Prescriber Update - medsafe.govt.nz

Prescriber UpdateVol. 24 No. 1

June 2003

NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe .govt.nz

A publication of

From the Editor 1

COX-2 inhibitors and hepatotoxicity 2

Atypical antipsychotics may cause hypertension 4

Helping medicine capsules go down 6

Unapproved use of medicines 8

Miconazole–warfarin interaction reminder 12

Clozapine and cardiac safety 13

I've missed a dose; what should I do? 14

Adverse Reactions of Current Concern 16

Medicines in the Intensive Medicines Monitoring Programme (IMMP) 18

ISSN 1172-5648

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Resources available to you on the Medsafeweb site, under the Health Professionals section:

• Data sheets

• Prescriber Update articles

• Adverse reactions reporting forms

• Consumer Medicine Information (CMI)

www.medsafe.govt.nz

www.medsafe.govt.nz

1Prescriber Update 2003; 24(1) June

On-line reporting of adverse events

It is now possible to lodge adverse reaction reportsdirectly on the web site of the Centre for AdverseReactions Monitoring (CARM). CARM valuesyour contribution to adverse reaction monitoringin New Zealand, so has introduced the on-lineoption to make it quicker and easier for you tosubmit adverse event reports. The on-linereporting system utilises encryption technology,enabling confidential patient data to be transmittedsecurely. To use the system, you first need toregister so please take a minute to do this as soonas convenient (go to www.otago.ac.nz/carm/report.asp). Please note that you will be asked toprovide your professional registration number.Once you have registered, you will be able totransmit your adverse event reports to CARMelectronically. Give it a try. Of course, you canalso use the mail, fax, e-mail or telephone modesof reporting to CARM.

Calling for all brand-switch adverseevents

Adverse events have been observed in somepatients when switching from one particular brandof a medicine to another brand of the samemedicine. Such brand-switch events may includedecreased therapeutic efficacy, loss of symptomcontrol or development of previously non-apparentside effects. The Centre for Adverse ReactionsMonitoring (CARM) in Dunedin encouragesprescribers to report adverse events arising frombrand-switching so that patterns and trends can beidentified, and brands of the medicinesinvestigated if necessary.

Reports of adverse events occurring followingchange to another brand have recently beenreceived by CARM for these medicines:

• Estelle®

• felodipine

• fluoxetine

• methylphenidate

• paracetamol

• simvastatin.

FROM THE EDITOR

Please send brand-switch reports for any medicineto CARM, PO Box 913, Dunedin; fax 03 479 7150.Use the reporting form inside the back cover ofthis bulletin, or download the form from theCARM or Medsafe web sites: www.otago.ac.nz/carm or www.medsafe.govt.nz/Profs/adverse.htm

Key to Prescriber Update articles

To assist readers in knowing the origin of articlespublished by Medsafe, the symbols below willappear next to the article title, where applicable.It is our editorial policy to ensure that articlesdispm/ying either of these symbols have undergoneindependent peer review. During the developmentof an article, the pharmaceutical companysupplying the medicine referred to in the articlemay be given the opportunity to comment on thedraft.

Adverse Drug Reaction Updatearticles are written in response toadverse reaction reports lodged with

CARM and material in the international literature.These articles may also be written to alertprescribers and pharmacists to potential problemswith medicines.

MARC Prescribing Advice articlesare recommendations from theMedicines Adverse Reactions

Committee (MARC) in response to medicinesafety issues and overseas experiences.

Free resources available

• Consumer Medicine Information (CMI ) poster

• Prescribing Medicines in Pregnancy –categorisation of risk of medicine use inpregnancy – booklet (4th edition)

• Medsafe patient information leaflet onoral contraceptives and blood clots(March 2002 update).

To order copies of any of these resources, contactWickliffe: phone 04 496 2277, fax 03 479 0979,email [email protected] or post an order tothe Ministry of Health, c/- Wickliffe Ltd.PO Box 932, Dunedin.

ADR UPDATE

MARCRx

ADVICE

2 Prescriber Update 2003; 24(1) June

COX-2 INHIBITORS AND HEPATOTOXICITY

Some case reports support causalassociation

As part of the Intensive Medicines MonitoringProgramme (IMMP) monitoring of COX-2inhibitors, 17 reports of hepatotoxicity have beenreceived. Most had an onset time of less than threemonths. There are three case reports of significantliver injury occurring in association withrofecoxib.

1. A woman aged 85 was being treated withrofecoxib 6.25mg daily for three weeks forinflammatory arthritis. Peak enzyme valueswere ALP 239, ALT 1409 and AST 1545 unitsper litre indicating hepatocellular liver injury.The total bilirubin rose to 43 µmol per litre.No other medicines were listed. The liverfunction test (LFT) results had been normalprior to taking regular rofecoxib and returnedto normal after it was withdrawn.

2. A man aged 81 with controlled congestive heartfailure and maturity onset diabetes wasprescribed rofecoxib (dose not stated) for a soreneck. He became unwell ‘almost immediately’and seven days later was admitted to hospitalwith hepatocellular liver injury. His LFT resultswere ALP 115, ALT 1111 and bilirubin normal.The only new medicine prescribed wasrofecoxib. There was no evidence of viralhepatitis. Two weeks after withdrawal ofrofecoxib the ALT level had returned to nearnormal without change in his other medicines.

3. A man aged 61 was prescribed rofecoxib (dosenot stated) for foot pain. After about threemonths he developed severe cholestatichepatitis, which was confirmed on liver biopsy.His total bilirubin peaked at 501 µmol/litre.

At the same time he developed acute renalfailure. He was taking no other medicines.Recovery was complete two months afterwithdrawal of rofecoxib.

Other case reports included other knownhepatotoxic medicines

While the clinical details concerning the abovecase reports were not complete and theinvestigations reported were not exhaustive, it isprobable that these hepatic events were related torofecoxib. There were three other reports ofsimilar severity involving celecoxib where therelationship was less clear due to concomitanthepatotoxic medicines including methotrexate andleflunomide.

In addition, there have been eight reports of mildliver function abnormalities with celecoxib andthree with rofecoxib. Two of these patientsrecovered following withdrawal of the COX-2inhibitor, but the outcome of the others is unknown.

Hepatotoxicity has been reportedinfrequently in the literature

A literature search revealed a small number ofreports of hepatic reactions to celecoxib1-5 and onewith rofecoxib.6 One patient had an allergy tosulphonamides, and this may have been the riskfactor that precipitated her cholestatic hepatitisbecause celecoxib has a sulphonamide moiety.2

The New Zealand data sheet for Celebrex®

(celecoxib) refers to borderline elevations of LFTsin clinical trials and notable elevations of ALT andAST occurring with no greater frequency thanplacebo.7 The Vioxx® (rofecoxib) data sheet statesthat hepatic failure, hepatitis and jaundice havebeen reported, but with no comment about causality.8

Dr David Coulter, IMMP Director, New Zealand Pharmacovigilance Centre, Dunedin

This article was published on the Medsafe web site and e-mailed to electronic Prescriber Update subscribers inMay 2003.

