillin

(=2.4 million IU) in 5-ml vial

benzylpenicillin Powder for injection: 600 mg(= 1 million IU); 3 g (= 5 million IU)

(sodium or potassium salt) in vial

cefazolin* Powder for injection: 1 g(as sodium salt) in vial

* For surgical prophylaxis.

cefixime* Capsule: 400 mg

* Only listed for single-dose treatment of uncompli-cated ano-genital gonorrhoea.

■ cloxacillin Powder for injection: 500 mg(as sodium salt) in vial

Capsule: 500 mg; 1 g (as sodium salt)

Powder for oral liquid: 125 mg(as sodium salt)/5 ml

phenoxymethylpenicillin Powder for oral liquid:250 mg (as potassium salt)/5 ml

Tablet: 250 mg (as potassium salt)

procaine benzylpenicillin Powder for injection:1 g (=1 million IU);

3 g (=3 million IU) in vial

Complementary List

ceftazidime Powder for injection: 250 mg(as pentahydrate) in vial

■ ceftriaxone Powder for injection: 250 mg,1 g (as sodium salt) in vial

imipenem* + Powder for injection:cilastatin * 250 mg (as monohydrate) +

250 mg (as sodium salt);500 mg (as monohydrate) +

500 mg (as sodium salt) in vial

* Only listed for the treatment of life-threatening hos-pital-based infection due to suspected or provenmultidrug-resistant infection.

6.2.2 Other antibacterials

azithromycin* Capsule: 250 mg or 500 mg


* Only listed for single-dose treatment of genitalChlamydia trachomatis and of trachoma.


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chloramphenicol Capsule: 250 mg

Oily suspension for injection:0.5 g (as sodium succinate)/ml

in 2-ml ampoule

Oral liquid: 150 mg (as palmitate)/5 ml

Powder for injection: 1 g(sodium succinate) in vial

■ ciprofloxacin* Tablet: 250 mg(as hydrochloride)

* Final selection depends on indication for use.

doxycycline* Capsule or tablet:100 mg (hydrochloride)


■ erythromycin Capsule or tablet: 250 mg (as stearate or ethyl succinate)

Powder for injection: 500 mg(as lactobionate) in vial

Powder for oral liquid: 125 mg(as stearate or ethyl succinate)

■ gentamicin* Injection: 10 mg;40 mg (as sulfate)/ml in 2-ml vial


■ metronidazole Injection: 500 mg in 100-ml vial

Oral liquid: 200 mg (as benzoate)/5 ml

Suppository: 500 mg; 1 g

Tablet: 200-500 mg

nitrofurantoin Tablet: 100 mg

spectinomycin Powder for injection: 2 g(as hydrochloride) in vial

sulfamethoxazole + Injection: 80 mg + 16 mg/mltrimethoprim in 5-ml and 10-ml ampoules

Oral liquid: 200 mg + 40 mg/5 ml

Tablet: 100 mg + 20 mg;400 mg + 80 mg

trimethoprim Tablet: 100 mg; 200 mg

Complementary List

clindamycin Capsule: 150 mg

Injection: 150 mg(as phosphate)/ml

sulfadiazine Injection: 250 mg(sodium salt) in 4-ml ampoule

Tablet: 500 mg

vancomycin Powder for injection: 250 mg(as hydrochloride) in vial

6.2.3 Antileprosy medicinesMedicines used in the treatment of leprosy shouldnever be used except in combination. Combinationtherapy is essential to prevent the emergence of drugresistance. Colour coded blister packs (MDT blisterpacks) containing standard two medicine(paucibacillary leprosy) or three medicine(multibacillary leprosy) combinations for adult andchildhood leprosy should be used. MDT blister packscan be supplied free of charge through WHO.

clofazimine Capsule: 50 mg; 100 mg

dapsone Tablet: 25 mg; 50 mg; 100 mg

rifampicin Capsule or tablet: 150 mg; 300 mg

6.2.4 Antituberculosis medicines

ethambutol Tablet: 100–400 mg (hydrochloride)

isoniazid Tablet: 100–300 mg

Tablet (scored): 50 mg

isoniazid + ethambutol Tablet: 150 mg + 400 mg

pyrazinamide Tablet: 400 mg

Tablet (dispersible): 150 mg

Tablet (scored): 150 mg

rifampicin Capsule or tablet: 150 mg; 300 mg

rifampicin + isoniazid Tablet: 60 mg + 30 mg;150 mg + 75 mg; 300 mg + 150 mg

60 mg + 60 mg (For intermittentuse three times weekly)

150 mg + 150 mg (For intermittentuse three times weekly)

rifampicin + isoniazid + Tablet: 150 mg +ethambutol 75 mg + 275 mg

rifampicin + isoniazid + Tablet: 60 mg +pyrazinamide 30 mg + 150 mg;

150 mg + 75 mg + 400 mg

150 mg + 150 mg + 500 mg(For intermittent use three times weekly)

rifampicin + isoniazid + Tablet: 150 mg + 75 mg +pyrazinamide + ethambutol 400 mg + 275 mg


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streptomycin Powder for injection:1 g (as sulfate) in vial

Complementary ListReserve second-line drugs for the treatment ofmultidrug-resistant tuberculosis (MDR-TB) should beused in specialized centres adhering to WHO stand-ards for TB control.

amikacin Powder for injection: 1000 mg in vial

ρ-aminosalicylic acid Granules: 4 g in sachet

Tablet: 500 mg

capreomycin Powder for injection: 1000 mg in vial

cycloserine Capsule or tablet: 250 mg

ethionamide Tablet: 125 mg; 250 mg

kanamycin Powder for injection: 1000 mg in vial

ofloxacin* Tablet: 200 mg; 400 mg

* Levofloxacin may be an alternative based onavailability and programme considerations.

6.3 Antifungal medicines

clotrimazole Vaginal cream: 1%; 10%

Vaginal tablet: 100 mg; 500 mg

■ fluconazole Capsule: 50 mg

Injection: 2 mg/ml in vial


griseofulvin Capsule or tablet: 125 mg; 250 mg

nystatin Lozenge: 100 000 IU

Pessary: 100 000 IU

Tablet: 100 000 IU; 500 000 IU

Complementary List

amphotericin B Powder for injection:50 mg in vial

flucytosine Capsule: 250 mg

Infusion: 2.5 g in 250 ml

potassium iodide Saturated solution

6.4 Antiviral medicines

6.4.1 Antiherpes medicines

■ aciclovir Powder for injection:250 mg (as sodium salt) in vial

Tablet: 200 mg

6.4.2 Antiretrovirals

Based on current evidence and experience of use,medicines in the following three classes of antiretro-virals are included as essential medicines for treat-ment and prevention of HIV (prevention of mother-to-child transmission and post exposure prophylaxis).The Committee emphasizes the importance of usingthese products in accordance with global and nationalguidelines. The Committee recommends and en-dorses the use of fixed-dose combinations and thedevelopment of appropriate new fixed-dose combi-nations, including modified dosage forms, non-refrig-erated products and paediatric dosage forms withassured pharmaceutical quality.

6.4.2.1 Nucleoside/nucleotide reversetranscriptase inhibitors

abacavir (ABC) Oral liquid: 100 mg(as sulfate)/5 m

Tablet: 300 mg (as sulfate)

didanosine (ddI) Buffered powder for oral liquid:100 mg; 167 mg; 250 mg packets

Capsule (unbuffered enteric-coated):125 mg; 200 mg; 250 mg; 400 mg

Tablet (buffered chewable,dispersible): 25 mg; 50 mg; 100 mg;

150 mg; 200 mg

emtricitabine (FTC)* Capsule: 200 mg

Oral liquid: 10 mg/ml

* 3TC is an acceptable alternative to FTC, based onknowledge of the pharmacology, the resistance pat-terns and clinical trials of antiretrovirals.

lamivudine (3TC) Tablet: 150 mg


stavudine (d4T) Capsule: 15 mg;20 mg; 30 mg; 40 mg*

* The Committee expects this dosage form to bereviewed for possible deletion at the next meeting.

Powder for oral liquid: 5 mg/5 ml

tenofovir Capsule: 300 mg (tenofovirdisoproxil fumarate – equivalent to

245 mg tenofovir disoproxil)

zidovudine Capsule: 100 mg; 250 mg

(ZDV or AZT) Oral liquid: 50 mg/5 ml

Solution for IV infusioninjection: 10 mg/ml in 20-ml vial

Tablet: 300 mg


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6.4.2.2 Non-nucleoside reverse transcriptaseinhibitors

efavirenz (EFV or EFZ) Capsule: 50 mg;100 mg; 200 mg


Tablet: 600 mg

nevirapine (NVP) Oral liquid: 50 mg/5 ml

Tablet: 200 mg

6.4.2.3 Protease inhibitorsSelection of protease inhibitor(s) from the Model Listwill need to be determined by each country after con-sideration of international and national treatmentguidelines and experience. Ritonavir is recommendedfor use in combination as a pharmacological booster,and not as an antiretroviral in its own right.

This section will be reviewed by the Committee as apriority at its next meeting. It is expected that appli-cation for a heat stable tablet formulation containing200/50 mg lopinavir + ritonavir will be submitted forthe next meeting.

indinavir (IDV) Capsule: 200 mg; 333 mg;400 mg (as sulfate).

lopinavir + Capsule: 133.3 mg + 33.3 mgritonavir (LPV/r)

Oral liquid: 400 mg + 100 mg/5 ml

nelfinavir (NFV) Oral powder: 50 mg/g

Tablet: 250 mg (as mesilate)

ritonavir Oral liquid: 400 mg/5 ml

Oral solid dosage form: 100 mg

saquinavir (SQV) Capsule: 200 mg

FIXED-DOSE COMBINATIONS

efavirenz + emtricitabine* Tablet: 600 mg ++ tenofovir 200 mg + 300 mg


emtricitabine* + tenofovir Tablet: 200 mg + 300 mg


stavudine + lamivudine + Tablet: 30 mg +nevirapine 150 mg + 200 mg

zidovudine + lamivudine Tablet: 300 mg + 150 mg

zidovudine + lamivudine + Tablet: 300 mg +nevirapine 150 mg + 200 mg

6.4.3 Other antivirals

ribavirin Injection for intravenous administration:1000 mg and 800 mg in 10-ml

phosphate buffer solution

Oral solid dosage forms: 200 mg;400 mg; 600 mg

6.5 Antiprotozoal medicines

6.5.1 Antiamoebic and antigiardiasis medicines

diloxanide Tablet: 500 mg (furoate)

■ metronidazole Injection: 500 mg in 100-ml vial

Oral liquid: 200 mg (as benzoate)/5 ml

Tablet: 200-500 mg

6.5.2 Antileishmaniasis medicines

■ meglumine antimoniate Injection, 30%,equivalent to approximately

8.1% antimony in 5-ml ampoule

paromomycin Solution for intramuscular injection:750 mg/2 ml (as sulfate)

Complementary List

amphotericin B Powder for injection:50 mg in vial

pentamidine Powder for injection: 200 mg;300 mg (isetionate) in vial

6.5.3 Antimalarial medicines

6.5.3.1 For curative treatment

Medicines for the treatment of P. falciparum malariacases should be used in combination. The list cur-rently recommends combinations according to treat-ment guidelines. The Committee recognizes that notall of these FDCs exist and encourages their devel-opment and rigorous testing. The Committee alsoencourages development and testing of rectal dos-age formulations.

amodiaquine* Tablet: 153 mg or 200 mg(as hydrochloride)

* To be used (a) in combination with artesunate 50mg OR (b) may be used alone for the treatment ofPlasmodium vivax, P.ovale and P.malariaeinfections.

artemether Oily injection: 80 mg/mlin 1-ml ampoule

For use in the management of severe malaria.


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artemether + Tablet: 20 mg + 120 mglumefantrine*

* Not recommended in the first trimester of pregnancyor in children below 5 kg.

artesunate* Injection: ampoules,containing 60 mg anhydrous

artesunic acid with a separateampoule of 5% sodium bicarbonate solution

For use in the management of severe malaria.

Tablet: 50 mg

* To be used in combination with either amodiaquine,mefloquine or sulfadoxine + pyrimethamine.

chloroquine Oral liquid: 50 mg (asphosphate or sulfate)/5 ml

Tablet: 100 mg; 150 mg(as phosphate or sulfate)

doxycycline* Capsule: 100 mg (as hydrochloride)

Tablet (dispersible): 100 mg(as monohydrate)

* For use only in combination with quinine.

mefloquine* Tablet: 250 mg (as hydrochloride)

* To be used in combination with artesunate 50 mg

primaquine* Tablet: 7.5 mg;15 mg (as diphosphate)

* Only for use to achieve radical cure of P.vivax andP.ovale infections, given for 14 days.

quinine* Injection: 300 mg quininehydrochloride/ml in 2-ml ampoule

Tablet: 300 mg (quinine sulfate)or 300 mg (quinine bisulfate)

* For use only in the management of severe malaria,and should be used in combination with doxycycline.

sulfadoxine + * Tablet: 500 mg + 25 mgpyrimethamine

* Only in combination with artesunate 50 mg

6.5.3.2 For prophylaxis

chloroquine* Oral liquid: 50 mg (asphosphate or sulfate)/5 ml

Tablet: 150 mg (asphosphate or sulfate)

* For use only in central American regions for P.vivax.

doxycycline Capsule or tablet:100 mg ( hydrochloride)

mefloquine Tablet: 250 mg(as hydrochloride)

proguanil* Tablet: 100 mg (hydrochloride)

* For use only in combination with chloroquine.

6.5.4 Antipneumocystosis andantitoxoplasmosis medicines

pyrimethamine Tablet: 25 mg

sulfamethoxazole + Injection: 80 mg + 16 mg/mltrimethoprim in 5-ml ampoule; 80 mg +

16 mg/ml in 10-ml ampoule

Complementary List

pentamidine Tablet: 200 mg; 300 mg

6.5.5 Antitrypanosomal medicines

6.5.5.1 African trypanosomiasis

Medicines for the treatment of 1st stageAfrican trypanosomiasis

pentamidine* Powder for injection: 200 mg(pentamidine isetionate) in vial

* To be used for the treatment of Trypansoma bruceigambiense infection.

suramin sodium* Powder for injection: 1 g in vial.

* To be used exclusively for the treatment of the ini-tial phase of T. brucei rhodesiense infection.

Medicines for the treatment of2nd stage African trypanosomiasis

eflornithine Injection: 200 mg(hydrochloride)/ml in 100-ml bottle

melarsoprol Injection: 3.6% solution,5-ml ampoules (180 mg

of active compound)

6.5.5.2 American trypanosomiasis

benznidazole Tablet: 100 mg

nifurtimox Tablet: 30 mg; 120 mg; 250 mg

7. Antimigraine medicines7.1 For treatment of acute attack

acetylsalicylic acid Tablet: 300-500 mg

paracetamol Tablet: 300-500 mg

7.2 For prophylaxis

■ propranolol Tablet: 20 mg; 40 mg(hydrochloride)


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8. Antineoplastic, immuno-suppressives and medicinesused in palliative care

8.1 Immunosuppressive medicines

Complementary List

azathioprine Powder for injection:100 mg (as sodium salt) in vial

Tablet: 50 mg

ciclosporin Capsule: 25 mg

Concentrate for injection: 50 mg/ml in1-ml ampoule for organ transplantation

8.2 Cytotoxic medicines

This section is expected to be reviewed at the nextmeeting.

Complementary List

asparaginase Powder for injection:10 000 IU in vial

bleomycin Powder for injection:15 mg (as sulfate) in vial

calcium folinate Injection: 3 mg/mlin 10-ml ampoule

Tablet: 15 mg

chlorambucil Tablet: 2 mg

cisplatin Powder for injection:10 mg; 50 mg in vial

cyclophosphamide Powder for injection:500 mg in vial

Tablet: 25 mg

cytarabine Powder for injection: 100 mg in vial

dacarbazine Powder for injection: 100 mg in vial

dactinomycin Powder for injection:500 micrograms in vial

daunorubicin Powder for injection:50 mg (as hydrochloride)

doxorubicin Powder for injection: 10 mg;50 mg (hydrochloride) in vial

etoposide Capsule: 100 mg

Injection: 20 mg/ml in 5-ml ampoule

fluorouracil Injection: 50 mg/mlin 5-ml ampoule

mercaptopurine Tablet: 50 mg

methotrexate Powder for injection:50 mg (as sodium salt) in vial

Tablet: 2.5 mg (as sodium salt)

procarbazine Capsule: 50 mg (as hydrochloride)

vinblastine Powder for injection:10 mg (sulfate) in vial

vincristine Powder for injection:1 mg; 5 mg (sulfate) in vial

8.3 Hormones and antihormones

Complementary List

dexamethasone Injection: 4 mgdexamethasone phosphate (asdisodium salt) in 1-ml ampoule

hydrocortisone Powder for injection: 100 mg (as sodium succinate) in vial

■ prednisolone* Tablet: 5 mg; 25 mg

* There is no evidence for complete clinical similaritybetween prednisolone and dexamethasone at highdoses.

tamoxifen Tablet: 10 mg; 20 mg (as citrate)

8.4 Medicines used in palliative care

The WHO Expert Committee recognizes the impor-tance of listing specific medicines in the PalliativeCare Section. Some medicines currently used in pal-liative care are included in the relevant sections ofthe Model List, according to their therapeutic use, e.g.analgesics. The Guidelines for Palliative Care thatwere referenced in the previous list are in need ofupdate. The Committee expects applications for medi-cines needed for palliative care to be submitted forthe next meeting.

9. Antiparkinsonism medicinesbiperiden Injection: 5 mg (lactate)

in 1-ml ampoule

Tablet: 2 mg (hydrochloride)

levodopa + ■ carbidopa Tablet: 100 mg + 10 mg;250 mg + 25 mg

10. Medicinces affectingthe blood10.1 Antianaemia medicines

ferrous salt Oral liquid: equivalent to 25 mgiron (as sulfate)/ml


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Tablet: equivalent to 60 mg iron

ferrous salt + Tablet equivalent to 60 mg iron +folic acid 400 micrograms folic acid

(Nutritional supplement for use during pregnancy)

folic acid Tablet: 1 mg; 5 mg

hydroxocobalamin Injection: 1 mg in1-ml ampoule

10.2 Medicines affecting coagulation

heparin sodium Injection: 1000 IU/ml;5000 IU/ml; 20,000

IU/ml in 1-ml ampoule

phytomenadione Injection: 10 mg/mlin 5-ml ampoule

Tablet: 10 mg

protamine sulfate Injection: 10 mg/mlin 5-ml ampoule

■ warfarin Tablet: 1 mg; 2 mg; 5 mg (sodium salt)

11. Blood products andplasma substitutes11.1 Plasma substitutes

■ dextran 70* Injectable solution: 6%

* Polygeline, injectable solution, 3.5% is consideredas equivalent

11.2 Plasma fractions for specific use

All plasma fractions should comply with the WHORequirements for the Collection, Processing andQuality Control of Blood, Blood Components andPlasma Derivatives (Revised 1992). (WHO Techni-cal Report Series, No. 840, 1994, Annex 2).

Complementary List

human normal Intravenous administration:immunoglobulin 5%, 10% protein solution

Intramuscular administration:16% protein solution

■ factor VIII concentrate Dried

■ factor IX complex Dried(coagulation factors, II, VII,IX, X) concentrate

12. Cardiovascular medicines12.1 Antianginal medicines

■ atenolol Tablet: 50 mg; 100 mg

glyceryl trinitrate Tablet (sublingual): 500micrograms

■ isosorbide dinitrate Tablet (sublingual): 5 mg

verapamil Tablet: 40 mg;80 mg (hydrochloride)

12.2 Antiarrhythmic medicines

This subsection will be reviewed at the next meetingof the Expert Committee.


digoxin Injection: 250 micrograms/ml in 2-ml ampoule

Oral liquid: 50 micrograms/ml

Tablet: 62.5 micrograms;250 micrograms

epinephrine Injection: 100 micrograms/ml(adrenaline) (as acid tartrate or hydrochloride)

in 10-ml ampoule

lidocaine Injection: 20 mg (hydrochloride)/ml in 5-ml ampoule

verapamil Injection: 2.5 mg (hydrochloride)/ml in 2-ml ampoule

Tablet: 40 mg; 80 mg (hydrochloride)

Complementary List

■ procainamide Injection: 100 mg (hydro-chloride)/ml in 10-ml ampoule.

■ quinidine Tablet: 200 mg (sulfate)

12.3 Antihypertensive medicines

■ amlodipine Tablet: 5 mg


■ enalapril Tablet: 2.5 mg

hydralazine* Powder for injection:20 mg (hydrochloride) in ampoule

Tablet: 25 mg, 50 mg (hydrochloride)

* Hydralazine is listed for use in the acute manage-ment of severe pregnancy-induced hypertension only.Its use in the treatment of essential hypertension isnot recommended in view of the availability of moreevidence of efficacy and safety of other medicines.

■ hydrochlorothiazide Tablet (scored): 25 mg

methyldopa* Tablet: 250 mg

* Methyldopa is listed for use in the management ofpregnancy-induced hypertension only. Its use in the


105


treatment of essential hypertension is not recom-mended in view of the availability of more evidenceof efficacy and safety of other medicines.

Complementary List

sodium nitroprusside Powder for infusion:50 mg in ampoule

12.4 Medicines used in heart failure

This subsection will be reviewed at the next meetingof the Expert Committee.

digoxin Injection: 250 micrograms/ml in 2-ml ampoule

Oral liquid: 50 micrograms/ml

Tablet: 62.5 micrograms; 250 micrograms

■ enalapril Tablet: 2.5 mg

■ furosemide Injection: 10 mg/mlin 2-ml ampoule

Tablet: 40 mg


Complementary List

dopamine Injection: 40 mg (hydrochloride)in 5-ml vial

12.5 Antithrombotic medicines

acetylsalicylic acid Tablet: 100 mg

Complementary List

streptokinase Powder for injection:1.5 million IU in vial

12.6 Lipid-lowering agents

■ simvastatin* Tablet: 5 mg; 10 mg;20 mg; 40 mg

* For use in high-risk patients.

13. Dermatological medicines(topical)13.1 Antifungal medicines

benzoic acid + Ointment or cream: 6% + 3%salicylic acid

■ miconazole Ointment or cream: 2% (nitrate)

sodium thiosulfate Solution: 15%

Complementary List

selenium sulfide Detergent-basedsuspension: 2%

13.2 Anti-infective medicines

■ methylrosanilinium Aqueous solution: 0.5%chloride (gentian violet)

Tincture: 0.5%

neomycin sulfate + Ointment: 5 mg neomycin■ bacitracin sulfate + 250 IU

bacitracin zinc/g

potassium permanganate Aqueous solution:1:10 000

silver sulfadiazine Cream: 1%, in 500-g container

13.3 Anti-inflammatory and antipruriticmedicines

■ betamethasone Ointment or cream:0.1% (as valerate)

■ calamine lotion Lotion

■ hydrocortisone Ointment or cream:1% (acetate)

13.4 Astringent medicines

aluminium diacetate Solution: 5%

13.5 Medicines affecting skindifferentiation and proliferation

benzoyl peroxide Lotion or cream: 5%

coal tar Solution: 5%

dithranol Ointment: 0.1%-2%

fluorouracil Ointment: 5%

■ podophyllum resin Solution: 10-25%

salicylic acid Solution: 5%

urea Ointment or cream: 10%

13.6 Scabicides and pediculicides

■ benzyl benzoate Lotion: 25%

permethrin Cream: 5%

Lotion: 1%

14. Diagnostic agents14.1 Ophthalmic medicines

fluorescein Eye drops: 1% (sodium salt)


106


■ tropicamide Eye drops: 0.5%

14.2 Radiocontrast media

■ amidotrizoate Injection: 140-420 mg iodine(as sodium or meglumine salt)/

ml in 20-ml ampoule

barium sulfate Aqueous suspension

■ iohexol Injection: 140-350 mg iodine/ml in 5-ml; 10-ml; 20-ml ampoule

Complementary List

■ meglumine iotroxate Solution: 5-8 g iodinein 100-250 ml

15. Disinfectants and antiseptics15.1 Antiseptics

■ chlorhexidine Solution: 5% (digluconate)for dilution

■ ethanol Solution: 70% (denatured)

■ polyvidone iodine Solution: 10%

15.2 Disinfectants

■ chlorine base Powder: (0.1% availablecompound chlorine) for solution

■ chloroxylenol Solution: 4.8%

glutaral Solution: 2%

16. Diureticsamiloride Tablet: 5 mg (hydrochloride)

■ furosemide Injection: 10 mg/mlin 2-ml ampoule

Tablet: 40 mg


mannitol Injectable solution: 10%; 20%

spironolactone Tablet: 25 mg

17. Gastrointestinal medicines17.1 Antacids and other antiulcermedicines

aluminium hydroxide Oral liquid: 320 mg/5 ml

Tablet: 500 mg

■ ranitidine Injection: 25 mg/ml in 2-ml ampoule


Tablet: 150 mg (as hydrochloride)

magnesium Oral liquid: equivalent tohydroxide 550 mg magnesium oxide/10 ml

17.2 Antiemetic medicines

metoclopramide Injection: 5 mg (hydrochloride)/ml in 2-ml ampoule


promethazine Injection: 25 mg (hydrochloride)/ml in 2-ml ampoule

Oral liquid: 5 mg (hydrochloride)/5 ml

Tablet: 10 mg; 25 mg (hydrochloride)

17.3 Anti-inflammatory medicines

■ sulfasalazine Retention enema

Suppository: 500 mg

Tablet: 500 mg

Complementary List

■ hydrocortisone Retention enema

Suppository: 25 mg (acetate)

(■ only applies to hydrocortisone retention enema).

17.4 Laxatives

■ senna Tablet: 7.5 mg (sennosides)(or traditional dosage forms)

17.5 Medicines used in diarrhoea

17.5.1 Oral rehydration

oral rehydration salts*

glucose: 75 mEqsodium: 75 mEq or mmol/lchloride: 65 mEq or mmol/lpotassium: 20 mEq or mmol/lcitrate: 10 mmol/losmolarity: 245 mOsm/l

glucose: 13.5 g/lsodium chloride: 2.6 g/lpotassium chloride: 1.5 g/ltrisodium citrate dihydrate+: 2.9 g/l

+ trisodium citrate dihydrate may be replaced bysodium hydrogen carbonate (sodium bicarbonate)2.5 g/l. However, as the stability of this latter formu-lation is very poor under tropical conditions, it is onlyrecommended when manufactured for immediateuse.


