Application for Inclusion of Oral Ibuprofen Suspension fileIbuprofen is now widely recognised...
Transcript of Application for Inclusion of Oral Ibuprofen Suspension fileIbuprofen is now widely recognised...
25Ih October 2004
The Secretary of the Expert Committee on the Selection and Use of
Essential Drugs and Medicines Policy World Health Organization 20 Avenue Appia CH-I211 Geneva 27
Essential Medicines Policy, Access and Rational Use
Dear Secretary
With this letter I am sending a completed application plus supporting documentation for the inclusion of paediatric ibuprofen in the WHO model list of essential drugs.
The International Ibuprofen Foundation (IIF) is now recognised as a leading authority on this important medicine. Its tolerance and effectiveness were fully covered at our conference at the Royal College of Physicians in London on April 15116, 2002. Participants were international scientists of considerable reputation and their presentatinns can be seen on our website at ~.ibupmfen-fo?lndationcom
Ibuprofen is now widely recognised worldwide as a highly effective analgesic anti- pyretic and anti-inflammatory medicine with a high safety profile in adults and also in paediatric use. It is freely available over the counter in Europe, the Americas and following a change in regulatory requirements, in Australia and New Zealand.
We believe that the case for the inclusion of paediatric ibuprofen on your list of essential drugs is substantial. We would be happy to enlarge upon the documentation here if this would be of help to your expert committee.
If this would be of practical benefit the IIF would be happy to come to Geneva to answer questions from the committee members.
I hope we may receive a favourable response and look forward to hearing from you
Yours sincerelv
G N H E N D E R ~ ~ L? i recto r ,SSnera I 1nternat:onai ibuprofen Foundation
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
APPLICATION BY THE INTERNATTONAL IBUPROFEN FOUNDATION (XF)
FOR THE INCLUSION OF IBUPROFEN SUSPENSION IN THE WHO MODEL
LIST OF ESSENTIAL MEDICINES
Summary statement of the proposal for inclusion
This is an application for inclusion of Paediatric Ibuprofen in the WHO list of essential
medicines. Ibuprofen is currently included in the Model formulary for the treatment of
pain and this application supports the inclusion of paediatric ibuprofen suspension for the
treatment of pyrexia.
Name of the organization(s) consulted and/or supporting the application
Various key Paediatricians around the world have been consulted and have given their
endorsement to this application. These include Professor John Pearn, Professor of
Paediatrics & Child Health at The University of Queensland, Australia and Doctor Dipak
Kanabar, Consultant Paediatrician at Guy’s and St. Thomas’ Hospital, London. A
supportive statement is included from both.(Appendix 11).
Professor John Van den Anker, Executive Director, Children’s National Medical Centre
at George Washington University School of Medicine and Health Sciences, Washington,
USA and Erasmus MC-Sophia Children’s Hospital, Rotterdam has also given his support
to this application.
Two of the Companies who market this drug have also been approached. Both Boots
Healthcare International and Wyeth Consumer Health have given their full support to this
application.
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
International Non proprietary Name of the mdiciiie
The International Non proprietary Name of the medicine is Ibuprofen.
Whether listing is requested as an individual medicine or as an example of a
therapeutic group
The application is being made so that the drug can be listed as the individual drug,
paediatric ibuprofen suspension and not as the therapeutic group antipyretics or NSAID.
Information supporting the public health relevance
Fever has been recognised as an important sign of disease since the beginning of recorded
history. Opinion has changed substantially about whether patients are better with or
without fever. In ancient times it was considered that fever was the body’s defence
mechanis= and shculd not be tretited. A change in this view occurred in the wake of
experiments by the French physiologist, Claude Bernard, who demonstrated that animals
died when their body temperature was raised 5 - 6 degrees Celsius above normal. These
findings? combined with the beginning of thermometer use in medical practice, resulted
in a dramatic shift in opinion and fever became generally regarded as a threat to health.
However it’s important to realise that the main purpose of using an antipyretic is to
control those symptoms associated with fever which have a negative impact on the
child’s wellbeing such as headache, rigors, nausea and vomiting and febrile convulsion.
Parents the world over have a preferred method of treating high temperature in their
children and when it comes to pharmacological methods, two main treatments seem to be
used. either paracetamol or ibuprofen. Fever is one of the most common symptoms in
children and is responsible Cor 1O-JO”a of visits to the General Practitioner or
Applicstion for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
Paediatrician. Parents are frightened when their child develops a fever w-hich is further
compounded by seeing their child in distress. It has been demonstrated that undue fear of
the effects of fever among parents of infants and young children is common and has led
to overly aggressive treatment. This has included treating children with temperatures
below 38 degrees Celsius, waking sleeping children to administer antipyretics and using
physical methods that are both uncomfortable and ineffective. Symptomatic treatment
with rapid onset is often required to avoid any distress or discomfort, dehydration and
febrile seizures. The efficacy of ibuprofen in the treatment of pyrexia has been studied in
many comparator and placebo-controlled studies and these are discussed extensively
below. For all licensed dosages ibuprofen has been shown to be at least as effective as
paracetamol in treating fever. Recent studies have shown that ibuprofen is superior in
effectiveness to paracetamol in treating fever and again these are discussed below. The
tolerability of ibuprofen when used as a short term antipyretic is similar to that of
paracetamol and again details of this are indicated in the studies below. The safety
profiles of both drugs are excel!ent yet not al! children will respond to each drug, it
therefore being important to offer choice. Aspirin is limited in the paediatric population
due to concerns over the association with Reye's syndrome.
All of this means that in terms of public health relevance it is essential that both
paracetamol and ibuprofen are available for the treatment of fever in children.
Treatment details
The posology detailed in the table below is based on a dose of 7-0-30mg/kg daily or 7.5-
1 Omgikg per single dose.
Doses should be given approxi~narely every 6-8 hours. or with a minimum interval of 4
hours benveen each dose.
Age
Babies 3-6 months
Babies 6-12 months
Children 1-3 years
Children 3-6 years
Average weight (kg) /Uni t dose Sr frequency ir. 24 hours
(approx)
5.6-7.6
7.7-9
10-15
16-20
2.5 mi 3 times a day
2.5 ml 3-4 times a day
5 m l 3 times a day
7.5 m l 3 times a day
Children 7-9 years
I I I I
21-29 110 ml3 times a day
There are a variety of dosing devices available to administer paediatric ibuprofen
suspension including a dosing spoon and dosing syringe that is available calibrated with
weight or volume. This will enable children who may be malnourished to be dosed
safely.
Children 10-12 years
Summary of comparative effectiveness in a variety nf c!inical settings:
- Identification of clinical evidence
Data Source
The following electronic databases were searched from their inception through October
2004 to identify randomised controlled trials, systematic reviews and meta-analyses
examining the efficacy of ibuprofen in fever. Medline, Embase, Cochrane Database,
Database of Abstracts Of Reviews Of Effects, Adis Clinical Trials Insight, Biosis
previews, British Nursing Index, CBIB, Derwent Drug File, International Pharmaceutical
Abstracts. Pharm-Line, Cinahl, Pascal. SCZZ- SciSearch. In implementing the search
strategy we used the following key words in combination: ibuprofen, Nurofen, Brufen,
Motrin. Ad\ il. isobutylphenyl, propionic acid, antipyretic, antipyresis. pyrexia, fever.
hypothermia. child. infant. paediatric. pediatric. The electronic search strategy is
30-40 115 m13 times a day
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
provided in appendix 1 . Hand searches o f reference lists of identified studies did not
provide any additional data
- Inclusion and Exclusion Criteria
We included studies with children aged less than 16 years receiving either ibuprofen or a
comparator antipyretic for the treatment of fever. Systematic reviews and meta-analyses
that included studies which satisfied these criteria were also included. Studies addressing
both fever and pain were also included however data representing the analgesic affect of
ibuprofen were excluded. Otherwise relevant studies measuring the antipyretic effect of
ibuprofen were excluded if no comparator therapy was used.
- Results
Following the electronic search 509 results were initially identified. From these, 150
results were eliminated from title checking using over inclusive methodology which also
included elimination of duplications. Following abstract reviews, and where abstracts
were not available papers were sourced, 3 1 papers were identified as meeting the
inclusion criteria. These are presented in the following tabulated summary.
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Application for Inclusion of Oral Ibuprofen Suspension T o The WHO Model List of Essential Medicines
Srimmary of comparative evidence on safety -
Disorders I
Nervous System Disorders
Renal and Urinary Disorders
Heparobiliary IDisorders
Blood and
-Estimnte of totulpatient e.uposure to date
Paediatric ibuprofen has been available since 1997 and is now marketed in more than 60
countries. Such a diverse international market makes it difficult to obtain valid global
patient exposure. In 1997 child specific ibuprofen accounted for 7.0% of the global child
specific non-prescription analgesics market, approximating to a value of f72.4 million
which is the equivalent of 27 million packs of product. This market share increased to
12.0% by 2003, approximating a value of L141.2 million which is the equivalent of 48
million packs of product.
Data was unavailable for the prescription market but the value is estimated to be the
equivalent of the non-prescription analgesics market.
Source- Euromonitor
Rare:
Very rare:
diarrhoea, flatulence, constipation and vomiting
gastro-intestinal ulcers, sometimes with bleeding and perforation can occur.
Uncommon: Headache
Very rare: Decrease of urea excretion and oedema can occur. Also, acute renal failure. Papillary necrosis, especially in long-term use, and increased serum urea concentrations have been reported.
Very rare'. liver disorders, especially in long-term treatment.
Vcry rare: 1 haematopoietic disorders (anaemia, leucopenia.
I
1
- Dmcripiieic?r? Q,f adxrs2 efi2cts,+eac;imis
The list of thc Following adverse effects relates to those experienced with ibuprofen.
Gastrointestinal IUncommon: \abdominal pain, dyspepsia and nausea.
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
Very rare:
Uncommon:
Very rare
\ /
epidermal necrolysis can occur.
In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed
Hypersensitivity reactions with urticaria and pruritus.
severe hypersensitivity reactions. Symptoms could be: facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).
Exacerbation of asthma and bronchospasm.
kin an( ubcutaneous )isorders
nmune Systen lisorders
Iypersensitivity .eactions
\d Very rare: Isevere forms of skin reactions such as erythema muitiforme and;
The frequencies are defined as follows and as defined by the ICH guidelines:
Very common: >:/IO
Commoii: ::: 00, :::I 0
Uncommon: >I / l , nnn , < I / l O O
Rare: >i/in,nnn, <i / i ,nno
Very Rare: <1/10,000, including isolated reports.
- Identification of variation in safety due health sy! ms and. rtient factors
No issues in variation in safety due to health systems have been identified; however
particularly in the developing countries there are possible issues with malnutrition and
dehydration within the patient population.
The issue of malnutrition can be addressed by dosing the child according to weight as
detailed in the dosing table presented earlier. The availability of a dosing syringe
calibrated with weight or volume will enable children who may be malnourished to be
dosed safely.
,,\buprnf;.,j $(&J5. P T?, u - - - - Application for Inclusion of Oral Ibuprofen Suspension
To The WHO Model List of Essential Medicines
As a precautionary measure as in the use of all NSAIDs including aspirin and ibuprofen
we recommend that all children be adequately hydrated before receiving paediatric
ibuprofen suspension. During periods of dehydration, which may occur in children with
high temperature or malnourishment, there is a small possibility of reversible pre-renal
acute renal insufficiency. In circumstances of severe volume depletion and reduced renal
glomerular filtration vasoconstrictor agents such as angiotensin I1 and noradrenaline are
generated. The vasodilator prostaglandins, PGE2 and PGI, modulate the effects of the
vasoconstrictor agents in the kidney by causing compensatory vasodilation8. Therefore
inhibition of prostaglandin synthesis may elicit a temporary affect on this compensatory
mechanism. However, this is reversible on stopping the NSAID and does not normally
occur in healthy indi~iduals '~.
Renal function was monitored in a subgroup of children (285 of 27 065) who were
admitted to hospital while participating in a randomised double-blind trial of 5 or 10
mgikg of ibuprofen or paracetamol 12 mg/kg for the treatment of febrile illness'*. There
was no difference between the treatments in blood urea nitrogen levels, serum creatinine
concentrations or the incidence of serum creatinine concentrations > 62 micromolil. The
authors concluded these data suggest that the short-term risk of less severe renal
impairment associated with short-term use of ibuprofen in children is small and not
significantly different from that with paracetamol. There was also no difference between
ibuprofen and paracetamol in the risk of admission for acute renal failure 1 9 .
Much ibuprofen safety data in premature infants have also become available in the last
few years. It is important to note that premature infants present as an extremely
vulnerable population since prematurity is associated with a relatively high risk of serious
complications including renal pathology. Approximately 95% of pretenn infants are
admitted io neonatal intensive care units. In developed countries complications include
respirarory distress syndrome (50 - 60% of infants), PDA (30 - 30%); nosocomial
inkction (IO - 15%). intraventricular hemorrhage (lo%), death (9 - 15%) and
Application for Inclusion of Oral Ibuprofen Suspension I
To The WHO Model List of Essential Medicines
neurodevelopmental delay 3’. The fact that ibuprofen is so well tolerated in these
vulnerable infants with high initial plasma levels, low protein binding and slow
elimination lends strong support for its safety in children aged 3 months and above who,
by comparison, are relatively healthy.
Var~arigou’~ concluded that treatment with ibuprofen in pre-term infants was not
connected with any neurological, intestinal, renal, hepatic or haematological
complications. Furthermore D a d concluded that ibuprofen reduced the incidence of
bronchopulmonary dysplasia without any renal, biochemical or haematological effect,
Romagnoli” found that ibuprofen did not have any direct effect on cerebral and renal
blood flow velocities in premature infants. Therefore, ibuprofen did not increase the risk
of either cerebral or renal hypoxia, with no effect on blood flow velocities in either the
anterior cerebral artery or renal artery, in these infants. This was also supported by further
blood flow velocity studies undertaken by Lago”. In a study examining the effects of
both ibuprofen and indomethacin in pretem infants treated for PDA, ibuprofen was
found not tc significaiily reduce mesenteric blood flow velocity compared with
indomethacin. Heyman’” showed oral ibuprofen to be effective and safe in PDA closure
with serum creatinine levels within normal range at all times. Subsequently there was no
contraindication for a second or third dose of ibuprofen when required. Good tolerability
was also demonstrated in PDA studies undertaken by Supappanachart” and Akisu’.
Supappanachart determined that following orally administered ibuprofen, infants had
serum creatinine levels that were not significantly different from pre-treatment levels.
Akisu also found that ibuprofen was not associated with significant side effects in pre-
term infants
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
- Summary of comparative safety against comparators
Many comparative studies have been conducted with ibuprofen which look at efficacy as
well as safety. The studies reviewed for the purpose of this application are those using
paracetamol as the key comparator. This is because paracetamol is one of the most
widely used paediatric medications and has an excellent safety profile. The first study
reviewed is a randomised double-blind clinical trial with over 84,000 subjects. The
second study is a multicentre open label prospective study with over 30,000 subjects.
These two studies provide an invaluable insight into the practical use of ibuprofen in a
clinical setting. The third is a meta-analysis which itself reviews 17 key comparative
clinical trials
Dr Samuel M. Lesko of Boston University and the Northeast Regional Cancer Institute,
Scranton, Pennsylvania, reported on the results fiom the Boston University Fever
Designed and conducted by the Slone Epidemiology Unit at the university, and
guided by an Independent Advisory Committee, it investigated the risk of rare and
serious adverse events after using ibuprofen suspension in febrile children.