As with the non-specific non-steroidal anti-inflammatory agents, liver toxicity may occur withthe cyclo-oxygenase-2 (COX-2) specific inhibitors, celecoxib and rofecoxib. They may causecholestatic, hepatocellular or mixed liver injury; all of which can be severe. Practitioners shouldbe alert to this possibility, particularly as the onset may be rapid.


Awareness and early recognitionimproves prognosis

Hepatotoxicity is known to occur infrequently withthe non-specific non-steroidal anti-inflammatoryagents (NSAIAs). The IMMP reports ofhepatotoxicity with COX-2 inhibitors suggest thatthis type of reaction is an uncommon class effectof all NSAIAs, both COX-2 specific and non-specific. Patients using COX-2 inhibitors whohave symptoms or signs suggestive of liverdysfunction (including an abnormal liver testresult) should have the COX-2 inhibitordiscontinued.

Competing interests (author): Unconditionalprogramme grants have been received fromvarious pharmaceutical companies, includingMerck Research Laboratories USA.

Correspondence to Dr David Coulter,New Zealand Pharmacovigilance Centre,PO Box 913, Dunedin.

References

1. Carrillo-Jimenez R, Nurnberger M. Celecoxib-induced acutepancreatitis and hepatitis: A case report. Arch Intern Med2000;160:553-554.

2. Galan MV, Gordon SC, Silverman AL. Celecoxib-inducedcholestatic hepatitis [letter]. Ann Intern Med 2001;134:254.

3. O’Beirne JP, Cairns SR. Cholestatic hepatitis in association withcelecoxib. BMJ 2001;323:23.

4. Nachimuthu S, Volfinzon L, Gopal L. Acute hepatocellular andcholestatic injury in a patient taking celecoxib. Postgrad Med J2001;77:548-550.

5. Alegria P, Lebre L, Chagas C. Celecoxib-induced cholestatichepatotoxicity in a patient with cirrhosis [letter]. Ann InternMed 2002; 137:E-75.

6. Huster D, Schubert C, Berr F, et al. Rofecoxib-inducedcholestatic hepatitis: treatment with molecular adsorbentrecycling system (MARS) [letter]. J Hepatol 2002;37:413-414.

7. Pharmacia. Celebrex Data Sheet 12 March 2002.www.medsafe.govt.nz/profs/Datasheet/c/Celebrexcap.htm

8. Merck Sharp & Dohme (New Zealand) Limited. Vioxx DataSheet 3 October 2002. www.medsafe.govt.nz/profs/Datasheet/v/Vioxxtab.htm


Adverse reaction identified throughIMMP monitoring

All of the atypical antipsychotics currentlyavailable in New Zealand (i.e. clozapine,olanzapine, quetiapine and risperidone) aremonitored in the Intensive Medicines MonitoringProgramme (IMMP). From the 572 case reportsanalysed, hypertension has been identified as apossible adverse reaction. Routine screening ofthe data revealed this unexpected association.

Hypotension with atypical antipsychotics is aknown effect and for all four medicines a total of19 reports of hypotension, or symptoms suggestinghypotension (e.g. faintness) have been received.In comparison, 13 reports of hypertension havebeen received; 10 with clozapine, two withrisperidone and one with quetiapine. At this stageof monitoring more data have been collected forclozapine and so the actual numbers of reports ofhypertension are not a guide to comparative risk.The two most severe cases occurred withrisperidone and these are described below.

Case 1

A woman aged 53 had been on risperidone 1mgdaily for three days when she collapsed withdiminished consciousness (unresponsive to voice)and was found to have a blood pressure (BP) of190/110 and a tachycardia of 140. The risperidonewas withdrawn and by the following day she hadrecovered. The patient had a history ofhypertension and was on treatment with enalapril2.5mg daily, but the BP had been “normal” priorto taking risperidone. She was also takingparoxetine 40mg and thioridazine 25mg daily.

ATYPICAL ANTIPSYCHOTICSMAY CAUSE HYPERTENSION

Dr David Coulter, IMMP Director, NZ Pharmacovigilance Centre, Dunedin


Acute hypertension may occur soon after the commencement of atypical antipsychotic treatmentand can be severe, with collapse and altered consciousness. There may be an increased risk ifselective serotonin reuptake inhibitors (SSRIs) are administered concomitantly. This adversereaction appears to be dose-related and it is recommended that blood pressure be monitoredduring the early stages of atypical antipsychotic therapy, particularly in the presence of SSRIs.

Case 2

A woman aged 54 was commenced on risperidone0.5mg daily and after the third dose developedrigidity and a BP of 210/110. Her level ofconsciousness was reduced. There was no fever,and her creatine kinase and renal function testresults were normal. Risperidone was withdrawnand the symptoms resolved within six hours ofadmission to hospital. She advised that her usualBP was around 145/100 and she was on treatmentwith cilazapril 5mg daily for hypertension. Othermedicines were paroxetine 30mg daily andpantoprazole 40mg daily.

Other cases had similar features

In the other 11 cases of hypertension occurringduring atypical antipsychotic treatment, the agesranged from 15 to 66 years, with eight patientsbeing under 35 years of age. There was a markedrise in BP in each case with the systolic rangingfrom 140 to 170 and diastolic pressures rangingfrom 95 to 120. In all but one case, the elevatedBP was noted within a month of atypicalantipsychotic treatment commencing.Concomitant medicines were recorded for fivepatients, two of whom were taking the selectiveserotonin reuptake inhibitors (SSRIs), fluoxetineand citalopram. In three patients the antipsychoticwas withdrawn and recovery was rapid, and in twothe BP returned to normal with dose reduction.

It seems likely that the hypertensive reaction toatypical antipsychotics is dose-related because itwas noted that the BP rose during upward titrationof the dose in several patients and two patientsrecovered with dose reduction. Hypertension


resolved in one patient while continuing ontreatment, and in two others the BP was controlledwith ACE inhibitors while continuing on theatypical antipsychotic. The outcome is unknownfor three patients.

Concomitant use of SSRIs may increaserisk of hypertension

Of note is that four of the 13 patients were alsotaking SSRIs, including the two patients with themost severe hypertension, both of whom weretaking paroxetine. The atypical antipsychotics andthe SSRIs share some common CYP450 enzymesin their metabolism and there is potential for anincrease in blood levels of the antipsychoticthrough competitive inhibition.