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18.3.3 Intrauterine devices

copper-containing device

18.3.4 Barrier methods

condoms

diaphragms

18.3.5 Implantable contraceptives

levonorgestrel-releasing Two-rod levonorgestrel-implant releasing implant, each

rod containing 75 mg of levonorgestrel (150 mg total)

18.4 Estrogens

■ ethinylestradiol* Tablet: 10 micrograms;50 micrograms

* The public health relevance and/or comparative ef-ficacy and/or safety of this item has been questionedand its continued inclusion on the list will be reviewedat the next meeting of the Expert Committee.

18.5 Insulins and other antidiabetic agents

glibenclamide Tablet: 2.5 mg; 5 mg

insulin injection Injection: 40 IU/ml in 10-ml vial;(soluble) 100 IU/ml in 10-ml vial

intermediate-acting Injection: 40 IU/ml ininsulin 10-ml vial; 100 IU/ml

in 10-ml vial (as compoundinsulin zinc suspension

or isophane insulin)

metformin Tablet: 500 mg (hydrochloride)

18.6 Ovulation inducers

Complementary List

clomifene Tablet: 50 mg (citrate)

18.7 Progestogens

norethisterone* Tablet: 5 mg


Complementary List

medroxyprogesterone acetate* Tablet: 5 mg


* In cases of cholera, a higher concentration ofsodium may be required.

17.5.2 Medicines for diarrhoea in children

zinc sulfate* Oral liquid: in 10 mgper unit dosage forms

Tablet: in 10 mgper unit dosage forms

* In acute diarrhoea zinc sulfate should be used asan adjunct to oral rehydration salts.

17.5.3 Antidiarrhoeal (symptomatic) medicinesin adults

codeine* Tablet: 30 mg (phosphate)

* The role of this item has been questioned and itscontinued inclusion on the list will be reviewed at thenext meeting of the Expert Committee.

18. Hormones, other endocrinemedicines and contraceptives18.1 Adrenal hormones and syntheticsubstitutes

Addison’s disease is a rare condition; adrenalhormones are already included in section 3.

18.2 Androgens

Complementary List

testosterone Injection: 200 mg(enantate) in 1-ml ampoule

18.3 Contraceptives

18.3.1 Oral hormonal contraceptives

■ ethinylestradiol + Tablet: 30 micrograms +■ levonorgestrel 150 micrograms

■ ethinylestradiol + Tablet: 35 micrograms +■ norethisterone 1.0 mg

levonorgestrel Tablet: 30 micrograms;750 micrograms (pack of two);

1.5 mg

18.3.2 Injectable hormonal contraceptives

medroxyprogesterone Depot injection:acetate 150 mg/ml in 1-ml vial

medroxyprogesterone acetate + Injection:estradiol cypionate 25 mg + 5 mg

norethisterone enantate Oily solution: 200 mg/mlin 1-ml ampoule


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18.8 Thyroid hormones and antithyroidmedicines

levothyroxine Tablet: 50 micrograms;100 micrograms (sodium salt)

potassium iodide Tablet: 60 mg

■ propylthiouracil Tablet: 50 mg

19. Immunologicals19.1 Diagnostic agents

All tuberculins should comply with the WHO Require-ments for Tuberculins (Revised 1985). WHO ExpertCommittee on Biological Standardization. Thirty-sixthreport. (WHO Technical Report Series, No. 745, 1987,Annex 1).

tuberculin, purified protein Injectionderivative (PPD)

19.2 Sera and immunoglobulins

All plasma fractions should comply with the WHORequirements for the Collection, Processing andQuality Control of Blood, Blood Components andPlasma Derivatives (Revised 1992). WHO ExpertCommittee on Biological Standardization. Forty-thirdreport. (WHO Technical Report Series, No. 840, 1994,Annex 2).

anti-D immunoglobulin Injection: 250 micrograms(human) in single-dose vial

antitetanus immunoglobulin Injection: 500 IU(human) in vial

antivenom immunoglobulin* Injection

* Exact type to be defined locally.

diphtheria antitoxin Injection: 10 000 IU;20 000 IU in vial

■ rabies immunoglobulin Injection: 150 IU/ml in vial

19.3 Vaccines

Selection of vaccines from the Model List will need tobe determined by each country after considerationof international recommendations, epidemiology andnational priorities. The list below details the vaccinesfor which there is either a recommendation from theStrategic Advisory Group of Experts on Immuniza-tion (SAGE) (http://www.who.int/immunization/sage_conclusions/en/index.html) and/or a WHO po-sition paper (http://www.who.int/immunization/docu-ments/positionpapers/en/index.html). This site will beupdated as new position papers are published andcontains the most recent information and recommen-dations.

All vaccines should comply with the WHO Require-ments for Biological Substances.

BCG vaccine

cholera vaccine

diphtheria vaccine

hepatitis A vaccine

hepatitis B vaccine

Haemophilus influenzae type b vaccine

influenza vaccine

Japanese encephalitis vaccine

measles vaccine

meningococcal meningitis vaccine

mumps vaccine

pertussis vaccine

pneumococcal vaccine

poliomyelitis vaccine

rabies vaccine

rotavirus vaccine

rubella vaccine

tetanus vaccine

typhoid vaccine

varicella vaccine

yellow fever vaccine

20. Muscle relaxants(peripherally acting) andcholinesterase inhibitors■ alcuronium Injection: 5 mg (chloride)/

ml in 2-ml ampoule

neostigmine Injection: 500 microgramsin 1-ml ampoule; 2.5 mg

(metilsulfate) in 1-ml ampoule

Tablet: 15 mg (bromide)

suxamethonium Injection: 50 mg (chloride)/ml in 2-ml ampoule

Powder for injection (chloride), in vial

Complementary List

pyridostigmine Injection: 1 mg in 1-ml ampoule


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Tablet: 60 mg (bromide)

■ vecuronium Powder for injection:10 mg (bromide) in vial

21. OphthalmologicalpreparationsThis section will be reviewed at the next meeting ofthe Expert Committee.

21.1 Anti-infective agents

aciclovir Ointment: 3% W/W

■ gentamicin* Solution (eye drops): 0.3% (sulfate)


■ tetracycline Eye ointment: 1% (hydrochloride)

21.2 Anti-inflammatory agents

■ prednisolone Solution (eye drops):0.5% (sodium phosphate)

21.3 Local anaesthetics

■ tetracaine Solution (eye drops):0.5% (hydrochloride)

21.4 Miotics and antiglaucoma medicines

acetazolamide Tablet: 250 mg

■ pilocarpine Solution (eye drops): 2%;4% (hydrochloride or nitrate)

■ timolol Solution (eye drops): 0.25%;0.5% (as maleate)

21.5 Mydriatics

atropine Solution (eye drops): 0.1%;0.5%, 1% (sulfate)

Complementary List

epinephrine Solution (eye drops): 2%(adrenaline) (as hydrochloride)

22. Oxytocics and antioxytocics22.1 Oxytocics

■ ergometrine Injection: 200 micrograms(hydrogen maleate) in 1-ml ampoule

oxytocin Injection: 10 IU in 1-ml ampoule

Complementary List

misoprostol Vaginal tablet: 25 micrograms

mifepristone* – Tablet 200 mg –misoprostol * tablet 200 micrograms

* Requires close medical supervision.

Where permitted under national lawand where culturally acceptable.

22.2 Antioxytocics (tocolytics)

nifedipine Immediate release capsule: 10 mg

23. Peritoneal dialysis solutionComplementary List

intraperitoneal dialysis solution Parenteral(of appropriate composition) solution

24. Psychotherapeuticmedicines24.1 Medicines used in psychoticdisorders

■ chlorpromazine Injection: 25 mg (hydrochloride)/ml in 2-ml ampoule

Oral liquid: 25 mg (hydrochloride)/5 ml


■ fluphenazine Injection: 25 mg (decanoateor enantate) in 1-ml ampoule

■ haloperidol Injection: 5 mg in 1-ml ampoule

Tablet: 2 mg; 5 mg

24.2 Medicines used in mood disorders

24.2.1 Medicines used in depressive disorders

■ amitriptyline Tablet: 25 mg (hydrochloride)

fluoxetine Capsule or tablet: 20 mg(present as hydrochloride)

24.2.2 Medicines used in bipolar disorders

carbamazepine Tablet (scored): 100 mg; 200 mg

lithium carbonate Capsule or tablet: 300 mg

valproic acid Tablet (enteric-coated): 200 mg;500 mg (sodium valproate)

24.3 Medicines used in generalizedanxiety and sleep disorders

■ diazepam Tablet (scored): 2 mg; 5 mg


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24.4 Medicines used for obsessivecompulsive disorders and panic attacks

clomipramine Capsule: 10 mg; 25 mg(hydrochloride)

24.5 Medicines used in substancedependence programmes

Complementary List

■ methadone* Concentrate for oral liquid:5 mg/ml; 10 mg/ml (hydrochloride)

Oral liquid: 5 mg/5 ml; 10 mg/5 ml

* The square box is added to include buprenorphine.The medicines should only be used within an estab-lished support programme.

25. Medicines acting on therespiratory tract25.1 Antiasthmatic and medicines forchronic obstructive pulmonary disease

■ beclometasone Inhalation (aerosol):50 micrograms per dose

(dipropionate); 250 micrograms(dipropionate) per dose

epinephrine Injection: 1 mg (as hydrochloride(adrenaline) or hydrogen tartrate) in

1-ml ampoule

ipratropium bromide Inhalation (aerosol): 20micrograms/metered dose

■ salbutamol Inhalation (aerosol): 100 micro-grams (as sulfate) per dose

Injection: 50 micrograms (assulfate)/ml in 5-ml ampoule


Respirator solution for use in nebulizers:5 mg (as sulfate)/ml

Tablet: 2 mg; 4 mg (as sulfate)

25.2 Other medicines acting on therespiratory tract

caffeine citrate Injection: 20 mg/ml (equivalent to 10 mg caffeine base/ml)

Oral liquid: 20 mg/ml (equivalent to10 mg caffeine base/ml)

26. Solutions correcting water,electrolyte and acid-basedisturbances26.1 Oral

oral rehydration salts See section 17.5.1

potassium chloride Powder for solution

26.2 Parenteral

glucose Injectable solution: 5%;10% isotonic; 50% hypertonic

glucose with Injectable solution: 4% glucose,sodium chloride 0.18% sodium chloride

(equivalent to Na+ 30 mmol/l,Cl- 30 mmol/l)

potassium chloride Solution: 11.2% in20-ml ampoule

(equivalent to K+ 1.5 mmol/ml,Cl- 1.5 mmol/ml)

sodium chloride Injectable solution: 0.9% isotonic(equivalent to Na+ 154 mmol/l,

Cl- 154 mmol/l

sodium hydrogen Injectable solution:carbonate 1.4% isotonic (equivalent to

Na+ 167 mmol/l, HCO3- 167 mmol/l)

Solution: 8.4% in 10-mlampoule (equivalent to

Na+ 1000 mmol/l, HCO3-1000 mmol/l)

■ sodium lactate, Injectable solutioncompound solution

26.3 Miscellaneous

water for injection 2-ml; 5-ml; 10-ml ampoules

27. Vitamins and mineralsascorbic acid Tablet: 50 mg

■ ergocalciferol Capsule or tablet:1.25 mg (50 000 IU)

Oral liquid: 250 micrograms/ml (10 000 IU/ml)

iodine Capsule: 200 mg

Iodized oil: 1 ml (480 mg iodine);0.5 ml (240 mg iodine) in ampoule

(oral or injectable); 0.57 ml (308 mg iodine)in dispenser bottle


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■ nicotinamide Tablet: 50 mg

pyridoxine Tablet: 25 mg (hydrochloride)

retinol Capsule: 50 000 IU; 100 000 IU;200 000 IU (as palmitate)

Oral oily solution: 100 000 IU(as palmitate)/ml in multidose dispenser

Tablet (sugar-coated): 10 000 IU (as palmitate)

Water-miscible injection: 100 000 IU(as palmitate) in 2-ml ampoule


riboflavin Tablet: 5 mg

sodium fluoride In any appropriatetopical formulation

thiamine Tablet: 50 mg (hydrochloride)

Complementary List

calcium gluconate Injection: 100 mg/mlin 10-ml ampoule

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Regulatory Action and News

Tegaserod: marketingsuspensionCanada — Marketing and sales oftegaserod hydrogen maleate (Zelnorm®)tablets have been suspended in Canadato permit further evaluation of importantsafety information.

Zelnorm® is a serotonin 5-HT4 receptorpartial agonist indicated for the sympto-matic treatment of irritable bowel syn-drome with constipation in female pa-tients whose main symptoms are consti-pation and abdominal pain and/or dis-comfort and for the treatment of chronicidiopathic constipation in patients under65 years of age.

A recent retrospective analysis of pooledclinical trial data showed that the inci-dence of cardiovascular ischemic events(1) in patients taking Zelnorm® washigher than in those taking placebo:

Canadian pharmacists and distributorshave been requested to return the prod-uct to the company. Patients shoulddiscontinue treatment and contact theirphysician for advice about alternativetherapies.

Reference: Communication from NovartisPharmaceuticals Canada Inc. 30 March 2007posted by Medeffect at http://www.hc-sc.gc.ca

United States of America — The Foodand Drug Administration (FDA) hasinformed patients and health care prof-essionals that tegaserod maleate(Zelnorm®) will no longer be marketed. Anew safety analysis has found a higherchance of heart attack, stroke, andworsening heart chest pain in patientstreated with tegaserod compared to

placebo. Zelnorm® is a prescriptionmedication approved for short termtreatment of women with irritable bowelsyndrome with constipation and forpatients younger than 65 years withchronic constipation.

Patients should contact their physician todiscuss alternative treatments for theircondition. Physicians should work withtheir patients and transition them to othertherapies as appropriate to their symp-toms and need.

Thirteen patients treated with Zelnorm®(0.1%) had serious and life-threateningcardiovascular side effects; among these,four patients had a heart attack (onedied), six had a type of severe heart chestpain which can quickly turn into a heartattack, and three had a stroke.

The FDA has indicated a willingness toconsider limited re-introduction ofZelnorm® at a later date if a population ofpatients can be identified in whom thebenefits of the drug outweigh the risks.However, before FDA makes a decisionabout limited re-introduction, any pro-posed plan would be discussed at apublic advisory committee meeting.

Reference: FDA Public Health Advisory, 30March 2007

Pergolide: voluntarywithdrawal of productsUnited States of America — The Foodand Drug Administration (FDA) hasannounced that manufacturers ofpergolide drug products, used to treatParkinson disease, will voluntarily removethese drugs from the market because ofthe risk of serious damage to patients’heart valves. The products being with-

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drawn are Permax®, the trade name forpergolide, and two generic versions

Two new studies showed that patientswith Parkinson disease who were treatedwith pergolide had an increased chanceof serious damage to their heart valveswhen compared to patients who did notreceive the drug. Pergolide is a dopamineagonist used with levodopa and carbi-dopa to manage the signs and symptomsof Parkinson disease.

Healthcare professionals who prescribepergolide should consider the following:

• If continued treatment is necessary,another dopamine agonist should besubstituted for pergolide. There areother dopamine agonists approved forthe treatment of Parkinson disease thatare not associated with heart valvedamage. Published transition regimensdescribe the conversion from one DA toanother.

• If treatment with a dopamine agonist isto be discontinued, pergolide should notbe stopped abruptly, because rapiddiscontinuation of all dopamine agonisttherapies can be dangerous. Instead,gradually decrease the dose ofpergolide.

• Patients who will be taken off pergolideshould be told that other effectiveoptions for treatment exist, includingthree other dopamine agonists that arenot associated with damage to heartvalves.

One of the drugs included in the recentstudies showing increased chance ofheart valve problems is cabergoline(Dostinex®), another dopamine agonist.This drug is approved in the US for thetreatment of hyperproteinaemia disorders.Dostinex® is not approved in the US forthe treatment of Parkinson disease. For

hyperproteinaemia disorders, a consider-ably lower dose of Dostinex® is used.

Reference: FDA News, P07-54 and PublicHealth Advisory, 29 March 2007 at http://www.fda.gov

Aliskiren approved forhypertensionUnited States of America — The Foodand Drug Administration (FDA) hasannounced the approval of aliskiren(Tekturna®) tablets for the treatment ofhypertension. Aliskiren acts by inhibitingrenin.

Effectiveness was demonstrated in sixplacebo-controlled eight-week clinicaltrials, which studied over 2000 patientswith mild to moderate hypertension. Theeffect was maintained for up to one year.When used in combination with hydro-chlorothiazide, further reductions in bloodpressure were achieved.

Aliskiren was effective across all demo-graphic subgroups, but African Americanpatients tended to have smaller reduc-tions in blood pressure than Caucasiansand Asians, as is generally true for drugsthat affect the renin-angiotensin system.

Side effects were usually mild and brief.Diarrhoea was reported by approximately2 percent of patients on the higher of thetwo approved doses, compared withapproximately 1 percent on placebo.Rarely, patients developed an allergicreaction with swelling of the face, lips ortongue and difficulty breathing. This hasbeen seen with other drugs for high bloodpressure that act directly on the renin-angiotensin system.

Aliskiren and other drugs that act directlyon the renin-angiotensin system shouldnot be used during pregnancy.

Reference: FDA News, P07-38. 6 March 2007at http://www.fda.gov


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Lapatinib approved foradvanced breast cancerUnited States of America —The Foodand Drug Administration (FDA) hasapproved lapatinib (Tykerb ®), a targetedanti-cancer treatment to be used incombination with capectabine (Xeloda®)for patients with advanced, metastaticbreast cancer that is HER2 positive. Thecombination treatment is indicated forwomen who have received prior therapywith other cancer drugs, including ananthracycline, a taxane, and trastuzumab.According to the American CancerSociety, about 180 000 new cases ofbreast cancer are diagnosed each year.

Lapatinib is a kinase inhibitor unlike, forexample, trastuzumab — a monoclonalantibody, which is a large protein mol-ecule that targets the part of the HER2protein on the outside of the cell. Be-cause of this difference in mechanism ofaction, Tykerb® works in some HER2positive breast cancers that are no longerbenefiting from trastuzumab.

Commonly reported side effects includeddiarrhoea, nausea, vomiting, rash andhand-foot syndrome which may includenumbness, tingling, redness, swelling anddiscomfort of hands and feet. Generallyreversible decreases in heart functionhave also been reported in a smallpercentage of patients.

Reference: FDA News, P07-44, 13 March2007 at http://www.fda.gov

Adalimumab approvedfor Crohn diseaseUnited States of America — The Foodand Drug Administration (FDA) hasapproved adalimumab (Humira®) to treatadult patients with moderate to severeCrohn disease. Adalimumab is a human-derived, genetically-engineered mono-clonal antibody to reduce excessive

levels of human tumour necrosis factoralpha, which plays an important role inabnormal inflammatory and immuneresponses. The labelling includes aboxed warning about potential seriousadverse events. Adalimumab has beenstudied in 1478 patients with Crohndisease in four clinical trials comparingthe drug to a placebo and two longer termextension studies.

Use of this product has been associatedwith serious, sometimes fatal, infections,including cases of tuberculosis, opportun-istic infections, and sepsis. Before initiat-ing adalimumab treatment, patientsshould be evaluated for tuberculosis riskfactors and tested for latent tuberculosisinfection. Other serious adverse eventsreported by adalimumab users includelymphoma. The most frequent adverseevents included upper respiratory infec-tions, sinusitis, and nausea.

Humira® was previously approved for thetreatment of three autoimmune diseases:rheumatoid arthritis, psoriatic arthritis,and ankylosing spondylitis.

Reference: FDA News, P07-30. 27 February2007 at http://www.fda.gov

Rapid test for meningitiscleared for marketingUnited States of America — The Foodand Drug Administration (FDA) hascleared for marketing a test that usesmolecular biology to quickly detect thepresence of viral meningitis.

The Xpert EV® test, when used in combi-nation with other laboratory tests, will helpphysicians distinguish between viral andbacterial meningitis.

Meningitis is diagnosed by testing thefluid obtained from a patient during aspinal tap. Typically, diagnostic tests formeningitis can take up to a week to get


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results. But results from the Xpert EV testare available in two and one-half hours.

The accuracy of the Xpert EV® test wasconfirmed in a multi-site study at sixinstitutions. A total of 255 patient sampleswere tested and demonstrated that 96percent of patients who tested positivedid have viral meningitis, and that 97percent of patients who tested negativedid not have viral meningitis.


Eculizumab approved forparoxysmal nocturnalhaemoglobinuriaUnited States of America —The Foodand Drug Administration (FDA) hasapproved eculizumab (Soliris®), the firstproduct for the treatment of paroxysmalnocturnal haemoglobinuria (PNH), a raretype of blood disorder that can lead todisability and premature death.

PNH, which usually develops in adults, isa disease characterized by red bloodcells that develop abnormally. Once theabnormal cells are present in the blood-stream, naturally occurring proteins

designed to destroy bacteria and otherinfection-causing organisms break thesecells down. This leads to abnormallydarkened urine and, more importantly,causes anaemia. Depending upon theseverity of the disorder, patients with PNHmay have pain, fatigue and debilitatingweakness, the need for frequent bloodtransfusions, blood clots, and life-threat-ening or fatal strokes, heart attacks andintestinal disease.

Eculizumab does not cure PNH, buttreats the breakdown of red blood cells,the most common characteristic of PNH.Eculizumab blockade of the body’snatural immune system increases thepatient’s susceptibility to certain seriousinfections, particularly meningococcalinfections. Serious meningococcal infec-tion was the most important adversereaction experienced by patients inclinical studies. Because of the high riskfor serious meningococcal infections, all196 PNH patients in the clinical studieswere vaccinated with a meningococcalvaccine; two of them developed meningo-coccal sepsis.



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Neglected tropical diseasesOne sixth of the world’s population sufferfrom one or more neglected tropicaldiseases such as Buruli ulcer, cholera,cysticercosis, dracunculiasis (guinea-worm disease), foodborne trematodeinfections, such as fascioliasis, hydatido-sis, leishmaniasis, lymphatic filariasis,onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, trachoma andtrypanosomiasis, although there are otherestimates that suggest the number couldbe much higher.

Several of these diseases are vector-borne. Populations most affected areoften the poorest and most vulnerableand are in tropical and subtropical areasof the world. Some diseases affect in-dividuals throughout their lives, causing ahigh degree of morbidity and physicaldisability and, in certain cases, grossdisfigurement. Others are acute infec-tions, with transient, severe and some-times fatal outcomes.

For a large group of these diseases –mainly helminthic infections – effective,inexpensive or donated drugs are avail-able for their prevention and control.However, there is second group whichrequires systematic case-finding andmanagement at an early stage. Simplediagnostic tools and safe and effectivetreatment regimens still need to bedeveloped for some of these diseases.For others, vector control is available, asin the case of Chagas disease.

Increased awareness and advocacy areneeded to draw attention to the realisticprospect of reducing the negative impactof neglected tropical diseases on the

health and social and economic well-being of affected communities.

Reference: WHO Department of Control ofNeglected Tropical Diseases at http://www.who.int/neglected_diseases/en/index.html

Open access databasefor neglected medicinesdevelopmentAn international network of researchershas announced the release of a newweb-based resource designed to facilitatethe development of medicines to fightinfectious diseases afflicting thedeveloping world. The Drug TargetPrioritization Database is available athttp://TDRtargets.org.

The database is described as a compre-hensive set of information pertinent todrug target discovery, for a diversearray of parasitic and bacterial diseases.The Drug Target Prioritization Networkwas established in 2005 by the SpecialProgramme for Research and Training inTropical diseases (TDR) of WHO andincludes a global team of academiclaboratories, research centres andindustry scientists, focusing on thepathogens responsible for malaria,tuberculosis, African sleeping sickness,leishmaniasis, Chagas disease andworm infections such as schistosomiasisand filariasis — all of which arein desperate need of new treatments.

Together, these diseases are responsiblefor billions of infections in the developingworld and more than six million deathsper year.

Access to Medicines

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WHO Drug Information Vol 21, No. 2, 2007 Access to Medicines

New avenues for drug discoveryThe database is unique in that it allowsany researcher — in both developed anddeveloping countries — to have access toinformation on the complete genomesequences for organisms responsible forfive tropical diseases, with more antici-pated for the parasitic worms known ashelminths. Pharmaceutical firms haveextensive libraries of chemicals that mightact against the disease pathogens. Themissing step, which this initiative takes, isto make available a list of proposed andvalidated drug targets, in addition toallowing users to define their own searchcriteria. This resource should expedite thetime-consuming and high-risk earlystages of drug development.

The TDRtargets.org web site combinesavailable genomic and bioinformaticdata for each priority organism withautomatically extracted and manuallycurated information from the research

literature and other databases relevant toeach putative drug target. The networkhas invested substantial effort in annota-tion to assist scientists in the identificationof high-value drug targets. The databasealso permits comments from experts inthe field.

User-defined weightings permit potentialdrug targets to be ranked according totheir desirability, providing prioritized,customized lists. While this network wasdeveloped to facilitate drug target identifi-cation, it is also useful for the identifica-tion of vaccine and diagnostic targets aswell, and could spur fundamental re-search into areas such as target valida-tion, assay development, biomarkers anddrug resistance.

Reference: Special Programme for Researchand Training in Tropical diseases (TDR) athttp://TDRtargets.org

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International Pharmacopoeia

Artemether and lumefantrine capsules

Draft proposal for the International Pharmacopoeia (March 2007). Pleaseaddress any comments to Quality Assurance and Safety: Medicines, Medi-cines Policy and Standards, World Health Organization, 1211 Geneva 27,Switzerland. Fax: ++41 22 791 4730 or e-mail to [email protected]

Category. Antimalarial.

Storage. Artemether and Lumefantrine capsules should be kept in a well-closedcontainer, protected from light.