In the Boston Study, 1,735 primary care physicians enrolled 84,192 children into a
randomised double-blind clinical trial. The children had to have febrile illnesses, be aged
between six months and 12 years, weigh between seven and 50 kg, be able to take
medication by mouth and be in the care of a parent or guardian who could follow written
instructions in English. Children known to be sensitive to ibuprofen or paracetamol were
excluded from the study.
Randomisation was to one of three treatment groups: paracetamol 12 mgikg, ibuprofen 5
mg/kg, and ibuprofen (10 mg/kg). The primary outcomes sought were admission to
hospital for the events seen in adults taking NSAIDs, such as acute gastrointestinal
bleeding, acute renal failure and anaphylaxis. There were approximately 28,000 children
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
in each treatment group. The median treatment age was 40 months, and 52 percent were
male
Two children died during the trial. The deaths were judged not to be related to
participation in the study. One was the result of a car accident and one was due to
complications of bacterial meningitis.
Fewer than 800 children were hospitalised during the study, the admission rate being
similar for all three groups. There were remarkably few primary outcomes. Four children
were admitted for gastrointestinal (GI) bleeding, all of whom were in an ibuprofen
treatment group. All the bleeds were mild, not needing surgery or transfusion, and
responding to conservative management. This was a risk of GI bleeding of 7.2 per
100,000 courses of treatment. This rate was not significantly different from that in the
paracetamol group.
There were no episodes of renal failure, but because of concern that ibuprofen might
increase the risk of milder renal impaimmi, Lhr: Study aulhors searched tiit. medical
records of 288 hospitalised children for blood urea nitrogen (BUN) and creatinine levels
on, or within 24 hours of admission. The three treatment groups did not differ
significantly in either measurement. It is concluded that the short-term use of ibuprofen
does not increase the risk of renal impairment relative to that of paracetamol.
Hospitalisation for cellulitis or for abdominal pain did not vary significantly for each of
the three treatment groups. Physician visits to children with abdominal pain after
analgesics ranged from 1 I O to 120 per 100,000 treatments, the differences between the
randomised groups being insignificant.
There were 1879 asthmatic children in this study and data from this population were
examined. There was no difference in the risk of hospitalisation due to asthma between
ibuprofen and paracetamol (Relative Risk [RR] = 0.63). There was no difference in the
risk of adverse events related to asthma occurring in asthmatic children treated with
u
Application for Inclusion of Oral Ibuprofen Suspension T o The WHO Model List of Essential Medicines
ibuprofen or paracetamol. The risk of hospitalisation due to asthma in the ibuprofen
group was less than 0.09%. There was a similar result among children treated for fever
with paracetamol. Further to this, outpatient physician visits for asthma were less
common in the ibuprofen treated children (RR = 0.56) than the paracetamol treated
children. This could suggest a beneficial anti-inflammatory effect of ibuprofen in
asthmatic children
The results from the Childrens Analgesic Medicine Project (CAMP)’ complements these
results. It was a multicentre open label prospective study comparing the safety of
ibuprofen suspension with paracetamol suspension in children with fever and/ or pain.
The intent of the study was to document clinical prescribing practices and patient use of
the medicines in a naturalistic setting outside the restrictions of a randomised clinical
trial. The trial also examined whether the use of childrens ibuprofen created a higher risk
for either serious or non serious AEs relative to paracetamol. 424 paediatricians enrolled
4 i ,8 i 0 chiidren aged I month to 18 years at 69 US clinics.
A total of 30,144 children took at least one dose of either drug and were included in the
analysis. Approximately 20,000 were treated with ibuprofen and 10,000 treated with
paracetamol. There was no increased incidence of serious AEs with either drug. For both
age groups there were no serious AEs that occurred in 2 1% of treated subjects. There
were no cases of Reyes Syndrome, anaphylaxis, renal failure, gastric bleeding,
necrotising fasciitis, Stevens Johnson Syndrome or any other serious disease related to
the use of either drug. Four,children died during the trial, all occurring in children < 2
years. The deaths were judged not to be related to participation in the study. The deaths
were attributed to Herpes encephalitis, sepsis due to S.pnentoniae, medullo blastoma, and
sudden infant death syndrome. There was a slightly higher overall incidence of AEs with
the ibuprofen group14.896 1’s 12.996. This may have been due to the preference of the
physicians to treat sicker children with ibuprofen as well as the disproportionate use of
Application for Inclusion o f Oral Ibuprofen Suspension To The WHO Model List ofEssentia1 Medicines
ibuprofen increasing the likelihood of observing AEs within the ibuprofen treatment
group.
The absence of both serious AEs and rare non-serious events confirms the safety of
ibuprofen suspension in children of all ages. Overall ibuprofen exhibited a similar AE
profile to paracetamol.
A recent meta-analysis" by Dr David Perrott and his colleagues from Sydney Childrens
hospital further supports these result. They performed a meta-analysis to investigate the
relative efficacy of the two drugs in treating pain, fever and their safety compared with
each other and placebo.
Electronic databases were searched from their inception until May 2002 for randomised
controlled trials of ibuprofen and paracetamol for paediatric pain and fever. 127 studies
of potential relevance were identified and 17 blinded randomised controlled trials with
chiidren aged less tinan 18 years, receiving eirher drug to treat fever or moderate IO severe
pain were selected. All 17 data sets were used for the analysis on safety.
The principal outcome measure for safety was the risk ratio for minor and major harm for
ibuprofen vs paracetamol treatment. Minor harm was defined as the occurrence of an AE
not leading to withdrawal from the study such as nausea or sweating. The risk ratio for
minor harm was calculated by dividing the number of minor harm events per patient for
the ibuprofen treatment arm by the corresponding figure for the paracetamol treatment
arm.
Major harm was defined as the occurrence of an AE causing withdrawal from the study
such as abdominal pain or vomiting. The risk ratio for major harm was calculated by
dividing the proportion of patients experiencing major harm of minor harm in the
ibuprofen rreatment ann by the corresponding proportion in the paracetamol treatment
Application for lnclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
arm. The risk ratios for minor and major harm for each drug compared with placebo was
also calculated
For the minor and major harm analyses, a risk ratio of 1 indicated that the drugs did not
differ in safety. Risk ratios greater than 1 indicate that ibuprofen was less safe than
paracetamol, and values less than 1 indicate tlic converse.
' h e point-estimate for the risk ratio was 0.96 (0.68-1.36) for minor hami and 1.00 (0.55-
1.82) for major harm. As the 95% CIS contained values on either side
of 1 .00, these data provide no clear evidence that the dniys differed from each other in
safety. There was also no evidence that the risk ratio varied in magnitude across the
individual studies
i. Nine studies reported minor and major harm data for a placebo arm. I hese data were
used tc calculate risk ratios for minor and major harm compared with placebo. For minor
harm. rhc risk r:ltio for paracetamol :s p!acebo was 0.79 (YJYOLI. 0.42 -i .48); the risk
ratio for ibuprofen vs placebo was 1.17 (95% C1. 0.68-2.03). For major harm, the risk
ratio for paracetamol vs placebo was 0.90 (95% CI_ 0.25- 3.29); the risk ratio for
ibuprofen vs placebo was 1.51 (95% CI. 0.45-5.05). Although for both minor and major
harm the risk ratic point-estimatcs were closc to i for both drug placebo comparisons, the
\\-idth of the 05% CIS suggests that these data are inconclusive as to safety. especially for
major harm.
,_-",<.
In summary these data do not provide any evidence to suggest that treatment with
ibuprofen and paracetamol are less safe than each other or placebo. ie both were more
effective than placebo and equally safe at the studied dosages. In addition the wide
therapeutic index of ibuprofen is also beneficial. The therapeutic index of ibuprofen is 20
(therapeutic dose of 10 mglkg and toxic dosc is between 300 and 400 mg/kg). By
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
contrast. the therapeutic indcx of paracetamol is only about 10 (therapeutic dose of 15
Drug Highest cost (US$/ml)
mg/kg and toxic dose of 150 mg/kg). Ibuprofen therefore has a therapeutic index at least
twice as high as that of paracetamol, w-hich is already licensed for children from 3
months. Unlike aspirin and paracetamol, the effects of ibuprofen in overdose are
predictable from its pharmacology at therapeutic doses. The large majority of patients
who take an overdose of ibuprofen suffer no symptoms or only mild symptoms".
Additionally in the developing world there are many children who are malnourished and
therefore will have depleted glutathione storages resulting in an increased risk of
hepatotoxicity related to acetaminophen
Lowest Cost Median Cost (US$/ml) (US$/rnl)
Summary of available data on comparative cost and cost-effectiveness within the
pharmacological class or therapeutic group.
The costs for ibuprofen and paracetamol have been sourced from the International Drug
Price Indicator Gdide (accessible fr=m the Wor!d wide Web) and were taken on 25'"
October 2004. The cost of ibuprofen has been provided and also the cost of paracetamol
to enable comparison. Since this is an application for paediatric ibuprofen then the costs
of suspension have been used.
Paracetamol 0.0086 0.0006 0.0032
I I I I ~l Ibuprofen 0.0025 0.0105
In order to give a comparative cost the maximum possible dose that a child could take for
a self-limiting illness has been used.
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
Drug
Paracetamol
______ Maximal daily Cost per ml Total cost pcr dose for 16 year (USYml) day treatment old child (US$) _ _ _ _ _ _ ~ ~ 49 0.0032 7
I Ibuprofen 1 0.630
Summary of regulatory status of the medicine
Ibuprofen is available for paediatric use, either with or without medical prescription, in
more than 6 1 countries. They include the following: Argentina, Austria, Australia,
Bulgaria, Botswana, Belgium, Brazil, Canada, China Colombia, Cyprus, Czech Republic,
Denmark, Finland, Egypt, France, Georgia, Germany, Greece, Hong Kong, Hungary,
India, Indonesia. Ireland. Israel, Italy, Japan, Jordan, Kazakhstan, Lebanon, Luxembourg,
Malaysia. Malta, Mexico, Morocco, Namibia. Netherlands: New Zealand, Philippines,
Poland, Puerto Rico, Portugal, Romania, Russia, Saudi Arabia, Serbia, Singapore, Slovak
Republic, South Africa. South Korea, Spain, Sweden, Swaziland, Taiwan, Thailand,
Turkey, United Kingdom, Ukraine, USA, Uzbekistan and Venezuela.
Availability of pharmacopoeial standards
A monograph for ibuprofen is available in the British Pharmacopoeia, European
Pharmacopoeia and the United States Pharmacopoeia. Ibuprofen tablets are also listed in
the International Pharmacopoeia.
Applicat ion f o r Inclusion of O r a l Ibupro fen Suspens ion To The WHO Model List of Essent ia l Medicines
PROPOSED TEXT FOR WHO MODEL FORMULARY
Paediatric Ibuprofen Suspension
Oral suspension 20mg/ml
Uses:
pyrexia
Contraindications:
Patients with a known hypersensitivity to ibuprofen or any other constituent of the medicinal product.
Patients with a history of bronchospasm, asthma, rhinitis, or urticaria associated with aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
Patients with a history of, or existing gastrointestinal ulceration or bleeding.
Patients with severe hepatic failure, severe renal failure or severe heart failure
During the last trimester of pregnancy.
Precautions:
Caution is required in patients wirh:
undesirable effects section) systemic lupus erythematosus as well as those with mixed connective tissue disease (see
gastrointestinal disorders and chronic inflammatory intestinal disease (ulcerative colitis,
hypertension andor cardiac impairment
renal impairment
hepatic dysfunction
dehydration
Crohn's disease)
Bronchospasm may be precipitated in patients suffering from, or with a history of, bronchial asthma or allergic disease.
The elderly are at increased risk of the consequence of adverse reactions.
Undesirable effects may he rniniinised by using the minimum effective dose for the shortest possible duration.
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
There is some evidence that drugs which inhibit cyclo-oxygenasel prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.
Age Average weight (kg) Unit dose & frequency in 24 hours
(approx) Babies 3-6 months 5.6-7.6 2.5 m l 3 times aday
Babies 6-12 months 7.7-9 2.5 ml3-4 times a day
Children 1-3 years 10-15 5 m13 times a day
Children 4-6 years 16-20 7.5 m13 times a day
Children 7-9 years 2 1-79 10 m13 times a day
Children 10-12 years 30-40 /15ml3 timesaday I I
Dosage: The dosage detailed in the table below is based on a dose of 20-30mg/kg daily or 7.5-lOmg'kg
per single dose.
Doses should be given approximately every 6-8 hours, or with a minimum interval of 4 hours
between each dose
I
Reiial and Urinary Very rare: Disorders
Decrease of urea excretion and oedema can occur. Also. acute renal failure. Papillarq. necrosis, especially in long-
iterm use, and increased serum urea concentrations have
Undesirable Effects
The list of the following adverse cffects relates to those experienced with ibuprofen
Gastrointestinal
Disorders Rare: diarrhoea, flatulence, constipation and vomiting
perforation can occur.
I Nervous System Uncommon: Headache Disorders
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
Hepatobiliary Very rare: liver disorders, especially in long-term treatment. Disorders
Blood and V q rare: haematopoietic disorders (anaemia, leucopenia, Lymphatic system thrombocytopenia, pancytopenia, agranulocytosis). First Disorders signs are: fever, sore throat, superficial mouth ulcers, flu-
like symptoms, severe exhaustion, nose and skin bleeding.
Skin severe forms of skin reactions such as erythema multiforme Subcutaneous and epidermal necrolysis can occur. Disorders
Immune System Very rare: In patients with existing auto-immune disorders (such as Disorders systemic lupus erythematosus, mixed connective tissue
disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed
and Very rare:
~~~
Hypersensitivity Uncommon: Hypersensitivity reactions with urticaria and pruritus. Reactions severe hypersensitivity reactions. Symptoms could be:
facial, tongue and larynx swelling, dyspnoea, tachycardia, ,hypotension, (anaphylaxis, angioedema or severe shock).
Very rare
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
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2. Amdekar YK, Desai RZ. Antipyretic efficacy of ibuprofen and paracetamol in children with pyrexia. Br J Clin Pract 1985;39:140-143.
3. Ashraf E, Ford L, Geetha R, Cooper S. Safety profile of ibuprofen suspension in young children. Inflammopharmacology 1999, 7: (3), 219-225
4. Autret E, Breart G, Jonville AP, Courcier S, Lassale C, Goehrs JM. Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen syrup in children with pyrexia associated with infectious diseases and treated with antibiotics. Eur J Clin Pharmacol 1994;46: 197-201.
5. Autret E, Reboul-Marty J, Henry-Launois B, Laborde C, Courcier S , Goehrs JM, Languillat G, Launois R. Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever. Eur J Clin Pharmacol 1997;51:367-371.
6. Dani C, Bertini G et al. Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants. Acta Paediatr. 2000;89(11): 1369-74.
7. Goldman RD, KO K, Linen LJ, Scolnik D. Antipyretic efficacy and safety of ibuprofen and acetaminophen in children. Ann Pharmacother. 2004 Jan;38(1):146-50.