Monitor BP when commencing atypicalantipsychotics or adding in SSRIs

The evidence from these case reports is sufficientto establish a signal of a reaction that seems littleknown. Only a few case reports in the literaturedescribe hypertension, all with clozapine.1-3 Thehypertensive reaction to the atypical antipsychoticsis generally of early onset and may be more likelyto occur with the concomitant administration ofSSRIs. At this stage, it is unclear whether pre-existing hypertension is a risk factor. It wouldseem prudent to monitor blood pressure duringearly stages of therapy with atypicalantipsychotics, particularly when SSRIs areprescribed concomitantly.

Competing interests (author): Novartis hasprovided research grants for the IMMP. Novartisis the sponsor of Clozaril® (clozapine).

Correspondence to Dr David Coulter,NZ Pharmacovigilance Centre, PO Box 913,Dunedin.

References

1. Gupta S. Paradoxical hypertension associated with clozapine.Am J Psychiatry 1994;151:148.

2. George TP, Winther LC. Hypertension associated with clozapine.Am J Psychiatry 1996;153:1368-1369.

3. Ennis LM, Parker RM. Paradoxical hypertension associated withclozapine. Med J Aust 1997;166:278.


Capsules can be more difficult toswallow than tablets

Many patients have difficulties, bothpsychologically and physically, swallowingmedicines. This may result in poor compliance,treatment failure and decreased quality of life. Theswallowing of capsules can be particularlydifficult. This is because capsules are lighter thanwater and float due to air trapped inside the gelatineshell.

In comparison, tablets are heavier than water anddo not float. The usual method of swallowing oralsolid dose forms – placing on the tongue, fillingthe mouth with water, tilting the head back and

HELPING MEDICINE CAPSULES GO DOWN

Dr A.D (Sandy) Macleod, Medical Director, Nurse Maude Hospice, Christchurch; Jane Vella-Brincat,Drug Utilisation Review Pharmacist, Clinical Pharmacology Department, Christchurch Hospital


The physical properties of capsules predispose them to floating in the mouth when taken withwater. As a result, the swallowing of capsules can be problematic. In patients who experiencesuch difficulty, it is suggested that they try leaning forward when swallowing, as this has beenfound to assist. It may be necessary to reassure patients about this technique as they mayinitially find it unnatural to execute.

swallowing – works well for tablets because theydo not float and gravity, when the head is tiltedback, assists swallowing. If this technique is usedwith a capsule, it will float on the water in thefront of the mouth, placing it in the anatomicallyincorrect location for ease of swallowing (seefigure 1).1

Leaning forward may assist

Instead a ‘lean-forward’ technique has beensuggested,1,2 in which the capsule floats to the backof the mouth and into a good position to beswallowed easily (see figure 2).

Figure 1 – Head tilted back Figure 2 – Head lent forward

Figures adapted from Kahn2


Brown1 in 1982 noted that this ‘lean-forward’technique was “almost universally unknown”amongst physicians, nurses and pharmacists. Thiswas borne out in a recent New Zealand study3 ofhealthcare worker volunteers, where very few ofthe volunteers were aware of this alternativetechnique to assist swallowing. In this study3 ninefound it easier to swallow a capsule with their headtilted back while 21 found it easier with their headleaning forward. This represented a statisticallysignificant difference, with the ‘lean-forward’technique making the swallowing of capsuleseasier.3

Practice may be required to reinforcetechnique

Although rated as easier by many of thesevolunteers, the ‘lean-forward’ technique was alsonoted to be “awkward” and “unnatural”. This isnot surprising as swallowing is habituallyassociated with tilting the head backwards.Patients require instruction, and ideally practice,to grasp this alternative technique. This isparticularly so for the elderly, the young, thecognitively compromised and the sick. Oncelearnt, the benefit rapidly reinforces the practice.This technique does not work for all but may be aviable option for those patients in whom theswallowing of capsules is a problem. It should,however, not be applied to any other oral dosageformulation.

Most capsules are intended to be swallowed wholeso patients should be encouraged to trial the ‘lean-forward’ technique. If swallowing difficultiesremain other options, such as a liquid or tablet formof the medicine, can be considered.

Competing interests (authors): none declared.

Correspondence to: Dr A.D (Sandy) Macleod,Medical Director, Nurse Maude Hospice,35 Mansfield Avenue, Christchurch. Phone(03) 355 0074, fax (03) 355 0067, [email protected]

References

1. Brown J A. Swallowing medication [letter]. JAMA1982;248(15):1833-1834.

2. Kahn G. Capsule swallowing: The lean-forward technique.CUTIS 1985;36(2):144.

3. Macleod A D,Vella-Brincat J, Frampton C. Swallowing capsules[letter]. Palliative Medicine (submitted).


Medsafe is aware that some medical practitionersare confused about their rights and responsibilitieswith respect to prescribing unapproved medicines,or approved medicines for unapproved uses (suchas unapproved indication, dosage or route ofadministration). Recent correspondence has raisedconcerns about the legal position of the practitionerwho prescribes a medicine in a situation in whichit is contraindicated, or against which there arewarnings in the data sheet. Examples of thesesituations are the use of Depo-Medrol injectionfor epidural administration, and nifedipinecapsules in the treatment of hypertensive crisis inpregnancy.

This article will attempt to clarify the situation withregard to the Medicines Act 1981. It will also applythe requirements of the Code of Health andDisability Services Consumers’ Rights to theunapproved use of medicines. On the Medsafeweb site (www.medsafe.govt.nz/Profs/RIss/unapp.htm), there are scenarios illustrating thepoints made. The reader may find the materialmore accessible if the scenarios are read first.

Use of medicines regulated by theMedicines Act

The Medicines Act 1981 regulates the use ofmedicines in New Zealand. It requires that in order

UNAPPROVED USE OF MEDICINES

This article has been reprinted from the April 1998 (No. 16) issue of Prescriber Update, and the Medsafe web site.There have been no substantial amendments to either the Medicines Act 1981 or the Code of Health and DisabilityServices Consumers’ Rights since this time, therefore this article is still relevant.

The Medicines Act 1981 permits a registered medical practitioner, dentist and midwife toprescribe, administer or arrange for the administration of medicines for the treatment of apatient in his or her care. The medicine and its use may or may not be approved. The Act alsopermits the sale or supply of unapproved medicines to registered medical practitioners, butrequires the supplier to notify the Director-General of Health. Approval is obtained when asponsor company has sought and received Ministerial consent to the marketing of that medicine,and the indications and contraindications etc are set out in the current data sheet.

The Code of Health and Disability Services Consumers’ Rights places obligations on the providerof services. The consumer has the right to treatment of an appropriate ethical and professionalstandard, and the provider has the responsibility to ensure treatment, whether approved orunapproved, meets this standard. The consumer also has the right to be fully informed. If theuse of a medicine is unapproved, the consumer should be so advised and the provider should befrank about the standard of support for the use and any safety concerns. The Code requireswritten consent for experimental use of a medicine. The unapproved use of a medicine wouldbe considered to be experimental if there is little or equivocal documented support for the use.

for a medicine to be marketed an application withsupporting documentation must be made for theconsent of the Minister. The Minister’s consent isnotified in the New Zealand Gazette, at which timethe medicine, along with a set of indications,dosage instructions and route(s) of administration,is regarded as being approved. Proposed changes,including new indications and changes to the datasheet, also have to be applied for.