Additional information. Strength in the current WHO Model List of Essential Medi-cines: 20 mg Artemether and 120 mg Lumefantrine.

[Note from the Secretariat: Artemether and Lumefantrine capsules are not included inthe current WHO Model list of essential medicines, only tablets of above strength.]

REQUIREMENTS

Complies with the monograph for “Capsules”.

Artemether and Lumefantrine capsules contain Artemether and Lumefantrine. Theycontain not less than 90.0% and not more than 110.0% of the amounts of artemether(C

16H

26O

5) and lumefantrine (C

30H

32Cl

3NO) stated on the label.

Identity tests

A Carry out test A.1 or, where UV detection is not available, test A.2.

A.1. Carry out the test as described under 1.14.1 Thin-layer chromatography, usingsilica gel R6 as the coating substance and a mixture of 40 volumes of lightpetroleum R1, 10 volumes of ethyl acetate R and 5 volumes of glacial acetic acidR as the mobile phase. Apply separately to the plate 10 µl of each of the following2 solutions in acetone R. For solution (A) shake a quantity of the contents of thecapsules equivalent to about 10 mg Artemether (about 60 mg Lumefantrine) for 5minutes with 10 ml, filter, and use the clear filtrate. For solution (B) use 1 mgartemether RS and 6 mg lumefantrine RS per ml. After removing the plate fromthe chromatographic chamber, allow it to dry exhaustively in air or in a current ofcool air.

Consultation Document

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WHO Drug Information Vol 21, No. 2, 2007 International Pharmacopoeia

(i) Examine the chromatogram in ultraviolet light (254 nm).

The principal spot obtained with solution A corresponds in position, appearance,and intensity to that obtained with solution B (identifying Lumefantrine).

(ii) Spray the plate with sulfuric acid/methanol TS. Heat the plate for 10 minutes at140 ˚C. Examine the chromatogram in daylight.

The principal spot obtained with solution A corresponds in position, appearance,and intensity to that obtained with solution B (identifying Artemether).

A.2. Carry out the test as described under 1.14.1 Thin-layer chromatography, usingsilica gel R5 as the coating substance and a mixture of 40 volumes of lightpetroleum R1, 10 volumes of ethyl acetate R and 5 volumes of glacial acetic acidR as the mobile phase. Apply separately to the plate 10 µl of each of the following2 solutions in acetone R. For solution (A) shake a quantity of the contents of thecapsules equivalent to about 10 mg Artemether (about 60 mg Lumefantrine) for 5minutes with 10 ml, filter, and use the clear filtrate. For solution (B) use 1 mgartemether RS and 6 mg lumefantrine RS per ml. After removing the plate fromthe chromatographic chamber, allow it to dry exhaustively in air or in a current ofcool air. Spray with sulfuric acid/methanol TS. Heat the plate for 10 minutes at140˚C, allow it to cool and expose to iodine vapours for 20 minutes. Examine thechromatogram immediately in daylight.

The principal spots obtained with solution A corresponds in position, appearance,and intensity to those obtained with solution B.

B. See the test described below under Assay. The retention times of the two principalpeaks in the chromatogram obtained with solution (1) are similar to those in the chro-matogram obtained with solution (2).

Artemether-related substances. Protect samples from light, also during chromato-graphy.

Carry out the test as described under 1.14.1 Thin-layer chromatography, using silicagel R5 as the coating substance and a mixture of 40 volumes of light petroleum R1, 10volumes of ethyl acetate R and 5 volumes of glacial acetic acid R as the mobile phase.

Prepare the following solutions in the solvent consisting of 1 volume of purified waterand 1 volume of acetonitrile R. For solution (1), weigh and mix the contents of 20capsules. To a quantity of the powder containing 100 mg of artemether add 20 ml ofthe solvent, sonicate for 15 minutes and centrifuge. Filter a portion of the supernatantthrough a 0.45 µm filter, discarding the first few ml of the filtered solution. For solution(2) dissolve 2 mg of each of artemether RS, dihydroartemisinin (artenimol RS) and á-artemether RS in 20 ml of the solvent. For solution (3) dilute 2.0 ml of solution (2) to 20ml with the solvent. For solution (4) dilute 3.0 ml of solution (2) to 20 ml with thesolvent. For solution (5) dilute 5.0 ml of solution (2) to 20 ml with the solvent. Forsolution (6) dilute 1.0 ml of solution (2) to 2 ml with the solvent. For solution (7) dilute3.0 ml of solution (2) to 4 ml with the solvent.

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Apply separately to the plate 20 µl of each of the solution (1), (3), (4), (5), (6) and (7).After application allow the spots to dry for 15 minutes in a current of cool air. Developover a path of 12 cm. After removing the plate from the chromatographic chamber,allow it to dry exhaustively in air or in a current of cool air. Dip the plate in sulfuric acid/methanol TS. Heat the plate for 10 minutes at 140 ˚C. Examine the chromatogram indaylight.

Artemether and related substances have the following Rf values: impurity A about

0.25; dihydroartemisinin about 0.3; impurity B about 0.35; α-artemether about 0.4;artemether about 0.55.

In the chromatogram obtained with solution (1):

–any spot corresponding in Rf value to impurity A is not more intense than the

spot corresponding to artemether obtained with solution (7) (1.5%);

–any spot corresponding in Rf value to dihydroartemisinin is not more intense

than the spot corresponding to dihydroartemisinin obtained with solution (6)(1.0%);

–any spot corresponding in Rf value to impurity B is not more intense than the

spot corresponding to artemether obtained with solution (5) (0.5%);

–any spot corresponding in Rf value to á-artemether is not more intense than the

spot corresponding to á-artemether obtained with solution (4) (0.3%);

–the spot of any other impurity is not more intense than the spot correspondingto artemether obtained with solution (3) (0.2%). Disregard any spot remaining atthe point of application.

Assay. Carry out the test as described under 1.14.4 High-performance liquid chroma-tography, using a stainless steel column (15 cm x 3.9 mm) packed with particles ofsilica gel, the surface of which has been modified with chemically bondedoctadecylsilyl groups (5 ìm) (1 Symmetry is suitable.)

Use the following conditions for gradient elution:

Mobile phase A: 700 volumes of ion pair reagent and 300 volumes ofacetonitrile R.

Mobile phase B: 300 volumes of ion pair reagent and 700 volumes ofacetonitrile R.

Prepare the ion pair reagent by dissolving 5.65 g of sodium hexanesulfonate R and2.75 g of sodium dihydrogen phosphate R in about 900 ml of purified water. Adjust thepH to 2.3 using phosphoric acid (~105 g/l) TS, dilute to 1000 ml and filter through a0.45 µm filter.

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Prepare the following solutions in the solvent which is obtained by mixing 200 ml ofion pair reagent, 60 ml of purified water and 200 ml of 1-propanol R and diluting to1000 ml with acetonitrile R. For solution (1), weigh and mix the contents of 20 cap-sules. Transfer a quantity of the powder containing about 20 mg of artemether (about120 mg of lumefantrine), accurately weighed, to a 100 ml volumetric flask. Add ap-proximately 85 ml of the solvent, sonicate for 20 minutes, allow to cool to room tem-perature and dilute to volume with the solvent. Filter through a 0.45 µm filter, discard-ing the first few ml of the filtered solution. For solution (2), accurately weigh 20 mgartemether RS and 120 mg lumefantrine RS in a 100 ml volumetric flask. Add approxi-mately 85 ml of solvent, sonicate until dissolved, allow to cool to room temperatureand dilute to volume.

Operate with a flow rate of 1.3 ml per minute. As a detector use an ultraviolet spectro-photometer set at a wavelength of about 210 nm for the first 28 minutes and thenswitch to about 380 nm.

Inject alternately 20 µl each of solutions (1) and (2). (The peak for artemether is elutedat a retention time of approximately 19 minutes, and that for lumefantrine at a reten-tion time of approximately 34 minutes.)

Measure the areas of the peak responses obtained in the chromatograms fromsolutions (1) and (2), and calculate the content of artemether (C

16H

26O

5) and lumefan-

trine (C30

H32

Cl3NO).

Impurities (artemether-related)

Dihydroartemisinin 284.4 C15H24O5

Time Mobile phase A Mobile phase B Comments(min) (% v/v) (% v/v)

0–28 60 40 Isocratic28–29 60 to 0 40 to 100 Linear gradient29–45 0 100 Isocratic45–46 0 to 60 100 to 40 Linear gradient46–55 60 40 Isocratic re-equilibration

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α-artemether 298.4 C16H26O5

B. 298.4 C16

H26

O5

A. 238.3 C14

H22

O3

[Names to be provided for A and B]

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Magnesi sulfatis injectioMagnesium sulfate Injection


Note from the Secretariat: Inclusion of a monograph for magnesium sulfateinjection is considered advisable in view of the potential for errors in dosagedue to confusion concerning the strength of this injection since “Magnesiumsulfate” is the heptahydrate (mol wt 246.5 compared with 120 for anhydroussubstance). This injection is included in the WHO Model List of EssentialMedicines and within the “Making Pregnancy Safer” programme of the Familyand Community Health cluster of WHO.

Description. A clear, colourless solution.

Category. Used in the prevention of seizures in eclampsia and pre-eclampsia.

Labelling. The designation of the container of Magnesium sulfate injection shouldindicate the quantity in terms of the amount of magnesium sulfate heptahydrate andas the approximate concentration of magnesium ions (Mg2+) in millimoles per ml.

Additional information. Strength in the current WHO Model list of essential medi-cines: 500 mg of magnesium heptahydrate /ml; the concentration of magnesium ions(Mg2+) is approximately2 millimoles per ml (2 mmolMg2+/ml).

REQUIREMENTS

Complies with the monograph for “Parenteral Preparations”.

Definition. Magnesium sulfate injection is a sterile solution of Magnesium SulfateHeptahydrate in water for injections. The solution is sterilized by “Heating in an Auto-clave” or by another suitable method (see 5.8 Methods of Sterilization).

Magnesium sulfate injection contains not less than 90.0% and not more than 110.0%of the amount of MgSO

4,7H

2O stated on the label.

Identity tests

A. Dilute the injection to give a solution containing 5 mg of magnesium sulfateheptahydrate per ml. To 2 ml of this solution, add 1 ml of ammonia (100g/l) TS; a whiteprecipitate is produced which redissolves after adding 1 ml of ammonium chloride(100g/l) TS. Add 1 ml of disodium hydrogen phosphate (40g/l) TS; a white, fine crystal-line precipitate is formed.

B. Dilute the injection to give a solution containing 20 mg of magnesium sulfateheptahydrate per ml; yields reaction A described under 2.1 General identification testsas characteristic of sulfates.

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pH value. (1.13) pH of the injection, diluted if necessary to contain 500 mg of magne-sium sulfate heptahydrate /ml: 5.5 - 7.0.

Assay. Dilute an accurately measured volume of the injection containing about 0.50 gof magnesium sulfate heptahydrate to 100 ml with water R and proceed with thetitration as described under 2.5 Complexometric titrations for magnesium. Each ml ofdisodium edetate (0.05 mol/l) VS is equivalent to 12.32 mg of MGSO4, 7H2O

Zinci sulfasZinc sulfate

Zinc sulfate monohydrateZinc sulfate heptahydrate


Note from the Secretariat: Preparation of the zinc monographs was initiatedbecause zinc supplementation is included in the revised the WHO/UNICEFrecommendations for the management of diarrhoea as an adjunct to oralrehydration therapy.]

ZnSO4,H

2O (monohydrate); ZnSO

4,7H

2O (heptahydrate)

Relative molecular mass. 179.5 (monohydrate); 287.5 (heptahydrate).

Chemical name. Zinc sulfate monohydrate; CAS Reg. No. 7446-19-7 (monohydrate).Zinc sulfate heptahydrate; CAS Reg. No. 7446-20-0 (heptahydrate).

Description. A white or almost white, crystalline powder, or colourless, transparentcrystals.

Solubility. Very soluble in water, practically insoluble in ethanol (~750 g/l) TS.

Category. Adjunct to oral rehydration salts in( prevention and) treatment of dehydra-tion due to diarrhoea; astringent.

Storage. Zinc sulfate should be kept in a well-closed non-metallic container.

REQUIREMENTS

Definition. Zinc sulfate monohydrate contains not less than 99.0% and not more than101.0% of ZnSO

4,H

2O. Zinc sulfate heptahydrate contains not less than 99.0% and not

more than 104.0% of ZnSO4,7H

2O.

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Identity tests

A. Dissolve 0.25 g in 5 ml of water R and add 0.2 ml of sodium hydroxide (400 g/l) TS.A white precipitate is formed. Add a further 2 ml of sodium hydroxide (400 g/l) TS. Theprecipitate dissolves. Add 10 ml of ammonium chloride (100 g/l) TS. The solutionremains clear. Add 0.1 ml of sodium sulfite TS. A flocculent white precipitate isformed.

B. A 50 mg/ml solution yields the reactions described under 2.1 General identificationtests as characteristic of sulfates.

C. The test substance complies with the limits of the assay.

pH value. (1.13) pH of a 50 mg/ml solution in carbon-dioxide-free water R, 4.4-5.6.

Chlorides. Use 0.83 g in 20 ml for the preparation of the test solution as describedunder 2.2.1 Limit test for chlorides; not more than 300 ìg/g.

Iron. Use 0.40 g for the preparation of the test solution as described under 2.2.4Limit test for iron; not more than 100 ìg/g.

Assay

For the monohydrate Dissolve about 80 mg, accurately weighed, in 5 ml of aceticacid (~120 g/l) TS and proceed with the titration as described under 2.5Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS isequivalent to 8.975 mg of ZnSO

4,H

2O.

For the heptahydrate Dissolve about 0.13 g, accurately weighed, in 5 ml of aceticacid (~120 g/l) TS and proceed with the titration as described under 2.5Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS isequivalent to 1.438 g of ZnSO

4,7H

2O.

Paediatric zinc sulfate tablets


Note from the Secretariat: The term “paediatric” has been used in the titleof this monograph since these tablets are included in the WHO Model List ofEssential Medicines (revised March 2005) under “medicines for diarrhoea inchildren” (section17.5.2).

Preparation of the zinc monographs was initiated because zinc supplementa-tion is included in the revised the WHO/UNICEF recommendations for themanagement of diarrhoea as an adjunct to oral rehydration therapy.

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Category. Adjunct to oral rehydration salts in (prevention and) treatment of dehydra-tion due to diarrhoea.

Storage. Paediatric zinc sulfate tablets should be kept in a well-closed container.

Labelling. The designation of the container of Paediatric zinc sulfate tablets shouldstate that the active ingredient is in the monohydrate form and indicate the quantity interms of the equivalent amount of elemental zinc.

Additional information. Strength in the current WHO Model list of essential medi-cines: 10 mg of elemental zinc (as zinc sulfate monohydrate).

REQUIREMENTS

Comply with the monograph for “Tablets”.

Definition. Paediatric zinc sulfate tablets contain Zinc Sulfate as the monohydrate ina suitable dispersible basis that may contain suitable flavouring agents. They containnot less than 90.0% and not more than 110.0% of the amount of zinc stated on thelabel.

Manufacture. The formulation of the tablets and the manufacturing process aredesigned and controlled so as to ensure that the metallic taste of the zinc salt isadequately masked.

Identity tests. For solution (A) shake a quantity of the powdered tablets containingthe equivalent of 100 mg of zinc with 20 ml, filter, and use the clear filtrate.

A. To 5 ml of solution (A) add 0.2 ml of sodium hydroxide (400 g/l) TS. A white precipi-tate is formed. Add a further 2 ml of sodium hydroxide (400 g/l) TS. The precipitatedissolves. Add 10 ml of ammonium chloride (100 g/l) TS. The solution remains clear.Add 0.1 ml of sodium sulfite TS. A flocculent white precipitate is formed.

B. Five ml of solution (A) yields reaction A described under 2.1 General identificationtests as characteristic of sulfates.

Disintegration. Comply with 5.4 Disintegration test for tablets and capsules, operat-ing the apparatus for 60 seconds.

Assay. Weigh and powder 20 tablets. To a quantity of the powder equivalent to about29 mg of zinc, accurately weighed, add 5 ml of acetic acid (~120 g/l), sonicate for 15minutes and add about 50 ml water R. Proceed with the titration as described under2.5 Complexometric titrations for zinc. Each ml of disodium edetate (0.05 mol/l) VS isequivalent to 3.27 mg of zinc.

.

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Paediatric zinc sulfate oral solution


Note from the Secretariat: The term “paediatric” has been used in the title ofthis monograph since these tablets are included in the WHO Model List ofEssential Medicines (revised March 2005) under “medicines for diarrhoea inchildren” (section17.5.2).

Preparation of the zinc monographs was initiated because zinc supplementa-tion is included in the revised the WHO/UNICEF recommendations for themanagement of diarrhoea as an adjunct to oral rehydration therapy.

Category. Adjunct to oral rehydration salts in (prevention and) treatment of dehydra-tion due to diarrhoea.

Storage. Paediatric zinc sulfate oral solution should be kept in a well-closed con-tainer.

Labelling. The designation of the container of Paediatric zinc sulfate oral solutionshould indicate the quantity in terms of the equivalent amount of elemental zinc.

Additional information. Strength in the current WHO Model list of essential medi-cines: 10 mg of zinc (as zinc sulfate) per 5 ml.

REQUIREMENTS

Complies with the monograph for “Liquids for Oral Use”.

Definition. Paediatric zinc sulfate oral solution is a solution of Zinc Sulfate as themonohydrate or heptahydrate in a suitable flavoured vehicle. It contains not less than90.0% and not more than 110.0% of the amount of zinc stated on the label.

Manufacture. The formulation of the oral solution and the manufacturing process aredesigned and controlled so as to ensure that the metallic taste of the zinc salt isadequately masked.

Identity tests

A. To 5 ml add 0.2 ml of sodium hydroxide (400 g/l) TS. A white precipitate is formed.Add a further 2 ml of sodium hydroxide (400 g/l) TS. The precipitate dissolves. Add 10ml of ammonium chloride (100 g/l) TS. The solution remains clear. Add 0.1 ml ofsodium sulfite TS. A flocculent white precipitate is formed.

B. Five ml yields reaction A described under 2.1 General identification tests as charac-teristic of sulfates.

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pH value. (1.13) pH of the oral solution: 2.5–4.5.

Relative density

Note from the Secretariat: Comment is invited as to whether inclusion of a require-ment for relative density is advisable and, if so, what limits would be considered suit-able using method 1.3 of Ph. Int. (20 ˚C).

Assay. To a quantity of the oral solution equivalent to about 10 mg of zinc, accuratelymeasured, add 50 ml of purified water and 5 ml of ammonia buffer TS and titrate withdisodium edetate (0.01 mol/l) VS using Mordant Black 11 indicator mixture R as indica-tor. Each ml of disodium edetate (0.01 mol/l) VS is equivalent to 0.6539 mg of zinc.

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Recent Publications,Information and EventsInformed consent for researchin resource-poor settingsEthical challenges in study design andinformed consent for health research inresource-poor settings considers ethicalchallenges to research design andinformed consent in biomedical andbehavioural studies conducted in re-source-poor settings. A review of theliterature explores relevant social, cul-tural, and ethical issues in the conduct ofbiomedical and social health research indeveloping countries. Ten case vignettesillustrate ethical challenges that arise ininternational research with culturallydiverse populations.

Professional and public debates concern-ing the application of guidelines forethical conduct in studies carried out indeveloping countries are likely to continueas new information becomes available.Researchers in biomedicine, publichealth, and the social and behaviouralsciences confront the challenging task ofadhering to national and internationalregulations in social and cultural environ-ments in which ethical guidelines may notbe easily translated or applied. Increasedawareness of ethical concerns associatedwith study design and informed consentamong researchers working in resource-poor settings is needed. But strengthen-ing professional knowledge about interna-tional research ethics is not enough.Investigators also require practical adviceon the best methods or models forarticulating ethical guidelines in the field.Empirical research on a wide range ofissues relevant to the application ofethical guidelines is needed, includingstudies of macro social and economicdevelopments that drive the globalizationof the biomedical research enterprise.

Technological and financial resources arealso necessary to build capacity for localcollaborators and communities to ensurethat results of research are integrated intoexisting health systems. This requirescollaborative efforts and engaged com-mitment on the part of investigators,funding agencies, policy-makers, govern-mental institutions, and industry.

Reference: Ethicalchallenges in studydesign and informedconsent for healthresearch in re-source-poor settingshttp:// www.who.int/tdr/publications/publications/seb_topic5.htm

UNDP/WorldBank/WHO-TDR http://www.who.int/tdr/topmenu/news/

Lessons learned in homemanagement of malariaImplementation research in fourAfrican countries

Studies on treatment-seeking behaviourhave shown that most malaria episodesare first treated at home using shop-bought drugs. Part of the reason for thisis poor access to formal health services.These treatments may be incorrect orsuboptimal. Since the majority of childrenwho die from malaria do so within 48hours of onset of illness, the early use ofeffective antimalaria medicines close tothe home can help to reduce the burdenof the disease in sub-Saharan Africa andminimize the life-threatening conse-quences of treatment delays.

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WHO Drug Information Vol 21, No. 2, 2007Recent Publications, Information and Events

This guide focuses in particular on fourcountries – Burkina Faso, Ghana, Nigeriaand Uganda – where country teams havecompleted community based studies inhome management of malaria.

Reference: WorldHealth Organiza-tion. Lessonslearned in HomeManagement ofMalaria. Imple-mentation re-search in fourAfrican countries,2007

Developing drug informationcentres in IndiaA unique training workshop was organ-ized in Bangalore in December 2006.Participants from India were provided withan introduction to drug informationpractice and rational drug use. Thecourse was a part of a programme toexpand the influence of the drug informa-tion centres and clinical pharmacy train-ing programmes which have developed inthe south of India over the last ten years.

The current programme is being coordi-nated by the Karnataka State PharmacyCouncil (KSPC) and is funded by WHO(India Office). KSPC established a druginformation centre in 1997 and also workswith hospital-based clinical pharmacytraining programs in Bangalore. Otherdepartments of pharmacy practice insouth India include drug informationtraining in their clinical programs and offerindependent information to clinicianswithin their institutions.

The centres will provide information tohealthcare professionals and the public,and will collect reports of suspectedadverse drug reactions. Limited fundingwill be provided to purchase informationresources but long-term support will berequired at the state level.

Reference: FIP pharmacy information sectionnewsletter. March 2007 www.fip.org

First-in-man clinical trialsfor high risk productsEuropean Union — The Committee forMedicinal Products for Human Use(CHMP) has adapted a draft guideline forfirst-in-man clinical trials for potentialhigh-risk medicinal products. This guide-line has been prepared as one of themeasures for minimizing the risk ofserious adverse reactions of the naturethat occurred during the first-in-manclinical trials of TGN1412 (gene therapy).It gives guidance on managing the

transition from non-clinical studies to firsttests in humans for high-risk medicinalproducts. The draft guideline has beenreleased for a two-month public consulta-tion.

Reference: Press Release. EMEA, 26 March2007. http://www.emea.europa.eu

Pakistan Pharmacists Societydiscussion forumThe Pakistan Pharmacists Societypromotes and expands the profession ofpharmacy and the role of pharmacists. Inorder to improve drug use and pharmacypractice in the country, the Society haslaunched a website to serve as an onlinesource of news, pharmacy jobs, and toprovde an opportunity for pharmacists tolink up, share ideas and develop activitiesof interest.

Reference: Pakistan Pharmacists Society(PPS) http:// www.pharmacist.pk and http://www. pharmacy.org.pk

New quality assurancecompendiumOver the years, WHO’s Expert Committeeon Specifications for PharmaceuticalPreparations has made numerousrecommendations to establish standards

131


and guidelines and to promote theeffective functioning of national regulatoryand control systems and implementationof internationally agreed standards.

Many of the relevant documents en-dorsed by the Expert Committee arereproduced in a recently publishedcompendium of guidelines and relatedmaterials Quality Assurance of Pharma-ceuticals. Second Edition aiming toprovide information covering all aspectsof WHO good manufacturing practicesand inspection. The compendium in-cludes.

1. WHO good manufacturing practices:main principles for pharmaceuticalproducts

• Quality management in the drug indus-try: philosophy and essential elements

• Heating Ventilation and air-conditioningsystems for non-sterile pharmaceuticaldosage forms

• Validation

• Water for pharmaceutical use

2. WHO good manufacturing practices:starting materials

• Active pharmaceutical ingredients (bulkdrug substances)

• Pharmaceutical excipients

3. WHO good manufacturing practices:specific pharmaceutical products

• Sterile pharmaceutical products

• Biological products

• Investigational pharmaceutical productsfor clinical trials in humans

• The manufacture of herbal medicines

• Radiopharmaceutical products

4. Inspection

• Pre-approval inspections

• Inspection of pharmaceutical manufac-turers

• Inspection of drug distribution channels

• Quality systems requirements fornational good manufacturingbpracticeinspectorates

• Guidance on good manufacturingpractices: inspection report

• Model certificate of good manufacturingpractices

5. Hazard and risk analysis in pharma-ceutical products

• Application of hazard analysis andcritical control point (HACCP) methodol-ogy to pharmaceuticals

6. Sampling operations

• Sampling of pharmaceutical productsand related materials

Reference: Quality Assurance of Pharmaceu-ticals. Second Edition. http://www.who.int/bookorders

Pharmacological managementof human H5N1 infectionThe recent geographical spread of highlypathogenic avian influenza A virus inpoultry and wild waterfowl has increasedopportunities for transmission of theH5N1 virus to humans. Outbreaks inpoultry have now been accompanied byhuman cases in nine countries. To date,human cases have remained rare andsporadic, but the disease is very severeand the case fatality is high. With theH5N1 virus now confirmed in birds inmore than 50 countries, additional spo-radic human cases should be anticipated.

Recent Publications, Information and Events

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WHO Drug Information Vol 21, No. 2, 2007Recent Publications, Information and Events

Although international experts agree thatantiviral drugs should be considered fortreatment of H5N1 patients and also forchemoprophylaxis, the efficacy andeffectiveness of these managementoptions have not been systematicallyassessed. Guidance on their use isneeded worldwide.