8. Guyton A, Hall J (eds), Textbook of medical physiology, 9th edn, W.B. Saunders Company, ch 3 1
9. Heremans G, Dehaen F, Rom N, Ramet J, Verboven M, Loeb H. A single-blind parallel group study investigating the antipyretic properties of ibuprofen syrup versus acetylsalicylic acid syrup in febrile children. Br J Clin Pract 1988;42:245-247.
10. Heyman E, Morag I. Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study. Pediatrics 2003; 112(5):354-8.
11. Joshi YM, Sovani VB, Joshi VV, Navrange JR, Benakappa DG, Shivananda P, Sankaranarayanan VS. Comparative evaluation of the antipyretic efficacy of ibuprofen and paracetamol. Indian Pediatr 1990;27:803-806.
12. Kandoth PW- Joshi MK. Joshi VR. Satoskar RS. Comparative evaluation of antipyretic activity of ibuprofen and aspirin in children with pyrexia of varied aetiology. .I Int Med Res 1984;12:292-297.
!3. Kauffman RE. S a y e r LA. Scheinbaum ML. .4ntipyretic efficacy o f ibuprofen vs acetaminophen. Am J Dis Child 1992;146:622-625.
c Application for Inclusion of Ordl Ibuprofen Suspension To The WHO Model List of Essential Medicines
14. Keinanen-Kiukaanniemi S. Simila S, Kouvalainen K. Oral antipyretic therapy. Evaluation of the propionic acid derivatives ibuprofen, ketoprofen, fenoprofen and naproxen. Paediatr Paedol 1980;15:239-244.
15. Kelley MT, Walson PD, Edge JH, Cox S, Mortensen ME. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther 1992;52: 18 1-1 89.
16. Khubchandani RP, Ghatikar KN, Keny S, Usgaonkar NGS. Choice of antipyretic in children. J Assoc Physicians India 1995;43:614-616
17. Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia 0. Safety and efficacy of ibuprofen vs indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur .I Pediatr 200;161 (4): 202-7.
18. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. J A M . 1995 273(12):929-33.
19. Lesko SM, Mitchell AA. Renal function after short-term ibuprofen use in infants and children. Pediatrics. 1997 100(6):954-7.
20. Lesko and Mitchell, The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics. 1999 Oct;104(4):e39.
21, Lesko SM, The safety nf ibuprafen suspension in childreii. In! J Clin Pract Suppl, 2003 Apr(135):
22. McIntyre J, Hull D. Comparing efficacy and tolerability of ibuprofen and paracetamol in fever. Arch Dis Child 1996;74:164-167.
23. Nahata MC, Powell DA, Durrell DE, Miller MA, Gupta N. Efficacy of ibuprofen in pediatric patients with fever. Int J Clin Pharmacol Ther Toxicol 1992;30:94-96.
24. Pelen F, Verriere F, Cournot A. [Nureflex children and nurslings' (ibuprofen 10 my/kg) in fever in the hospitalized child: a multicenter trial of acceptability, tolerance and efficacy (intermediate analysis)] (abstract). Arch Pediatr (Fr.) 1997;4 (suppl. 2):223S.
25. Perrott DA, Piira T, Goodenough B, Champion D. Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis. Arch Pediatr Adolesc Med 2004 158 (6), 521-6
26. Phadke MA, Paranjape PV, Joshi AS. Ibuprofen in children with infective disorders - antipyrctic efficacy. Br J Clin Pract 1985;39:437-440.
27. Purssell E. Treating fever in children: paracetamol or ibuprofen?.Br J Community Nurs. 2002 Jun:7(6):? 16-20.
28. Rang H. Dale bl , Ritter J jeds), Pharmacology, 3rd edn. Churchill Livingstone. ch 12
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
29. Romagnoli C, De Carolis MP, Papacci P, Polimeni V, Luciano R, Piersigilli F, Delogu AB et al. Clin Pharmacol Ther 2000 ; 67(6) : 676-83.
30. Schachtel BP, Thoden WR. A placebo-controlled model for assaying systemic analgesics in children. Clin Pharmacol Ther 1993;53:593-601..
31. Sidler J, Frey B, Baerlocher K. A double-blind comparison of ibuprofen and paracetamol in juvenile pyrexia. Br J Clin Pract 199O;Suppl. 70:22-25.
32. Simila S, Kouvalainen K, Keinanen S. Oral antipyretic therapy. Evaluation of ibuprofen. Scand J Rheumatol 1976;5:81-83.
33. Supapannachart S, Limrungsikul A, Khowsathit P. Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomised trial at Ramathibodi Hospital. J Med Assoc Thai 2002 Nov; 85 Suppl4, S1252-8
children with fever. J-Clin-Pharmacol, 2000 40:9;1053,
Pharmacokinetic-Pharmacodynamic Modelling of the antipyretic effect of two oral formulations of ibuprofen. Clin Pharmacokinetic 2000, Jun 38 (6) 505-518.
36. Van Esch A, Van Steensel-Moll HA, Steyerberg EW, Offringa M, Habbema JDF, Derksen-Lubsen G. Antipyretic efficacy of ibuprofen and acetaminophen in children wit!i febrile seizures. 3 r c h Pediatr A#dolesc Med 1995;14?:632-637.
37. Van Overmeire B. The use of ibuprofen in neonates in the treatment ofpatent ductus arteriosus. Int J Clin Pract 2003; Suppl 135: 23-27
38. Varvarigou A, Bardin CL et al. Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. JAMA. 1996 Feb 21;275(7):539-44
39. Vauzelle-Kervroedan F, d'Athis P, Pariente-Khayat A, Debregeas S, Olive G, Pons G. Equivalent antipyretic activity of ibuprofen and paracetamol in febrile children. J Pediatr 1997;131:683-687.
40. Vinh H, Parry CM et al. Double blind comparison of ibuprofen and paracetamol for adjunctive treatment of uncomplicated typhoid fever. Pediatr-Infect-Dis-J 2004: 23:
41. Volans G. Monaghan J, Colbridge M. Ibuprofen overdose. Int J Clin Pract Suppl.
12. Wahba H, The .4ntipyretic Effect of Ibuprofen and Acetaminophen in Children,
43. Walson PD, Galletta G. Braden NJ, Alexander L. Ibuprofen, acetaminophen, and
34. Thoden-W-R, Bomhofen-J. Antipyretic efficacy of ibuprofen and acetaminophen in
35. Troconiz IF,Armenteros S, Planelles MV, Benitez J, Calvo R, Dominguez-R.
226-230.
2003 Apr(135):54-60
Pharmacotherapy 2004; 24: 280-284
piacebo treatment o t febrile children. Clin Pharmacoi 'rher 1989;46:9-17.
q s s - I Application for Inclusion of Oral Ibuprofen Suspension
To The WHO Model List of Essential Medicines
44. Walson PD, Ibuprofen versus paracetamol for the treatment of fever in children. Br Clin Pract Suppl. 1990 Aug;70: 19-2 1.
45. Walson PD, Galletta G, Chomilo F, Braden NJ, Sawyer LA, Scheinbaurn ML Comparison of multidose ibuprofen and acetaminophen therapy in febrile children. Am J Dis Child. 1992;146(5):626-32.
46. Wilson G, Guerra, AJMS, Santos NT. Comparative study of the antipyretic effect of ibuprofen (oral suspension) and paracetamol (suppositories) in paediatrics. J Int Med Res 1984;12:250-254,
47. Wilson JT, Brown RD, Kearns GL, Eichler VF, Johnson VA, Bertrand KM, Lowe BA. Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen in children. J Pediatr 1991;119:803-811.
48. Wong A, Sibbald A et al. Antipyretic effects of dipyrone versus ibuprofen versus acetaminophenin children: results of a multinational, randomized, modified double- blind study. Clin-Pediatr.2001 4016 (3 13-324)
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
APPENDIX I ELECTRONIC SEARCH STRATEGY AND RESULTS
OCTOBER 2004
!'
ELECTRONIC SEARCH STRATEGY AND RESULTS OCTOBER 2004
I MEZZ 2 MEZZ 3 MEZZ
4 MEZZ 5 MEZZ
6 MEZZ 7 MEZZ 8 MEZZ 9 MEZZ 10 MEZZ I I MEZZ 12 MEZZ 13 MEZZ 14 MEZZ 15 MEZZ
16 MEZZ 17 MEZZ
I S MEZZ 19 MEZZ 20 MEZZ 21 MEZZ 22 EMZZ 23 EMZZ 24 EMZZ
25 EMZZ 26 EMZZ
27 EMZZ 28 EMZZ 29 EMZZ 30 EMZZ 31 EMZZ 32 EMZZ 33 EMZZ 34 EMZZ jj EMZZ 36 EM22
5686 IBUPROFEN 157 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 25 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACID
1692062 (CHILD$? OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$I)
545 4 AND 5 124438 PYREXI$l OR FEVER$3 OR HYPERTHERMI$ 4168 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$l) 167 ANTIPYRESIS OR (ANTI ADJ P Y E S I S )
81 634 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 181049 7 OR 8 O R 9 OR 10
5722 1 OR 2 OR 3
1 4 6 6 A N D I I
95 12 AND 13 2638 4.TL OR 4.MJ.
216648 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR (CLIN ADJ TRIAL).DE.
0 CLINICAL-TRIAL# 129709 (RANDOMIZ$ OR RANDOMIS$) NEAR (TRIAL$l OR STUDY OR
95851 DOUBLE ADJ BLIND$2 332298 15 OR 16 OR I7 OR 18
STIJDIES,!
37 14 AND 19 58 14 NOT 20
17528 IBUPROFEN I834 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 29 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACID
1029887 (CHILD$3 OR INFANT$l OR PAEDIATRIC$I OR PEDIATRIC$I)
17543 22 OR 23 OR 24
1762 25 AND 26 104267 PYREXI$I OR FEVER$3 OR HYPERTHEMI$ 4167 ANTIPYRETIC$I OR (ANTI .4DJ PYRETIC$I)
71 538 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 1 3 0 3 2 8 2 8 O R 2 9 O R 3 0 O R 3 1
148 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
387 27 AND 32 7513 25.TI. OR25.MJ. I39 33 AND 34
356607 (CLINICAL ADJ TRIALS]) OR CLINICAL-TRIALS# OR
37 EMZZ 38 EMZZ
39 EMZZ 40 EMZZ 41 EMZZ 42 EMZZ 43 DDNS 44 DDNS 45 DDNS
46 DDNS 47 DDNS
48 DDNS 49 DDNS 50 DDNS 51 DDNS 52 DDNS 53 DDNS 54 DDNS 55 DDNS 56 DDNS 57 DDNS
58 DDNS 59 DDNS
60 DD~NS 61 DDNS 62 DDNS 63 DDNS 64 IPAB 65 IPAB 66 IPAB
67 IPAB 68 IPAB
69 IPAB 70 IPAB 71 lPAB 72 IPAB 73 IPAB 74 IPAB 75 IPAB 76 IPAB 77 IPAB 78 IP.AB
(CLIN ADJ TRIAL).DE. 342290 CLINICAL-TRIAL# 150262 (RANDOMIZ$ OR RANDOMISS) NEAR (TRIAL$I OR STUDY OR
S9379 DOUBLE ADJ BLIND$2 455058 36 OR 37 OR 38 OR 39
STUDIES)
55 35 AND 40 134 35 NOT 41
8106 IBUPROFEN 41 4 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL
3 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ ACID
8122 43 OR 44 OR 45 68643 (CHILD$3 OR MFANT$l OR PAEDIATRIC$I OR
PEDIATRIC$l) 604 46 AND 41
26030 PYREXI$l OR FEVERS3 OR HYPERTHERMIS 34747 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$l)
9860 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 65053 49 OR 50 OR 51 OR 52
236 48 AND 53 8122 46.TI. OR 46.MJ. 236 54 AND 55
58 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
195988 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR (CLIN ADJ TRIAL).DE.
0 CLINICAL-TRIAL# 75302 (RANDOMIZS OR RANDOMISS) NEAR (TRIALS1 OR STUDY OR
68043 DOUBLE ADJ BLINDTI 2 1 8 8 1 8 5 7 O R S 8 O R 5 9 O R 6 0
STUDIES)
79 56 AND 61 157 56 NOT 62
1499 IBUPROFEN 136 NUROFEN OR BRUFEN OR iviOTWI OR ADVIL 5 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPlONIC ADJ
AClD
23055 (CHILD$3 OR INFANT$I OR PAEDIATRIC$l OR PEDIATRIC$l)
1502 64 OR 65 OR 66
89 67 AND 68 3 173 PYREXI$I OR FEVER$3 OR HYPERTHERMI$ 9787 ANTIPYRETIC31 OR (ANTI ADJ PYRETIC$I)
973 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE
47 69 AND 74
47 75 AND 76
18 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
13339 70 OR 71 OR 72 OR 73
1502 67.TI. OR 67.MJ.
7342 (CLINICAL ADJ TRIALSI) OR CLINICAL-TRIALS# OR (CLIN ADJ TRIAL).DE.
79 IPAB SO IPAB
S I IPAB 82 IPAB 83 IPAB 84 !PAR 85 BlZZ 86 BIZZ 87 BIZZ
88 BIZZ 89 BIZZ
90 BIZZ 91 BIZZ 92 BIZZ 93 BIZZ 94 BIZZ 95 BIZZ 96 BIZZ 97 BIZZ 98 BIZZ 99 BIZZ
100 BIZZ 101 BIZZ
102 BIZZ IO3 BIZZ 104 BIZZ 105 BIZZ 106 LINE 107 LINE 108 LINE
IO9 LINE 110 LINE
1 1 1 L N ? 112 LINE 113 LINE 114 LINE 115 LINE I I6 LINE 117 LINE I 1 8 LINE 119 LINE 110 LINE
121 LINE
0 CLINICAL-TRIAL# I1 157 (RANDOMIZ$ OR RANDOMISQNEAR (TRIAL$I OR STUDY OR
IO807 DOUBLE ADJ BLIND$? STUDIES)
23155 78 OR 79 OR 80 OR 81 1 I 77 AND 82 36 11 NOT 83
133 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 37 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
6900 lBUPROFEN
ACID
1035852 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$ I)
544 88 AND 89 140310 PYREXI$I OR FEVER$3 OR HYPERTHEMI$ 4220 ANTIPYRETIC$l OR (ANTI ADJ PYRETIC$l)
26927 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 162009 9 1 OR 92 OR 93 OR 94
6962 85 OR 86 OR 87
I 81 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
131 90 AND 95 6962 %.TI. OR 8S.MJ. 131 96 AND 97
71780 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR (CLIN ADJ TRIAL).DE.