Because of this requirement for seeking andobtaining consent, it follows that there will bemedicines that may be effective and safe, andapproved in other countries, but do not haveapproval in New Zealand. There will also be othermedicines that have been approved with aparticular set of indications, but for which thereare other recognised indications not applied for inNew Zealand. Some unapproved medicines maybe used for rare diseases, for which there are fewor no treatments approved in this country.

Hence, the need to provide for access tounapproved medicines was recognised when theMedicines Act was formulated. Section 25 of theAct permits registered medical practitioners,dentists and midwives (hereafter referred tocollectively as “practitioners”) to procure,administer and arrange the administration of an


unapproved medicine. Section 29 permits anauthorised supplier or a medical practitioner tosupply or sell an unapproved medicine to a medicalpractitioner provided the Director-General ofHealth is notified. Both sections of the Act needfurther explanation.

Section 25 of the Medicines Act permitsuse of unapproved medicines

The terms of section 25 are inclusive andpermissive, allowing the practitioner to “procurethe sale or supply of any medicine” for a particularpatient in his or her care. “Any medicine” includesapproved and unapproved medicines. For dentists“any medicine” applies only to medicines fordental treatment, and for midwives it applies onlyto medicines for antenatal, intrapartum andpostnatal care (Regulation 39, MedicinesRegulations 1984).

“Procure the sale or supply” refers to obtainingthe medicine through the usual channels such as apharmacy or a pharmaceutical company, and it alsopermits the practitioner to use other means ofobtaining a medicine such as importation.However, section 25 does not envisage bulkpurchase by the practitioner. The use is to be forthe treatment of a particular patient under the careof that or another practitioner.

It is worth mentioning, at this point, the use ofapproved medicines for unapproved uses.Section 25 permits a practitioner to use anymedicine (approved or unapproved) for thetreatment of a particular patient in his or her care.The Act puts no restriction on the use of amedicine, even in a situation in which it iscontraindicated. However, whether thepractitioner uses approved or unapprovedmedicines, he or she must provide care of anadequate professional and ethical standard (see thediscussion of the Code of Health and DisabilityConsumers’ Rights later in this article).

Section 29 requires notification of saleor supply of unapproved medicines

Section 29 of the Act permits the sale or supply tomedical practitioners of medicines that have notbeen approved, and requires the “person” who sellsor supplies the medicine to notify the Director-General of Health of that sale or supply in writing

naming the medical practitioner and the patient,describing the medicine and the date and place ofsale or supply.

No notification is required for an unapproved useof an approved medicine, nor is notificationrequired if a practitioner imports a medicine to treathis or her patient. However, if an unapprovedmedicine is sold or supplied to a medicalpractitioner, that sale or supply should be notified.If the supply is from one medical practitioner toanother, the supplying medical practitioner isencouraged to notify the supply, but notificationof supply is not mandatory in this case.

It should be noted that section 29 specifies onlymedical practitioners. This means that if dentistsand midwives wish to procure unapprovedmedicines their sources are limited to otherpractitioners or to direct importation.

On occasions a pharmacist working in a pharmacymay be involved in the supply of an unapprovedmedicine as the medical practitioner’s agent. Ifthe pharmacy has imported the medicine, it is thepharmacist’s responsibility to ensure that thedetails of supply are sent to Medsafe. If themedicine has been obtained from a distributor foran identified patient then that distributor shouldbe given sufficient information to enable them toreport the supply to Medsafe.

Anyone who imports an unapproved medicine forsupply to a doctor under Section 29 (other than ahospital or pharmacy) should ensure that they holda licence to sell medicines by wholesale. Theyshould also ensure that they hold the productspecifications and certificates of analysis for eachbatch imported as required by Section 42.

Patient should be advised of theforwarding of information undersection 29

Note that under the Health Information PrivacyCode, Rule 3, the medical practitioner must advisethe patient that the information about supply ofthe medicine will be forwarded to Medsafe andrecorded on a database as a requirement of theMedicines Act. The keeping of the databaseenables Medsafe to contact the prescriber if aproblem subsequently arises with the medicine,which may require follow-up with the patient.


Consumers’ rights spelt out in the Code

The Code of Health and Disability ServicesConsumers’ Rights, which was introduced in July1996, specifies certain rights of consumers ofhealth and disability services and as a result placesobligations on the practitioner. The Code coversthe right to treatment of an appropriate ethical andprofessional standard, the right to be fully informedabout condition and treatment options, and theright to make an informed choice.

Right to services of an appropriate standard

Right 4 of the Code refers to the right to servicesof an appropriate standard. This right includes:

2) Every consumer has the right to have servicesprovided that comply with legal, professional,ethical, and other relevant standards.

4) Every consumer has the right to have servicesprovided in a manner that minimises thepotential harm to, and optimises the quality oflife of, that consumer.

This right covers the professional standard of theservice provided. Whether the medicine or useof the medicine is approved or unapproved, thepractitioner must approach the decision for itsadministration in a professional, scientificmanner which includes weighing the expectedbenefits and risks.

This right also applies to the situation where apatient requests the prescription of an unapprovedmedicine, about which the practitioner knowsnothing. In such cases, the practitioner must seekto be adequately informed before assisting thepatient to obtain supplies of the medicine. Onlythen will the practitioner be in a position to complywith Rights 6 and 7, which are discussed below.

It is conceivable that the medical practitioner willbe unable to find sufficient information to convincehim or her of either the efficacy or the safety of amedicine requested by a patient. The decision mustthen be made whether or not to assist the patientto obtain the medicine and conduct a clinical trialof one patient. In anticipation of such situationsthe medical practitioner needs to pre-determinewhat are his or her minimum criteria for regardinga medicine as a treatment option, and also whatwill be his or her standard of patient monitoringto minimise harm should the decision be to proceedwith treatment in situations where documentationis severely limited.

Right to be fully informed

Right 6 of the Code covers the right to be fullyinformed:

1) Every consumer has the right to the informationthat a reasonable consumer, in that consumer’scircumstances, would expect to receive,including...

b) An explanation of the options available,including an assessment of the expected risks,side effects, benefits, and cost of each option;...

For an unapproved medicine or unapproved use,the consumer should be advised of the unapprovedstatus. The consumer should also be advised ofthe degree and standard of the support for the useof the medicine, and of any safety concerns, orwarnings or contraindications regarding its use intheir particular condition. In using the phrase“Right to be fully informed”, the Code requiresfrank disclosure of information includinginformation that may dissuade the consumer fromagreeing to use of the medicine.