In March 2006, the World Health Organi-zation (WHO) convened an internationalpanel of clinicians experienced in thetreatment of H5N1 patients, infectiousdisease experts, public health officersand methodologists to develop rapidadvice for the pharmacological manage-ment of patients with H5N1 infection. Todevelop evidence-based guidelines, thepanel used a transparent methodologicalguideline process, based on the GRADEapproach, that included evaluation ofexisting systematic reviews, literaturesearches and expert consultation. Theresulting guidelines separate strong fromweak recommendations for or against aspecific action and assign four categoriesof quality of evidence (high, moderate,low and very low).

The panel considered several differentspecific patient and exposure groups andmade a number of strong recommenda-tions for or against specific actionsregarding the treatment and chemo-prophylaxis of H5N1 virus infection. Allrecommendations are specific to the

current pre-pandemic situation. Recom-mendations were based on carefulconsideration of the benefits, harms,burdens and cost of interventions. Riskcategorizations for exposure were devel-oped to assist countries in prioritizing theuse of antiviral drugs where theiravailability is limited.

Overall, the quality of the underlyingevidence for all recommendations wasvery low. No data from controlled clinicaltrials of H5N1 infection are available. Theexisting evidence is based on smallobservational case series of H5N1patients, results from in vitro and animalmodel studies of H5N1, or the extrapola-tion of data from high quality studiesconducted to evaluate the treatment andchemoprophylaxis of normal, or “sea-sonal”, influenza. These shortcomingshighlight the need for further research.While the quality of the evidence for someof the critical outcomes was moderate orlow, the overall quality of evidence onwhich to base a summary assessmentwas very low for all antiviral drugs.Differences exist in the quality of evi-dence for individual critical outcomesamong the various antiviral drugs (annex3 sets out the gradings and ratings).

Reference: World Health Organization. WHORapid Advice Guidelines on pharmacologicalmanagement of humans infected with avianinfluenza A (H5N1) virus. WHO/PSM/PAR/2006 at http://www.who.int/medicines

WHO Drug Information, Vol. 21, No. 2, 2007 Proposed INN: List 97

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International Nonproprietary Names for Pharmaceutical Substances (INN) Notice is hereby given that, in accordance with article 3 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances, the names given in the list on the following pages are under consideration by the World Health Organization as Proposed International Nonproprietary Names. The inclusion of a name in the lists of Proposed International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–96) and Recommended (1–57) International Nonproprietary Names can be found in Cumulative List No. 12, 2007 (available in CD-ROM only). The statements indicating action and use are based largely on information supplied by the manufacturer. This information is merely meant to provide an indication of the potential use of new substances at the time they are accorded Proposed International Nonproprietary Names. WHO is not in a position either to uphold these statements or to comment on the efficacy of the action claimed. Because of their provisional nature, these descriptors will neither be revised nor included in the Cumulative Lists of INNs.

Dénominations communes internationales des Substances pharmaceutiques (DCI) Il est notifié que, conformément aux dispositions de l'article 3 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques les dénominations ci-dessous sont mises à l'étude par l'Organisation mondiale de la Santé en tant que dénominations communes internationales proposées. L'inclusion d'une dénomination dans les listes de DCI proposées n'implique aucune recommandation en vue de l'utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d'autres listes de Dénominations communes internationales proposées (1–96) et recommandées (1–57) dans la Liste récapitulative No. 12, 2007 (disponible sur CD-ROM seulement). Les mentions indiquant les propriétés et les indications des substances sont fondées sur les renseignements communiqués par le fabricant. Elles ne visent qu'à donner une idée de l'utilisation potentielle des nouvelles substances au moment où elles sont l'objet de propositions de DCI. L'OMS n'est pas en mesure de confirmer ces déclarations ni de faire de commentaires sur l'efficacité du mode d'action ainsi décrit. En raison de leur caractère provisoire, ces informations ne figureront pas dans les listes récapitulatives de DCI.

Denominaciones Comunes Internacionales para las Sustancias Farmacéuticas (DCI) De conformidad con lo que dispone el párrafo 3 del "Procedimiento de Selección de Denominaciones Comunes Internacionales Recomendadas para las Sustancias Farmacéuticas", se comunica por el presente anuncio que las denominaciones detalladas en las páginas siguientes están sometidas a estudio por la Organización Mundial de La Salud como Denominaciones Comunes Internacionales Propuestas. La inclusión de una denominación en las listas de las DCI Propuestas no supone recomendación alguna en favor del empleo de la sustancia respectiva en medicina o en farmacia. Las listas de Denominaciones Comunes Internacionales Propuestas (1–96) y Recomendadas (1–57) se encuentran reunidas en Cumulative List No. 12, 2007 (disponible sólo en CD-ROM). Las indicaciones sobre acción y uso que aparecen se basan principalmente en la información facilitada por los fabricantes. Esta información tiene por objeto dar una idea únicamente de las posibilidades de aplicación de las nuevas sustancias a las que se asigna una DCI Propuesta. La OMS no está facultada para respaldar esas indicaciones ni para formular comentarios sobre la eficacia de la acción que se atribuye al producto. Debido a su carácter provisional, esos datos descriptivos no deben incluirse en las listas recapitulativas de DCI.

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Proposed International Nonproprietary Names: List 97 Comments on, or formal objections to, the proposed names may be forwarded by any person to the INN Programme of the World Health Organization within four months of the date of their publication in WHO Drug Information, i.e., for List 97 Proposed INN not later than 31st of October 2007. Publication date: 25th of June 2007 Dénominations communes internationales proposées: Liste 97 Des observations ou des objections formelles à l'égard des dénominations proposées peuvent être adressées par toute personne au Programme des Dénominations communes internationales de l'Organisation mondiale de la Santé dans un délai de quatre mois à compter de la date de leur publication dans WHO Drug Information, c'est à dire pour la Liste 97 de DCI Proposées le 31 octobre 2007 au plus tard. Date de Publication: 25 juin 2007 Denominaciones Comunes Internacionales Propuestas: Lista 97 Cualquier persona puede dirigir observaciones u objeciones respecto de las denominaciones propuestas, al Programa de Denominaciones Comunes Internacionales de la Organización Mundial de la Salud, en un plazo de cuatro meses, contados desde la fecha de su publicación en WHO Drug Information, es decir, para la Lista 97 de DCI Propuestas el 31 de Octubre de 2007 a más tardar. Fecha de publicación: el 25 de Juno de 2007.

Proposed INN (Latin, English, French, Spanish) DCI Proposée DCI Propuesta

Chemical name or description: Action and use: Molecular formula Chemical Abstracts Service (CAS) registry number: Graphic formula Nom chimique ou description: Propriétés et indications: Formule brute Numéro dans le registre du CAS: Formule développée Nombre químico o descripción: Acción y uso: Fórmula molecular Número de registro del CAS: Fórmula desarrollada

alaninati brivanibum brivanib alaninate (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo

[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl L-alaninate angiogenesis inhibitor

alaninate de brivanib L-alaninate de (2R)-1-({4-[(4-fluoro-2-méthyl-1H-indol-5-yl)oxy]- 5-méthylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yle inhibiteur de l'angiogénèse

alaninato de brivanib L-alaninato de (2R)-1-({4-[(4-fluoro-2-metil-1H-indol-5-il)oxi]- 5-metilpirrolo[2,1-f][1,2,4]triazin-6-il}oxi)propan-2-ilo inhibidor de la angiogénesis

C22H24FN5O4

649735-63-7

H2N

O

OO

H CH3

CH3H

NN

N

O NH

CH3FCH3


135

albiglutidum* albiglutide ([8-glycine]human glucagon-like peptide 1-(7-36)-peptidyl)

([8-glycine]human glucagon-like peptide 1-(7-36)-peptidyl)(human serum albumin (585 residues)) antidiabetic

albiglutide ([8-glycine]peptide 1 analogue au glucagon humain-(7-36)-peptidyl)([8-glycine]peptide 1 analogue au glucagon humain-(7-36)-peptidyl)(albumine sérique humaine (585 aminoacides)) antidiabétique

albiglutida ([8-glicina]péptido1 análogo al glucagón humano-(7-36)-peptidil) ([8-glicina]péptido 1 análogo al glucagón humano-(7-36)-peptidil)(albumina séria humana (585 aminoácidos)) antidiabético

C3232H5032N864O979S41

782500-75-8

HGEGTFTSDV SSYLEGQAAK EFIAWLVKGR HGEGTFTSDV SSYLEGQAAK 50EFIAWLVKGR DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV 100KLVNEVTEFA KTCVADESAE NCDKSLHTLF GDKLCTVATL RETYGEMADC 150CAKQEPERNE CFLQHKDDNP NLPRLVRPEV DVMCTAFHDN EETFLKKYLY 200EIARRHPYFY APELLFFAKR YKAAFTECCQ AADKAACLLP KLDELRDEGK 250ASSAKQRLKC ASLQKFGERA FKAWAVARLS QRFPKAEFAE VSKLVTDLTK 300VHTECCHGDL LECADDRADL AKYICENQDS ISSKLKECCE KPLLEKSHCI 350AEVENDEMPA DLPSLAADFV ESKDVCKNYA EAKDVFLGMF LYEYARRHPD 400YSVVLLLRLA KTYETTLEKC CAAADPHECY AKVFDEFKPL VEEPQNLIKQ 450NCELFEQLGE YKFQNALLVR YTKKVPQVST PTLVEVSRNL GKVGSKCCKH 500PEAKRMPCAE DYLSVVLNQL CVLHEKTPVS DRVTKCCTES LVNRRPCFSA 550LEVDETYVPK EFNAETFTFH ADICTLSEKE RQIKKQTALV ELVKHKPKAT 600KEQLKAVMDD FAAFVEKCCK ADDKETCFAE EGKKLVAASQ AALGL 645

Disulfide bridges location Position des ponts disulfure / Posiciones de los puentes disulfuro113-122 135-151 150-161 184-229 228-237 260-306 305-313 325-339 338-349

376-421 420-429 452-498 497-508 521-537 536-547 574-619 618-627

albinterferonum alfa-2b* albinterferon alfa-2b human serum albumin (585 residues) fusion protein with human

interferon α-2b (165 residues) antiviral

albinterféron alfa-2b protéine de fusion entre l’albumine sérique humaine (585 aminoacides) et l'interféron α-2b humain (165 aminoacides) antiviral

albinterferón alfa 2b proteína de fusión entre la albumina sérica humana (585 aminoácidos) y el interferón α-2b humano (165 aminoácidos) antiviral


136

C3796H5937N1015O1143S50

472960-22-8

DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV KLVNEVTEFA 50KTCVADESAE NCDKSLHTLF GDKLCTVATL RETYGEMADC CAKQEPERNE 100CFLQHKDDNP NLPRLVRPEV DVMCTAFHDN EETFLKKYLY EIARRHPYFY 150APELLFFAKR YKAAFTECCQ AADKAACLLP KLDELRDEGK ASSAKQRLKC 200ASLQKFGERA FKAWAVARLS QRFPKAEFAE VSKLVTDLTK VHTECCHGDL 250LECADDRADL AKYICENQDS ISSKLKECCE KPLLEKSHCI AEVENDEMPA 300DLPSLAADFV ESKDVCKNYA EAKDVFLGMF LYEYARRHPD YSVVLLLRLA 350KTYETTLEKC CAAADPHECY AKVFDEFKPL VEEPQNLIKQ NCELFEQLGE 400YKFQNALLVR YTKKVPQVST PTLVEVSRNL GKVGSKCCKH PEAKRMPCAE 450DYLSVVLNQL CVLHEKTPVS DRVTKCCTES LVNRRPCFSA LEVDETYVPK 500EFNAETFTFH ADICTLSEKE RQIKKQTALV ELVKHKPKAT KEQLKAVMDD 550FAAFVEKCCK ADDKETCFAE EGKKLVAASQ AALGLCDLPQ THSLGSRRTL 600MLLAQMRRIS LFSCLKDRHD FGFPQEEFGN QFQKAETIPV LHEMIQQIFN 650LFSTKDSSAA WDETLLDKFY TELYQQLNDL EACVIQGVGV TETPLMKEDS 700ILAVRKYFQR ITLYLKEKKY SPCAWEVVRA EIMRSFSLST NLQESLRSKE 750

Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro

53-62 75-91 90-101 124-169 168-177 200-246 245-253 265-279278-289 316-361 360-369 392-438 437-448 461-477 476-487 514-559558-567 586-683 614-723

Glycosylation sites : N-318 T-691

anamorelinum anamorelin (3R)-3-benzyl-N,N',N'-trimethyl-1-(2-methylalanyl-D-tryptophyl)=

piperidine-3-carbohydrazide growth hormone-releasing factor

anamoréline (3R)-3-benzyl-N,N',N'-triméthyl-1-(2-méthylalanyl-D-tryptophyl)= pipéridine-3-carbohydrazide facteur de libération de l'hormone de croissance

anamorelina (3R)-3-bencil-N,N',N'-trimetil-1-(2-metilalanil-D-triptofil)piperidina- 3-carbohidrazida factor estimulante de la liberación de la hormona del crecimiento

C31H42N6O3

249921-19-5

N

HN

H2N NN

CH3

CH3

CH3

CH3H3C

HO

HN

O O

apremilastum apremilast N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methanesulfonyl)ethyl]-

1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide antiasthmatic

aprémilast N-{2-[(1S)-1-(3-éthoxy-4-méthoxyphényl)-2-(méthanesulfonyl)éthyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acétamide antiasthmatique

apremilast N-{2-[(1S)-1-(3-etoxy-4-metoxifenil)-2-(metansulfonil)etil]-1,3-dioxo-2,3-dihidro-1H-isoindol-4-il}acetamida antiasmático


137

C22H24N2O7S

608141-41-9

N

O

ONHH3C

O

H

SCH3

OCH3

OCH3

OO

arbaclofenum placarbilum arbaclofen placarbil (3R)-3-(4-chlorophenyl)-4-[({(1S)-2-methyl-1-[(2-methylpropanoyl)=

oxy]propoxy}carbonyl)amino]butanoic acid antispasmodic

arbaclofène placarbil acide (3R)-3-(4-chlorophényl)-4-[({(1S)-2-méthyl- 1-[(2-méthylpropanoyl)oxy]propoxy}carbonyl)amino]butanoïque antispasmodique

arbaclofeno placarbilo ácido (3R)-3-(4-clorofenil)-4-[({(1S)-2-metil-1-[(2-metilpropanoil)oxi]= propoxi}carbonil)amino]butanoico antiespasmódico

C19H26ClNO6

847353-30-4

CO2HNH

OOH

Cl

OH3C CH3

O

H3C

CH3

H

arterolanum arterolane N-(2-amino-2-methylpropyl)-2-{cis-dispiro[adamantane-

2,3'-[1,2,4]trioxolane-5',1"-cyclohexan]-4"-yl}acetamide antimalarial

artérolane N-(2-amino-2-methylpropyl)-2-{cis-dispiro[adamantane- 2,3'-[1,2,4]trioxolane-5',1"-cyclohexan]-4"-yl}acétamide antipaludique

arterolano N-(2-amino-2-metilpropil)-2-{cis-dispiro[adamantano- 2,3'-[1,2,4]trioxolano-5',1"-ciclohexan]-4"-il}acetamida antipalúdico

C22H36N2O4

664338-39-0

H

NH

O

CH3

H2N CH3

OO

O


138

azilsartanum medoxomilum azilsartan medoxomil (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-

4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-yl]methyl}- 1H-benzimidazol-7-carboxylate angiotensine II receptor antagonist

azilsartan médoxomil 2-éthoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)- 1,1'-biphényl-4-yl]méthyl}-1H-benzimidazole-7-carboxylate de (5-méthyl-2-oxo-1,3-dioxol-4-yl)méthyle antagoniste du récepteur de l’angiotensine II

azilsartán medoxomilo 2-etoxi-1-{[2'-(5-oxo-4,5-dihidro-1,2,4-oxadiazol-3-il)-1,1'-bifenil- 4-il]metil}-1H-benzoimidazol-7-carboxilato de (5-metil-2-oxo- 1,3-dioxol-4-il)metilo antagonista del receptor de la angiotensina II

C30H24N4O8

863031-24-7

NO

HN

N

N

O

CH3

OO

OO

H3C

O

O

azoximeri bromidum azoximer bromide poly{[1-(carboxymethyl)piperazin-1-ium-1,4-diyl bromide]ethylene-

co-[(piperazin-1,4-diyl 1-oxide)ethylene]} immunomodulator

bromure d'azixomère poly{[bromure de 1-(carboxyméthyl)pipérazin-1-ium- 1,4-diyl]éthylène-co-[(1-oxyde de pipérazine-1,4-diyl)éthylène]} immunomodulateur

bromuro de azoxímero poly{[bromuro de 1-(carboximetil)piperazin-1-io-1,4-diil]etileno- co-[(1-óxido de piperazin-1,4-diil)etileno]} inmunomodulador

[[C8H15BrN2O2]x[C6H12N2O]y]n

892497-01-7

N+

N

CO2H

xBr N NO y n


139

begacestatum begacestat 5-chloro-N-[(2S)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-

2-yl]thiophene-2-sulfonamide gamma secretase inhibitor

bégacestat 5-chloro-N-[(2S)-4,4,4-trifluoro-1-hydroxy-3-(trifluorométhyl)butan- 2-yl]thiophène-2-sulfonamide inhibiteur de la secrétase gamma

begacestat 5-cloro-N-[(2S)-4,4,4-trifluoro-1-hidroxi-3-(trifluorometil)butan- 2-il]tiofeno-2-sulfonamida inhibidor de la secretasa gamma

C9H8ClF6NO3S2

769169-27-9

NH

CF3

SH

SCl

CF3

OHOO

belinostatum belinostat N-hydroxy-3-[3-(N-phenylsulfamoyl)phenyl]prop-2-enamide

antitumour agent, inhibitor of histone deacetylase

bélinostat N-hydroxy-3-[3-(phénylsulfamoyl)phényl]prop-2-ènamide agent antitumoral, inhibiteur de la déacétylase de l'histone

belinostat N-hidroxi-3-{3-[(fenilsulfamoil]fenil}prop-2-enamida antitumoral, inhibidor de la desacetilasa de histona

C15H14N2O4S

414864-00-9

S

HN

O

NH

OH

O O

boceprevirum boceprevir (1R,2S,5S)-N-[(2Ξ)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)]-

3-{(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-dimethylbutanoyl}- 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide antiviral

bocéprévir (1R,2S,5S)-N-[(2Ξ)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)]- 3-{(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-diméthylbutanoyl}- 6,6-diméthyl-3-azabicyclo[3.1.0]hexane-2-carboxamide antiviral

boceprevir (1R,2S,5S)-N-[(2Ξ)-4-amino-1-ciclobutil-3,4-dioxobutan-2-il)]- 3-{(2S)-2-[(terc-butilcarbamoil)amino]-3,3-dimetilbutanoil}-6,6-dimetil-3-azabiciclo[3.1.0]hexano-2-carboxamida antiviral


140

C27H45N5O5

394730-60-0

H3C NH

NH

O

N

O

H3C CH3

CH3

H

HN

H

H

O

HNH2

O

OH

CH3

CH3

CH3H3C

canakinumabum* canakinumab immunoglobulin G1, anti-[Homo sapiens interleukin 1, beta (IL1B)]

human monoclonal ACZ885; gamma1 heavy chain (Homo sapiens VH-IGHG1*03) (221-214’)-disulfide with kappa light chain (Homo sapiens V-KAPPA-IGKC*01); (227-227’’:230-230’’)-bisdisulfide dimer immunomodulator

canakinumab immunoglobuline G1, anti-[Homo sapiens interleukine 1, beta (IL1B)] anticorps monoclonal humain ACZ885; chaîne lourde gamma1 (Homo sapiens VH-IGHG1*03) (221-214’)-disulfure avec la chaîne légère kappa (Homo sapiens V-KAPPA-IGKC*01); dimère (227-227’’:230-230’’)-bisdisulfure immunomodulateur

canakinumab inmunoglobulina G1, anticuerpo monoclonal humano ACZ885 anti-[ interleukina 1 de Homo sapiens, beta (IL1B)]; cadena pesada gamma1 (Homo sapiens VH-IGHG1*03) (221-214’)-disulfuro con la cadena ligera kappa (Homo sapiens V-KAPPA-IGKC*01); dímero (227-227’’:230-230’’)-bisdisulfuro inmunomodulador

C6452H9958N1722O2010S42

Light chain 402710-27-4 Heavy chain 402710-25-2

carfilzomibum carfilzomib {(2S)-2-[(morpholin-4-yl)acetamido]-4-phenylbutanoyl}-L-leucyl-

N1-{(2S)-1-[(2R)-2-methyloxiran-2-yl]-4-methyl-1-oxopentan-2-yl}- L-phenylalaninamide antineoplastic

carfilzomib {(2S)-2-[(morpholin-4-yl)acétamido]-4-phénylbutanoyl}-L-leucyl- N1-{(2S)-1-[(2R)-2-méthyloxiran-2-yl]-4-méthyl-1-oxopentan-2-yl}- L-phénylalaninamide antinéoplasique

carfilzomib {(2S)-2-[(morfolin-4-il)acetamido]-4-fenilbutanoil}-L-leucil- N1-{(2S)-1-[(2R)-2-metiloxiran-2-il]-4-metil-1-oxopentan-2-il}- L-fenilalaninamida antineoplásico


141

C40H57N5O7

868540-17-4

O

NNH

HN

NH

HN

O H

H

H

HO

O

H3CCH3

O

H3CCH3

O

CH3

O

ceftarolinum fosamilum ceftaroline fosamil (6R,7R)-7-{(2Z)-2-(ethoxyimino)-2-[5-(phosphonoamino)-

1,2,4-thiadiazol-3-yl]acetamido}-3-{[4-(1-methylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene- 2-carboxylate antibiotic

céftaroline fosamil (6R,7R)-7-{(2Z)-2-(éthoxyimino)-2-[5-(phosphonoamino)- 1,2,4-thiadiazol-3-yl]acétamido}-3-{[4-(1-méthylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ène- 2-carboxylate antibiotique

ceftarolina fosamilo (6R,7R)-7-{(2Z)-2-(etoxiimino)-2-[5-(fosfonoamino)-1,2,4-tiadiazol- 3-il]acetamido}-3-{[4-(1-metilpiridin-1-io-4-il)-1,3-tiazol-2-il]sulfanil}- 8-oxo-5-tia-1-azabiciclo[4.2.0]oct-2-eno-2-carboxilato antibiótico

C22H21N8O8PS4

229016-73-3

N

S

CO2

SO

HN

O

NO

NS

NH H

S

N

NH

CH3

PO

HOHO

N+ CH3

cenersenum cenersen antisense oligonucleotide inhibitor of p53 expression

2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')- 2'-deoxy-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thioguanylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')- P-thiothymidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thioguanylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-2'-deoxycytidine antineoplastic


142

cénersen oligonucléotide antisense inhibiteur de l'expression de p53 2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')- 2'-déoxy-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thioguanylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')- P-thiothymidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thioguanylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-2'-déoxycytidine antinéoplasique

cenersén oligonucleótido antisentido inhibidor de la expresión de p53 2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-P-tiotimidilil- (3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P-tioguanilil- (3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi- P-tiocitidilil-(3'→5')-2'-desoxicitidina antineoplásico

C187H226N62O103P19S19

872847-66-0

cholini fenofibratum choline fenofibrate 2-hydroxy-N,N,N-trimethylethanaminium 2-[4-(4-chlorobenzoyl)=

phenoxy]-2-methylpropanoate antihyperlipidaemic

fénofibrate de choline 2-[4-(4-chlorobenzoyl)phénoxy]-2-méthylpropanoate de 2-hydroxy-N,N,N-triméthyléthanaminium antihyperlipidémiant

fenofibrato de colina 2-[4-(4-clorobenzoil)fenoxi]-2-metilpropanoato de 2-hidroxi- N,N,N-trimetiletanaminio antihiperlipémico

C5H14NO+.C17H14ClO4-

856676-23-8

O CO2-

H3C CH3

Cl

O

HON+

H3C

CH3

CH3


143

cinaciguatum cinaciguat 4-({(4-carboxybutyl)[2-(2-{[4-(2-phenylethyl)phenyl]methoxy}phenyl)=

ethyl]amino}methyl)benzoic acid guanylate cyclase activator

cinaciguat acide 4-({(4-carboxybutyl)[2-(2-{[4-(2-phényléthyl)phényl]méthoxy}= phényl)éthyl]amino}méthyl)benzoïque activateur de la guanylate cyclase

cinaciguat ácido 4-({(4-carboxibutil)[2-(2-{[4-(2-feniletil)fenil]metoxi}fenil)= etil]amino}metil)benzoico activador de la guanilato ciclasa

C36H39NO5

329773-35-5

NCO2H

CO2H

O

contusugenum ladenovecum* contusugene ladenovec (Recombinant) replication restricted adenovirus (type 5) vector, E1

deleted, partial E3 deletion, containing/expressing a wild type p53 gene driven by a cytomegalovirus promoter induce cell growth arrest and apotopsis

contusugène ladénovec Vecteur adénovirus (type 5) recombinant défectif, délété de E1 et partiellement de E3, contenant le gène p53 sauvage sous le contrôle du promoteur cytomégalovirus induit l'arrêt de la croissance cellulaire et l'apoptose

contusugén ladenovec Vector adenovirus (tipo 5) recombinante defectivo, con deleción de E1 y parcialmente de E3, que contiene el gen p53 salvaje controlado por el promotor de cytomegalovirus induce la detención del crecimiento celular y la apoptosis

600735-73-7

dapagliflozinum dapagliflozin (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-

D-glucitol antidiabetic

dapagliflozine (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-éhoxyphényl)méthyl]phényl}- D-glucitol antidiabétique

dapagliflozina (1S)-1,5-anhidro-1-C-{4-cloro-3-[(4-etoxifenil)metil]fenil}-D-glucitol hipoglucemiante


144

C21H25ClO6

461432-26-8

O

OH

OH

HO

HO

O

Cl

CH3

delimotecanum delimotecan poly{[2-O-(carboxymethyl)-α-D-glucopyranosyl-(1→6)]-co-[2-O-(15-