0 CLINICAL-TRIAL# 78451 (RANDOMIZ$ OR RANDOMIS$) NEAR (TRIAL$I OR STUDY OR
STUDIES) 56884 DOUBLE ADJ BLIND$? I66927 9 9 0 R 100 OR IO1 OR IO2
30 98 AND 103 101 98NOT 104 850 IBUPROFEN
6 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 0 '2' ADJ '4' ADJ ISOBLITYLPHENYL ADJ PROPIONIC ADJ
ACID 851 I06 OR IO7 OR 108
19001 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$I)
124 IO9 AND 110 2466 PYREXI$I OR FEVER$3 OR HYPERTHERMI$
88 ANTIPYRETIC$l OR (ANTI ADJ PYRETIC$I) 4 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
592 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 2825 1 12 OR I I3 OR 1 I4 OR 115
37 I l l AND 116 851 109.TI. OR 109 MJ. 37 I17 AND 1 I S
(CLIN ADJ TRIAL).DE. 11718 (CLINICAL 4DJ TRIAL$I) OR CLINICAL-TRIALS# OR
0 CLINICAL-TRIAL#
122 LEVE
123 LINE 124 LINE 125 LINE 126 LINE I27 ACZZ 128 ACZZ 129 ACZZ
130 ACZZ 131 ACZZ
132 ACZZ 133 ACZZ 134 ACZZ 135 ACZZ 136 ACZZ 137 ACZZ 138 ACZZ 139 ACZZ 140 ACZZ 141 ACZZ
142 ACZZ 143 ACZZ
144 ACZZ 145 ACZZ 146 ACZZ 147 ACZZ 148 AC89 149 AC89 150 AC89
I 5 1 AC89 152 AC89
153 AC89 154 AC89 155 AC89 156 AC89 157 AC89 158 AC89 159 AC89 160 AC89 161 AC89 162 AC89
163 AC89 164 AC89
1085 1 (RANDOM!Z$ OR RANDOMIS$) NEAR (TR!AL$ I OR STUDY OF. STUDIES)
735 DOUBLE ADJ BLIND$2 15984 l20OR121 O R 1 2 2 O R 1 2 3
7 I I9 AND 124 30 1 I9 NOT 125 2 1 19 IBUPROFEN
64 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 0 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPlONIC ADJ
ACID 2121 127 OR 128 OR I29
42552 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$l)
202 130AND 131 9557 PYREXI$I OR FEVER$3 OR HYPERTHERMI$ 9008 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$l)
2597 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 20062 133 OR 134 OR 135 OR 136
2121 I3O.TI. OR 130.MJ.
49037 (CLINICAL ADJ TRIAL$l) OR CLINICAL-TRIALS# OR
10 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
94 132 AND 137
94 138 AND 139
(CLIN ADJ TRIAL).DE. 0 CLINICAL-TRIAL#
63688 (RANDOMIZ$ OR RANDOMIS$) NEAR (TRIAL$I OR STUDY OR
33 179 DOUBLE ADJ BLIND$2 89757 141 OR 142 OR 143 OR 144
STUDIES)
30 I40 AND I45 64 140 NOT 146
446 IBUPROFEN 25 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 0 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACii) 446 148 OR 149 OR 150
2306 (CHILD$3 OR INFANT$I OR PAEDIATRlC$I OR PEDIATRICS 1)
43 151 AND 152 1867 PYREXI$l OR FEVER$3 OR HYPERTHERMB 125 ANTIPYRETIC$l OR (ANTI ADJ PYRETIC$l)
465 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 2159 154OR 155OR 156OR 157
446 IjI.T!.OR 151.MJ.
1055 (CLINICAL ADJ TRIAL$l) OR CLINICAL-TRIALS# OR
0 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
15 153 AND 158
15 159AND 160
(CLIN ADJ TRIAL).DE. 0 CLINICAL-TRIAL#
1584 (RANDOMES OR RANDOMIS$) NEAR (TRLAL$I OR STUDY OR
165 AC89 166 AC89 167 AC89 168 AC89 169 CDSR 170 CDSR 171 CDSR
172 CDSR 173 CDSR
174 CDSR 175 CDSR 176 CDSR 177 CDSR 178 CDSR 179 CDSR I 8 0 CDSR 181 CDSR 182 CDSR 183 CDSR
184 CDSR 185 CDSR
186 CDSR 187 CDSR 188 CDSR i s 9 CDSR 190 DARE 191 DARE 192 DARE
193 DARE 194 DARE
195 DARE 196 DARE 197 DARE 198 DARE 199 DARE 200 DARE 201 DARE 202 DARE 203 DARE 204 DARE
205 DARE 206 DARE
STUDIES) 4946 DOUBLE ADJ BLIND$2 6430 162 OR 163 OR 164 OR 165
6 161 AND 166 9 161 NOT 167 14 IBUPROFEN 0 NIJROFEN OR BRUFEN OR MOTKN OR ADVIL 0 '2' ADJ 'q ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
14 I69 OR I70 OR 171 ACID
619 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$I)
5 172AND 173 49 PYREXI$I OR FEVER$3 OR HYPERTHEMI$ 5 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$l) 0 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
21 FEVER# OR (BODY ADJ TEMPERATURE) O R FEBRILE 64 175 OR 176 OR 177 OR 178
1 174AND 179 4 172.TI. OR 172.MJ. 0 180AND 181
( C L N ADJ TRIAL).DE. 476 (CLINICAL ADJ TRIALS]) OR CLINICAL-TRIALS# OR
0 CLINICAL-TRIAL# 2063 (RANDOME$ OR RANDOMIS$) NEAR (TRIALS1 OR STUDY OR
STUDIES) I60 DOUBLE ADJ BLIND$:
2097 183 OR 184 OR 185 OR 186 0 152AND 187 0 i82NOT I88 26 IBUPROFEN 0 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 0 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
26 I90 OR 191 OR 192 790 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR
ACID
PEDIATRIC$I) 5 193 AND 194
66 PYREXI$I OR FEVER$3 OR HYPERTHEMI$ 3 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$I) 0 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
30 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 87 196 OR 197 OR 198 OR 199 2 195 AND 200
26 193 TI. OR 193.MJ. 2 201 AND 202
(CLIN ADJ TRIAL).DE. 1261 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR
0 CLINICAL-TRIAL$ 2696 (RANDOMIZ$ OR RANDOMISS) NEAR (TRIALS1 OR S rUDY OR
STUDLES)
207 DARE 496 DOUBLE ADJ BLIND$2 208 DARE 2907 204 OR 205 OR 206 OR 207 209 DARE 2 203 AND 208 210 DARE 0 203 NOT 209 211 BNID 12 IBUPROFEN 212 BNID 0 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 213 BNID
214 BNID 12211 O R 2 1 2 O R 2 1 3 21 5 BNID 10740 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR
216 BNID 5 2 1 4 A N D 2 1 5 2 17 BNID 218 BNID 6 ANTIPYRETIC$l OR (ANTI ADJ PYRETIC$]) 219 BNID 0 ANTIPYRESIS OR (ANTI ADJ PYRESIS) 220 BNID 236 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 221 BNID 222 BNID 3 216 AND 221 223 BNID 12 214.T1. OR214.MJ. 224 BNID 3 222 AND 223 225 BNID 187 (CLINICAL ADJ TRLAL$I) OR CLINICAL-TRIALS# OR
226 BNID 0 CLINICAL-TRIAL# 227 BNID
228 BNID 41 DOUBLE ADJ BLIND$2 229 BNID 981 225 OR 226 OR 227 OR 228 230 BNID 0 224 AND 229
232 "AH, 7 I8 IBUPROFEN 233 NAHL 26 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 234 NAHL
235 NAHL 729 232 OR 233 OR 234 236 NAHL 362745 (CHILD$3 OR INFANT$I OR PAEDIATRIC$i OR
237 NAHL 246 235 AND 236 238 NAHL 5243 PYREXBI OR FEVER$3 OR HYPERTHEMI$ 239 NAHL 187 ANTIPYRETIC$l OR (ANTI ADJ PYRETIC$I) 240 NAHL 37 ANTIPYRESIS OR (ANTI ADJ PYRESIS) 241 NAHL 3766 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 242 NAHL 7394 238 OR 239 OR 240 OR 241 243 NAHL 87 237 AND 242 244 NAHL 179 235.TI. OR 235.MJ. 245 NAHL 20 243 AND 244 246 NAHL 38462 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR
247 NAHL 0 CLINICAL-TRIAL# 248 NAHL 33362 (RANDOMIZ$ OR RANDOMIS$) NEAR(TRIAL$I OR STUDY OR
249 NAHL 107345 DOUBLE ADJ BLIND$?
0 '2' ADJ '4' i\DJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ ACID
PEDIATRIC$I)
16 1 PYREXI$ 1 OR FEVER$3 OR HYPERTHEMI$
337 21 7 OR 21 8 OR 219 OR 220
(CLIN ADJ TRIAL).DE.
821 (RANDOME$ OR RANDOMIS$) NEAR (TRIAL$I OR STUDY OR STUDIES)
231 BNID 3 224 NOT 230
0 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ ACID
PEDIATRIC$I)
(CLIN ADJ TRIAL).DE.
STUDIES)
250 NAIHL 251 NAHL 252 NAHL 253 PASC 254 PASC 255 PASC
256 PASC 257 PASC
258 PASC 259 PASC 260 PASC 261 PASC 262 PASC 263 PASC 264 PASC 265 PASC 266 PASC 267 PASC
268 PASC 269 PASC
270 PASC 271 PASC 272 PASC 273 PASC 214 CBIB 275 CBIB 216 CBIB
277 CBIB 278 CBIB
279 CBIB 280 CBlB 281 CBIB 282 CBIB 283 CBIB 284 CBIB 285 CBlB 286 CBlB 287 CBIB 288 CBIB
289 CBlB 290 CBIB
291 CBlB 292 CBIB
21 I997 246 OR 247 OR 218 OK 249 I 1 245 AND 250
2495 IBUPROFEN 9 245 NOT 2.5 1
22 NUKOFEN OR BRUFEN OR MOTRIN OK ADVIL 15 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACID 2506 253 OR 254 OR 255
486254 (CHILD$3 OR INFANTK OR PAEDIATRIC$l OR PEDIATRIC$I)
221 256 AND 251 3 1032 PYREXI$I OR FEVER$3 OR HYPERTHERMI$ 2920 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$I)
13449 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 43586 259 OR 260 OR 261 OR 262
2506 256.TI. OR 256.MJ.
48466 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR
53 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
70 258 AND 263
70 264 AND 265
(CLIN ADJ TRIAL).DE. 0 CLINICAL-TRIAL#
57791 (RANDOMIZ$ OR RANDOMIS$) NEAR (TRIAL$I OR STUDY OR
36321 DOUBLE ADJ BLIND$2 110809 267 OR 268 OR 269 OR 270
STUDIES)
21 266AND271 49 266 NOT 272
3015 IBLTPROFEV 20 NUROFEN OK BRUFEN~ OR MOTTRIN OR ADVIL 19 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACID 3028 274 OR 275 OR 276
381606 (CHILD$3 OR INFANT$I ORPAEDIATRIC$I OR PEDIATRIC$I)
298 217 AND 278 35322 PYREXI$I OR FEVER$3 OR HYPERTHEMI$
841 ANTIPYRETIC$I OR (ANTI ADJ PYRETlC$l) 77 ANTIPYRESIS OR (ANTI ADJ P Y E S I S )
13 100 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 45444 280 OR 281 OR 282 OR 283
3028 277.TI. OR 277.MJ.
59901 ( C L N C A L ADJ TRIAL$l) OR CLINICAL-TRIALS# OR
88 279 AND 284
88 285 AND 286
(CLIN ADJ TR1AL):DE. 0 CLINICAL-TRIAL#
93814 (IWNDOMIZ$ OR RANDOMIS) NEAR (TRlAL$I OR STUDY OR
501 73 DOUBLE .4DJ BLIND$? STUDIES)
I61 2.53 288 OR 289 OR 290 OR 291
293 CBIB 294 CBIB 295 SCZZ 296 SCZZ 297 sczz 298 SCZZ 299 SCZZ
300 SCZZ 301 SCZZ 302 SCZZ 303 SCZZ 304 SCZZ 305 SCZZ 306 SCZZ 307 SCZZ 308 SCZZ 309 SCZZ
310 SCZZ 311 SCZZ
312 sczz 313 sczz 314 SCZZ 315 SCZZ 316
317 318 319
320 321
34 287 AND 292 54 287 NOT 293
7301 IBUPROFEN 68 NUROFEN OR BRUFEN OR MOTRIN OR ADVIL 29 '2' ADJ '4' ADJ ISOBUTYLPHENYL ADJ PROPIONIC ADJ
ACID 733 1 295 OR 296 OR 297
773408 (CHILD$3 OR INFANT$I OR PAEDIATRIC$I OR PEDIATRIC$ I )
667 298 AND 299 72500 PYREXI$I OR FEVER$3 OR HYPERTHEMI$ 1598 ANTIPYRETIC$I OR (ANTI ADJ PYRETIC$I) 169 ANTIPYRESIS OR (ANTI ADJ PYRESIS)
23 160 FEVER# OR (BODY ADJ TEMPERATURE) OR FEBRILE 91482 301 OR 302 OR 303 OR 304
146 300 AND 305 7331 298.TI. OR 298.MJ. 146 306 AND 307
89100 (CLINICAL ADJ TRIAL$I) OR CLINICAL-TRIALS# OR (CLIN ADJ TRIAL).DE.
0 CLINICAL-TRIAL# 144780 (RANDOMIZ$ OR RANDOMIS$) NEAR (TRIAL$l OR STUDY OR
75865 DOUBLE ADJ BLIND$2 250342 309 OR 310 OR 31 I OR 312
STUDIES)
47 308 AND 313 99308NOT314
370 ..COMBINE 20.41.62.83.104.125.146.167.1 88,209,2?0.251,772.293
194 DUPLICATES FROM STATEMENT 0316 176 KEPT FROM STATEMENT 03 16 803 ..COMBINE 21,42,63,84,105,126,147,168,189,~l0,23l,252,273,294 ,315
294 DUPLICATES FROM STATEMENT 0319 509 KEPT
,3 I4
FROM STATEMENT 03 19
Search line 318 - ibuprofen + fever + children + clinical trials 1 MEZZ
TI Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis.
2 EMZZ TI How safe is ibuprofen in febrile asthmatic children?
3 AC89 TI Carprofen: n new nonsteroidal antiinflammatory drug. Pharmacology,
clinical efficacy and adverse effects.
4 DARE
TI Treating fever in children: paracetamol or ibuprofen? (Structured abstract).
5 NAHL T1 Antipyretic efficacy and safety of ibuprofen and acetaminophen in
children.
6 PASC TI Comparison of Benzydamine hydrochloride and Salvia officinalis as an
adjuvant local treatment to systemic nonsteroidal anti-inflammatory drug in controlling pain after tonsillectomy, adenoidectomy, or both: An open-label, single-blind, randomized clinical trial.
7 MEZZ Tl Double blind comparison of ibuprofen and paracetamol for adjunctive
treatment of uncomplicated typhoid fever.
8 EMZZ TI Fever and pain: Ibuprofen suppositories for small children.
9 DDNS TI A meta-analysis comparison of ibuprofen (IBU) and indomethacin (INDO)
for closure of patent ductus arteriosus (PDA).
I O IPAB TI Multicenter parallel comparison of the efficacy and tolerability of
ibuprofen vs metaizole.
!! RIZZ TI Orai ibuprofen and intravenous indomethacin for treatment of patent
ductus arteriosus in newborn infants: retrospective study.
12 ACZZ TI Pragmatic randomised controlled trial of two prescribing strategies for
childhood acute otitis media.
13 AC89 TI Ibuprofen overdose and exposure in utero: results from a postmarketing
voluntary reporting system.
14 DARE TI The nursing management of fever in children: a systematic review
(Structured abstract).
15 NAHL TI Evidence-based practice. Alternating acetaminophen and ibuprofen in the
febrile child: examination of the evidence regarding efficacy and safety
16 MEZZ TI Asthma morbidity after the short-term use of ibuprofen in children.
17 DDNS TI Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in
combination for pediatric day-case adenoidectomy.