The following are examples of the information thatshould be conveyed, as appropriate:

• The medicine is widely used for this indicationand its use is supported by well conductedclinical trials;

• The medicine is contraindicated for use in thissituation;

• This medicine is approved for use in adults butno studies have yet been published on its usein children;

• The medicine is innovative and little is knownabout its potential adverse effects; and

• The published studies of the use of thismedicine for this indication do not provideconsistent evidence of its efficacy.

With regard to the first point above, it is worthnoting that a medicine only obtains approval ifthere has been an application, with adequatesupporting documentation, from a sponsorcompany to the Director-General of Health. Theremay be adequate data supporting the use of amedicine, or supporting a different indication ordosage regimen, but if no company has submittedan application there can be no marketing approvalin this country.

The use of medicines in certain groups, such asinfants and small children, pregnant women, and


frail or elderly patients can be a dilemma for thepractitioner. Usually trials have not beenconducted in these groups for a number of reasonsincluding ethical ones. Therefore, the sponsorcompany is unwilling and unable to recommendsuch use in its data sheet and this becomes anunapproved indication.

Right to give informed consent

Right 7 refers to the right to make an informedchoice and give informed consent:

6) Where informed consent to a health careprocedure is required, it must be in writing if...

b) The procedure is experimental;....

The use of an unapproved medicine, or unapproveduse of a medicine will not always be experimental,but in some circumstances the requirement toobtain written consent will apply. These wouldinclude situations where:

• There is minimal evidence to support this use;

• The evidence of the efficacy or safety of themedicine used in this manner is equivocal; or

• The use is part of a clinical trial.

Prescribers need to take responsibility for thinkingthrough the issues, deciding in each situationwhether the use is experimental or not, and takingthe necessary action. If the use is not judged to beexperimental the consumer still has the right tomake an informed choice and give informedconsent to the treatment.

Note that the obtaining of written consent doesnot mean that the requirements of the Code havebeen complied with. The obtaining of informedconsent is a process which involves effectivecommunication, frank information disclosure andfreely given consent. It also involves carefulinvestigation of the clinical condition of the patientand maintaining a current knowledge of treatmentoptions.

Visit the Medsafe web site for scenarios thatillustrate what is permitted under the MedicinesAct, and what is required by both the MedicinesAct and the Code of Health and Disability ServicesConsumers’ Rights: www.medsafe.govt.nz/Profs/RIss/unapp.htm

This article was prepared in consultation with theHealth and Disability Commissioner. The readershould note that the Health and DisabilityCommissioner does not give advance rulings oninterpretation and application of the Code, andhence it is not possible to say in advance that aparticular practice is or is not in breach of theCode. This provision is to ensure that eachcomplaint is considered impartially and with anopen mind.

Disclaimer: Mention of the therapies in this articleshould not be regarded as implied endorsementon the part of Medsafe.

Medsafe accepts no responsibility or liability inrespect of the actions or omissions of any personarising from or as a consequence of any statementin this article.


MICONAZOLE – WARFARININTERACTION REMINDER

Significant systemic absorption of miconazole oralgel can occur when the oral mucosa is inflamed,or from the bowel after the gel has been swallowed.The interaction with warfarin is probably lesslikely when miconazole is administered to the skinor vaginally but in Australia there has been onereport of an interaction involving topicalmiconazole cream.1

In other reports in Australia, the increase in INRhas usually occurred within a week or two ofcommencing miconazole oral gel. In the 17patients on warfarin in whom INR values wereknown, the INR rose to between 7.5 and more than18. In eight of these cases, patients presented withbruising, haematuria or mucocutaneous bleeding.Most patients required the withdrawal of one orboth medicines.1

There have been six reports in New Zealand ofthe warfarin and miconazole oral gel interactionresulting in INR increases. Four patientspresented with bleeding symptoms such ashaemarthrosis, haematuria, haemoptysis orepistaxis. INR values ranged from 7.5 to 18 andthose patients with bleeding symptoms all hadan INR in excess of 10.

As miconazole oral gel can be purchased frompharmacists, without a prescription, bothpharmacists and prescribers are reminded toinform patients taking warfarin about the potentialfor miconazole oral gel to interact with warfarin.Patients taking warfarin who are also givenmiconazole oral gel should be monitored forchange in anticoagulant effect and the dose ofwarfarin adjusted, if necessary.2 Both the datasheet and Consumer Medicine Information (CMI)for Daktarin oral gel contain warnings about thisinteraction.

Competing interests (authors): none declared.

References

1. Australian Adverse Drug Reactions Advisory Committee(ADRAC). Miconazole oral gel elevates INR - a reminder. AustAdv Drug React Bull 2002;21(4):14.

2. Janssen-Cilag Pty Ltd. Daktarin oral gel data sheet 23October 2000. www.medsafe.govt.nz/profs/Datasheet/d/daktarinoralgel.htm

Medsafe Editorial Team

This article was published on the Medsafe web site and e-mailed to electronic Prescriber Update subscribers in May 2003.

Prescribers and pharmacists are reminded of the potentially severe interaction betweenmiconazole oral gel (Daktarin® oral gel) and warfarin. Clinically significant increases in theinternational normalised ratio (INR) of patients who have been stabilised on warfarin canoccur following concomitant use of miconazole oral gel.

ADR UPDATE


Patients who develop clozapine-inducedmyocarditis or cardiomyopathy should notbe re-exposed to clozapine.

Clozapine is an atypical antipsychotic agentcontraindicated in patients with severe cardiacdisorders. An increased incidence of myocardialdisease in clozapine users has been recognised forsome years and information for prescribers has beenupdated accordingly. A recent re-evaluation ofserious adverse cardiac events in association withuse of clozapine has resulted in a strengthening ofthese warnings.

Before starting clozapine therapy, patients arerequired undergo a history and physicalexamination. Patients with a history of cardiacillness or abnormal cardiac findings on physicalexamination should be referred to a specialist forother examinations that might include an ECG andechocardiogram. Clozapine should only be initiatedif severe heart disease is excluded and the benefitsof treatment are considered to clearly outweigh therisks. The prescribing doctor should considerperforming a pre-treatment ECG to allowcomparisons if symptoms develop later.

Rare cases of myocarditis have been reported, someof which have been fatal. Post-marketingexperience suggests that the increased risk ofmyocarditis occurs most commonly in the first twomonths of treatment. Very rare cases ofcardiomyopathy have also been reported; thesecases generally occurred later in treatment and somewere fatal. Pericarditis and pericardial effusion havealso been associated with clozapine treatment.