{[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro- 1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy}-2,5,8,11-tetraoxo-3,6,9,12-tetraazapentadecyl)-α-D-glucopyranosyl- (1→6)]-co-[α-D-glucopyranosyl-(1→6)]} antineoplastic

délimotécan poly{[2-O-(carboxyméthyl)-α-D-glucopyranosyl-(1→6)]-co-[2-O-(15-{[(4S)-4,11-diéthyl-4-hydroxy-3,14-dioxo-3,4,12,14-tétrahydro- 1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoléin-9-yl]oxy}-2,5,8,11-tétraoxo-3,6,9,12-tétraazapentadécyl)-α-D-glucopyranosyl-(1→6)]-co-[α-D-glucopyranosyl-(1→6)]} antinéoplasique

delimotecán poli{[2-O-(carboximetil)-α-D-glucopiranosil-(1→6)]-co-[2-O-(15-{[(4S)-4,11-dietil-4-hidroxi-3,14-dioxo-3,4,12,14-tetrahidro- 1H-pirano[3',4':6,7]indolizino[1,2-b]quinolin-9-il]oxi}-2,5,8,11-tetraoxo-3,6,9,12-tetraazapentadecil)-α-D-glucopiranosil-(1→6)]- co-[α-D-glucopiranosil-(1→6)]} antineoplásico


145

[C39H46N6O14[C6H10O5]x[C8H12O7]y]n

187852-63-7 (for Na salt)

N

O

N

O

O

OH

CH3

H3C

O

O

OH

OHHO

HO

O

O

OH

O

HO

O

O

OH

O

HO

O

H

HO2C

HN

NH

HN

O

O

O

ONH

x

y

n

dovitinibum dovitinib 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazole-

2-yl]quinolin-2(1H)-one antineoplastic

dovitinib 4-amino-5-fluoro-3-[6-(4-méthylpipérazin-1-yl)-1H-benzimidazol- 2-yl]quinoléin-2(1H)-one antinéoplasique

dovitinib 4-amino-5-fluoro-3-[6-(4-metilpiperazin-1-il)-1H-benzoimidazol- 2-il]quinolin-2(1H)-ona antineoplásico

C21H21FN6O

405169-16-6

HN

O

NH2

F

NH

N N N CH3

eldecalcitolum eldecalcitol (5Z,7E)-2β-(3-hydroxypropoxy)-9,10-secocholesta-5,7,10(19)-triene-

1α,3β,25-triol vitamin D analogue

eldécalcitol (5Z,7E)-2β-(3-hydroxypropoxy)-9,10-sécocholesta-5,7,10(19)-triène-1α,3β,25-triol analogue de la vitamine D

eldecalcitol (5Z,7E)-2β-(3-hidroxipropoxi)-9,10-secocolesta-5,7,10(19)-trieno-1α,3β,25-triol análogo de la vitamina D


146

C30H50O5

104121-92-8

H3C

CH3

H

H

HOH H

OH

CH2

O HHO

H

HOCH3

CH3

elvitegravirum elvitegravir 6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan-

2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid antiviral

elvitégravir acide 6-[(3-chloro-2-fluorophényl)méthyl]-1-[(2S)-1-hydroxy- 3-méthylbutan-2-yl]-7-méthoxy-4-oxo-1,4-dihydroquinoline- 3-carboxylique antiviral

elvitegravir ácido 6-[(3-cloro-2-fluorofenil)metil]-1-[(2S)-1-hidroxi-3-metilbutan- 2-il]-7-metoxi-4-oxo-1,4-dihidroquinolina-3-carboxílico antiviral

C23H23ClFNO5

697761-98-1

N

CO2H

O

O

F

Cl

CH3

CH3

HHO

CH3

epetirimodum epetirimod 1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine

immunomodulator

épétirimod 1-(2-méthylpropyl)-1H-imidazo[4,5-c][1,5]naphtyridin-4-amine immunomodulateur

epetirimod 1-(2-metilpropil)-1H-imidazo[4,5-c][1,5]naftiridin-4-amina inmunomodulador


147

C13H15N5

227318-71-0

N

N

NN

H3C

H3C

NH2

epoetinum kappa epoetin kappa 1-165-erythropoietin (human JR-013), glycoform κ

antianaemic

époétine kappa érythropoïétine (humaine JR-013)-(1-165), glycoforme κ antianémique

epoetina kappa 1-165-eritropoyetina (humana JR-013), glicoforma κ antianémico

C809H1301N229O240S5

879555-13-2

eribulinum eribulin (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24

S,26R,28R,29aS)-2-[(2S)-3-amino-2-hydroxypropyl]-3-methoxy- 26-methyl-20,27-dimethylidenehexacosahydro-11,15:18,21:24,28-triepoxy-7,9-ethano-12,15-methano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one antineoplastic

éribuline (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24S,26R,28R,29aS)-2-[(2S)-3-amino-2-hydroxypropyl]-3-méthoxy- 26-méthyl-20,27-diméthylidènehexacosahydro-11,15:18,21:24,28-triépoxy-7,9-éthano-12,15-méthano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one antinéoplasique

eribulina (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24S,26R,28R,29aS)-2-[(2S)-3-amino-2-hidroxipropil]-26-metil- 20,27-dimetilideno-3-metoxihexacosahidro-11,15:18,21:24,28-triepoxi-7,9-etano-12,15-metano-9H,15H-furo[3,2-i]furo[2',3':5,6]= pirano[4,3-b][1,4]dioxaciclopentacosin-5(4H)-ona antineoplásico

C40H59NO11

253128-41-5

O

O

O

OO

O

H

OCH2

OH

H3CH

H2C

HH

HH

CH3

HO

H

H

H2NHO H H

HO

H

H

HH

H


148

faxeladolum faxeladol 3-[(1R,2R)-2-(dimethylaminomethyl)cyclohexyl]phenol

analgesic

faxéladol 3-{(1R,2R)-2-[(diméthylamino)méthyl]cyclohexyl}phenol analgésique

faxeladol 3-[(1R,2R)-2-(dimetilaminometil)ciclohexil]fenol analgésico

C15H23NO

433265-65-7

HH

OH

N

CH3

CH3

ferricum carboxymaltosum ferric carboxymaltose poly[D-glucopyranosyl(1→4)]-D-gluconic acid complex of hydrated

iron(III) oxide haematinic

carboxymaltose ferrique complexe d'oxide de fer(III) et d'acide poly[D-glucopyranosyl(1→4)]-D-gluconique hydraté hématinique

carboximaltosa férrica ácido poli[D-glucopiranosil(1→4)]-D-glucónico complejo de óxido de hierro(III) hidratado hematínico

FeIIIw([C6H10O5]aC6H11O7)x(OH)yOz.nH2O

9007-72-1

flovagatranum flovagatran (1R)-1-{N-[(benzyloxy)carbonyl]-D-phenylalanyl-L-prolinamido}=

butylboronic acid thrombin inhibitor

flovagatran acide (1R)-1-{N-[(benzyloxy)carbonyl]-D-phénylalanyl-L-prolinamido} butylboronique inhibiteur de la thrombine

flovagatrán ácido (1R)-1-{N-[(benciloxi)carbonil]-D-fenilalanil-L-prolinamido}= butilborónico inhibidor de la trombina


149

C27H36BN3O7

871576-03-3

NH

B

OH

OH

O

N

HNO

O

HO

CH3

H

H

O

gantenerumabum* gantenerumab immunoglobulin G1, anti-(human beta-amyloid peptides Aβ42 and

Aβ40) human monoclonal antibody; gamma1 heavy chain (Homo sapiens VH-IGHG1) (229-215’)-disulfide with kappa light chain (Homo sapiens V-KAPPA-IGKC); (235-235”:238-238”)-bisdisulfide

oured immunomodulator

ganténérumab immunoglobuline G1, anti-(peptides beta-amyloides Aβ42 et Aβ40 humains) anticorps monoclonal humain; chaîne lourde gamma1 (Homo sapiens VH-IGHG1) (229-215’)-disulfure avec la chaîne légère kappa (Homo sapiens V-KAPPA-IGKC); dimère (235-235”:238-238”)-bisdisulfure immunomodulateur

gantenerumab inmunoglobulina G1, anticuerpo monoclonal humano anti-(péptidos beta-amiloides Aβ42 et Aβ40 humanos); cadena pesada gamma1 (Homo sapiens VH-IGHG1) (229-215’)-disulfuro con la cadena ligera kappa (Homo sapiens V-KAPPA-IGKC); dimero (235-235”:238-238”)-bisdisulfuro inmunomodulador

89957-37-9 γ1- heavy chain / Chaîne lourde γ1 / Cadena pesada γ1

QVELVESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA 50INASGTRTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARGK 100GNTHKPYGYV RYFDVWGQGT LVTVSSASTK GPSVFPLAPS SKSTSGGTAA 150LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS 200SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PELLGGPSVF 250LFPPKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP 300 REEQYNSTYR VVSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG 350QPREPQVYTL PPSRDELTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY 400KTTPPVLDSD GSFFLYSKLT VDKSRWQQGN VFSCSVMHEA LHNHYTQKSL 450SLSPGK 456

κ-light chain / Chaîne légère κ / Cadena ligera κ

DIVLTQSPAT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY 50GASSRATGVP ARFSGSGSGT DFTLTISSLE PEDFATYYCL QIYNMPITFG 100QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200GLSSPVTKSF NRGEC 215

The position of cysteine (C) residues that form disulphide bridges and asparagine residues that are N-glycosylated are in bold.


150

golotimodum golotimod D-γ-glutamyl-L-tryptophan

immonomudulator

golotimod D-γ-glutamyl-L-tryptophane immunomodulateur

golotimod D-γ-glutamil-L-triptófano inmunomodulador

C16H19N3O5

229305-39-9

HN CO2H

HHO2C

NH

O

NH2H

ibalizumabum* ibalizumab immunoglobulin G4, anti-(human CD4) humanized monoclonal

antibody Hu5A8 (TNX-355); gamma4 heavy chain [humanized VH (Homo sapiens FR/Mus musculus CDR [8.8.15] from clone Mu5A8)-Homo sapiens IGHG4*01] (136-219’)-disulfide with kappa light chain [humanized V-KAPPA (Homo sapiens FR/Mus musculus CDR [12.3.8] from clone Mu5A8)-Homo sapiens IGKC*01] ; (228-228’:231-231”)-bisdisulfide dimer antiviral

ibalizumab immunoglobuline G4, anti-(CD4 humain) anticorps monoclonal humanisé Hu5A8 (TNX-355); chaîne lourde gamma4 [VH humanisé (Homo sapiens FR/Mus musculus CDR [8.8.15] du clone 5A8)-Homo sapiens IGHG4] (136-219’)-disulfure avec la chaîne légère kappa [V-KAPPA humanisé (Homo sapiens FR/Mus musculus CDR [12.3.8] du clone Mu5A8)-Homo sapiens IGKC*01]; dimère (228-228”:231-231”)-bisdisulfure antiviral

ibalizumab inmunoglobulina G4, anti-(CD4 humano) anticuerpo monoclonal humanizado Hu5A8 (TNX-355); cadena pesada gamma4 [VH humanizado (Homo sapiens FR/Mus musculus CDR [8.8.15] del clon 5A8)-Homo sapiens IGHG4] (136-219’)-disulfuro con la cadena ligera kappa [V-KAPPA humanizada (Homo sapiens FR/Mus musculus CDR [12.3.8] del clon Mu5A8)-Homo sapiens IGKC*01]; dímero (228-228”:231-231”)-bisdisulfuro antiviral


151

680188-33-4

Ig γ4-heavy chain / Chaîne lourde Ig γ4 / Cadena pesada Ig γ4

QVQLQQSGPE VVKPGASVKM SCKASGYTFT SYVIHWVRQK PGQGLDWIGY 50 INPYNDGTDY DEKFKGKATL TSDTSTSTAY MELSSLRSED TAVYYCAREK 100 DNYATGAWFA YWGQGTLVTV SSASTKGPSV FPLAPCSRST SESTAALGCL 150VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT 200 KTYTCNVDHK PSNTKVDKRV ESKYGPPCPS CPAPEFLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY VDGVEVHNAK TKPREEQFNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK AKGQPREPQV 350 YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 449

Ig κ-light chain / Chaîne légère Ig κ / Cadena ligera Ig κ

DIVMTQSPDS LAVSLGERVT MNCKSSQSLL YSTNQKNYLA WYQQKPGQSP 50 KLLIYWASTR ESGVPDRFSG SGSGTDFTLT ISSVQAEDVA VYYCQQYYSY 100 RTFGGGTKLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK 150 VQWKVDNALQ SGNSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE 200 VTHQGLSSPV TKSFNRGEC 219

idrabiotaparinuxum natricum idrabiotaparinux sodium nonasodium methyl (2-deoxy-3,4-di-O-methyl-2-{6-[5-(2-

oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido]= hexanamido}-6-O-sulfo-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1→4)-(2,3,6-tri-O-sulfo- α-D-glucopyranoside)-(1→4)-(2,3-di-O-methyl- α-L-idopyranosyluronate)-(1→4)-2,3,6-tri-O-sulfo- α-D-glucopyranoside antithrombotic

idrabiotaparinux sodique 2-déoxy-3,4-di-O-méthyl-2-{[6-({5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thiéno[3,4-d]imidazol-4-yl]pentanoyl}amino)hexanoyl]amino}- 6-O-sulfo-α-D-glucopyranosyl-(1→4)-2,3-di-O-méthyl- β-D-glucopyranuronosyl-(1→4)-2,3,6-tri-O-sulfo-α-D-glucopyranosyl-(1→4)-2,3-di-O-méthyl-α-L-idopyranuronosyl-(1→4)-2,3,6-tri-O-sulfo-α-D-glucopyranoside de méthyle nonasodique antithrombotique

idrabiotaparinux sódico 2-desoxy-3,4-di-O-metil-2-{[6-({5-[(3aS,4S,6aR)-2-oxohexahidro- 1H-tieno[3,4-d]imidazol-4-il]pentanoil}amino)hexanoil]amino}- 6-O-sulfo-α-D-glucopiranosil-(1→4)-2,3-di-O-metil- β-D-glucopiranuronosil-(1→4)-2,3,6-tri-O-sulfo-α-D-glucopiranosil-(1→4)-2,3-di-O-metil-α-L-idopiranuronosil-(1→4)-2,3,6-tri-O-sulfo- α-D-glucopiranosido de metilo y nonasodico antitrombótico


152

C53H79N4Na9O51S8

405159-59-3

O

OCH3

OCH3

CO2Na

O

O

O

O

O

O

OCH3

HN

H3CO

O

OO

O

O

O

O

O

OCH3

OCH3

O

CO2NaSO3Na

OCH3

SO3Na

NaO3S

NaO3S

SO3Na

SO3Na

SO3Na

O

NH

O

H

S

HNNHH

H

O

laropiprantum laropiprant [(3R)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-(methanesulfonyl)-

1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid prostanoid DP1 receptor antagonist

laropiprant acide [(3R)-4-[(4-chlorophényl)méthyl]-7-fluoro-5-(méthanesulfonyl)-1,2,3,4-tétrahydrocyclopenta[b]indol-3-yl]acétique antagoniste du récepteur DP1 des prostanoïdes

laropiprant ácido [(3R)-4-[(4-clorofenil)metil]-7-fluoro-5-(metanosulfonil)- 1,2,3,4-tetrahidrociclopenta[b]indol-3-il]acético antagonista del receptor DP1 de prostanoides

C21H19ClFNO4S

571170-77-9

N H

SCH3

OO

F

Cl

CO2H

levamlodipinum levamlodipine 3-ethyl 5-methyl (4S)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-

6-methyl-1,4-dihydropyridine-3,5-dicarboxylate calcium channel blocker

lévamlodipine (4S)-2-[(2-aminoéthoxy)méthyl]-4-(2-chlorophényl)-6-méthyl- 1,4-dihydropyridine-3,5-dicarboxylate de 3-éthyle et de 5-méthyle antagoniste des canaux calciques

levamlodipino (4S)-2-[(2-aminoetoxi)metil]-4-(2-clorofenil)-6-metil- 1,4-dihidropiridina-3,5-dicarboxilato de 3-etilo y 5-metilo antagonista de los canales del calcio


153

C20H25ClN2O5

103129-82-4

HN

ONH2

O CH3OH3C

H3C

OOCl

H

lonaprisanum lonaprisan 11β-(4-acetylphenyl)-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-

17α-pregna-5,9-dien-3-one progesterone receptor antagonist

lonaprisan 11β-(4-acétylphényl)-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-prégna-5,9-dién-3-one antagoniste des récepteurs de la progestérone

lonaprisán 11β-(4-acetilfenil)-20,20,21,21,21-pentafluoro-17-hidroxi-19-nor- 17α-pregna-5,9-dien-3-ona antagonista de los receptores de progesterona

C28H29F5O3

211254-73-8

OH

O

H3C

H

CH3

H

H

O

CF3

FF

metenkefalinum metenkefalin L-tyrosylglycylglycyl-L-phenylalanyl-L-methionine

β-endorphin human-(1-5)-peptide µ and δ opioid receptors agonist

métenkefaline L-tyrosylglycylglycyl-L-phénylalanyl-L-méthionine β-endorphine humaine-(1-5)-peptide agoniste des récepteurs opioïdes µ et δ

metencefalina L-tirosilglicilglicil-L-fenilalanil-L-metionina β-endorfina humana-(1-5)-peptido agonista de los receptores µ y δ de opiáceos

C27H35N5O7S

58569-55-4

H L-Tyr Gly Gly L-Phe L-Met OH


154

milveterolum milveterol N-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[2-(4-{[(2R)-2-hydroxy-

2-phenylethyl]amino}phenyl)ethyl]amino}ethyl]phenyl}formamide bronchodilator

milvétérol N-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[2-(4-{[(2R)-2-hydroxy- 2-phényléthyl]amino}phényl)éthyl]amino}éthyl]phényl}formamide bronchodilatateur

milveterol N-{2-hidroxi-5-[(1R)-1-hidroxi-2-{[2-(4-{[(2R)-2-hidroxi- 2-feniletil]amino}fenil)etil]amino}etil]fenil}formamida broncodilatador

C25H29N3O4

652990-07-3

HN

OHH

HN

HO

O

H

NH H OH

motesanibum motesanib N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-{[(pyridin-4-yl)methyl]=

amino}pyridine-3-carboxamide antineoplastic

motésanib N-(3,3-diméthyl-2,3-dihydro-1H-indol-6-yl)-2-{[(pyridin-4-yl)méthyl]= amino}pyridine-3-carboxamide antinéoplasique

motesanib N-(3,3-dimetil-2,3-dihidro-1H-indol-6-il)-2-{[(piridin-4-il)metil]= amino}piridina-3-carboxamida antineoplásico

C22H23N5O

453562-69-1

N NH

O

HN

NH

N

CH3

CH3

nepiderminum nepidermin human epidermal growth factor, recombinant DNA origin

epidermal growth factor

népidermine facteur humain de croissance épidermique, origine ADN recombinant facteur de croissance épidermique

nepidermina factor de crecimiento epidérmico humano; origen: ADN recombinante factor de crecimiento epidérmico


155

C270H401N73O83S7

62253-63-8

H Asn Ser Asp Ser Glu Cys Pro Leu Ser His Asp Gly Tyr Cys

Leu His Asp Gly Val Cys Met Tyr Ile Glu Ala Leu Asp Lys

Tyr Ala Cys Asn Cys Val Val Gly Tyr Ile Gly Glu Arg Cys

Gln Tyr Arg Asp Leu Lys Trp Trp Glu Leu Arg OH

10

20

30 40

50

neratinibum neratinib (2E)-N-[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-

7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide antineoplastic

nératinib (2E)-N-[4-({3-chloro-4-[(pyridin-2-yl)méthoxy]phényl}amino)-3-cyano-7-éthoxyquinoléin-6-yl]-4-(diméthylamino)but-2-énamide antinéoplasique

neratinib (2E)-N-[4-({3-cloro-4-[(piridin-2-yi)metoxi]fenil}amino)-3-ciano- 7-etoxiquinolin-6-il]-4-(dimetilamino)but-2-enamida antineoplásico

C30H29ClN6O3

698387-09-6

N

HN

CN

O

HN

O

Cl

H3C

ON

H3C

CH3

N

perampanelum perampanel 2-(6'-oxo-1'-phenyl-1',6'-dihydro[2,3'-bipyridin]-5'-yl)benzonitrile

AMPA receptor antagonist

pérampanel 2-(6'-oxo-1'-phenyl-1',6'-dihydro[2,3'-bipyridin]-5'-yl)benzonitrile antagoniste des récepteurs de l'AMPA

perampanel 2-(1'-fenil-6'-oxo-1',6'-dihidro[2,3'-bipiridin]-5'-il)benzonitrilo antagonista de los receptores del AMPA

C23H15N3O

380917-97-5

N

N

O

CN


156

peretinoinum peretinoin (2E,4E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,4,6,10,14-

pentaenoic acid retinoid derivative, antineoplastic

pérétinoin acide (2E,4E,6E,10E)-3,7,11,15-tétraméthylhexadéca-2,4,6,10,14-penténoïque rétinoïde, antinéoplasique

peretinoína ácido (2E,4E,6E,10E)-3,7,11,15-tetrametilhexadeca-2,4,6,10,14-pentaenoico retinoide, antineoplásico

C20H30O2

81485-25-8

CO2H

CH3 CH3

H3C

CH3CH3

pexacerfontum pexacerfont N-[(2R)-butan-2-yl]-8-(6-methoxy-2-methylpyridin-3-yl)-

2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4-amine antidepressant

pexacerfont N-[(2R)-butan-2-yl]-8-(6-méthoxy-2-méthylpyridin-3-yl)- 2,7-diméthylpyrazolo[1,5-a][1,3,5]triazin-4-amine antidépresseur

pexacerfont N-[(2R)-butan-2-il]-8-(6-metoxi-2-metilpiridin-3-il)- 2,7-dimetilpirazolo[1,5-a][1,3,5]triazin-4-amina antidepresivo

C18H24N6O

459856-18-9

N

NN

NN

H3C

HN

H3C H

H3C

H3C OCH3

CH3

pimavanserinum pimavanserin 1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-

3-{[4-(2-methylpropoxy)phenyl]methyl}urea serotonin receptor antagonist

pimavansérine 1-[(4-fluorophényl)méthyl]-1-(1-méthylpipéridin-4-yl)- 3-{[4-(2-méthylpropoxy)phényl]méthyl}urée antagoniste des récepteurs de la sérotonine

pimavanserina 1-[(4-fluorofenil)metil]-1-(1-metilpiperidin-4-il)- 3-{[4-(2-metilpropoxi)fenil]metil}urea antagonista del receptor de la serotonina


157

C25H34FN3O2

706779-91-1

NHN

O

F

N

CH3

OCH3

CH3

piragliatinum piragliatin (2R)-2-[3-chloro-4-(methanesulfonyl)phenyl]-

3-[(1R)-3-oxocyclopentyl]-N-(pyrazin-2-yl)propanamide antidiabetic

piragliatine (2R)-2-[3-chloro-4-(méthanesulfonyl)phényl]- 3-[(1R)-3-oxocyclopentyl]-N-(pyrazin-2-yl)propanamide antidiabétique

piragliatina (2R)-2-[3-cloro-4-(metanosulfonil)fenil]-3-[(1R)-3-oxociclopentil]- N-(pirazin-2-il)propanamida hipoglucemiante

C19H20ClN3O4S

625114-41-2

Cl

SH3C

NH

N

N

H

O

OO

H

O

pomalidomidum pomalidomide 4-amino-2-[(3RS)-2,6-dioxopiperidin-3-yl]-2H-isoindole-1,3-dione

antineoplastic

pomalidomide 4-amino-2-[(3RS)-2,6-dioxopipéridin-3-yl]-2H-isoindole-1,3-dione antinéoplasique

pomalidomida 4-amino-2-[(3RS)-2,6-dioxopiperidin-3-il]-2H-isoindol-1,3-diona antineoplásico

C13H11N3O4

19171-19-8

NH

O

and enantiomeret énantiomèrey enantiómero

O

NH

O

NH2O


158

posaraprostum posaraprost propan-2-yl (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hydroxy-5-phenylpent-

1-en-1-yl]-5-oxocyclopent-3-en-1-yl}hept-5-enoate anti-inflammatory

posaraprost (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hydroxy-5-phénylpent-1-én-1-yl]- 5-oxocyclopent-3-én-1-yl}hept-5-énoate de propan-2-yle anti-inflammatoire

posaraprost (5Z)-7-{(1R,2S)-2-[(1E,3S)-3-hidroxi-5-fenilpent-1-en-1-il]- 5-oxociclopent-3-en-1-ilo}-hept-5-enoato de propan-2-ilo antiinflamatorio

C26H34O4

172740-14-6

O

H OHH

HO

O

CH3

CH3

pyronaridinum pyronaridine 4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]-

2,6-bis[(pyrrolidin-1-yl)methyl]phenol antimalarial

pyronaridine 4-[(7-chloro-2-méthoxybenzo[b][1,5]naphthyridin-10-yl)amino]- 2,6-bis[(pyrrolidin-1-yl)méthyl]phénol antipaludique

pironaridina 4-[(7-cloro-2-metoxibenzo[b][1,5]naftiridin-10-il)amino]- 2,6-bis[(pirrolidin-1-il)metil]fenol antipalúdico

C29H32ClN5O2

74847-35-1

N

N Cl

H3CO

HN

OH

N

N


159

rabeximod rabeximod 2-(9-chloro-2,3-dimethyl-6H-indolo[2,3-b]quinoxalin-6-yl)-

N-[2-(dimethylamino)ethyl]acetamide immunomodulator

rabeximod 2-(9-chloro-2,3-diméthyl-6H-indolo[2,3-b]quinoxalin-6-yl)- N-[2-(diméthylamino)éthyl]acétamide immunomodulateur

rabeximod 2-(9-cloro-2,3-dimetil-6H-indolo[2,3-b]quinoxalin-6-il)- N-[2-(dimetilamino)etil]acetamida inmunomodulador

C22H24ClN5O

872178-65-9

O

NHN

NCH3

CH3

N

N

CH3

CH3

Cl

raltegravirum raltegravir N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[2-(5-methyl-