18 AC89 T! Hepatic toxicity of nonsteroid;! antiinflammatory drugs.
19 NAHL TI Ibuprofen was more protective against asthma morbidity than
acetaminophen in asthmatic children with fever.
20 MEZZ TI The safety of ibuprofen suspension in children
21 AC89 TI Suprofen.
22 MEZZ TI A general overview of the use of ibuprofen in paediatrics.
23 EMZZ TI The Antipyretic Effect of Ibuprofen and Acetaminophen in Children
24 DDNS TI Effects of postoperative, nonsteroidal, anti-inflammatory drugs on
bleeding risk after tonsillectomy. Meta-analysis of randomized, controlled trials.
25 IPAB TI Assessment of the safety of pediatric ibuprofen: practitioner-based
randomized clinical trial.
26 AC89 Ti Fentiazac suspension inthe treatment of acute inflammation of the upper
respiratory tract in children.
21 MEZZ TI Oral ibuprofen and indomethacin for treatment of patent ductus
arteriosus in premature infants: a randomized trial at Ramathibodi Hospital.
28 EMZZ TI Intramuscular dipyrone versus oral ibuprofen or nimesulide for reduction
of fever in the outpatient setting.
29 DDNS TI Evidence on the use of paracetamol i n febrile children
30 BlZZ TI Antipyretics in pediatric practice
31 AC89 TI Clinical pharmacokinetics of nonsteroidal antiinflammatory drugs.
32 NAHL TI A study of the efficacy of antipyretic drugs in the prevention of
febrile seizure recurrence.
33 CBIB TI Symptomatic intravenous antipyretic therapy: Efficacy of metamizol,
diclofenac, and propacetamol.
34 MEZZ TI Treating fever in children: paracetamol or ibuprofen?
35 DDNS TI Valdecoxib provides similar efficacy and improved upper GI safety
compared with nonspecific NSAIDs in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA).
36 IPAB TI Placebo-controlled model for assaying systemic analgesics in children
37 NAHL TI Paracetamol or ibuprofen in febrile children.
38 CBIB TI Comparison of oral versus normal and high-dose rectal acetaminophen in
the treatment of febrile children,
39 MEZZ TI Effectiveness and tolerability of ibuprofen-arginine versus paracetamol
in children with fever of likely infectious origin.
40 BIZZ TI How did such a bad report get published in the EJCP? Trial of
paracetamol, ibuprofen and nimesulide in children with upper respiratory infections (B. Ulukol et al., EJCP November 1999, 55: 615-618).
41 ACZZ
complications.
42 NAHL
TI Ibuprofen for tonsillectomy pain in children: efficacy and
TI Clinicians' forum. Managing a child's pain and fever.
43 MEZZ TI Antipyretic effects of dipyrone versus ibuprofen versus acetaminophen in
children results of a multinational, randomized, modified double-blind study.
44 DDNS TI Safety and efficacy of ibuprofen versus indomethacin in preterin infants
treated for patent ductus arteriosus: a randomised controlled trial.
45 NAHL TI Ibuprofen suspension: pediatric antipyretic.
46 PASC TI Treatment of fever : monotherapy with ibuprofen. Ibuprofen pediatric
suspension containing 100 mg/5 ml<SUP>(<SUP>*<SUP>), Multicentre acceptability study conducted in hospital.
Traitement de la fievre en monotherapie, ibuprofene suspension pediatrique a 100 mg/5 ml<SUP>(<SUP>*<SUP>), etude multicentrique d'acceptabilite menee en milieu hospitalier.
47 MEZZ
paracetamol.
48 DDNS
TI Antipyretic effects of nimesulide, paracetamol and ibuprofen-
TI Premarketing surveillance of oral ibuprofen solution in febrile children.
49 NAHL TI The many uses of ibuprofen
50 MEZZ TT (haluat ion of thc antipyretic safety and accuracy of TWO pediatric
ibuprofen formuiations).
51 EMZZ TI Ibuprofen versus paracetamol in febrile asthmatic children.
52 DDNS TI Double-blind, placebo-controlled analgesic study of ibuprofen or
rofecoxib in combination with paracetamol for tonsillectomy in children
53 NAHL
children's fever. TI Pediatric ibuprofen: researchers study safety of ibuprofen use for
54 CBlB TI Antipyretic efficacy of an initial 30-mdkg loading dose of
acetaminophen versus a 15-mgkg maintenance dose.
55 MEZZ TI Pharmacokinetic-Pharmacodynamic Modelling of the antipyretic effect of
two oral formulations of ibuprofen.
56 EMZZ
TI !buprofen in !iquid form fer the treatment of fever and pain in children.
57 DDNS TI Reactogenicity of DTPa-HBVIHib vaccine administered as a single
injection vs DTPa-HBV and Hib vaccines administered simultaneously at separate sites, to infants at 2, 4 and 5 months of age.
58 MEZZ TI Parents' fear regarding fever and febrile seizures.
59 EMZZ TI lbuprofene in pediatrics
60 DDNS TI Analgesia after ambulatory amygdalectomy in the child. Comparison
between tramadol and propacetamol-paracetamol. (Fr.).
61 PASC TI Tube placement : A prospective, randomized double-blind study
62 MEZZ
two years old.
63 DDNS
TI The safety of acetaminophen and ibuprofen among children younger than
TI A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus.
64 CEiE TI Acetaminophen controlled-release sprinkles versus acetaminophen
immediate-release elixir in febrile children.
65 SCZZ TI Over-the-counter analgesics and antipyretics: A critical assessment.
66 MEZZ
counter dose.
67 EMZZ
TI Gastrointestinal safety and tolerance of ibuprofen at maximum over-the
TI Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella.
68 DDNS TI Pharmacokinetic-pharmacodynamic modelling of the antipyretic effect of 2
oral formulations of ibuprofen.
69 MEZZ TI Towards evidence based emergency medicine: best BETS from the Manchester
Royal Infirmary. Paraceramol or ibuprofen in febrile children.
70 BIZ2 TI Antipyretic therapy: Clinical trials 1990 through 1995
71 CBIB TI Morphine-sparing effect of acetaminophen in pediatric day-case surgery.
72 MEZZ TI Randomized. controlled trial of ibuprofen syrup administered during
febrile illnesses to prevent febrile seizure recurrences.
13 EMZZ
care setting.
74 DDNS
TI The antipyretic use of acetaminophen versus ibuprofen in a pediatric
TI Renal safety profile of rofecoxib, a specific inhibitor of COX-2, in controlled clinical trials.
75 CBIB TI Acetaminophen has greater antipyretic efficacy than aspirin in
endotoxemia: A randomized, double-blind, placebo-controlled trial,
76 MEZZ TI Equivalent antipyretic activity of ibuprofen and paracetamol in febrile
children.
I1 DDNS TI Effects of indomethacin and ibuprofen on mesenteric and renal blood flow
in preterm infants with patent ductus arteriosus.
78 MEZZ TI Renal function after short-term ibuprofen use in infants and children
79 EMZZ TI Safety profile of ibuprofen suspension in young children.
80 CBIB TI Treatment of fever: monotherapy with Ibuprofen. Ibuprofen pediatric
suspension containing 100 mg 5 ml, multicentre acceptability study conducted in hospital.
81 MEZZ T1 A comparison of ibuprofen versus acetaminophen with codeine in the young
tonsillectomy patient.
82 EMZZ TI Assessment of the efficacy and safety of paracetamol. ibuprofen and
nimesulide in children with upper respiratory tract infections.
83 MEZZ
TI Eva!uation of ibuprofen ve r su aspirin and paracetamol on efficacy and comfort in children with fever.
84 EMZZ TI Ibuprofen or acetaminophen for management of fever in children?
85 CS!B TI What we don't know about paracetamol in children
86 MEZZ TI Comparing efficacy and tolerability of ibuprofen and paracetamol in
fever.
87 ACZZ TI Ibuprofen or acetaminophen for the acute treatment of migraine in
children: a double-b!ind, randomized, placebo-controlled, crossover study.
88 MEZZ TI When a randomised controlled trial is needed to assess drug safety. The
case of paediatric ibuprofen.
89 DDNS TI Treatment of pain with sustained-release tramadol 100, 150, 200 rng:
results of a post-marketing surveillance study.
90 CBIB TI Antipyretic activity and safety of ibuprofen tablets in the treatment of
fever in adults: Multicentre study among general practitioners.
91 MEZZ
febrile seizures. TI Antipyretic efficacy of ibuprofen and acetaminophen in children with
92 EMZZ TI Integrated pharmacokinetic-pharmacodynamic model for acetaminophen,
I
ibuprofen, and placebo antipyresis in children.
93 CBIB TI Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children.
94 MEZZ TI An assessment of the safety of pediatric ibuprofen. A practitioner-based
randomized clinical trial.
95 EMZZ TI Paracetamol and ibuprofen for treatment of fever in Malawian children
aged less than five years.
96 BIZZ
TI CLINICAL AND LABORATORY OBSERVATIONS RANDOMIZED DOUBLE-BLIND MULTICENTER
CONTROLLED TRIAL OF IBUPROFEN VERSUS ACETAMINOPHEN
PLACEBO FOR TREATMENT OF SYMPTOMS OF TONSILLITIS AND
CHILDREN.
97 ACZZ
PARACETAMOL AND
PHARYNGITIS IN
TI Renal function following short-term ibuprofen use in febrile children
98 MEZZ TI Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen
syrup in children with pyrexia associated with infectious diseases and treated with antibiotics.
99 EMZZ TI Treatment of fever: Monotherapy with ibuprofen. Ibuprofen pediatric
suspension containing 100 mg/S rnl(*), multicentre acceptability study conducted in hospital.
100 DDNS TI The effect of nonsteroidal antiinflammatory drugs on electrolyte
homeostasis and blood pressure in young and elderly persons with and without renal insufficiency.
101 MEZZ TI Efficacy of ibuprofen in pediatric patients with fever.
102 EMZZ TI Temperature, age, and recurrence of febrile seizure.
103 DDNS TI Comparative effects of nabumetone, sulindac and ibuprofen on renal
function.
104 BIZ2 TI A RANDOMIZED DOUBLE-BLIND MULTICENTER CONTROLLED TRIAL OF IBUPROFEN FOR
ACUTE OTITIS MEDIA IN CHILDREN.
105 MEZZ TI Comparison of inultidose ibuprofen and acetaminophen therapy in febrile
children.
106 EMZZ TI Antipyretic activity and safety of ibuprofen tablets in the treatment of
fever in adults: Multicentre study among general practitioners.
107 DDNS TI Suppression of renal inflammation with vitamins A and E along wtih non-
steroidal anti-inflammatory agetits in ascending pyelonephritis in rats.
108 CBIB TI Postoperative analgesia with preoperative oral ibuprofen or
acetaminophen in cliildren undergoing myringotomy.
109 MEZZ TI Antipyretic efficacy of ibuprofen vs acetaminophen.
110 EMZZ TI Ibuprofen prophylaxis for adverse reactions to diphtheria-tetanus-
pertussis vaccination: A randomized trial.
111 MEZZ TI Single-dose, placebo-controlled comparative study of ibuprofen and
acetaminophen antipyresis in children.
112 EMZZ TI Informed consent, parental awareness, and reasons for participating in a
randotnised controlled study.
113 DDNS TI A randomized, double-blind, multicentre controlled trial of ibuprofen
versus acetaminophen and placebo for symptoms of acute otitis media in children.
114 CBIB TI Antipyretic efficacy of tiaprofenic acid in febrile children.
. ._ I 1 3 ivIEZZ
TI A dose ranging study of ibuprofen suspension as an antipyretic.
116 DDNS TI Pediatric ibuprofen and leukopenia
117 MEZZ TI A double-blind comparison of ibuprofen and paracetamol in juvenile
pyrexia.
118 DDNS TI Confounders of antipyretic drug pharmacodynamics.
119 MEZZ TI A double-blind dose-ranging trial with paediatric ibuprofen
120 EMZZ TI Ibuprofen and/or acetaminophen: What price for 'eutliennia'? (1)
(rnulti ple letters).
121 DDNS TI Acute and chronic effects of nonsteroidal antiinflammatory drugs on
glomerular filtration rate in elderly patients,
122 MEZZ TI Ibuprofen, acetaminophen, and placebo treatment of febrile children
I23 DDNS T! Efficacy and safety of ibuprofen (! 0 mgkg), acetaminophen (! 5 mdkg),
and placebo in the relief of orthodontic pain in children.
124 MEZZ TI A single-blind parallel group study investigating the antipyretic
properties of ibuprofen syrup versus acetylsalicylic acid syrup in febrile children.
125 EMZZ TI Ibuprofen: Proven efficacy in treatment of febrile seizures.
126 DDNS TI Nonsteroidal antiinflammatory drug-induced gastroduodenal injury in
children.
127 MEZZ TI Antipyretic activity of ibuprofen and paracetamol in children with
pyrexia.
128 EMZZ TI Efficacy and safety of acetaminophen vs ibuprofen in the febrile child,
129 DDNS Ti ibuprofen treatment of patent ductus arteriosus.
130 SCZZ TI EVALUATION OF THE ANTIPYRETIC EFFECT OF KETOROLAC, ACETAMINOPHEN, AND
PLACEBO IN ENDOTOXIN-INDUCED FEVER.
131 MEZZ TI A comparative study of two dosage levels of ibuprofen syrup in children
with pyrexia.
Id2 EMZZ TI Safety of ibuprofen use in febrile children.
133 SCZZ TI IBUPROFEN IN THE TREATMENT OF POSTOPERATIVE PAIN IN SMALL CHILDREN - A
STUDY. RANDOMIZED DOUBLE-BLIND-PLACEBO CONTROLLED PARALLEL-GROUP
154 DDNS TI An assessment of the safety of pediatric ibuprofen.
135 SCZZ T1 TREATMENT OF FEVER N CHILDHOOD
136 DDNS TI Prophylactic oral acetaminophen or ibuprofen are not effective for
postoperative pain relief in children undergoing myringotomy.
137 DDNS TI Intravenous immunoglobulin in the treatment of systemic juvenile
rheumatoid arthritis: a randomized placebo controlled trial.
138 SCZZ TI PEDIATRIC LABELING REQUIREMENTS - IMPLICATIONS FOR PHARMACOKINETIC
STUDIES.
139 EMZZ TI Short-term ibuprofen use is safe in children with fever.
140 DDNS TI Development and use of a gastropathy index for ranking the safety of
non-steroidal anti-inflammatory drugs in the elderly.
141 EMZZ TI Ibuprofen as an antipyretic drug in childhood.
142 DDNS TI Comparison of Ibuprofen, .4cetaminophen and Placebo Treatment of Fever in
Children.
143 EMZZ TI Safety of paracetamol and ibuprofen in febrile children
144 DDNS TI Efficacy and Safety of Nabumetone Versus Diclofenac, Naproxen,
Ibuprofen, and Piroxicam in the Elderly.
145 DDNS TI Safety Experience With Nabumetone Versus Diclofenac, Naproxen Ibuprofen,
and Piroxicam in Osteoarthritis and Rheumatoid Arthritis.
146 DDNS TI Efficacy of Nabumetone Versus Diclofenac, Naproxen, Ibuprofen. and
Piroxicam in Osteoarthritis and Rheumatoid Arthritis.