Tachycardia is a common side effect of clozapinetreatment that occurs in about 25% of users,especially during dose titration in early treatment.However, it is also a key symptom of myocardialdisease. It is therefore essential that patients whohave persistent tachycardia at rest, especially in thefirst two months of treatment, are closely observedfor other signs and symptoms of myocarditis/

Committee on Safety of Medicines, and Medicines Control Agency, United Kingdom

Reprinted from Current Problems in Pharmacovigilance 2002;28:8 with permission from the Medicines andHealthcare products Regulatory Agency (previously the Medicines Control Agency), London, United Kingdom.

This article was published on the Medsafe web site and e-mailed to electronic Prescriber Update subscribers in May 2003.

CLOZAPINE AND CARDIAC SAFETY:UPDATED ADVICE FOR PRESCRIBERS

cardiomyopathy. These include palpitations,arrhythmias, symptoms mimicking myocardialinfarction, chest pain and other unexplainedsymptoms of heart failure.

A minority of clozapine-treated patients experienceECG changes similar to those seen with otherantipsychotic drugs, including S-T segmentdepression and flattening or inversion of T-waves,which normalise after discontinuation of clozapine.The clinical significance of these changes is unclear.However, such abnormalities have been observedin patients with myocarditis, which should thereforebe considered. If clozapine-induced myocarditisor cardiomyopathy is suspected, clozapine treatmentshould be discontinued promptly and the patientreferred urgently to a cardiologist for diagnosticevaluation.

Key information for prescribers

• Patients must have a history and physicalexamination prior to starting therapy. Thetreating physician should consider performinga pre-treatment ECG.

• Patients who have persistent tachycardia at rest,especially during the first two months oftreatment, should be closely observed for othersigns or symptoms of myocarditis orcardiomyopathy. These include palpitations,arrhythmias, symptoms mimicking myocardialinfarction, chest pain and other unexplainedsymptoms of heart failure.

• Patients in whom myocarditis or cardiomyopathyis suspected should stop clozapine and undergourgent diagnostic evaluation by a cardiologist.

• Patients with clozapine-induced myocarditis orcardiomyopathy must not be re-exposed toclozapine.

Copies of this article can be obtained from:www.mca.gov.uk/ourwork/monitorsafequalmed/currentproblems/cpoct2002.pdf


Introduction

Why don’t consumers know what to do when theymiss a dose of their medication? As healthprofessionals we know that the vast majority ofpatients occasionally miss a dose of theirmedication. This unintentional non-compliance,and request for advice after the event, is verycommon in practice. In a study of 205 people,90% rated having information on ‘what to do if adose is missed’ as very important or important andonly 1.5% did not want information on this topic.1

A USA study2 found that less than 50% of patientsreceived this information.

Given our understanding of the difficulties aroundcompliance with medication regimens, it must beour expectation that many patients will miss doses.Informing them about what to do about a misseddose at the time of prescribing, dispensing andadministration would seem to be a logical steptowards improved compliance.

Pre-emptive advice

Missed doses could be viewed within theframework of patient non-compliance, howeverthe problems which arise often result becausehealth professionals do not give enoughinformation to allow the patient to safely use themedication. Teaching a patient what to do if adose is missed and providing strategies to minimisethe number of missed doses appears a sensibleapproach.3 Providing written information, thatincludes what to do if a dose is missed, improvespeople’s self-administration of medicines,including corrective action when a dose is missed.4

I’VE MISSED A DOSE; WHAT SHOULD I DO?

Andrew Gilbert, Libby Roughead and Lloyd Sansom; Quality Use of Medicines and Pharmacy ResearchCentre, University of South Australia, Adelaide, Australia

Reprinted from Australian Prescriber 2002;25(1):16-18 with permission.


More than 80% of patients occasionally miss a dose of their medication. Health practitionersought to plan with their patients what to do if a dose is missed. Patients believe that this planshould be a required part of the information received when a medication is prescribed anddispensed. Consumer Medicine Information sheets, which are available for most commonlyprescribed medications, contain a section on what to do if a dose is missed. The routine use ofthese sheets or similar advice may help patients to know what to do when they miss a dose.

In practice, giving information on what to do if adose is missed should not be too onerous a taskfor medical practitioners or pharmacists. Most ofthe commonly prescribed medications in Australiacome with, or have available, a ConsumerMedicine Information (CMI) sheet.a All CMIsheets have a section entitled ‘What to do if youmiss a dose’. Giving patients a CMI sheet the firsttime they receive a medication, and using thismaterial in discussion with patients at the time ofprescribing and dispensing would prepare themfor this eventuality.

Assessing the importance of a misseddose

The severity of the patient’s condition, whetherclinically significant breakthrough effects arelikely to be observed, and the characteristics ofthe medication should be considered whendeciding the most appropriate strategy followinga missed dose. Vulnerable patients are easilyrecognisable in any practice and include those onmedications of low therapeutic index,b or sufferingfrom conditions which require constantmaintenance of therapeutic concentrations (forexample epilepsy and thromboembolicdiseases requiring anticoagulation). On the otherhand, for most people with hypertension orhypercholesterolaemia a single missed dose willbe of little consequence.

The patients should be informed at the time ofprescribing and dispensing, of strategies tominimise missed doses and to redeem the situationwhen a dose is missed. Highlighting the strategy


as it appears on the CMI or writing out an actionplan as a reminder to the patient may prove veryuseful.

While a pre-emptive approach is ideal it isrecognised that requests for information aboutmissed doses are common. Knowledge of a drug’shalf-life, a major determinant of the fluctuation ininterdose concentrations at steady state, is usefulfor making recommendations on what to do if adose is missed. Upon cessation of therapy, it takesfour to five half-lives for the drug to be completelyeliminated.

In general, medications, or their active metabolites,with a long half-life tend to create less problemswhen a dose is missed than medications with ashort half-life. However, the clinical effect of somedrugs is not related to the half-life. This usuallyoccurs when the drug is acting via an irreversiblemechanism (for example aspirin’s effect onplatelets), via an indirect mechanism (for examplethe effect of warfarin on blood coagulation), whenthe drug is a pro-drug (in which case it is the half-life of the active species that is important) or whenthe drug is converted to an active metabolite whichhas a long half-life.5

Missing several consecutive doses raises additionalproblems. For example, for drugs with long half-lives it can take a significant time to re-establishtherapeutic concentrations when regular dosingresumes unless loading doses are given (forexample digoxin). Drugs with short half-lives willlose therapeutic effect rapidly. Further, drugs withfirst-dose effects, for example an ACE inhibitorin combination with diuretics, may also presentclinical problems when normal dosing is resumed.Overall, surprisingly few studies have examinedthe clinical significance of a missed dose.