1,3,4-oxadiazole-2-carboxamido)propan-2-yl]-6-oxo- 1,6-dihydropyrimidine-4-carboxamide antiviral

raltégravir N-[(4-fluorophényl)méthyl]-5-hydroxy-1-méthyl-2-[2-(5-méthyl- 1,3,4-oxadiazole-2-carboxamido)propan-2-yl]-6-oxo- 1,6-dihydropyrimidine-4-carboxamide antiviral

raltegravir N-[(4-fluorofenil)metil]-5-hidroxi-1-metil-2-[2-(5-metil-1,3,4-oxadiazol-2-carboxamido)propan-2-il]-6-oxo-1,6-dihidropirimidina- 4-carboxamida antiviral

C20H21FN6O5

518048-05-0

N

NNH

O

O

H3C OH

NH

O

O

N N

CH3H3C

H3C

F

regrelorum regrelor N6-(N-ethylcarbamoyl)-2',3'-O-[(1S,2E)-3-phenylprop-2-ene-1,1-diyl]-

5'-adenylic acid platelet aggregation inhibitor


160

régrélor acide N6-(N-éthylcarbamoyl)-2',3'-O-[(1S,2E)-3-phénylprop-2-ène-1,1-diyl]-5'-adénylique antiagrégant plaquettaire

regrelor ácido N6-(N-etilcarbamoil)-2',3'-O-[(1S,2E)-3-fenilprop-2-eno- 1,1-diilo]-5'-adenílico inhibidor de la agregacion plaqueteria

C22H25N6O8P

787548-03-2

N

N N

N

O

O

OP

O

NHNH

H3C

HO OH

O

O

H

rolapitantum rolapitant (5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl)-

8-phenyl-1,7-diazaspiro[4.5]decan-2-one neurokinin NK1 receptor antagonist

rolapitant (5S,8S)-8-({(1R)-1-[3,5-bis(trifluorométhyl)phényl]éthoxy}méthyl)- 8-phényl-1,7-diazaspiro[4.5]décan-2-one antagoniste du récepteur NK1 de la neurokinine

rolapitant (5S,8S)-8-({(1R)-1-[3,5-bis(trifluorometil)fenil]etoxi}metil)-8-fenil- 1,7-diazaspiro[4.5]decan-2-ona antagonista del receptor NK1 de neurokinina

C25H26F6N2O2

552292-08-7

O

H CH3

CF3

CF3

NH

HN

O


161

romiplostimum* romiplostim L-methionyl[human immunogloblin heavy constant gamma 1-(227

C-terminal residues)-peptide (Fc fragment)] fusion protein with 41 amino acids peptide, (7-7':10,10')-bisdisulfide dimer platelet stimulating factor (through Mpl receptor)

romiplostim (7-7':10,10')-bisdisulfure du dimère de la protéine de fusion entre le L-méthionyl[chaine constante gamma 1 de l’immunoglobuline humaine-(227 aminoacides C-terminaux)-peptide (fragment Fc)] et un peptide de 41 aminoacides facteur de stimulation plaquettaire (par le récepteur MpI)

romiplostim (7-7':10,10')-bisdisulfuro del dímero de la proteína de fusión entre la L-metionil[cadena constante gamma 1 de la inmunoglobulina humana-(227 aminoácidos C-terminales)-péptido (fragmento Fc)] y un péptido de 41 aminoácidos factor estimulante de plaquetas (mediante el receptor Mpl)

C2634H4086N722O790S18

267639-76-9

MDKTHTCPPC PAPELLGGPS VFLFPPKPKD TLMISRTPEV TCVVVDVSHE 50DPEVKFNWYV DGVEVHNAKT KPREEQYNST YRVVSVLTVL HQDWLNGKEY 100KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSRDELT KNQVSLTCLV 150KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ 200GNVFSCSVMH EALHNHYTQK SLSLSPGKGG GGGIEGPTLR QWLAARAGGG 250GGGGGIEGPT LRQWLAARA 269

Monomer / Monomère / Monómero

Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro

7-7' 10-10' 42-102 42'-102' 148-206 148'-206'

ronacaleretum ronacaleret 3-{3-[(2R)-3-{[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-

2-yl]amino}-2-hydroxypropoxy]-4,5-difluorophenyl}propanoic acid antagonist of the G-protein coupled calcium sensing receptor

ronacaléret acide 3-{3-[(2R)-3-{[1-(2,3-dihydro-1H-indèn-2-yl)-2-méthylpropan- 2-yl]amino}-2-hydroxypropoxy]-4,5-difluorophényl}propanoïque antagoniste du récepteur sensible au calcium couplé à la protéine G

ronacaleret ácido3-{3-[(2R)-3-{[1-(2,3-dihidro-1H-inden-2-il)-2-metilpropan- 2-il]amino}-2-hidroxipropoxi]-4,5-difluorofenil}propanoico antagonista del receptor sensible al calcio acoplado a proteína G

C25H31F2NO4

753449-67-1

NH

O

CH3H3C

H OHCO2H

F

F


162

ropidoxuridinum ropidoxuridine 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-iodopyrimidin-2(1H)-one

antineoplastic

ropidoxuridine 1-(2-déoxy-β-D-érythro-pentofuranosyl)-5-iodopyrimidin-2(1H)-one antinéoplasique

ropidoxuridina 1-(2-desoxi-β-D-eritro-pentofuranosil)-5-iodopirimidin-2(1H)-ona antineoplásico

C9H11IN2O4

093265-81-7

N

NOO

OH

HO

I

rosonabantum rosonabant (5RS)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-

4,5-dihydro-1H-pyrazole-3-carboxamide cannabinoid receptor antagonist

rosonabant (5RS)-5-(4-chlorophényl)-1-(2,4-dichlorophényl)-N-(pipéridin-1-yl)-4,5-dihydro-1H-pyrazole-3-carboxamide antagoniste des récepteurs cannabinoïdes

rosonabant (5RS)-5-(4-clorofenil)-1-(2,4-diclorofenil)-N-(piperidin-1-il)- 4,5-dihidro-1H-pirazol-3-carboxamida antagonista del receptor de cannabinoides

C21H21Cl3N4O

861151-12-4

NN N

H

N

O

Cl

Cl

Cl

H

and enantiomeret énantiomèrey enantiómero

salirasibum salirasib 2-{[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]sulfanyl}benzoic

acid antineoplastic

salirasib acide 2-{[(2E,6E)-3,7,11-triméthyldodéca-2,6,10-trién-1-yl]sulfanyl}= benzoïque antinéoplasique

salirasib ácido 2-{[(2E,6E)-3,7,11-trimetildodeca-2,6,10-trien-1-il]sulfanil}= benzoico antineoplásico


163

C22H30O2S

162520-00-5

CO2H

S CH3

CH3CH3CH3

sitimagenum ceradenovecum* sitimagene ceradenovec (recombinant) replication restricted adenovirus (type 5) vector, E1

and E3 deleted, containing/expressing the Herpes simplex virus thymidine kinase (HSV-tk) gene antineoplastic

sitimagène céradénovec Vecteur adénovirus (type 5 recombinant défectif, délété de E1 et E3, contenant le gène thymidine kinase du virus de l’herpès simplex (Herpes simplex virus - HSV-tk) antinéoplasique

sitimagén ceradenovec Vector adenovirus (tipo 5 recombinante defectivo,con deleción de E1 y E3, que contiene el gen timidina kinasa del virus del herpes simplex (Herpes simplex virus - HSV-tk) antineoplásico

898830-54-1

sotrastaurinum sotrastaurin 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-

1H-pyrrole-2,5-dione protein kinase C inhibitor

sotrastaurine 3-(1H-indol-3-yl)-4-[2-(4-méthylpipérazin-1-yl)quinazolin-4-yl]- 1H-pyrrole-2,5-dione inhibiteur de la protéine kinase C

sotrastaurina 3-(1H-indol-3-il)-4-[2-(4-metilpiperazin-1-il)quinazolin-4-il]-1H-pirrol-2,5-diona inhibidor de la proteinquinasa C

C25H22N6O2

425637-18-9

HN

NHN

N

N

NCH3

O O


164

taranabantum taranabant N-[(2S,3S)-4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl}-

2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide cannabinoid receptor antagonist

taranabant N-[(2S,3S)-4-(4-chlorophényl)-3-(3-cyanophényl)butan-2-yl}- 2-méthyl-2-{[5-(trifluorométhyl)pyridin-2-yl]oxy}propanamide antagoniste des récepteurs cannabinoïdes

taranabant N-[(2S,3S)-4-(4-clorofenil)-3-(3-cianofenil)butan-2-il}-2-metil- 2-{[5-(trifluorometil)piridin-2-il]oxi}propanamida antagonista de los receptores de cannabinoides

C27H25ClF3N3O2

701977-09-5

NC NH

O

H

Cl

HH3C

H3C CH3 N

O

CF3

tarenflurbilum tarenflurbil (2R)-2-(2-fluoro-[1,1'-biphenyl-4-yl])propanoic acid

apoptosis regulator

tarenflurbil (2R)-2-(2-fluoro-[1,1'-biphényl-4-yl])propanoic acid régulateur de l'apoptose

tarenflurbilo ácido (2R)-2-(2-fluoro-[1,1'-bifenil-4-il])propanoico regulador de la apoptosis

C15H13FO2

051543-40-9

CO2H

CH3HF

teplizumabum* teplizumab immunoglobulin G1, anti-[human CD3 epsilon (CD3E)] humanized

monoclonal antibody MGA031 [hOKT3gamma1(Ala-Ala)]; gamma1 heavy chain 236L>A, 337L>A [humanized VH (Homo sapiens FR/Mus musculus CDR from clone OKT3)-Homo sapiens IGHG1*01, 117L>A (CH2 1.3), 118L>A (CH2 1.2)] (222-213’)-disulfide with kappa light chain [humanized V-KAPPA (Homo sapiens FR/Mus musculus CDR from clone OKT3)-Homo sapiens IGKC*01] ; (228-228”: 231-231”)-bisdisulfide dimer immunomodulator


165

téplizumab immunoglobuline G1, anti-[CD3 epsilon humain (CD3E)] anticorps monoclonal humanisé MGA031 [hOKT3gamma1(Ala-Ala)]; chaîne lourde gamma1 [VH humanisé (Homo sapiens FR/Mus musculus CDR du clone OKT3)-Homo sapiens IGHG1*01, 117L >A (CH2 1.3), 118L>A (CH2 1.2)] (222-213’)-disulfure avec la chaîne légère kappa [V-KAPPA humanisé (Homo sapiens FR/Mus musculus CDR du clone OKT3)-Homo sapiens IGKC*01]; dimère (228-228”: 231-231”)-bisdisulfure immunomodulateur

teplizumab inmunoglobulina G1, anti-[CD3 epsilon humano (CD3E)] anticuerpo monoclonal humanizado MGA031 [hOKT3gamma1(Ala-Ala)]; cadena pesada gamma1 [VH humanizada (Homo sapiens FR/Mus musculus CDR del clon OKT3)-Homo sapiens IGHG1*01, 117L >A (CH2 1.3) , 118L>A (CH2 1.2)] (222-213’)-disulfuro con la cadena ligera kappa [V-KAPPA humanizada (Homo sapiens FR/Mus musculus CDR del clon OKT3)-Homo sapiens IGKC*01]; dímero (228-228”: 231-231”)-bisdisulfuro inmunomodulador

C6462H9938N1738O2022S46

876387-05-2

Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGGG VVQPGRSLRL SCKASGYTFT RYTMHWVRQA PGKGLEWIGY 50INPSRGYTNY NQKVKDRFTI SRDNSKNTAF LQMDSLRPED TGVYFCARYY 100DDHYCLDYWG QGTPVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD 150YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200ICNVNHKPSN TKVDKKVEPK SCDKTHTCPP CPAPEAAGGP SVFLFPPKPK 250DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV 350YTLPPSRDEL TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449

Light chain / Chaîne légère / Cadena ligeraDIQMTQSPSS LSASVGDRVT ITCSASSSVS YMNWYQQTPG KAPKRWIYDT 50'SKLASGVPSR FSGSGSGTDY TFTISSLQPE DIATYYCQQW SSNPFTFGQG 100'TKLQITRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD 150'NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL 200'SSPVTKSFNR GEC 213'

Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro22-96 22''-96'' 23'-87' 23'''-87''' 133'-193' 133'''-193''' 146-202 146''-202''213'-222 213'''-222'' 228-228'' 231-231'' 263-323 263''-323'' 369-427 369''-427''

terameprocolum terameprocol 1,1'-[(2R,3S)-2,3-dimethylbutane-1,4-diyl]bis(3,4-dimethoxybenzene)

antineoplastic

térameprocol 1,1'-[(2R,3S)-2,3-diméthylbutane-1,4-diyl]bis(3,4-diméthoxybenzène) antinéoplasique

terameprocol 1,1'-[(2R,3S)-2,3-dimetilbutano-1,4-diil]bis(3,4-dimetoxibenceno) antineoplásico

C22H30O4

24150-24-1

OCH3

OCH3

H3CO

H3COCH3H

H3C H


166

thrombinum alfa* thrombin alfa human thrombin (recombinant, glycoform α)

coagulation promoting agent

thrombine alfa thrombine humaine (recombinante, glycoforme α) facteur de promotion de la coagulation

trombina alfa trombina humana (recombinante, glicoforma α) factor promotor de la coagulación

C1511H2342N418O436S15

869858-13-9

Light chain / Chaîne légère / Cadena ligeraTFGSGEADCG LRPLFEKKSL EDKTERELLE SYIDGR 36

Heavy chain / Chaîne lourde / Cadena pesada IVEG SDAEIGMSPW 50QVMLFRKSPQ ELLCGASLIS DRWVLTAAHC LLYPPWDKNF TENDLLVRIG 100KHSRTRYERN IEKISMLEKI YIHPRYNWRE NLDRDIALMK LKKPVAFSDY 150IHPVCLPDRE TAASLLQAGY KGRVTGWGNL KETWTANVGK GQPSVLQVVN 200LPIVERPVCK DSTRIRITDN MFCAGYKPDE GKRGDACEGD SGGPFVMKSP 250FNNRWYQMGI VSWGEGCDRD GKYGFYTHVF RLKKWIQKVI DQFGE 295

Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro9-155 64-80 209-223 237-267

Glycosylation site / Site de glycosylation / Posición de glicosilaciónAsn-89

tiliquinatinum tiliquinatine (2R)-2-{4-[(7-bromoquinolin-2-yl)oxy]phenoxy}propanoic acid

antineoplastic

tiliquinatine acide (2R)-2-{4-[(7-bromoquinoléin-2-yl)oxy]phénoxy}propanoïque antinéoplasique

tiliquinatina ácido (2R)-2-{4-[(7-bromoquinolin-2-il)oxi]fenoxi}propanoico antineoplásico

C18H14BrNO4

445041-75-8

O CO2H

CH3HONBr

totrombopagum totrombopag (4Z)-2-(3,4-dimethylphenyl)-4-(2-{2-hydroxy-3'-(1H-tetrazol-5-yl)

[1,1'-biphenyl-3-yl]}hydrazinylidene)-5-methyl-2,4-dihydro- 3H-pyrazol-3-one thrombopoietin receptor agonist

totrombopag (4Z)-2-(3,4-diméthylphényl)-4-{2-[2-hydroxy-3'-(1H-tétrazol-5-yl) [1,1'-biphényl-3-yl]]diazanylidène}-5-méthyl-2,4-dihydro-3H-pyrazol-3-one agoniste du récepteur de la thrombopoïétine

totrombopag (4Z)-2-(3,4-dimetilfenil)-4-{2-[2-hidroxi-3'-(1H-tetrazol-5-il)- [1,1'-bifenil-3-il]]hidrazinilideno}-5-metil-2,4-dihidro-3H-pirazol-3-ona agonista de los receptores de trombopoyetina


167

C25H22N8O2

376592-42-6

NH

NN

NO

H3C

OH

CH3H3C

NN

NHN

trabedersenum trabedersen 2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-

deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-P-thiocytidylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thioadenylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy- P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxyadenosine antineoplastic

trabedersen 2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxy-P-thiocytidylyl-(3'→5')-2'-déoxy-P-thioadénylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thioadénylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxy- P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-déoxyadénosine antinéoplasique

trabedersén 2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')-2'-desoxi- P-tioadenilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi-P-tiocitidilil-(3'→5')- P-tiotimidilil-(3'→5')-2'-desoxi-P-tioadenilil-(3'→5')-P-tiotimidilil-(3'→5')-P-tiotimidilil-(3'→5')-P-tiotimidilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-P-tiotimidilil-(3'→5')-2'-desoxiadenosina antineoplásico

C177H225N60O94P17S17

925681-61-4


168

trelanserinum trelanserin 2-(7-fluoro-2-oxo-4-{2-[4-(thieno[3,2-c]pyridin-4-yl)piperazin-

1-yl]ethyl}-1,2-dihydroquinolin-1-yl)acetamide serotonin receptor antagonist

trélansérine 2-(7-fluoro-2-oxo-4-{2-[4-(thiéno[3,2-c]pyridin-4-yl)pipérazin- 1-yl]éthyl}-1,2-dihydroquinolein-1-yl)acétamide antagoniste des récepteurs de la sérotonine

trelanserina 2-(7-fluoro-2-oxo-4-{2-[4-(tieno[3,2-c]piridin-4-il)piperazin-1-il]etil}-1,2-dihidroquinolin-1-il)acetamida antagonista de los receptores de serotonina

C24H24FN5O2S

189003-92-7

N

N N

NH2N

O

O

F

S

tridecactidum* tridecactide alpha-1-13-corticotropin, human

L-seryl-L-tyrosyl-L-seryl-L-methionyl-L-glutamyl-L-histidyl- L-phenylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valine corticotropin-like activity

tridécactide alpha-1-13-corticotropine, humaine L-séryl-L-tyrosyl-L-séryl-L-méthionyl-L-glutamyl-L-histidyl- L-phénylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valine activité corticotrope

tridecactida alfa-1-13-corticotropina, humana L-seril-L-tirosil-L-seril-L-metionil-L-glutamil-L-histidil-L-fenilalanil- L-arginil-L-triptofilglicil-L-lisil-L-prolil-L-valina actividad corticotropa

C75H106N20O19S

22006-64-0

H Ser Tyr Ser Met Glu His Phe Arg Trp Gly Lys Pro Val10

OH

tropantiolum tropantiol 2-({[(1R,2R,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]

octan-2-yl]methyl}{2-[(2-sulfanylethyl)amino]ethyl}amino)ethanethiol chelating agent

tropantiol 2-({[(1R,2R,3S,5S)-3-(4-chlorophényl)-8-méthyl-8-azabicyclo[3.2.1] octan-2-yl]méthyl}{2-[(2-sulfanyléthyl)amino]éthyl}amino)éthanethiol chélateur

tropantiol 2-({[(1R,2R,3S,5S)-3-(4-clorofenil)- 8-azabiciclo[ 3.2.1]octan- 2-il]metil}{2-[(2-sulfaniletil)amino]etil}amino)etanotiol quelante


169

C21H34ClN3S2

189950-11-6

N CH3H

H H

H

NHS N

H

Cl

SH

vatreptacogum alfa (activated)* vatreptacog alfa (activated) [158-aspartic acid, 296-valine, 298-glutamine]human coagulation

factor VII activated, recombinant DNA origin blood coagulation factor

vatreptacog alfa (activé) [158-acide aspartique, 296-valine, 298-glutamine]facteur de coagulation VII humain activé, origine ADN recombinant facteur de coagulation sanguine

vatreptacog alfa (activada) [158-ácido aspártico, 296-valina, 298-glutamina]factor de coagulación VII humano activado ; origen ADN recombinante factor de coagulación sanguínea

C1981H3051N561O620S27

897936-89-9

Light chain / Chaîne légère / Cadena ligeraANAFLEELRP GSLERECKEE QCSFEEAREI FKDAERTKLF WISYSDGDQC 50ASSPCQNGGS CKDQLQSYIC FCLPAFEGRN CETHKDDQLI CVNENGGCEQ 100YCSDHTGTKR SCRCHEGYSL LADGVSCTPT VEYPCGKIPI LEKRNASKPQ 150GR 152

Heavy chain / Chaîne lourde / Cadena pesada IVGGKDCP KGECPWQVLL LVNGAQLCGG TLINTIWVVS AAHCFDKIKN 200WRNLIAVLGE HDLSEHDGDE QSRRVAQVII PSTYVPGTTN HDIALLRLHQ 250PVVLTDHVVP LCLPERTFSE RTLAFVRFSL VSGWGQLLDR GATALVLQVL 300NVPRLMTQDC LQQSRKVGDS PNITEYMFCA GYSDGSKDSC KGDSGGPHAT 350HYRGTWYLTG IVSWGQGCAT VGHFGVYTRV SQYIEWLQKL MRSEPRPGVL 400LRAPFP 406

Modified residues / Résidus modifiés / Residuos modificadosE

6-7-14-16-19-20-25-26-29-354-carboxyGlu

HO2C CO2H

NH2HHO2C D63

3-hydroxyAsp

HO2CCO2H

NH2H

OH

Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro17-22 50-61 55-70 72-81 91-102 98-112114-127 135-262 159-164 178-194 310-329 340-368

Glycosylation sites / Sites de glycosylation / Posiciones de glicosilaciónSer-52 Ser-60 Asn-145 Asn-322

velimogenum aliplasmidum* velimogene aliplasmid plasmid DNA vector, expressing HLA-B7 and beta-2 microglobulin,

driven by a Rous sarcoma virus promoter stimulates destruction of melanoma cells

vélimogène aliplasmide vecteur ADN plasmidique, contenant les gènes HLA-B7 et beta2-microglobuline, sous le contrôle du promoteur virus de sarcome de Rous stimule la destruction des cellules mélaniques

velimogén aliplásmido vector ADN de plásmído, que contiene los genes HLA-B7 y beta2-microglobulina, controlado por el promotor de virus del sarcoma de Rous estimula la destrucción de las células del melanoma

296251-72-4


170

voclosporinum voclosporin 1,11-anhydro[L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-

N-methyl-L-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-methyl- 2-(methylamino)nona-6,8-dienoyl][(2S)-2-aminobutanoyl]- N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucine] immunosuppressant

voclosporine 1,11anhydro{L-alanyl-D-alanyl-N-méthyl-L-leucyl-N-méthyl-L-leucyl-N-méthyl-L-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-méthyl- 2-(méthylamino)nona-6,8-diénoyl]-(2S)-2-aminobutanoyl- N-méthylglycyl-N-méthyl-L-leucyl-L-valyl-N-méthyl-L-leucyl] immunosuppresseur

voclosporina 1,11-anhidro[L-alanil-D-alanil-N-metil-L-leucil-N-metil-L-leucil-N-metil-L-valil-[(2S,3R,4R,6E)-3-hidroxi-4-metil-2-(metilamino)nona- 6,8-dienoil][(2S)-2-aminobutanoil]-N-metilglicil-N-metil-L-leucil-L-valil-N-methyl-L-leucina] inmunosupresor

C63H111N11O12

515814-01-4

N

CH3 O

N

CH3 O

NH

N

OO

N

NO

HN

O H3C

NHN

OHN

NCH3

H

HH CH3H3C H

H3CHH3C

CH3

H3CCH3

H H

OHH

O

CH3

H3CH

H

O

H3C

H

O

H3CCH3

CH3

H3C

CH3

CH3O

H

H3C

H3C

CH3

CH2


171

AMENDMENTS TO PREVIOUS LISTS MODIFICATIONS APPORTÉES AUX LISTES ANTÉRIEURES

MODIFICACIONES A LAS LISTAS ANTERIORES Proposed International Non Proprietary Names (Prop. INN): List 31 (WHO Chronicle, Vol. 28, No. 3, 1974) p. 22 dimemorfanum dimemorfan replace graphic formula by the following

N

H3C

CH3

H

H

Dénominations communes internationales proposées (DCI Prop.): Liste 31 (Chronique OMS, Vol. 28, No. 3, 1974) p. 22 dimemorfanum dimémorfane remplacer la formule développée par la suivante

N

H3C

CH3

H

H

Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 31 (Crónica de la OMS, Vol. 28, No. 3, 1974) p. 23 dimemorfanum dimemorfano sustitúyase la formúla désarollada por la siguiente

N

H3C

CH3

H

H


172

Proposed International Non Proprietary Names (Prop. INN): List 71 Dénominations communes internationales proposées (DCI Prop.): Liste 71 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 71 (WHO Drug Information, Vol. 8, No. 2, 1994) p. 26 suprimáse insértese afovirseno afovirsén

Proposed International Non Proprietary Names (Prop. INN): List 75 Dénominations communes internationales proposées (DCI Prop.): Liste 75 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 75 (WHO Drug Information, Vol. 10, No. 2, 1996) p. 100 suprimáse insértese fomivirseno fomivirsén

Proposed International Non Proprietary Names (Prop. INN): List 77 Dénominations communes internationales proposées (DCI Prop.): Liste 77 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 77 (WHO Drug Information, Vol. 11, No. 2, 1997) p. 102 suprimáse insértese trecovirseno trecovirsén