147 sczz TI A NEW CLINICAL BIOASSAY FOR ANTIPYRESIS
148 sczz
TI IBLJPRGFEN IN CI-IILDREN WIT: I CYSTIC-FIBROSIS - PMAR?v~ACOXINETICS AND
ADVERSE-EFFECTS
149 DDNS TI A Placebo-Controlled Model for Assaying Systemic Analgesics in Children.
150 DDNS TI Renovascular Effects of Nonprescription Ibuprofen in Elderly
Hypertensive Patients with Mild Renal Impairment.
151 EMZZ TI Ibuprofen versus paracetamol for the treatment of fever in children
152 DDNS TI Pharmacokinetics and Pharmacodynamics of Ibuprofen Isomers and
Acetaminophen in Febrile Children.
153 EMZZ
paracetamol.
154 DDNS
TI Comparative evaluation of the antipyretic efficacy of ibuprofen and
TI Single-Dose Pharmacokinetics of Ibuprofen and Acetaminophen in Febrile Children.
155 EMZZ TI Induction of prostaglandin synthesis as the mechanism responsible for
the chills and fever produced by inksiiig amphotericiu B.
156 EMZZ TI Fentiazac suspension in the treatment of acute inflammation of the upper
respiratory tract in children.
157 DDNS TI Efficacy of Ibuprofen Versus Paracetamol in Juvenile Pyrexia
158 DDNS TI Randomized, Double-Blind, Multicenter, Controlled Trial of Ibuprofen
Versus Acetaminophen (Paracetamol) and Placebo for Treatment of Symptoms of Tonsillitis and Pharyngitis in Children.
159 DDNS TI Randomized, Double-Blind, Multicentre, Controlled Trial of Ibuprofen for
Acute Otitis Media in Children.
160 DDNS TI Sore Throat Pain Model for the Evaluation of Analgesics in Children
161 DDNS TI Comparative Study of Suspensions of lbuprofeii and Paracetamol in Soft
Tissue Injuries i n Children.
162 DDNS TI Recombinant Interferon beta: A Phase 1-11 Trial in Children with
Recurrent Brain Tumors.
163 DDNS Ti Pharmacokinetics/Dynamics (PKIPD) of Ibuprofen (IBU) Isomers vs
Acetaminophen (APAPI in Febrile Children.
164 DDNS TI Effect of NSAIDs on Inulin Clearance in Healthy Elderly Persons.
165 DDNS TI Ibuprofen Suspension in the Treatment of Juvenile Rheumatoid Arthritis.
166 DDNS TI Efficacy, Safety and Pharmacodynamics of ibuprofen in Pediatric Patients
with Fever.
167 DDNS TI Pharmacodynamics of Ibuprofen (IB) Antipyresis in Children.
168 DDNS TI Renal Effects of Nonsteroidal Anti-Inflammatory Drugs in the Elderly
169 DDNS TI Ibuprofen Suspension in the Treatment of JRA: Results of the Double-
Blind, Aspirin Controlled Trial.
170 DDNS TI Ibuprofen (I) in Elderly Hypertensive Patients with Mild Renal
Impairment.
171 DDNS TI Treatment of Nephrogenic Diabetes insipidus with Prostaglandin Synthesis
Inhibitors.
172 DDNS TI Postextraction Pain Relief in Children: a Clinical Trial of Liquid
Analgesics.
173 DDNS TI Aluminum Ibuprofen Analgesia Following Extractions in Children
174 DDNS TI A Comparison of Aluminum Ibuprofen Suspension and Acetaminophen Elixir
in the Treatment of Fever in Children.
175 DDNS TI Comparative Evaluation of .\ntipyretic Activity of Ibuprofen and Aspirin
in Children with Pyrexia of Varied Aetiology.
176 DDNS Ti Comparative Study of the Antipyretic Effect of Ibuprofen (Oral ..
Suspension) and Paracetamol (Suppositories) in Paediatrics
Search line 321 - iboprofen + h e r + chi!dren 1 MEZZ TI Ibuprofen or acetaminophen i n children? As the debate continues. the
evidence may favor ibuprofen.
2 EMZZ TI Effect of recent antipyretic use on measured fever in the pediatric
emergency department.
3 DDNS TI Genetic predisposition to acute gastrointestinal bleeding after NSAIDs
use.
4 IPAB TI The use of non-opioid analgesics and antipyretics among infants and
children in Finland from 1990 to 2002.
5 BIZZ TI The use of recombinant activated factor VI1 for controlling life-
threatening bleeding in Dengue Shock Syndrome.
6 ACZZ TI Current medication choices in iuvenile rheumatoid arthritis 11 - uodatc
of a survey performed in i993
7 BNID TI Managing fever and pain in children. (Use of paracetamol and ibuprofen
for children treated at home by parents. 13 refs).
8 NAHL TI Advisor forum. Liver damage concerns in childhood fever treatment.
9 PASC TI Antipyretique activity of ibuprofen syrup in children emergency unit
Evaluation de la reponse antipyretique a 30 minutes de I'ibuprofene suspension aux urgences pediatriques.
10 CBIB
considerations.
1 1 MEZZ
TI The febrile patient: Diagnostic. prognostic and therapeutic
TI How safe is ibuprofen in febrile asthmatic children?
12 EMZZ TI Oral ibuprofen and intravenous indomethacin for treatment of patent
ductus arteriosus i n newborn infants: Retrospective study.
13 BlZZ TI Prescribing habits of general practitioners in the treatment of
chi ldhod :espiratory-tract infections.
14 LINE TI Evidence based paediatrics: evidence based management of seizures
associated with fever.
15 ACZZ TI Intravenous ketorolac in the treatment of fever
16 AC89 TI Adverse reactions to nonsteroidal antiinflammatory drugs: diclofenac
compared with other nonsteroidal antiinflammatory drugs.
17 BNID TI Managing the febrile child. (Review of latest evidence on aspirin,
ibuprofen and paracetamol).
18 NAHL TI Pain and fever in children
19 MEZZ TI The antipyretic effect of ibuprofen and acetaminophen in children.
20 DD” TI Relationship between selective cyclooxygenase-2 inhibitors and acute
myocardial infarction in older adults.
21 LINE TI Primary care treatment of pain and fever.
22 ACZZ TI Intramuscular ceftriaxone in the treatment of childhood meningitis due
to Haemophilus influenzae type F
23 AC89 TI Update on ibuprofen: review article.
24 BNID TI Treating fever in children: paracetamol or ibuprofen? (Mini-review of
the research literature. 33 refs).
25 NAHL TI Clinical update. Managing fever and pain in children
26 CBIB
TI Renal complications of non-steroidal anti-inflammatories.
27 MEZZ TI Acute renal failure after treatment with non-steroidal anti-inflammatory
drugs.
28 EMZZ TI Ibuprofen and acute renal failure in a toddler
29 DDNS TI Potential interaction between acenocoumard and diclofenac, naproxen and
ibuprofen and role of CYP2C9 genotype.
30 IPAB TI Systematic review of prevalence of aspirin induced asthma and its
implications for clinical practice.
31 LINE TI Licensed drugs in the treatment of childhood fever in Italy
32 NAHL TI How often do pediatricians recommend alternating acetaminophen and
ibuprofen for fever?
33 CBIB TI When body temperature changes, does rectal temperature lag?
34 MEZZ TI Fcver phobia revisited
35 EMZZ TI Unsubstantiated alarmist declarations need to be examined (1)
36 IPAB TI Pediatric OTC medications.
31 BIZ2 TI Platelet activity in sickle cell vaso-occlusive episodes.
38 ACZZ TI Antiepileptic hypersensitivity syndrome in children
39 AC89 TI Clinical experience and results of treatment with suprofen in
pediatrics. 3rd communication: antipyretic effect and tolerability of repeat doses of suprofen and paracetamol syrup in hospitalized children. A single blind study.
40 PASC TI The effect ofrecalling paracetamol on hospital admissions for poisoning
in Western Australia.
41 MEZZ TI Antipyretic efficacy and safety of ibuprofen and acetaminophen in
children.
42 EMZZ TI Effectiveness of Pretreatment in Decreasing .4dverse Events Associated
with Pamidronate in Children and Adolescents.
43 DDNS T1 Cerebral malaria. Optimising management.
44 NAHL TI Commentary on Acetaminophen and ibuprofen: fever control and overdose
(original article by Murphy K appears in PED NURS 1992; 18(4):428-32).
45 MEZZ TI Alternating acetaminophen and ibuprofen in the febrile child:
examination of the evidence regarding efficacy and safety.
46 EMZZ TI No evidence for practice of alternating doses of paracetamol and
ibuprofen in children with fever.
41 DDNS TI Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-
term risk of acute myocardial infarction in the elderly.
48 LINE -_ 1.
I I muprofen or acetaminophen (paraceiamoij for management of h e r in children?
49 ACZZ TI Allergic reactions due to ibuprofen in children.
50 CBIB TI Underdosing of acetaminophen by parents and emergency department
utilization.
51 MEZZ TI Ibuprofen and increased morbidity in children with asthma : fact or
fiction?
52 EMZZ TI Fever phobia revisited (2)
53 DDNS TI The risk of peptic ulcer in elderly acute and chronic users of aspirin
and other nonsteroidal antiinflammatory drugs: the role of gastroprotective drugs.
54 IPAE TI Caution is key in pediatric pain relief.
55 BiZZ TI Black widow bites in children.
56 LINE TI Antipyretic therapy. Physiologic rationale, diagnostic implications, and
clinical consequences.
57 AC89 TI Analgesic overdosage an overview of the problem
58 NAHL TI Ibuprofen suspension for children.
59 MEZZ TI Ibuprofen was more protective against asthma morbidity than
acetaminophen in asthmatic children with fever.
60 DDNS TI Paracetamol in childhood. Current state of knowledge and advice for
rational use for postoperative analgesia. (Ger.).
61 IPAB TI Treatment of otitis media with observation and a safety-net antibiotic
prescription.
62 BIZ2 TI Kecombinant Activated Factor Vi1 in Controliing Life-T'nrearening
Bleeding in Dengue Shock Syndrome.
63 ACZZ TI Aseptic meningitis in a child after systemic treatment with high dose
cytarabine.
64 AC89 TI Nonsteroidal antiinflammatory drugs as analgesics
6 5 MEZZ TI Fever: to treat or not to treat. Counterpoint.
66 EMZZ TI Antipyretique activity of ibuprofen syrup in children emergency unit.
67 DDNS TI Macrophage activation syndrome following initiation ofetanercept in a
child with systemic onset juvenile rheumatoid arthritis.
68 IP.4B TI Feverish debate.
69 BIZZ TI Ethnic differences in parental antipyretic use
70 LINE TI Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and
comfort in children with fever.
71 ACZZ TI Patent ductus arteriosus in the premature neonate: current concepts in
pharmacological management.
12 PASC TI Simple febrile seizures in children.
Convulsions febriles simples de I'enfant : expliquer et rassurer les parents plutot que prescrire.
13 CBIB TI Population pharmacokinetics of high dose ibuprofen in cystic fibrosis
74 MEZZ TI Fever: to treat or not to treat. Point
IS EMZZ TI Polyarthritis and mediterranean spotted fever ( 2 )
76 DDNS TI Determinants and sequelae associated with utilization of acetaminophen
versus rradirionai nonsreroidai antiinflammatory drugs in an elderly population.
I1 IPAB TI Nonsteroidal anti-inflammatory drugs for postoperative pain - A focus on
children.
7 8 LINE TI Comparing efficacy and tolerability of ibuprofen and paracetamol in
fever.
I 9 CBIB TI Kawasaki disease with facial nerve paralysis
80 MEZZ TI Childhood fever revisited
81 EMZZ Ti Use of ibuprofen in pediatrics.
82 DDNS TI Observational study of upper gastrointestinal haemorrhage in elderly
patients given selective cyclo-oxygenase-? inhibitors or conventional non-steroidal anti-inflammatory drugs.
83 IPAB TI When your child has a headache
84 BIZZ TI Poisoning in children 2: Painkillers.
85 LINE TI Reliability of health information for the public on the world wide web:
systematic survey of advice on managing fever in children at home.
86 ACZZ TI Asthma morbidity following short-term use of acetaminophen and ibuprofen
in asthmatic children.
87 CBIB TI Management of fever: Making evidence-based decisions.
88 MEZZ TI (Current opinions on embryotoxic and teratogenic effects of ibuprofen)
89 EMZZ TI Effect of antipyretics on polymorphonuclear leukocyte functions in
children.
90 DDNS TI Indomethacin and ibuprofen effect on IL-lra production by mononuclear
ceiis of preterm newborns and aduirs.
91 IPAB TI Asthma and analgesics.
92 LINE TI Ibuprofen or paracetamol for children's fever?
93 ACZZ TI Severe ehrlichiosis in an adolescent taking trimethoprim-
sulfamethoxazole.
94 CBIB TI The safety of ibuprofen suspension in children
95 EMZZ TI Information and education for the general public.
96 DDNS TI Rofecoxib in a child w,ith nonsteroidal anti-inflammatory drug induced
urticaria and angioedema.
91 IPAB TI Risks and benefits of nonsteroidal anti-inflammatory drugs in children -
A comparison with paracetamol.
98 BIZZ TI Comparison of incidence of reported adverse events with pretreatment for
pamidronate administration in children.
99 LPJE TI Antipyretic efficacy of ibuprofen and acetaminophen in children with
febrile seizures.
100 CBIB TI Pharmacokinetics of intravenous and rectal ketoprofen in young children.
101 EMZZ TI Antipyretic poisoning.
102 DDNS TI Ibuprofen induced acute renal failure in an infant.
103 IPAB TI Evidence-based management of seizures associated with fever.
104 BIZZ
community TI Fever: Knowledge, attitude and management in the Latin American
in5 LTNE Ti ibuprofen oral suspension - cniia.
106 PASC TI Pediatric ibuprofen use increases while incidence of Reye's syndrome
continues to decline.
107 CBIB TI Development of oral acetaminophen chewable tablets with inhibited bitter
taste.
108 EM22 TI Emergency department visits for poisoning: Epidemiological changes in
the last I0 years.
109 DDNS TI Toxicity of over-the-counter cough and cold medicines.
I10 IPAB TI Crying shame.
1 1 1 BIZ2 TI Alternating antipyretics to treat fever in children: Parental practices.
112 LINE TI Fever: definition and management in children
113 MEZZ TI (Analysis of prognostic factors for the antipyretic response to
ibuprofen).
114 EMZZ TI Antithermics: Modes of use in the Primary Attention System. Experience
in a municipium of Buenos Aires conurbation (Argentina).
115 DDNS TI Fixed drug eruption due to naproxen; lack of cross-reactivity with other
propionic acid derivatives.
116 BIZZ
Prescription.
117 LINE
TI Treatment of otitis media with observation and a Safety-Net
TI The febrile child.
118 ACZZ TI Drug-induced liver disease
119 PASC TI Pharmacology of antipyretic drugs for their use in pediatrics,
n rharmacologie des aniipyreiiqut-s : appiicatiuns a ieur uiiiisation eii pediatrie. XXXIIe Congres de I'Association des pediatres de langue francaise - Societe francaise de pediatrie. Congres annuel.
120 MEZZ TI Acetaminophen and ibuprofen dosing by parents
121 EMZZ TI Antipyretics in children
122 DDNS TI Invasive group A streptococcal infection and nonsteroidal
antiinflammatory drug use among children with primary varicella.