Missed doses of the oral contraceptive pill havebeen well studied. Women taking the pill need tobe aware of the risk associated with missed dosesand of what to do when a dose is missed. Giventhe complexity of this information, and the risk ofan unwanted pregnancy, it is important that anyverbal counselling is supported with appropriatewritten material. Where a CMI sheet is availablethis can be used during the consultation. If noCMI sheet is available for the prescribed product,written notes based on the recommendations in theAustralian Medicines Handbook are useful.6

A table providing examples of medications forwhich missed doses may be clinically important,and information for patients on what to do, can beviewed at www.medsafe.govt.nz/profs/PUarticles/missed.htm

Conclusion

For the vast majority of patients an occasionalmissed dose will have little impact on the outcomeof therapy. Most CMI sheets include statementssuch as:

• If you forget to take one or more doses: takeyour next dose at the normal time and in thenormal amount. Do not take any more thanyour doctor prescribed.

• If you miss one dose, skip it and continue withyour normal schedule.

Having this knowledge when starting therapy maybe a simple way to alleviate much patient anxietyand in some cases avoid unwanted clinicalconsequences.

a In New Zealand, CMI fact sheets are availablefor some medicines. These CMI can be freelyaccessed from the Medsafe web site:www.medsafe.govt.nz/cons.htm

b The therapeutic index reflects the range ofconcentrations between the drug concentrationwhich produces toxic effects and the drugconcentration required for therapeutic effects. Anarrow therapeutic index means only smallincreases in concentration can cause toxicity andsmall decreases in concentration can result in lossof efficacy.

Conflict of interest: none declared

References

1. Howard J, Wildman K, Blain J, Wills S, Brown D.The importance of drug information from a patient perspective.J Soc Admin Pharm 1999;16:115-26.

2. Lyons RF, Rumore MM, Merola MR. An analysis of druginformation desired by the patient. J Clin Pharm Ther1996;21:221-8.

3. Zind R, Furlong C, Stebbins M. Educating patients about missedmedication doses. J Psychosoc Nurs Ment Health Serv1992;30:10-4.

4. Paulson PT, Bauch R, Paulson ML, Zilz DA. Medication datasheets - an aid to patient education. Drug Intell Clin Pharm1976;10:448-53.

5. Sansom L, editor. Australian Pharmaceutical Formulary andHandbook. 17th ed. Canberra: Pharmaceutical Society ofAustralia; 2000.

6. Australian Medicines Handbook 2000. 2nd ed. Adelaide:Australian Medicines Handbook Pty Ltd.; 2000. p. 17-9.


ADVERSE REACTIONSOF CURRENT CONCERN

MARCRx

ADVICE

The Medicines Adverse Reactions Committee(MARC) initiated the list of adverse reactions ofcurrent concern to bring particular medicineadverse reactions to the attention of prescribers.The intention is to encourage prescribers to reportthese reactions to the Centre for Adverse ReactionsMonitoring (CARM) so that more information canbe gathered, and further action taken if necessary.

As with any adverse reactions monitoring scheme,analysis can only be based on reports that arereceived. Prescribers are therefore encouraged tocontinue reporting adverse reactions to CARM sothat the MARC can make the best possiblerecommendations based on information reflectingthe New Zealand situation.

Regular amendments to the list of reactions aremade either in response to adverse events reportedin New Zealand or internationalpharmacovigilance issues.

Recent additions

Adrenal insufficiency, hypoglycaemia,or seizure with inhaled fluticasone(Flixotide®) – new listing as from March 2003

Due to concerns arising from international reportsof these adverse reactions occuring in associationwith inhaled fluticasone, MARC would like tobring them to the attention of New Zealandprescribers with the intention of obtaining a localperspective on an emerging safety issue. Adrenalinsufficiency associated with inhaledcorticosteroids can occur due to systemicabsorption of the corticosteroid and consequentsuppression of endogenous glucocorticoids,leaving insufficient adrenal reserve to respond tostress (e.g. infection). Adrenal insufficiency mayalso result from abrupt discontinuation or non-compliance with treatment, leading to acute steroiddeficiency. It may present as hypoglycaemia,abdominal pain, tiredness or vomiting, with orwithout seizures or coma. Although adrenalinsufficiency can occur with any inhaledcorticosteroid, it may be more common withfluticasone because of its greater potency.1

Recent deletions

In March 2003, the following adverse reactionsof current concern were removed from the list,due to a good level of awareness by prescribersbeing achieved:

• hepatic reactions with nefazodone

• serious soft-tissue infection with NSAIAs

• venous thromboembolism (VTE) with oralcontraceptives

• warfarin interaction with celecoxib orrofecoxib.

Note: VTE with Diane®, Estelle® and HRT are stillbeing monitored.

Nefazodone (Serzone®) and hepatic reactions

This has been an adverse reaction of currentconcern since February 2000. During this period,up until February 2003, CARM has received 14reports of hepatic reactions including seven casesof hepatocellular liver injury and five of abnormalliver function test results occurring duringtreatment with nefazodone. Doses ranged from200mg to 500mg daily (recommended dose rangeis 300mg to 600mg/day2), and onset of the adverseevent occurred between nine days and 15 monthsfrom when nefazodone therapy was initiated. Ofthe 14 cases, 11 had an onset time of four monthsor less. While hepatic reactions with nefazodoneare no longer an adverse reaction of currentconcern, nefazodone continues to be monitoredin the Intensive Medicines MonitoringProgramme. This will enable MARC to maintaina watching brief. At this stage, no additional safetyadvice is being issued by MARC however,prescribers are reminded that patients should bealerted to signs and symptoms suggestive of liverdysfunction, such as jaundice, dark urine, anorexia,nausea, malaise, gastrointestinal complaints, orabdominal pain and told to report these to theirdoctor immediately. If signs, symptoms orevidence of hepatocellular injury occur duringtreatment with nefazodone, it should bewithdrawn. These patients should be presumedto be at increased risk of liver injury if nefazodoneis reintroduced. Accordingly, such patients should


not be considered for re-treatment withnefazodone. Initiation of treatment withnefazodone is not recommended in patients withactive liver disease or elevated baseline serumtransaminases.2

References

1. Adverse Drug Reactions Advisory Committee (ADRAC).Fluticasone and adrenal crisis. Aust Adv Drug React Bull2003;22(2). www.health.gov.au/tga/adr/aadrb/aadr0304.htm#1

2. Bristol-Myers Squibb (NZ) Limited. Serzone data sheet 5 March2002. www.medsafe.govt.nz/profs/Datasheet/s/Serzonetab.htm

* includes herbal medicines, bee products, homoeopathic products, dietary supplements, minerals, and any othermedicines containing animal or plant extracts.