Proposed International Non Proprietary Names (Prop. INN): List 80 Dénominations communes internationales proposées (DCI Prop.): Liste 80 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 80 (WHO Drug Information, Vol. 12, No. 4, 1998) p. 276 solimastatum solimastat insert the following CAS

solimastat insérer le numéro de CAS suivant

solimastat insértese el nombre del CAS siguiente

226072-63-5 Proposed International Non Proprietary Names (Prop. INN): List 81 Dénominations communes internationales proposées (DCI Prop.): Liste 81 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 81 (WHO Drug Information, Vol. 13, No. 2, 1999) p. 117 ganstigminum ganstigmine insert the following CAS

ganstigmine insérer le numéro de CAS suivant

ganstigmina insértese el nombre del CAS siguiente

457075-21-7


173

Proposed International Non Proprietary Names (Prop. INN): List 82 Dénominations communes internationales proposées (DCI Prop.): Liste 82 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 82 (WHO Drug Information, Vol. 14, No. 4, 1999) p. 268 cangrelorum cangrelor insert the following CAS number

cangrélor insérer le numéro de CAS suivant

cangrelor insértese el nombre del CAS siguiente

163706-06-7 p. 270 crobenetinum crobenetine insert the following CAS

crobénétine insérer le numéro de CAS suivant

crobenetina insértese el nombre del CAS siguiente

221019-25-6 p. 273 epitumomabum epitumomab insert the following CAS

épitumomab insérer le numéro de CAS suivant

epitumomab insértese el nombre del CAS siguiente

263547-71-3 p. 277 figopitantum figopitant insert the following CAS

figopitant insérer le numéro de CAS suivant

figopitant insértese el nombre del CAS siguiente

502422-74-4 p. 288 sulamserodum sulamserod insert the following CAS

sulamsérod insérer le numéro de CAS suivant

sulamserod insértese el nombre del CAS siguiente

219757-90-1 Proposed International Non Proprietary Names (Prop. INN): List 85 Dénominations communes internationales proposées (DCI Prop.): Liste 85 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 85 (WHO Drug Information, Vol. 15, No. 2, 2001) p. 98 suprimáse insértese alicaforseno alicaforsén


174

p. 121 pralnacasanum pralnacasan replace the action and use by the following

pralnacasan remplacer les proprietés et indications par les suivantes

pralnacasán sustitúyase el acción y uso por los siguientes

caspase inhibitor inhibiteur de la caspase inhibidor de la caspasa Proposed International Non Proprietary Names (Prop. INN): List 86 Dénominations communes internationales proposées (DCI Prop.): Liste 86 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 86 (WHO Drug Information, Vol. 16, No. 1, 2002) p. 65 ozogamicinum ozogamicin insert the following CAS

ozogamicine insérer le numéro de CAS suivant

ozogamicina insértese el nombre del CAS siguiente

400046-53-9 p. 70 zoticasonum zoticasone insert the following CAS

zoticasone insérer le numéro de CAS suivant

zoticasona insértese el nombre del CAS siguiente

678160-57-1 Proposed International Non Proprietary Names (Prop. INN): List 87 Dénominations communes internationales proposées (DCI Prop.): Liste 87 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 87 (WHO Drug Information, Vol. 16, No. 2, 2002) p. 177 suprimáse insértese oblimerseno oblimersén

Proposed International Non Proprietary Names (Prop. INN): List 89 Dénominations communes internationales proposées (DCI Prop.): Liste 89 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 89 (WHO Drug Information, Vol. 17, No. 3, 2003) p. 186 suprimáse insértese aprinocarseno aprinocarsén


175

Proposed International Non Proprietary Names (Prop. INN): List 90 Dénominations communes internationales proposées (DCI Prop.): Liste 90 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 90 (WHO Drug Information, Vol. 18, No. 1, 2004) p. 49 certolizumabum pegolum certolizumab pegol replace the description by the following

certolizumab pégol remplacer la description par la suivante

certolizumab pegol sustitúyase la descripción por la siguiente

immunoglobulin, anti-(human tumor necrosis factor α) Fab' fragment (human

mouse monoclonal CDP870 heavy chain, disulfide bonded with human mouse monoclonal CDP870 light chain), pegylated at Cys-227 on the heavy chain

immunoglobuline, anti-(facteur α de nécrose tumorale humain) ; (disulfure entre le fragment Fab' de la chaîne lourde et la chaîne légère de l'anticorps monoclonal de souris CDP870 humanisé), pégylée à Cyst-227 sur la chaîne lourde

inmunoglobulina, anti-(factor α de necrosis tumoral humano) fragmento Fab' (cadena pesada del anticuerpo monoclonal humanizado de ratón CDP870, disulfuro con la cadena ligera del anticuerpo monoclonal humanizado de ratón CDP870), pegilado Cis-227 de la cadena pesada

Proposed International Non Proprietary Names (Prop. INN): List 95 Dénominations communes internationales proposées (DCI Prop.): Liste 95 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 95 (WHO Drug Information, Vol. 20, No. 2, 2006) p. 117 aclidinii bromidum bromuro de aclidinio sustitúyase el nombre químico por el siguiente:

bromuro de (3R)-1-(3-fenoxipropil)-3-[(hidroxibis(tiofen-2-il)acetiloxi)]-1-2-butil-

3-{4-[3-(dibutilamino)propil]benzoil}- 1λ5-azabiciclo[2.2.2]octan-1-ilio p. 151 delete/supprimer/suprimáse insert/insérer/insértese

ticilimumabum tremelimumabum ticilimumab tremelimumab ticilimumab trémélimumab ticilimumab tremelimumab


176

Proposed International Non Proprietary Names (Prop. INN): List 96 Dénominations communes internationales proposées (DCI Prop.): Liste 96 Denominaciones Comunes Internacionales Propuestas (DCI Prop.): Lista 96 (WHO Drug Information, Vol. 20, No. 4, 2006) p. 290 managlinatum dialanetilum managlinat dialanetil replace graphic formula by the following:

managlinat dialanétil remplacer la formule développée par la suivante:

managlinat dialanetilo sustitúyase la formúla désarollada por la siguiente:

HN

PNHO

O

NS

H2N

H3C

H3C

O O CH3

CH3

H

O

O CH3HH3C

* Electronic structure available on Mednet: http://mednet.who.int/ * Structure électronique disponible sur Mednet: http://mednet.who.int/ * Estructura electrónica disponible en Mednet: http://mednet.who.int/


177

ANNEX 1

PROCEDURE FOR THE SELECTION OF RECOMMENDED INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES1

The following procedure shall be followed by the World Health Organization (hereinafter also referred to as “WHO”)

in the selection of recommended international nonproprietary names for pharmaceutical substances, in accordance with resolution WHA3.11 of the World Health Assembly, and in the substitution of such names. Article 1 - Proposals for recommended international nonproprietary names and proposals for substitution of such names shall be submitted to WHO on the form provided therefore. The consideration of such proposals shall be subject to the payment of an administrative fee designed only to cover the corresponding costs of the Secretariat of WHO (“the Secretariat”). The amount of this fee shall be determined by the Secretariat and may, from time to time, be adjusted. Article 2 - Such proposals shall be submitted by the Secretariat to the members of the Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations designated for this purpose, such designated members hereinafter referred to as “the INN Expert Group”, for consideration in accordance with the “General principles for guidance in devising International Nonproprietary Names for Pharmaceutical Substances”, annexed to this procedure2. The name used by the person discovering or first developing and marketing a pharmaceutical substance shall be accepted, unless there are compelling reasons to the contrary. Article 3 - Subsequent to the examination provided for in article 2, the Secretariat shall give notice that a proposed international nonproprietary name is being considered. a) Such notice shall be given by publication in WHO Drug Information3

and by letter to Member States and to national and regional pharmacopoeia commissions or other bodies designated by Member States.

i) Notice shall also be sent to the person who submitted the proposal (“the original applicant”) and other persons known to be concerned with a name under consideration.

b) Such notice shall:

i) set forth the name under consideration; ii) identify the person who submitted the proposal for naming the substance, if so requested by such person; iii) identify the substance for which a name is being considered; iv) set forth the time within which comments and objections will be received and the person and place to whom they should be directed; v) state the authority under which WHO is acting and refer to these rules of procedure.

c) In forwarding the notice, the Secretariat shall request that Member States take such steps as are necessary to prevent the acquisition of proprietary rights in the proposed name during the period it is under consideration by WHO. Article 4 - Comments on the proposed name may be forwarded by any person to WHO within four months of the date of publication, under article 3, of the name in WHO Drug Information.

1 See Annex 1 in WHO Technical Report Series, No. 581, 1975; proposed amendments are shown in bold-face type. The original text was adopted by the Executive Board in resolution EB15.R7 and amended in resolution EB43.R9.

2 See Annex 2.

3 Before 1987, lists of international nonproprietary names were published in the Chronicle of the World Health Organization.


178

Article 5 - A formal objection to a proposed name may be filed by any interested person within four months of the date of publication, under article 3, of the name in WHO Drug Information.

Such objection shall:

i) identify the person objecting;

ii) state his or her interest in the name; iii) set forth the reasons for his or her objection to the name proposed. Article 6 - Where there is a formal objection under article 5, WHO may either reconsider the proposed name or use its good offices to attempt to obtain withdrawal of the objection. Without prejudice to the consideration by WHO of a substitute name or names, a name shall not be selected by WHO as a recommended international nonproprietary name while there exists a formal objection thereto filed under article 5 which has not been withdrawn. Article 7 - Where no objection has been filed under article 5, or all objections previously filed have been withdrawn, the Secretariat shall give notice in accordance with subsection (a) of article 3 that the name has been selected by WHO as a recommended international nonproprietary name. Article 8 - In forwarding a recommended international nonproprietary name to Member States under article 7, the Secretariat shall: a) request that it be recognized as the nonproprietary name for the substance; and b) request that Member States take such steps as are necessary to prevent the acquisition of proprietary rights in the name and to prohibit registration of the name as a trademark or trade name. Article 9 a) In the extraordinary circumstance that a previously recommended international nonproprietary name gives rise to errors in medication, prescription or distribution, or a demonstrable risk thereof, because of similarity with another name in pharmaceutical and/or prescription practices, and it appears that such errors or potential errors cannot readily be resolved through other interventions than a possible substitution of a previously recommended international nonproprietary name, or in the event that a previously recommended international nonproprietary name differs substantially from the nonproprietary name approved in a significant number of Member States, or in other such extraordinary circumstances that justify a substitution of a recommended international nonproprietary name, proposals to that effect may be filed by any interested person. Such proposals shall be submitted on the form provided therefore and shall: i) identify the person making the proposal;

ii) state his or her interest in the proposed substitution; and iii) set forth the reasons for the proposal; and

iv) describe, and provide documentary evidence regarding the other interventions undertaken in an effort to resolve the situation, and the reasons why these other interventions were inadequate.

Such proposals may include a proposal for a new substitute international nonproprietary name, devised in accordance with the General principles, which takes into account the pharmaceutical substance for which the new substitute international nonproprietary name is being proposed. The Secretariat shall forward a copy of the proposal, for consideration in accordance with the procedure described in subsection (b) below, to the INN Expert Group and the original applicant or its successor (if different from the person bringing the proposal for substitution and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations). In addition, the Secretariat shall request comments on the proposal from:

i) Member States and national and regional pharmacopoeia commissions or other bodies designated by Member States (by including a notice to that effect in the letter referred to in article 3(a), and


179

ii) any other persons known to be concerned by the proposed substitution. The request for comments shall:

i) state the recommended international nonproprietary name that is being proposed for substitution (and the proposed substitute name, if provided);

ii) identify the person who submitted the proposal for substitution (if so requested by such person);

iii) identify the substance to which the proposed substitution relates and reasons put forward for substitution; iv) set forth the time within which comments will be received and the person and place to whom they should be directed; and v) state the authority under which WHO is acting and refer to these rules of procedure.

Comments on the proposed substitution may be forwarded by any person to WHO within four months of the date of the request for comments. b) After the time period for comments referred to above has elapsed, the Secretariat shall forward any comments received to the INN Expert Group, the original applicant or its successor and the person bringing the proposal for substitution. If, after consideration of the proposal for substitution and the comments received, the INN Expert Group, the person bringing the proposal for substitution and the original applicant or its successor all agree that there is a need to substitute the previously recommended international nonproprietary name, the Secretariat shall submit the proposal for substitution to the INN Expert Group for further processing. Notwithstanding the foregoing, the original applicant or its successor shall not be entitled to withhold agreement to a proposal for substitution in the event the original applicant or its successor has no demonstrable continuing interest in the recommended international nonproprietary name proposed for substitution.

In the event that a proposal for substitution shall be submitted to the INN Expert Group for further processing, the INN Expert Group will select a new international nonproprietary name in accordance with the General principles referred to in article 2 and the procedure set forth in articles 3 to 8 inclusive. The notices to be given by the Secretariat under article 3 and article 7, respectively, including to the original applicant or its successor (if not the same as the person proposing the substitution, and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations), shall in such event indicate that the new name is a substitute for a previously recommended international nonproprietary name and that Member States may wish to make transitional arrangements in order to accommodate existing products that use the previously recommended international nonproprietary name on their label in accordance with national legislation.

If, after consideration of the proposal for substitution and the comments received in accordance with the procedure described above, the INN Expert Group, the original applicant or its successor and the person bringing the proposal for substitution do not agree that there are compelling reasons for substitution of a previously recommended international nonproprietary name, this name shall be retained (provided always that the original applicant or its successor shall not be entitled to withhold agreement to a proposal for substitution in the event that the original applicant or its successor has no demonstrable continuing interest in the recommended international nonproprietary name proposed to be substituted). In such an event, the Secretariat shall advise the person having proposed the substitution, as well as the original applicant or its successor (if not the same as the person proposing the substitution, and provided that the original applicant or its successor is known or can be found through diligent effort, including contacts with industry associations), Member States, national and regional pharmacopoeia commissions, other bodies designated by Member States, and any other persons known to be concerned by the proposed substitution that, despite a proposal for substitution, it has been decided to retain the previously recommended international nonproprietary name (with a description of the reason(s) why the proposal for substitution was not considered sufficiently compelling). Article 10 - A working process, intended to serve as a guide for the INN Expert Group in the implementation of this procedure, is attached hereto as an appendix.


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ANNEX 2

GENERAL PRINCIPLES FOR GUIDANCE IN DEVISING INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES1

1. International Nonproprietary Names (INN) should be distinctive in sound and spelling. They should not be inconveniently long and should not be liable to confusion with names in common use. 2. The INN for a substance belonging to a group of pharmacologically related substances should, where appropriate, show this relationship. Names that are likely to convey to a patient an anatomical, physiological, pathological or therapeutic suggestion should be avoided. These primary principles are to be implemented by using the following secondary principles: 3. In devising the INN of the first substance in a new pharmacological group, consideration should be given to the possibility of devising suitable INN for related substances, belonging to the new group. 4. In devising INN for acids, one-word names are preferred; their salts should be named without modifying the acid name, e.g. “oxacillin” and “oxacillin sodium”, “ibufenac” and “ibufenac sodium”. 5. INN for substances which are used as salts should in general apply to the active base or the active acid. Names for different salts or esters of the same active substance should differ only in respect of the name of the inactive acid or the inactive base. For quaternary ammonium substances, the cation and anion should be named appropriately as separate components of a quaternary substance and not in the amine-salt style. 6. The use of an isolated letter or number should be avoided; hyphenated construction is also undesirable. 7. To facilitate the translation and pronunciation of INN, “f” should be used instead of “ph”, “t” instead of “th”, “e” instead of “ae” or “oe”, and “i” instead of “y”; the use of the letters “h” and “k” should be avoided. 8. Provided that the names suggested are in accordance with these principles, names proposed by the person discovering or first developing and marketing a pharmaceutical preparation, or names already officially in use in any country, should receive preferential consideration. 9. Group relationship in INN (see General principle 2) should if possible be shown by using a common stem. The following list contains examples of stems for groups of substances, particularly for new groups. There are many other stems in active use.2 Where a stem is shown without any hyphens it may be used anywhere in the name. Latin English -acum -ac anti-inflammatory agents, ibufenac derivatives -adolum -adol } analgesics -adol- -adol-} -astum -ast anti-asthmatic, anti-allergic substances not acting primarily as

antihistaminics -astinum -astine antihistaminics -azepamum -azepam diazepam derivatives bol bol steroids, anabolic -cain- -cain- class I antiarrhythmics, procainamide and lidocaine derivatives -cainum -caine local anaesthetics 1

In its Twentieth report (WHO Technical Report Series, No. 581, 1975), the WHO Expert committee on Nonpropriety Names for Pharmaceutical Substances reviewed the general principles for devising, and the procedures for selecting, INN in the light of developments in pharmaceutical compounds in recent years. The most significant change has been the extension to the naming of synthetic chemical substances of the practice previously used for substances originating in or derived from natural products. This practice involves the use of a characteristic “stem” indicative of a common property of the members of a group. The reason for, and the implications of, the change are fully discussed. The guiding principles were updated during the 13th consultation on nonproprietary names for pharmaceutical substances (Geneva, 27-29 April 1983) (PHARM S/NOM 928 13 May 1983, revised 18 August 1983).

2 A more extensive listing of stems is contained in the working document WHO/PSM/QSM/2006.3 which is regularly updated and can be requested from the INN Programme, WHO, Geneva.


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cef- cef- antibiotics, cefalosporanic acid derivatives -cillinum -cillin antibiotics, 6-aminopenicillanic acid derivatives -conazolum -conazole systemic antifungal agents, miconazole derivatives cort cort corticosteroids, except prednisolone derivatives -coxibum -coxib selective cyclo-oxygenase inhibitors -entanum -entan endothelin receptor antagonists gab gab gabamimetic agents gado- gado- diagnostic agents, gadolinium derivatives -gatranum -gatran thrombin inhibitors, antithrombotic agents gest gest steroids, progestogens gli gli antihyperglycaemics io- io- iodine-containing contrast media -metacinum -metacin anti-inflammatory, indometacin derivatives -mycinum -mycin antibiotics, produced by Streptomyces strains -nidazolum -nidazole antiprotozoal substances, metronidazole derivatives -ololum -olol β-adrenoreceptor antagonists -oxacinum -oxacin antibacterial agents, nalidixic acid derivatives -platinum -platin antineoplastic agents, platinum derivatives -poetinum -poetin erythropoietin type blood factors -pril(at)um -pril(at) angiotensin-converting enzyme inhibitors -profenum -profen anti-inflammatory substances, ibuprofen derivatives prost prost prostaglandins -relinum -relin pituitary hormone release-stimulating peptides -sartanum -sartan angiotensin II receptor antagonists, antihypertensive (non-peptidic) -vaptanum -vaptan vasopressin receptor antagonists vin- vin- } vinca-type alkaloids -vin- -vin-}

ANNEXE 1

PROCEDURE A SUIVRE EN VUE DU CHOIX DE DENOMINATIONS COMMUNES INTERNATIONALES RECOMMANDEES POUR LES SUBSTANCES

PHARMACEUTIQUES1

L’Organisation mondiale de la Santé (également désignée ci-après sous l’appellation « OMS ») observe la procédure exposée ci-dessous pour l’attribution de dénominations communes internationales recommandées pour les substances pharmaceutiques, conformément à la résolution WHA3.11 de l’Assemblée mondiale de la Santé, et pour le remplacement de telles dénominations. Article 1 - Les propositions de dénominations communes internationales recommandées et les propositions de remplacement de telles dénominations sont soumises à l’OMS sur la formule prévue à cet effet. L’examen de telles propositions est soumis au paiement d’une taxe administrative destinée uniquement à couvrir les coûts correspondants assumés par le Secrétariat de l’OMS (« le Secrétariat »). Le montant de cette taxe est déterminé par le Secrétariat et peut être modifié de temps à autre. Article 2 - Ces propositions sont soumises par le Secrétariat aux experts désignés à cette fin parmi les personnalités inscrites au Tableau d’experts de la Pharmacopée internationale et des Préparations pharmaceutiques, ci-après désignés sous l’appellation « le Groupe d’experts des DCI » ; elles sont examinées par les experts conformément aux « Directives générales pour la formation de dénominations communes internationales pour les substances pharmaceutiques » reproduites ci-après2.

La dénomination acceptée est la dénomination employée par la personne qui découvre ou qui, la première, fabrique et lance sur le marché une substance pharmaceutique, à moins que des raisons majeures n’obligent à s’écarter de cette règle.

1 Voir annexe 1 dans OMS, Série de Rapports techniques, N° 581, 1975 ; les amendements proposés sont indiqués en caractères gras. Le texte original a été adopté par le Conseil exécutif dans sa résolution EB15.R7 et amendé dans sa résolution EB43.R9.

2 Voir annexe 2.


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Article 3 - Après l’examen prévu à l’article 2, le Secrétariat notifie qu’un projet de dénomination commune internationale est à l’étude. a) Cette notification est faite par une insertion dans WHO Drug Information1 et par l’envoi d’une lettre aux Etats Membres et aux commissions nationales et régionales de pharmacopée ou autres organismes désignés par les Etats Membres.

i) Notification est également faite à la personne qui a soumis la proposition (« le demandeur initial ») et à d’autres personnes portant à la dénomination mise à l’étude un intérêt notoire.

b) Cette notification contient les indications suivantes :

i) dénomination mise à l’étude;

ii) nom de l’auteur de la proposition tendant à attribuer une dénomination à la substance, si cette personne le demande ;

iii) définition de la substance dont la dénomination est mise à l’étude ;

iv) délai pendant lequel seront reçues les observations et les objections à l’égard de cette dénomination ; nom et adresse de la personne habilitée à recevoir ces observations et objections ;

v) mention des pouvoirs en vertu desquels agit l’OMS et référence au présent règlement.

c) En envoyant cette notification, le Secrétariat demande aux Etats Membres de prendre les mesures nécessaires pour prévenir l’acquisition de droits de propriété sur la dénomination proposée pendant la période au cours de laquelle cette dénomination est mise à l’étude par l’OMS. Article 4 - Des observations sur la dénomination proposée peuvent être adressées à l’OMS par toute personne, dans les quatre mois qui suivent la date de publication de la dénomination dans WHO Drug Information (voir l’article 3). Article 5 - Toute personne intéressée peut formuler une objection formelle contre la dénomination proposée dans les quatre mois qui suivent la date de publication de la dénomination dans WHO Drug Information (voir l’article 3). Cette objection doit s’accompagner des indications suivantes :

i) nom de l’auteur de l’objection ; ii) intérêt qu’il ou elle porte à la dénomination en cause ; iii) raisons motivant l’objection contre la dénomination proposée. Article 6 - Lorsqu’une objection formelle est formulée en vertu de l’article 5, l’OMS peut soit soumettre la dénomination proposée à un nouvel examen, soit intervenir pour tenter d’obtenir le retrait de l’objection. Sans préjudice de l’examen par l’OMS d’une ou de plusieurs appellations de remplacement, l’OMS n’adopte pas d’appellation comme dénomination commune internationale recommandée tant qu’une objection formelle présentée conformément à l’article 5 n’est pas levée. Article 7 - Lorsqu’il n’est formulé aucune objection en vertu de l’article 5, ou que toutes les objections présentées ont été levées, le Secrétariat fait une notification conformément aux dispositions du paragraphe a) de l’article 3, en indiquant que la dénomination a été choisie par l’OMS en tant que dénomination commune internationale recommandée. Article 8 - En communiquant aux Etats Membres, conformément à l’article 7, une dénomination commune internationale recommandée, le Secrétariat : a) demande que cette dénomination soit reconnue comme dénomination commune de la substance considérée ; et b) demande aux Etats Membres de prendre les mesures nécessaires pour prévenir l’acquisition de droits de propriété sur cette dénomination et interdire le dépôt de cette dénomination comme marque ou appellation commerciale.

1

Avant 1987, les listes de dénominations communes internationales étaient publiées dans la Chronique de l’Organisation mondiale de la Santé.


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Article 9 - a) Dans le cas exceptionnel où une dénomination commune internationale déjà recommandée donne lieu à des erreurs de médication, de prescription ou de distribution ou en comporte un risque démontrable, en raison d’une similitude avec une autre appellation dans la pratique pharmaceutique et/ou de prescription, et où il apparaît que ces erreurs ou ces risques d’erreur ne peuvent être facilement évités par d’autres interventions que le remplacement éventuel d’une dénomination commune internationale déjà recommandée, ou dans le cas où une dénomination commune internationale déjà recommandée diffère sensiblement de la dénomination commune approuvée dans un nombre important d’Etats Membres, ou dans d’autres circonstances exceptionnelles qui justifient le remplacement d’une dénomination commune internationale recommandée, toute personne intéressée peut formuler une proposition dans ce sens. Cette proposition est présentée sur la formule prévue à cet effet et doit s’accompagner des indications suivantes :

i) nom de l’auteur de la proposition ;

ii) intérêt qu’il ou elle porte au remplacement proposé ;

iii) raisons motivant la proposition ; et

iv) description, faits à l’appui, des autres interventions entreprises pour tenter de régler le problème et exposé des raisons pour lesquelles ces interventions ont échoué.

Les propositions peuvent comprendre une proposition de nouvelle dénomination commune internationale de remplacement, établie conformément aux Directives générales, compte tenu de la substance pharmaceutique pour laquelle la nouvelle dénomination commune internationale de remplacement est proposée. Le Secrétariat transmet une copie de la proposition pour examen, conformément à la procédure exposée plus loin au paragraphe b), au Groupe d’experts des DCI et au demandeur initial ou à son successeur (s’il s’agit d’une personne différente de celle qui a formulé la proposition de remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse être retrouvé moyennant des efforts diligents, notamment des contacts avec les associations industrielles). De plus, le Secrétariat demande aux entités et personnes ci-après de formuler des observations sur la proposition :

i) les Etats Membres et les commissions nationales et régionales de pharmacopée ou d’autres organismes désignés par les Etats Membres (en insérant une note à cet effet dans la lettre mentionnée à l’article 3.a), et

ii) toutes autres personnes portant au remplacement proposé un intérêt notoire. La demande d’observations contient les indications suivantes : i) dénomination commune internationale recommandée pour laquelle un remplacement est proposé (et la dénomination de remplacement proposée, si elle est fournie) ; ii) nom de l’auteur de la proposition de remplacement (si cette personne le demande) ; iii) définition de la substance faisant l’objet du remplacement proposé et raisons avancées pour le remplacement ; iv) délai pendant lequel seront reçus les commentaires et nom et adresse de la personne habilitée à recevoir ces commentaires ; et v) mention des pouvoirs en vertu desquels agit l’OMS et référence au présent règlement. Des observations sur la proposition de remplacement peuvent être communiquées par toute personne à l’OMS dans les quatre mois qui suivent la date de la demande d’observations. b) Une fois échu le délai prévu ci-dessus pour la communication d’observations, le Secrétariat transmet les observations reçues au Groupe d’experts des DCI, au demandeur initial ou à son successeur et à l’auteur de la proposition de remplacement. Si, après avoir examiné la proposition de remplacement et les observations reçues, le Groupe d’experts des DCI, l’auteur de la proposition de remplacement et le demandeur initial ou son successeur reconnaissent tous qu’il est nécessaire de remplacer la dénomination commune internationale déjà recommandée, le Secrétariat soumet la proposition de remplacement au Groupe d’experts des DCI pour qu’il y donne suite.