123 IPAB TI Drug treatment ofjuvenile arthritis: accepted therapeutic options.
124 BIZZ TI Pediatric fever and Nurofen as anti-peretic.
125 LINE TI Headache.
126 ACZZ TI Pharmacodynamics of ibuprofen antipyresis in children.
127 MEZZ TI Alternating antipyretics: is this an alternative?
128 DDNS TI Analysis of nonsteroidal antiinflammatory drugs in meconium and its
relation to persistent pulmonary hypertension of the newborn.
129 lPAB TI Caregiver knowledge: assessment of common pediatric illnesses and over
the counter medications.
130 BIZ2 TI Home management of sickle pain: A daily diary study of analgesic usage
by children and adolescents with sickle cell disease.
131 ACZZ TI Acetaminophen in the management of background pain in children post-
burn.
132 CBIB TI Acetaminophen toxicity in children.
133 MEZZ TI Assessment of the efficacy and safety of paracetamol, ibuprofen and
nimesiilide in children with upper respiratory tract infections.
134 EMZZ TI An epidemiological investigation of a sustained high rate of pediatric
parapneumonic empyema: Risk factors and microbiological associations.
I35 DDNS TI Methotrexate as a possible trigger of macrophage activation syndrome in
systemic juvenile idiopathic arthritis.
136 lPAB TI Ibuprofen and paracetamol: relative safety in non-prescription dosages
137 LINE TI Counter prescribing for patients at risk. Pregnancy and breastfeeding.
138 MEZZ TI Paracetamol and ibuprofen for treatment of fever in Malawian children
aged less than five years.
139 EMZZ TI Premarketing surveillance of oral ibuprofen solution in febrile
children.
140 DDNS
children. (Ger.). TI First experience with ibuprofen suspension in the treatment of fever in
141 IPAB TI Safety of acute and chronic ibuprofen therapy in children
142 ACZZ TI A n assessment of the safety of ibuprofen suspension among ambulatory
children (the Boston University Fever Study): rationale and design.
143 MEZZ TI Pyloric channel stricture secondary to high-dose ibuprofen therapy in a
patient with cystic fibrosis.
144 EMZZ T1 Poststreptococcal reactive arthritis.
145 DDNS TI Preventive treatment for recurrent febrile seizures.
146 IPAB TI What's the best pain reliever? Depends on your pain
147 ACZZ TI Non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity
in children with juvenile arthritis.
148 MEZZ TI Integrated pharmacokinetic-pharmacodynamic model for acetaminophen,
ibuprofen, and placebo antipyresis in children.
149 EMZZ Ti Alternating antipyretics: Is this an alternative? (3).
150 DDNS TI No association between non-steroidal anti-inflammatory drugs, alone 01
with prophylactic anticoagulants. and blood transfusion following knee replacement surgery.
151 IPAB TI Ibuprofen: proven efficacy in treatment of febrile seizures
152 LINE TI Cooling the feverish child.
I53 CBlB TI Perforated peptic ulcer in an infant.
154 MEZZ
TI Combined antipyretic therapy: another potential source of chronic acetaminophen toxicity.
155 DDNS TI Antipyretic efficacy of ibuprofen and acetaminophen in children with
fever.
156 IPAB T I Ibuprofen: child
157 BlZZ TI (Untitled).
158 ACZZ TI Home antipyretics use in febrile children brought to the emergency
department.
159 CBIB TI Pliarmacokineticipharmacodynamic modeling of antipyretic and anti-
inflammatory effects of naproxen in the rat.
160 MEZZ TI Reevaluation of antipyretics in children with enteric fever.
161 EMZZ TI Exacerbation of asthma by ibuprofen in a very young child ( I ) .
162 DDNS TI Over-the-counter analgesics and antipyretics: a critical assessment.
163 IPAB TI Pediatric ibuprofen and leukopenia.
164 ACZZ TI Pediatric postoperative pain management
165 MEZZ TI Circulating leptin levels during acute experimental endotoxemia and
antiinflammatory therapy in humans.
166 EMZZ TI Home antipyretic use in children brought to the emergency department.
167 DDNS TI Non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity
in a practice-based cohort of children with juvenile arthritis.
168 IPAB T I New OTC drugs and devices: selected review
169 ACZZ
T! Peri-operative use ofnonsteroidiil anti-inflammatory drugs in children: analgesic efficacy and bleeding.
170 MEZZ TI Care in the use of ibuprofen as an autipyretic in children
!7! EMZZ TI Incidence of Reye's syndrome in France: A hospital-based survey
172 DDNS TI Non-steroidal anti-inflammatory drug-induced central nervous system
toxicity in a practice-based cohort of children with juvenile arthritis.
173 IPAB TI Headache: classic opportunity for advice and sales
174 BIZZ TI Use of dipyrone i n a community clinic population
175 PASC TI Advil<SUP>o children and infants, Nurofen<SUP>o children and infants
(ibuprofene in pediatrics).
Advil<SUP>o eufants et nourrissons, Nurofen<SUDo enfants et nourrissons (ibuprofene en pediatrie).
176 CBIB TI Diagnostic implications and clinical consequences of antipyretic
therapy.
177 MEZZ TI Acetaminophen: a clarification.
178 EMZZ TI Are we losing good drugs?
179 DDNS TI Effects of rheumatic disease and corticosteroid treatment on calcium
metabolism and bone density in children assessed one year after diagnosis, using stable isotopes and dual energy X-ray absorptiometry.
I80 IPAB TI Study on the awareness of the use of medicines among high school
students aged 13-16 years in a co-educational school in North India.
181 BIZZ TI Right thigh pain.
I82 LINE TI Cystitis.
(83 CBIB TI Toxicities of drugs used in the management of fever.
184 ME22 TI Ibuprofen use in pediatric patients
IS5 EMZZ TI External cooling in the management of fever
186 DDNS
gastric ulcer.
187 BIZZ
TI Non-steroidal anti-inflammatory drugs, Helicobacter pylori and bleeding
TI Ibuprofen as an antipyretic substance.
188 CBIB TI Pharmacokinetics of rectal paracetamol after repeated dosing in
children.
189 MEZZ TI Ibuprofen and/or acetaminophen: what price for "euthermia"?
190 EMZZ TI Effect of antipyretic drugs in children with malaria.
191 DDNS TI Judging the effectiveness of analgesia for children and adolescents
during vaso-occlusive events of sick1e cell diseasc.
192 BIZZ TI Is recall of pregnancy exposures influenced by interview timing?
193 CBIB TI Pharmacokinetics of ibuprofen enantiomers in children with cystic
fibrosis.
194 EMZZ TI Use of ibuprofen in pediatric infections with febrile convulsion.
195 DDNS TI Hypersensitivity reaction to acetylcysteine and carbocisteine.
196 BlZZ
in 20 years? TI Fever phobia revisited: Have parental misconceptions about fever changed
197 MEZZ TI (Focus on the safety of ibuprofen at the analgesic-antipyretic dose).
198 EMZZ
TI Headache, emesis. and fexver i n a l?-year-o!d boy
199 DDNS T1 Pharmacokinetic/pharmacodynamic modelling of the antipyretic effect of
two oral formulations of ibuprofen: suspension and effervescent granules.
200 PASC TI Interactions of ibuprofen with influenza infection and hyperammonemia in
an animal model of Reye's syndrome.
201 CBIB T1 Home management of fever in children: Rational or ritual?
202 MEZZ TI Choice of antipyretic in children.
203 EMZZ TI Ibuprofen fulfills the expectations of pediatricians.
204 DDNS TI Effects of ibuprofen and indomethacin on the regional circulation in
newborn piglets.
205 IPAB TI Use of nonprescription medications in the treatment of pain.
206 CBIB TI Pediatric febrile seizures and childhood headaches in primary care.
207 MEZZ TI Ibuprofen suspension: pediatric antipyretic.
208 DDNS TI Fixed drug eruptions in children.
209 IPAB TI Management of minor pain with OTC medications.
210 BIZ2 TI Ibufen (Ibuprofen) in cases of fever due to pediatric acute respiratory
tract infections-clinical efficacy and safety of usage.
211 MEZZ TI Ibuprofen as an over-the-counter drug: is there a risk for renal injury?
212 EMZZ TI Tubulointerstitial nephritis and asymptomatic uveitis
213 DDNS TI Severe falciparum malaria in children: current understanding of
pathophysiology and supportive treatment.
214 IPAB TI Determination of ibuprofen by high performance liquid chromatography.
215 BIZZ TI NS.A.ID facial angioedema in a selected pediatric atopic population
216 PASC TI A dose ranging study of ibuprofen suspension as an antipyretic. Reply
217 CBIB TI Predicting concentrations in children presenting with acetaminophen
overdose.
218 MEZZ TI Effect of age on ibuprofen pharmacokinetics and antipyretic response
219 EMZZ TI Prevesical abscess secondary to pubis symphysis septic arthritis.
220 DDNS TI A major role for prostacyclin in nitric oxide-induced ocular
vasorelaxation in the piglet.
221 PASC TI Antipyretic efficacy of ibuprofen vs acetaminophen
222 MEZZ -T
I I Acetaminophen and ibuprofen: <ever coniroi and overdose.
223 EMZZ
complications.
224 BIZZ
TI Fever in burned children and its association with infectious
TI Invasive group A streptococcal infection and antipyretic use among children with primary varicella.
225 PASC TI Comparison of multidose ibuprofen and acetaminophen therapy in febrile
children.
226 CBIB TI Pharniacology of anti-inflammatories: application to their usage in
pediatrics.
277 MEZZ TI Pharmacokinetics and pharmacodynamics of ibuprofen isomers and
acetaminophen in febrile children.
228 EMZZ TI Ibuprofen as antipyretic in children
229 DDNS TI Drug-associated acute-onset vanishing bile duct and Stevens-Johnson
syndromes in a child.
230 MEZZ TI Ibuprofen safety
231 EMZZ TI Fever: A weapon of defence too often disregarded
232 DDNS TI Pain medication during terminal care of children with cancer.
233 BIZZ TI Pharmacokinetic-pharmacodynamic modelling of the antipyretic effect of
two oral formulations of ibuprofen.
234 ACZZ TI Comparative efficacy and tolerance of ibuprofen syrup and acetaminophen
syrup in children with pyrexia associated with infectious diseases and treated with antibiotics.
235 PASC TI Efficacy of ibuprofen in pediatric patients with fever.
236 MEZZ -I ̂ . I I singie-dose pharmacokinetics OT ibuprdtm arid acetaminophen in febrile
children.
237 DDNS TI NSAIDs associated with increased risk of congestive heart failure in
elderly patients taking diuretics.
238 ACZZ TI Use of medication by adolescents for the management of menstrual
discomfort.
239 MEZZ TI Ibuprofen lowers body temperature and metabolic rate of humans with burn
injury
240 EMZZ TI How did such a bad report get published in the EJCP? Trial of
paracetamol. ibuprofen and nimesulide in children with upper respiratory infections (B. Ulukol et al., EJCP November 1999, 55: 615-618) (2).
241 DDNS TI Effects of indomethacin and ibuprofen on regional perfusion in the
newborn piglet
242 BlZZ
in children. TI Comparative study of dipyrone, ibuprofen and acetaminophen antipyresis
243 .4czz TI Treatment of fever: monotherapy with ibuprofen. Ibuprofen pediatric
suspension containing 100 mg 5 ml, multicentre acceptability study conducted in hospital.
244 CBIB TI Combined antipyretic therapy: Another potential source of chronic
acetaminophen toxicity - Reply.
245 sczz TI Benefits and risks of antipyretic therapy
246 MEZZ TI Drugs for childhood fever
241 EMZZ TI Fever in children: Paracetamol is mostly sufficient
248 DDNS TI Comparative evaluation of the effects of indomethacin and ibuprofen on
cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus.
249 aizz TI Safety profile of ibuprofen suspension in young children
250 CBlB TI Recombinant interleukin-6 in the treatment of congenital
thrombocytopenia associated with absent radii.
251 MEZZ TI Ibuprofin safety
252 EMZZ TI Fever in critically i l l patients.
253 DDNS TI Nonsteroidal anti-inflammatory drugs (NSAIDs) associated liver disease
in Black and Hispanic elderly patients.
254 ACZZ TI A placebo-controlled model for assaying systemic analgesics in children.
255 MELZ TI Junifen suspension--ibuprofen for febrile children
156 DDNS TI Consumption of non-steroidal antinflammatory drugs and the development
of functional venal impairment in elderly subjects. Results of a cas- [control study.
257 BIZ2 TI Pharmacology of antipyretics: Applications to their use in pediatrics.
258 PASC TI Ibuprofen, acetaminophen, and placebo treatment of febrile children.
259 MEZZ TI Pharmacokinetics of ibuprofen in febrile children.
260 EMZZ TI Ibuprofen for children
261 DDNS TJ Suppression of fever and the acute-phase response in a patient with
juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2).
262 ACZZ TI Pain management in children
263 PASC TI Ulcerative proctitis in juvenile systemic lupus erythematosus after
ibuprofen treatment.
264 MEZZ TI Ibuprofen versus paracetamol for the treatment of fever in children
265 EMZZ Ti A case-control study of necrotizing fasciitis during primary varicella
266 DDNS
year-old child.
261 PASC
TI Acetaminophen-induced urticaria and tolerance of ibuprofen in an eight-
TI Induction of prostaglandin synthesis as the mechanism responsible for the chills and fever produced by infusing amphotericin B.
7-68 CBIB TI Ibuprofen and/or acetaminophen: What price for "euthermia"? - Reply
269 MEZZ TI Paediatric ibuprofen--an overview
270 EMZZ
TI Paracetamol or ibuprofen in febrile children.
211 DDNS TI Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for
acute renal failure.
272 ACZZ TI The use of non-steroidal anti-inflammatory drugs in paediatric rheumatic
diseases.
273 SCZZ TI Clinical pharmacokinetics of ibuprofen - The first 30 years.
274 MEZZ TI Ibuprofen: a monograph.
275 EMZZ TI Neurovascular emergencies: Always rectal administration of diazepam in -
first convulsive seizure in children.
276 DDNS TI Protective effect of chronic NSAID use on cognitive decline in older
persons.
217 EIZZ TI Fever in children: A survey of health care professionals' knowledge and
treatment preferences.
278 ACZZ -. _. I I muprofen and paraceiamoi: eKeciive antipyretics i n children wi:h
febrile seizures.
279 CBIB TI Clinical pharmacology of antipyretic agents.
280 MEZZ
paracetamol.
281 EMZZ
TI Comparative evaluation of the antipyretic efficacy of ibuprofen and
TI Combined antipyretic therapy: Another potential source of chronic acetaminophen toxicity (2) (multiple letters).
282 DDNS TI The toxicity of antirheumatic medications in children
283 ACZZ
adolescents. TI Serum-sickness-like reaction associated with minocycline therapy in
284 MEZZ
TI Ibuprofen for fever
285 EMZZ TI Home-based therapies for the common cold among European American and
ethnic minority families: The interface between alternative /complementary and folk medicine.
286 DDNS TI A survey of NSAID usage in hospital and community and serious NSAID
related gastrointestinal toxicity.
287 BlZZ TI Effects of risperidone in overdose.
288 ACZZ TI Heat stroke-like episode in a child caused by zonisamide.
289 CBIB TI Pharmacokinetics and protein binding of intravenous ibuprofen in the
prPmature newborn infant.