Medicine/s Adverse reactions of current concern Prescriber Update reference

Atypical antipsychotics hyperglycaemia Vol.23(1), Apr 2002 &No.18, Jun 1999

Celecoxib cardiovascular events Vol.23(1), Apr 2002

Complementary and all adverse reactions Vol.23(2), July 2002 &alternative medicines* No.13, Oct 1996

Diane 35® and 35 ED® venous thromboembolism Vol.23(1), Apr 2002No.20, Feb 2001

Estelle 35® and 35 ED® venous thromboembolism Vol.23(1), Apr 2002 &No.22, Oct 2001

Fluticasone (inhaled) adrenal insufficiency, hypoglycaemia, This issueor seizure (see previous page)

Hormone replacement therapy venous thromboembolism Vol.23(3), Nov 2002 &No.16, Apr 1998

Rofecoxib cardiovascular events Vol.23(1), Apr 2002

SSRIs severe agitation, severe Vol.23(3), Nov 2002restlessness/akathisia, and/orincreased suicidality

Please report all cases of the following adverse reactions (additions are in bold) to: CARM,PO Box 913, Dunedin. Use the reporting form inside the back cover of Prescriber Update,or download the form from the CARM or Medsafe web sites: www.otago.ac.nz/carm orwww.medsafe.govt.nz/Profs/adverse.htm


INTENSIVE MEDICINESMONITORING PROGRAMME

About the IMMP

The purpose of the Intensive MedicinesMonitoring Programme (IMMP) is to identifypreviously unrecognised adverse reactions to newmedicines. It also develops adverse reactionprofiles for these medicines, as well as measuringincidence and characterising reactions of clinicalconcern. In addition, the IMMP is able to identifyany high-risk groups amongst the patients beingtreated. The results of IMMP findings are used toenhance the safe use of medicines.

Which medicines are monitored?

Medicines of a new class are added to the IMMPso that unknown adverse effects can be identifiedas soon as possible. Medicines may also beincluded in the programme if they are similar toother medicines for which safety concerns exist.

The medicines currently being monitored are listedin the following table (latest additions are in bold).

What to report

Successful assessment of the significance of eventsdepends on you reporting all events occurring withIMMP medicines, including adverse reactions andrandom clinical incidents. Please report:

• all new events including common minor ones

• any change in a pre-existing condition

• abnormal changes in laboratory test results

• accidents

• all deaths and causes

• possible interactions.

Where to report

Please report all cases of adverse events occurringwith IMMP medicines to: Centre for AdverseReactions Monitoring (CARM), PO Box 913,Dunedin. Use the reporting form inside the backcover of Prescriber Update, or download the formfrom either the CARM or Medsafe web sites:www.otago.ac.nz/carm or www.medsafe.govt.nz/Profs/adverse.htm


Medicine Proprietary name/s Indications/Action

Celecoxib Celebrex COX-2 inhibitor (selective NSAIA)

Clozapine Clozaril, Clopine atypical antipsychotic

Entacapone Comtan Parkinson’s disease – adjunctivetreatment only

Etoricoxib* Arcoxia COX-2 inhibitor (selective NSAIA)

Levonorgestrel Mirena progestogen-releasing intrauterine systemintrauterine system

Montelukast Singulair anti-asthmatic / leukotriene inhibitor

Nefazodone Serzone antidepressant / 5HT2 blocker

Olanzapine Zyprexa atypical antipsychotic

Parecoxib* Dynastat COX-2 inhibitor (selective NSAIA)

Quetiapine Seroquel atypical antipsychotic

Risperidone Risperdal atypical antipsychotic

Rofecoxib Vioxx COX-2 inhibitor (selective NSAIA)

Sibutramine Reductil centrally acting anorexiant

Tolcapone Tasmar Parkinson’s disease – adjunctivetreatment only

Zafirlukast Accolate anti-asthmatic / leukotriene inhibitor

* Etoricoxib (tablets) and parecoxib (injection) are new COX-2 inhibitors, which have been added to the IMMP dueto on-going concerns about COX-2 inhibitors in general.

Medicines on the IMMP


Prescriber Update is published and distributed by Medsafe in the interests of safer, more effective use ofmedicines, medical devices and methods of diagnosis and treatment.

Medsafe: New Zealand Medicines and Medical Devices Safety AuthorityA business unit of the Ministry of Health.

Editor: Sarita Von AfehltMedsafe, PO Box 5013, Wellington, New ZealandPh: (04) 496 2107 Fax: (04) 496 2229E-mail: [email protected]

Editorial Team: Dr Stewart Jessamine Principal Technical SpecialistDr Karyn Maclennan Advisor (Science)

Manager, Medsafe: Clare Van der Lem

Medsafe web site: www.medsafe.govt.nz

Published with the permissionof the Director-General of Health.

Reporting form for Adverse Reactionsto Medicines, Vaccines and Devices

and all Clinical Events for IMMP

Surname: First Name(s):

Address:

ALL MEDICINES IN USE – ASTERISK SUSPECT MEDICINE(S)

Medicine(s) / Vaccine(s)+ batch no. Daily Dose Route Date Started Date Stopped Reason for Use

DESCRIPTION OF ADVERSE REACTION OR EVENT

Date of Onset:

Recovered Not yet recovered Unknown Fatal Date of Death:

Severe? No Yes Rechallenge? No Yes Result:

OTHER FACTORS

Renal Disease Hepatic Disease Allergy Describe:

OTC Use? Industrial Chemicals Other Medical Conditions? Describe:

REPORTING DOCTOR/PHARMACIST/NURSE

Name: Telephone:

Address:

Date:

Email address:

Send completed form to CARM

Post: Freepost 112002, CARM, PO Box 913, Dunedin or Fax: (03) 479 7150

NHI No:

Ethnicity:

Date of Birth:

Sex: M F

PATIENT DETAILS H1574

Fax: (03) 479 7150Phone: (03) 479 7247

ADVERSE REACTIONSREPORTING GUIDELINES

Please do not hesitate to report any suspect reaction of clinical concern.The following general guidelines apply.

Report adverse reactions to:

• All medicines• Vaccines• Over-the-counter” (OTC) medicines• Herbal, complementary and alternative remedies

Report adverse reactions and interactions that are:

• serious

• adverse reactions of current concern1

Report all reactions to new medicines and all events to IMMP medicines.2

Report serious allergic reactions so that a danger or warning can be enteredagainst the patient’s name in the national health database.

If in doubt, report.

Reporting may be made on-line, by mail, fax, e-mail or phone

On-line reporting: Register and report on-line at www.otago.ac.nz/carm/report.asp

Reporting form: Use the form overleaf or the card supplied with New EthicalsCatalogue. The reporting form can also be downloaded fromwww.otago.ac.nz/carm/report.asp orwww.medsafe.govt.nz/profs/adverse.htm

Mail the form to: Freepost 112002The Medical AssessorCentre for Adverse Reactions MonitoringP O Box 913, Dunedin

Or fax it to: (03) 479 7150

Phone: (03) 479 7247

E-mail: [email protected]

Web site: www.otago.ac.nz/carm

1. The list of Adverse Reactions of Current Concern is on page 17.2. The list of medicines in the Intensive Medicines Monitoring Programme (IMMP)

is on page 19.

Prescriber Update - medsafe.govt.nz

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