Nonobstant ce qui précède, le demandeur initial ou son successeur n’est pas habilité à refuser son accord à une


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proposition de remplacement au cas où il ne peut être démontré qu’il porte un intérêt durable à la dénomination commune internationale recommandée qu’il est proposé de remplacer.

Dans le cas où une proposition de remplacement est soumise au Groupe d’experts des DCI pour qu’il y donne

suite, le Groupe choisit une nouvelle dénomination commune internationale conformément aux Directives générales mentionnées à l’article 2 et selon la procédure décrite dans les articles 3 à 8 inclus. La notification faite par le Secrétariat en vertu de l’article 3 et de l’article 7, respectivement, y compris au demandeur initial ou à son successeur (si ce n’est pas la même personne que celle qui a proposé le remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse être retrouvé moyennant des efforts diligents, notamment des contacts avec les associations industrielles), doit dans un tel cas indiquer que la nouvelle dénomination remplace une dénomination commune internationale déjà recommandée et que les Etats Membres peuvent souhaiter prendre des mesures transitoires pour les produits existants qui utilisent la dénomination commune internationale déjà recommandée sur leur étiquette conformément à la législation nationale.

Si, après examen de la proposition de remplacement et des observations communiquées conformément à la

procédure exposée plus haut, le Groupe d’experts des DCI, le demandeur initial ou son successeur et l’auteur de la proposition de remplacement ne s’accordent pas sur le fait qu’il y a des raisons impératives de remplacer une dénomination commune internationale déjà recommandée, cette dernière est conservée (étant entendu toujours que le demandeur initial ou son successeur n’est pas habilité à refuser son accord à une proposition de remplacement au cas où il ne peut être démontré qu’il porte un intérêt durable à la dénomination commune internationale recommandée qu’il est proposé de remplacer). Dans un tel cas, le Secrétariat informe l’auteur de la proposition de remplacement, ainsi que le demandeur initial ou son successeur (s’il s’agit d’une personne différente de celle qui a formulé la proposition de remplacement et pour autant que le demandeur initial ou son successeur soit connu ou puisse être retrouvé moyennant des efforts diligents, notamment des contacts avec les associations industrielles), les Etats Membres, les commissions nationales et régionales de pharmacopée, les autres organismes désignés par les Etats Membres et toutes autres personnes portant un intérêt notoire au remplacement proposé que, malgré une proposition de remplacement, il a été décidé de conserver la dénomination commune internationale déjà recommandée (avec une brève description de la ou des raisons pour lesquelles la proposition de remplacement n’a pas été jugée suffisamment impérative). Article 10 - Une méthode de travail, destinée à servir de guide pour le Groupe d’experts des DCI en vue de la mise en œuvre de cette procédure, est jointe en appendice au présent texte.

ANNEXE 2

DIRECTIVES GENERALES POUR LA FORMATION DE DENOMINATIONS

COMMUNES INTERNATIONALES APPLICABLES AUX SUBSTANCES PHARMACEUTIQUES1

1. Les dénominations communes internationales (DCI) devront se distinguer les unes des autres par leur consonance et leur orthographe. Elles ne devront pas être d’une longueur excessive, ni prêter à confusion avec des appellations déjà couramment employées. 2. La DCI de chaque substance devra, si possible, indiquer sa parenté pharmacologique. Les dénominations susceptibles d’évoquer pour les malades des considérations anatomiques, physiologiques, pathologiques ou thérapeutiques devront être évitées dans la mesure du possible. Outre ces deux principes fondamentaux, on respectera les principes secondaires suivants : 3. Lorsqu’on formera la DCI de la première substance d’un nouveau groupe pharmacologique, on tiendra compte de la possibilité de former ultérieurement d’autres DCI appropriées pour les substances apparentées du même groupe. 1

Dans son vingtième rapport (OMS, Série de Rapports techniques, N° 581, 1975), le Comité OMS d’experts des Dénominations communes pour les Substances pharmaceutiques a examiné les directives générales pour la formation des dénominations communes internationales et la procédure à suivre en vue de leur choix, compte tenu de l’évolution du secteur pharmaceutique au cours des dernières années. La modification la plus importante a été l’extension aux substances de synthèse de la pratique normalement suivie pour désigner les substances tirées ou dérivées de produits naturels. Cette pratique consiste à employer des syllabes communes ou groupes de syllabes communes (segments-clés) qui sont caractéristiques et indiquent une propriété commune aux membres du groupe des substances pour lequel ces segments-clés ont été retenus. Les raisons et les conséquences de cette modification ont fait l’objet de discussions approfondies. Les directives ont été mises à jour lors de la treizième consultation sur les dénominations communes pour les substances pharmaceutiques (Genève, 27-29 avril 1983) (PHARM S/NOM 928, 13 mai 1983, révision en date du 18 août 1983).


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4. Pour former des DCI des acides, on utilisera de préférence un seul mot. Leurs sels devront être désignés par un terme qui ne modifie pas le nom de l’acide d’origine : par exemple «oxacilline» et «oxacilline sodique», «ibufénac» et «ibufénac sodique». 5. Les DCI pour les substances utilisées sous forme de sels devront en général s’appliquer à la base active (ou à l’acide actif). Les dénominations pour différents sels ou esters d’une même substance active ne différeront que par le nom de l’acide inactif (ou de la base inactive). En ce qui concerne les substances à base d’ammonium quaternaire, la dénomination s’appliquera de façon appropriée au cation et à l’anion en tant qu’éléments distincts d’une substance quaternaire. On évitera de choisir une désignation évoquant un sel aminé. 6. On évitera d’ajouter une lettre ou un chiffre isolé ; en outre, on renoncera de préférence au trait d’union. 7. Pour simplifier la traduction et la prononciation des DCI, la lettre « f » sera utilisée à la place de « ph », « t » à la place de « th », « e » à la place de « ae » ou « oe », et « i » à la place de « y » ; l’usage des lettres « h » et « k » sera aussi évité. 8. On retiendra de préférence, pour autant qu’elles respectent les principes énoncés ici, les dénominations proposées par les personnes qui ont découvert ou qui, les premières, ont fabriqué et lancé sur le marché les préparations pharmaceutiques considérées, ou les dénominations déjà officiellement adoptées par un pays. 9. La parenté entre substances d’un même groupe (voir Directive générale 2) sera si possible indiquée dans les DCI par l’emploi de segments-clés communs. La liste ci-après contient des exemples de segments-clés pour des groupes de substances, surtout pour des groupes récents. Il y a beaucoup d’autres segments-clés en utilisation active. 1 Les segments-clés indiqués sans trait d’union pourront être insérés n’importe où dans une dénomination. Latin Français -acum -ac substances anti-inflammatoires du groupe de l’ibufénac -adolum -adol } analgésiques -adol- -adol- }

-astum -ast antiasthmatiques, antiallergiques n’agissant pas principalement en tant qu’antihistaminiques -astinum -astine antihistaminiques -azepamum -azépam substances du groupe du diazépam bol bol stéroïdes anabolisants -cain- -caïn- antiarythmiques de classe I, dérivés du procaïnamide et de la lidocaïne -cainum -caïne anesthésiques locaux cef- céf- antibiotiques, dérivés de l’acide céphalosporanique -cillinum -cilline antibiotiques, dérivés de l’acide 6-aminopénicillanique -conazolum -conazole agents antifongiques systémiques du groupe du miconazole cort cort corticostéroïdes, autres que les dérivés de la prednisolone -coxibum -coxib inhibiteurs sélectifs de la cyclo-oxygénase -entanum -entan antagonistes du récepteur de l’endothéline gab gab gabamimétiques gado- gado- agents diagnostiques, dérivés du gadolinium -gatranum -gatran antithrombines, antithrombotiques gest gest stéroïdes progestogènes gli gli antihyperglycémiants io- io- produits de contraste iodés -metacinum -métacine substances anti-inflammatoires du groupe de l’indométacine -mycinum -mycine antibiotiques produits par des souches de Streptomyces -nidazolum -nidazole substances antiprotozoaires du groupe du métronidazole -ololum -olol antagonistes des récepteurs β-adrénergiques -oxacinum -oxacine substances antibactériennes du groupe de l’acide nalidixique -platinum -platine antinéoplasiques, dérivés du platine -poetinum -poétine facteurs sanguins de type érythropoïétine -pril(at)um -pril(ate) inhibiteurs de l’enzyme de conversion de l’angiotensine -profenum -profène substances anti-inflammatoires du groupe de l’ibuprofène prost prost prostaglandines

1

Une liste plus complète de segments-clés est contenue dans le document de travail WHO/PSM/QSM/2006.3 qui est régulièrement mis à jour et qui peut être demandé auprès du programme des DCI, OMS, Genève.


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-relinum -réline peptides stimulant la libération d’hormones hypophysaires -sartanum -sartan antagonistes d’un récepteur de l’angiotensine II, antihypertenseurs (non peptidiques) -vaptanum -vaptan antagonistes du récepteur de la vasopressine vin- vin- } alcaloïdes du type vinca -vin- -vin- }

ANEXO 1

PROCEDIMIENTO DE SELECCIÓN DE DENOMINACIONES COMUNES INTERNACIONALES RECOMENDADAS PARA SUSTANCIAS FARMACÉUTICAS1

La Organización Mundial de la Salud (OMS) seguirá el procedimiento que se expone a continuación tanto para seleccionar denominaciones comunes internacionales recomendadas para las sustancias farmacéuticas, de conformidad con lo dispuesto en la resolución WHA3.11, como para sustituir esas denominaciones. Artículo 1 - Las propuestas de denominaciones comunes internacionales recomendadas y las propuestas de sustitución de esas denominaciones se presentarán a la OMS en los formularios que se proporcionen a estos efectos. El estudio de estas propuestas estará sujeto al pago de una tasa destinada a sufragar los costos de administración que ello suponga para la Secretaría de la OMS («la Secretaría»). La Secretaría establecerá la cuantía de esa tasa y podrá ajustarla periódicamente. Artículo 2 - Estas propuestas serán sometidas por la Secretaría a los miembros del Cuadro de Expertos en Farmacopea Internacional y Preparaciones Farmacéuticas encargados de su estudio, en adelante designados como «el Grupo de Expertos en DCI», para que las examinen de conformidad con los «Principios generales de orientación para formar denominaciones comunes internacionales para sustancias farmacéuticas», anexos a este procedimiento.2 A menos que haya poderosas razones en contra, la denominación aceptada será la empleada por la persona que haya descubierto o fabricado y comercializado por primera vez esa sustancia farmacéutica. Artículo 3 - Tras el examen al que se refiere el artículo 2, la Secretaría notificará que está en estudio un proyecto de denominación internacional. a) Esa notificación se hará mediante una publicación en Información Farmacéutica OMS3

y el envío de una carta a los Estados Miembros y a las comisiones nacionales y regionales de las farmacopeas u otros organismos designados por los Estados Miembros.

i) La notificación será enviada también a la persona que haya presentado la propuesta («el solicitante inicial») y a otras personas que tengan un interés especial en una denominación objeto de estudio.

b) En esa notificación se incluirán los siguientes datos: i) la denominación sometida a estudio; ii) la identidad de la persona que ha presentado la propuesta de denominación de la sustancia, si lo pide esa persona; iii) la identidad de la sustancia cuya denominación está en estudio; iv) el plazo fijado para recibir observaciones y objeciones, así como el nombre y la dirección de la persona a quien deban dirigirse; y v) los poderes conferidos para el caso a la OMS y una referencia al presente procedimiento.

1 Véase el anexo 1 en OMS, Serie de Informes Técnicos, Nº 581, 1975; las modificaciones propuestas se indican en negrita. El texto vigente fue adoptado por el Consejo Ejecutivo en su resolución EB15.R7 y modificado en la resolución EB43.R9.

2 Véase el anexo 2.

3 Hasta 1987 las listas de DCI se publicaban en la Crónica de la Organización Mundial de la Salud.


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c) Al enviar esa notificación, la Secretaría solicitará de los Estados Miembros la adopción de todas las medidas necesarias para impedir la adquisición de derechos de patente sobre la denominación propuesta, durante el periodo en que la OMS la tenga en estudio. Artículo 4 - Toda persona puede formular a la OMS observaciones sobre la denominación propuesta dentro de los cuatro meses siguientes a su publicación en Información Farmacéutica OMS, conforme a lo dispuesto en el artículo 3. Artículo 5 - Toda persona interesada puede presentar una objeción formal a una denominación propuesta dentro de los cuatro meses siguientes a su publicación en Información Farmacéutica OMS, conforme a lo dispuesto en el artículo 3. Esa objeción deberá acompañarse de los siguientes datos:

i) la identidad de la persona que formula la objeción; ii) las causas que motivan su interés por la denominación; y iii) las causas que motivan su objeción a la denominación propuesta.

Artículo 6 - Cuando se haya presentado una objeción formal en la forma prevista en el artículo 5, la OMS podrá reconsiderar el nombre propuesto o utilizar sus buenos oficios para intentar lograr que se retire la objeción. La OMS no seleccionará como denominación común internacional una denominación a la que se haya hecho una objeción formal, presentada según lo previsto en el artículo 5, que no haya sido retirada, todo ello sin perjuicio de que la Organización examine otra denominación o denominaciones sustitutivas. Artículo 7 - Cuando no se haya formulado ninguna objeción en la forma prevista en el artículo 5, o cuando todas las objeciones presentadas hayan sido retiradas, la Secretaría notificará, conforme a lo dispuesto en el párrafo a) del artículo 3, que la denominación ha sido seleccionada por la OMS como denominación común internacional recomendada. Artículo 8 - Al comunicar a los Estados Miembros una denominación común internacional, conforme a lo previsto en el artículo 7, la Secretaría: a) solicitará que esta denominación sea reconocida como denominación común para la sustancia de que se trate; y b) solicitará a los Estados Miembros que adopten todas las medidas necesarias para impedir la adquisición de derechos de patente sobre la denominación, y prohíban que sea registrada como marca de fábrica o como nombre comercial. Artículo 9 a) En el caso excepcional de que, debido a su semejanza con otra denominación utilizada en las prácticas farmacéuticas y/o de prescripción, una denominación común internacional recomendada anteriormente ocasione errores de medicación, prescripción o distribución, o suponga un riesgo manifiesto de que esto ocurra, y parezca que tales errores o potenciales errores no sean fácilmente subsanables con otras medidas que no sean la posible sustitución de esa denominación común internacional recomendada anteriormente; en el caso de que una denominación común internacional recomendada anteriormente difiera considerablemente de la denominación común aprobada en un número importante de Estados Miembros, o en otras circunstancias excepcionales que justifiquen el cambio de una denominación común internacional recomendada, cualquier persona interesada puede presentar propuestas en este sentido. Esas propuestas se presentarán en los formularios que se proporcionen a estos efectos e incluirán los siguientes datos:

i) la identidad de la persona que presenta la propuesta;

ii) las causas que motivan su interés en la sustitución propuesta;

iii) las causas que motivan la propuesta; y

iv) una descripción, acompañada de pruebas documentales, de las otras medidas que se hayan adoptado con el fin de resolver la situación y de los motivos por los cuales dichas medidas no han sido suficientes.

Entre esas propuestas podrá figurar una relativa a una nueva denominación común internacional sustitutiva,

formulada con arreglo a los Principios generales y que tenga en cuenta la sustancia farmacéutica para la que se proponga la nueva denominación común internacional sustitutiva.

La Secretaría enviará al Grupo de Expertos en DCI y al solicitante inicial o a su sucesor (en el caso de que sea una persona diferente de la que ha presentado la propuesta de sustitución y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones


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industriales) una copia de la propuesta, para que sea examinada de conformidad con el procedimiento descrito en el párrafo b) infra. Además, la Secretaría solicitará observaciones sobre la propuesta:

i) a los Estados Miembros y a las comisiones nacionales y regionales de las farmacopeas u otros organismos designados por los Estados Miembros (ello se hará incluyendo una notificación a tal efecto en la carta a la que se refiere el párrafo a) del artículo 3), y

ii) a cualquier persona que tenga un interés especial en la sustitución propuesta.

Al solicitar que se formulen estas observaciones se facilitarán los siguientes datos: i) la denominación común internacional recomendada que se propone sustituir (y la denominación sustitutiva propuesta, si se ha facilitado);

ii) la identidad de la persona que ha presentado la propuesta de sustitución (si lo pide esa persona); iii) la identidad de la sustancia a la que se refiere la sustitución propuesta y las razones para presentar la propuesta de sustitución; iv) el plazo fijado para recibir observaciones, así como el nombre y la dirección de la persona a quien deban dirigirse; y

v) los poderes conferidos para el caso a la OMS y una referencia al presente procedimiento.

Toda persona puede formular a la OMS observaciones sobre la sustitución propuesta dentro de los cuatro meses siguientes a la fecha en que se realizó la solicitud de observaciones. b) Una vez agotado el mencionado plazo para la formulación de observaciones, la Secretaría enviará todos los comentarios recibidos al Grupo de Expertos en DCI, al solicitante inicial o a su sucesor, y a la persona que haya presentado la propuesta de sustitución. Si después de examinar la propuesta de sustitución y las observaciones recibidas, el Grupo de Expertos en DCI, la persona que haya presentado la propuesta de sustitución y el solicitante inicial, o su sucesor, están de acuerdo en la necesidad de sustituir la denominación común internacional recomendada anteriormente, la Secretaría remitirá la propuesta de sustitución al Grupo de Expertos en DCI para que la tramite. No obstante lo anterior, el solicitante inicial o su sucesor no tendrán derecho a impedir el acuerdo sobre una propuesta de sustitución en el caso de que hayan dejado de tener un interés demostrable en la denominación común internacional cuya sustitución se propone.

En caso de que la propuesta de sustitución sea presentada al Grupo de Expertos en DCI para que la tramite, este grupo seleccionará una nueva denominación común internacional de conformidad con los Principios generales a los que se refiere el artículo 2 y al procedimiento establecido en los artículos 3 a 8 inclusive. En ese caso, en las notificaciones que la Secretaría ha de enviar con arreglo a los artículos 3 y 7, respectivamente, incluida la notificación al solicitante inicial o a su sucesor (en el caso de que no sea la misma persona que propuso la sustitución y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones industriales), se indicará que la nueva denominación sustituye a una denominación común internacional recomendada anteriormente y que los Estados Miembros podrán, si lo estiman oportuno, adoptar disposiciones transitorias aplicables a los productos existentes en cuya etiqueta se utilice, con arreglo a la legislación nacional, la denominación común internacional recomendada anteriormente que se haya sustituido.

En caso de que, después de haber estudiado la propuesta de sustitución y los comentarios recibidos de conformidad con el procedimiento descrito anteriormente, el Grupo de Expertos en DCI, el solicitante inicial o su sucesor y la persona que haya presentado la propuesta de sustitución no lleguen a un acuerdo sobre la existencia de razones poderosas para sustituir una denominación común internacional recomendada anteriormente, esta denominación se mantendrá (siempre en el entendimiento de que el solicitante inicial o su sucesor no tendrán derecho a impedir el acuerdo sobre una propuesta de sustitución en el caso de que hayan dejado de tener un interés demostrable en la denominación común internacional cuya sustitución se propone). En ese caso, la Secretaría comunicará a la persona que haya propuesto la sustitución, así como al solicitante inicial o a su sucesor (en el caso de que no sea la misma persona que propuso la sustitución y siempre que el solicitante inicial o su sucesor sean conocidos o puedan ser encontrados mediante esfuerzos diligentes, como el contacto con las asociaciones industriales), a los Estados Miembros, a las comisiones nacionales y regionales de las farmacopeas o


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a otros organismos designados por los Estados Miembros y a cualquier otra persona que tenga interés en la sustitución propuesta, que, pese a la presentación de una propuesta de sustitución, se ha decidido mantener la denominación común internacional recomendada anteriormente (con una descripción de la o las razones por las que se ha considerado que la propuesta de sustitución no estaba respaldada por razones suficientemente poderosas). Artículo 10 - A fin de proporcionar orientación al Grupo de Expertos en DCI para la aplicación del presente procedimiento, se incluye como apéndice un texto relativo al método de trabajo.

ANEXO 2

PRINCIPIOS GENERALES DE ORIENTACIÓN PARA FORMAR DENOMINACIONES COMUNES INTERNACIONALES PARA SUSTANCIAS FARMACÉUTICAS1

1. Las denominaciones comunes internacionales (DCI) deberán diferenciarse tanto fonética como ortográficamente. No deberán ser incómodamente largas, ni dar lugar a confusión con denominaciones de uso común. 2. La DCI de una sustancia que pertenezca a un grupo de sustancias farmacológicamente emparentadas deberá mostrar apropiadamente este parentesco. Deberán evitarse las denominaciones que puedan tener connotaciones anatómicas, fisiológicas, patológicas o terapéuticas para el paciente. Estos principios primarios se pondrán en práctica utilizando los siguientes principios secundarios: 3. Al idear la DCI de la primera sustancia de un nuevo grupo farmacológico, deberá tenerse en cuenta la posibilidad de poder formar DCI convenientes para las sustancias emparentadas que se agreguen al nuevo grupo. 4. Al idear DCI para ácidos, se preferirán las de una sola palabra; sus sales deberán denominarse sin modificar el nombre del ácido: p. ej. «oxacilina» y «oxacilina sódica», «ibufenaco» y «ibufenaco sódico». 5. Las DCI para las sustancias que se usan en forma de sal deberán en general aplicarse a la base activa o al ácido activo. Las denominaciones para diferentes sales o esteres de la misma sustancia activa solamente deberán diferir en el nombre del ácido o de la base inactivos. En los compuestos de amonio cuaternario, el catión y el anión deberán denominarse adecuadamente por separado, como componentes independientes de una sustancia cuaternaria y no como sales de una amina. 6. Deberá evitarse el empleo de letras o números aislados; también es indeseable el empleo de guiones. 7. Para facilitar la traducción y la pronunciación, se emplearán de preferencia las letras «f» en lugar de «ph», «t» en lugar de «th», «e» en lugar de «ae» u «oe», e «i» en lugar de «y»; se deberá evitar el empleo de las letras «h» y «k». 8. Siempre que las denominaciones propuestas estén de acuerdo con estos principios, recibirán una consideración preferente las denominaciones propuestas por la persona que haya descubierto las sustancias, o que fabrique y comercialice por primera vez una sustancia farmacéutica, así como las denominaciones ya adoptadas oficialmente en cualquier país. 9. El parentesco entre sustancias del mismo grupo se pondrá de manifiesto en las DCI (véase el Principio 2) utilizando una partícula común. En la lista que figura a continuación se indican ejemplos de partículas para grupos de sustancias, en particular para grupos nuevos. Existen muchas otras partículas que se usan habitualmente.2 Cuando una partícula aparece sin guión alguno, puede utilizarse en cualquier lugar de la palabra. 1 En su 20º informe (OMS, Serie de Informes Técnicos, Nº 581, 1975), el Comité de Expertos de la OMS en Denominaciones Comunes para las Sustancias Farmacéuticas revisó los Principios generales para formar denominaciones comunes internacionales (DCI), y su procedimiento de selección, a la luz de las novedades registradas en los últimos años en materia de compuestos farmacéuticos. El cambio más importante había consistido en hacer extensivo a la denominación de sustancias químicas sintéticas el método utilizado hasta entonces para las sustancias originadas en productos naturales o derivadas de éstos. Dicho método conlleva la utilización de una «partícula» característica que indica una propiedad común a los miembros de un grupo. En el citado informe se examinan en detalle las razones y consecuencias de este cambio. Los Principios generales de orientación se actualizaron durante la 13ª consulta sobre denominaciones comunes para sustancias farmacéuticas (Ginebra, 27 a 29 de abril de 1983) (PHARM S/NOM 928, 13 de mayo de 1983, revisado el 18 de agosto de 1983). 2 En el documento de trabajo WHO/PSM/QSM/2006.3, que se actualiza periódicamente y puede solicitarse al Programa sobre Denominaciones Comunes Internacionales, OMS, Ginebra, figura una lista más amplia de partículas.


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Latin Español -acum -aco antiinflamatorios derivados del ibufenaco -adolum -adol ) analgésicos -adol- -adol- ) -astum -ast antiasmáticos, sustancias antialérgicas cuya acción principal no es la antihistamínica -astinum -astina antihistamínicos -azepamum -azepam derivados del diazepam bol bol esteroides anabolizantes -cain- -caína- antiarrítmicos de clase I, derivados de procainamida y lidocaína -cainum -caína- anestésicos locales cef- cef- antibióticos, derivados del ácido cefalosporánico -cillinum - cilina antibióticos derivados del ácido 6-aminopenicilánico -conazolum -conazol antifúngicos sistémicos derivados del miconazol cort cort corticosteroides, excepto derivados de prednisolona -coxibum -coxib inhibidores selectivos de ciclooxigenasa -entanum -entán antagonistas del receptor de endotelina gab gab gabamiméticos gado- gado- agentes para diagnóstico derivados de gadolinio -gartranum -gatrán inhibidores de la trombina antitrombóticos gest gest esteroides progestágenos gli gli hipoglucemiantes, antihiperglucémicos io- io- medios de contraste iodados -metacinum -metacina antiinflamatorios derivados de indometacina -mycinum -micina antibióticos producidos por cepas de Streptomyces -nidazolum -nidazol antiprotozoarios derivados de metronidazol -ololum -olol antagonistas de receptores β-adrenérgicos -oxacinum -oxacino antibacterianos derivados del ácido nalidíxico -platinum -platino antineoplásicos derivados del platino -poetinum -poetina factores sanguíneos similares a la eritropoyetina -pril(at)um -pril(at) inhibidores de la enzima conversora de la angiotensina -profenum -profeno antiinflamatorios derivados del ibuprofeno prost prost prostaglandinas -relinum -relina péptidos estimulantes de la liberación de hormonas hipofisarias -sartanum -sartán antihipertensivos (no peptídicos) antagonistas del receptorde angiotensina II -vaptanum -vaptán antagonistas del receptor de vasopresina vin- vin- ) alcaloides de la vinca -vin- -vin- )

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