290 SCZZ TI Clinical pharmacology at antipyretic agents
291 MEZZ TI Hepatic granulomata. Presenting with prolonged
anti-inflammatory treatment.
292 DDNS
ver. Resc tion with
-.. r I I ivonsieroidai antiinllamniaiory drugs aid cogiiiiive d e c h in the
elderly.
293 CBIB TI Use of ibuprofen in juvenile chronic arthritis.
294 MEZZ TI Ibuprofen vs acetaminophen in children.
295 EMZZ TI Acetaminophen: A clarification ( 5 ) .
296 DDNS TI Comparative evaluation of indometacin (INDO) and ibuprofen (IBU) on
cerebral blood volume in very-low-birth-weight infants.
297 ACZZ TI Serum sickness-like disease after immunization with a recombiiiant
hepatitis B vaccine.
298 MEZZ TI Ibuprofen: an alternative for children's fevers,
299 DDNS TI Nonsteroidal anti-inflammatory drugs inhibit expression of the inducible
nitric oxide synthase gene.
300 BIZZ TI Hypothermia from Azithromycin? (and response).
301 ACZZ TI Antipyretic activity and safety of ibuprofen tablets in the treatment of
fever in adults: multicentre study among general practitioners.
302 CBIB TI Short-Term Ibuprofen Use Is Safe in Children with Fever.
303 EMZZ TI Symptomatic therapy of common febrile states in children.
304 DDNS TI How many elderly general practice patients taking regular non-steroidal
anti-inflammatory drugs can be converted to taking regular paracetamol?
305 BIZZ TI NUREFLEX children and infants (ibuprofen 10 milligrams per kilogram) in
fever of the hospitalized child: Multicentric trial of acceptability, tolerance and efficacy (intermediate analysis).
306 ACZZ TI Juvenile arthritis: a practical guide to drug therapy.
307 CBIB TI Acetaminophen and other antipyretic analgesic drugs: Optimal dosages in
pediatric patients.
308 MEZZ TI Comparative evaluation of antipyretic activity of ibuprofen and aspirin
in children with pyrexia of varied aetiology.
309 EMZZ TI Ibuprofen and skin and soft tissue superinfections in children with
varicella.
310 DDNS TI Experience with misoprostol therapy for NSAID gastropathy in children
31 I ACZZ TI Simultaneous pharmacokinetic-pharmacodynamic modeling of ibuprofen in
febrile children.
312 EIMZZ TI The role of ibuprofen in the treatment offever in pediatrics.
313 DDNS TI Epidural corticosteroid injections for acute radiculopathy in a 95-year-
old woman.
314 BlZZ TI A large population trial for pediatric ibuprofen: A new method for
evaluating risk in actual use.
315 ACZZ TI Attack treatment of migraine in children
316 MEZZ TI Measurement of antipyretic activity of ibuprofen and paracetamol in
children.
317 EMZZ TI Antipyretic therapy
318 DDNS TI Effect of NSAIDs on electrolyte homeostasis in elderly and young
persons.
319 BIZZ TI A recent case of congenital malaria in Singapore
310 ACZZ TI Integrated pharrnacokineticipharmacodynamic model for acetaminophen and
ibuprofen antipyresis in children.
321 MEZZ TI Oral antipyretic therapy.
322 EMZZ TI Evaluation of sponging and antipyretic medicztion to reduce body
temperature in febrile children.
323 DDNS TI Up-regulation of brain PGE? and PGF2-alpha receptors and receptor-
coupled second messengers by cyclooxygenase inhibition in newborn pigs.
324 BlZZ TI Confounders of antipyretic drug pharmacodynamics
325 SCZZ TI STEREOSELECTIVE DISPOSITION OF IBUPROFEN ENANTIOMERS IN INFANTS
326 EMZZ TI Acute renal failure associated with amoxicillin and ibuprofen in an l l -
year-old boy (2).
327 ODNS TI Nonsteroidal anti-inflammatory drugs inhibit expression of the nitric
oxide synthase gene in rat alveolar macrophages.
328 BlZZ TI Are inajor cardiovascular malformations defects of a single developmental
field?
329 ACZZ TI Safety of tion steroidal antiinflammatory drugs in pregnant patients with
rheumatic disease.
330 EMZZ '1'1 Childhood fever
331 DDNS TI Gastroduodenal damage in children treated with nonsteroidal
antiinflammatory drugs is a common occurrence.
332 BlZZ TI Lactic aciduria after ibuprofen treatment in febrile children.
333 ACZZ TI Efficacy and safety of ibuprofen (IOmdkg), acetaminophen (1 5mg/kg), and
placebo in the relief of orthodontic pain in children.
334 sczz TI ANTIBIOTIC-INDUCED MENINGITIS.
^ ^ - 5 3 3 C1VIL.L
TI Management of fever in children.
336 DDNS TI Increased risk of facial scars in children taking nonsteroidal -
antiinflaniinatory drugs.
331 ACZZ TI Parents' management of children's pain following minor surgery
338 EMZZ TI Pediatric ibuprofen and leukopenia (3).
339 DDNS TI Serum antioxidative enzyme activity and juvenile chronic arthritis.
340 BlZZ TI Evaluation of the antipyretic efficacy of single dose ibuprofen
suspension compared to acetaminophen elixir in febrile children.
34 1 ACZZ TI A n assessment of the safety of ibuprofen suspension among ambulatory
children (the Boston University Fever Study): results.
341 sczz TI EVALUATION OF THE RAT EMBRYO CULTURE SYSTEM AS A PREDICTIVE TEST FOR
HUMAN TERATOGENS.
343 EMZZ TI Rash and fever in a 3-year-old girl.
344 DDNS TI Nimesulide. An update of its pharmacodynamic and pharmacokinetic
properties, and therapeulic efficacy.
345 BIZZ TI A model for apparent antipyresis in placebo-treated febrile children.
346 ACZZ TI Pharmacokinetics/dynamics of ibuprofen isomers vs acetaminophen in
febrile children.
341 SCZZ TI PHARMACODYNAMIC MODELING OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS -
ANTIPYRETIC EFFECT OF IBUPROFEN.
345 EMZZ TI Treatment of febrile children.
349 DDi<'S TI Cutaneous polyarteritis nodosa. Reports of two cases in children and
review of the literature.
350 ACZZ TI Clinical efficacy af nimesulide against paracetamol and ibuprofen for
the treatment of headache in children with upper respiratory tract infections.
351 SCZZ TI FEVER IN CHILDHOOD - ITS TREATMENT.
352 EMZZ TI FDA advisory panels endorse motrin for children
353 DDNS TI Correlation between NSAID accumulation and creatinine clearance in
elderly patients without and with renal insufficiency (RI).
351 BIZZ 1'1 Childhood fever: l a treatment
355 EMZZ T1 Use of ibuprofen in juvenile chronic arthritis.
356 DDNS TI Epidural Analgesia in the Management of Severe Vaso-Occlusive Sickle
Cell Crisis.
3 5 1 EMZZ TI Poststreptococcal reactive arthritis in children: A potential
predecessor of rheumatic heart disease.
358 DDNS TI Adverse Events Related to Drugs and Drug Withdrawal in Nursing Home
Residents.
359 EMZZ TI Alterations in the electroretinogram of newborn piglets by propionic
acid- derivative nonsteroidal antiinflammatory drugs but not by indomethacin and diclofenac.
360 DDNS TI Fixed Drug Eruptions in Children: A Series of 23 Cases with Provocative
Tests.
361 EMZZ TI The pharmacokinetics of ibuprofen after burn injury
362 DDNS TI Acute Flank Pain and Reversible Renal Dysfunction Associated with .~ iuonsreroidai Anri-inflammatory Drug %e.
363 SCZZ TI A PROBABILITY NOMOGRAM TO PREDICT RECTAL TEMPERATURE IN CHILDREN.
364 EMZZ TI Children with fever
365 DDNS TI Safety of Non-Steroidal Anti-Inflammatories Before Adenotonsillectomy.
366 DDNS TI The Relationship Between Phenazone (Antipyrine) Metabolite Formation and
Theophylline Metabolism in Healthy and Frail Elderly Women.
361 SCZZ TI PHARMACOKINETICS AND PHARMACODYNAMICS IN THE DESiGN OF CONTROLLED-
RELEASE BEADS WITH ACETAMiNOPHEN AS MODEL-DRUG.
368 DDNS
T! Concurrent Use of Nonstcroida! Anti-inflammatory Drugs and Oral Anticoagulants Places Elderly Persons at High Risk for Hemorrhagic Peptic Ulcer Disease.
369 SCZZ TI IST TRIMESTER MATERNAL MEDICATION USE IN RELATION TO GASTROSCHISIS.
370 DDNS TI Indomethacin Compromises, Hemodynamics During Positive-Pressure
Ventilation, Independently of Prostanoids.
371 EMZZ TI Antipyretic therapy in the febrile child.
372 DDNS TI Prospective Follow-up of Adverse Reactions in Breast-Fed Infants Exposed
to Maternal Medication.
373 DDNS TI A Prospective Study of Aspirin Use and Cataract Extraction in Women,
374 EMZZ TI Problematic of the febrile syndrome in the urgencies services. Facts for
a practical orientation.
375 DDNS TI Uses of Nonsteroidal Anti-Inflammatory Drugs in Pediatrics.
376 SCZZ TI INTERLEUKIN-6 AS AN ENDOGENOUS PYROGEN - INDUCTION OF PROSTAGLANDIN-E2
IN BRAIN BUT NOT IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS
377 EMZZ TI Ibuprofen safety (2) .
378 DDNS TI Renal Effects of NSAIDs in Healthy Elderly Persons.
379 BlZZ TI PHARMACOKINETICS-DYNAMICS PK-PD OF IBUPROFEN IBU ISOMERS VS
ACETAMINOPHEN APAP N FEBRILE CHILDREN.
380 DDNS TI Integrated Pharmacokinetic (PKN)/Pharmacodynamic (PDN) Model for
Acetaminophen and Ibuprofen Anripyresis in Children.
381 DDNS TI Pain-Fever PliarmacokineticsiDynamics (PWPD) in Children.
382 BIZZ TI COMPARATIVE EFFICACY OF IBUPROFEN IBU AND ACETAMINOPHEN APAP IN FEBRILE
CHILDREN.
383 EiMZZ TI First trimester maternal medication use in relation te gastroschisis.
384 DDNS TI Prevention of Activation of HIV-1 by Antiviral Agents in OM-10.1 Cells
385 BIZZ TI EFFICACY SAFETY AND PHARMACODYNAMICS OF IBUPROFEN IN PEDIATRIC PATIENTS
WITH FEVER.
386 EMZZ T1 Ibuprofin safety (1).
387 DDNS TI Risk of Major Gastrointestinal (GI) Complications with Individual Non-
Steroid Anti-Inflammatory Drugs (NSAIDs).
388 BIZZ TI ANTIPYRETICS IN PEDIATRIC PRACTICE
389 EMZZ TI Management of childhood fever (34).
390 DENS TI Simultaneous Pharmacokinetic (PK)-Pharmacodynamic (PD) Modeling of
Ibuprofen in Febrile Children.
391 BIZZ TI PHARMACODYKAMICS OF IBUPROFEN IB ANTIPYRESIS IN CHILDREN.
392 EMZZ TI Management of childhood fever
393 EMZZ TI Single-dose, placebo-centrolled comparative study of ibuprofen and
acetaminophen antipyresis in children.
394 DDNS
Induced Fever.
395 EMZZ
TI Pharmacodynamics of Ibuprofen Input Rate on Antipyresis in Rats with
TI Pediatric rheumatology
396 DDNS
T! Paediatric P.heumato!ogy: Re-vieTw. The Use of Non-Steroidal h t i - Inflammatory Drugs i n Paediatric Rheumatic Diseases,
397 EMZZ TI Ibuprofen paediatric suspension
398 DDNS TI Paediatric Rheumatology: Original Paper. Gastro-Duodenal Damage Due to
Non-Steroidal Anti-inflammatory Drugs in Children.
399 BIZZ TI IBUPROFEN SUSPENSION IN CHILDREN.
400 EMZZ TI Determination of ibuprofen in human plasma by high-performance liquid
chromatography.
401 BIZZ TI VIEWS ON THE USE OF ANTIPYRETICS IN CHILDREN.
402 DDNS TI Amyloidosis of Juvenile Chronic Arthritis in Turkish Children,
403 BIZZ TI A COMPARATIVE STUDY OF 2 DOSAGE LEVELS OF IBUPROFEN SYRUP IN CHILDREN
WITH PYREXIA.
I C 4 sczz 1 I LuMPAiiiSON OF IBUPRSFEN, ACETAiviiKOPHEN AND PLACEBO-TREATiviEXiu'T OF FEVER IN
CHILDREN.
405 DDNS
-. - _ _
TI Non-Steroidal Anti-Inflammatory Drug-Induced Jejunal and Colonic Diaphragm Disease: A Report of Two Cases.
406 EMZZ TI Antipyretic analgesic overdosage in children. Comparative risks
407 DDNS TI Prevalence of Upper Gastrointestinal Lesions in Patients Taking Chronic
Nonsteroidal Anti-Inflammatory Drug Therapy.
408 DDNS TI Anticholinergic Effects of Drugs Commonly Prescribed for the Elderly:
Potential Means for Assessing Risk of Delirium.
409 EMZZ TI Paediatric antipyrerics. The story so far,
410 DDNS TI Toxicity of' Antirheumatic Medications in Children with Juvenile
Arthritis.
411 BIZZ TI A COMPARISON OF ALUMINUM IBUPROFEN SUSPENSION AND P.CETAMINOPHEN ELIXIR
IN THE TREATMENT OF FEVER IN CHILDREN.
412 SCZZ TI EICOSANOIDS IN HEALTH AND IN DISEASE - AN APPRAISAL.
413 BIZZ TI ANALGESIC-ANTIPYRETIC CHOICES FOR CHILDREN WITH ASTHMA A REVIEW OF
SAFETY AND RISK OF COMMON PREPARATIONS.
414 DDNS TI Colitis Induced by Nonsteroidal Anti-Inflammatory Drugs: Report of Four
Cases and Review of the Literature.
415 BIZZ TI COMPARATIVE STUDY OF THE CYTO GENETIC ACTIVITY OF ACETYL SALICYLIC-ACID
AND BRUFEN.
316 EMZZ TI Pharmacokinetics of common analgesics, anti-inflammatories and
antipyretics in children.
417 DDNS TI Risk for Serious Gastrointestinal Complications Related to Use of
Nonsteroidal Anti-Inflammatory Drugs: A Meta-Analysis.
418 BIZZ TI MEASUREMENT OF ANTI PYRETIC ACTIVITY OF IBUPROFEN AND PARACETAMOL IN
CHILDREN.
419 DDNS TI The Successful Medical Management of Gastric Outflow Obstruction
Associated with the Use of Son-Steroidal Anti-Inflammatory Drugs in the Elderly.
420 BIZZ TI ORAL ANTI PYRETIC THERAPY EVALUATION OF THE PROPIONIC-ACID ~~
DERIVATIVES IBUPROFEN KETOPROFEN FENOPROFEN AND NAPROXEN.
121 DDNS TI Paucity of Renal Complications Associated with Nonsteroidal
Antiinflammatory Drugs in Children With Chronic Arthritis
422 EMZZ TI Calcified thoracic disc with herniation of the nucleus pulposus in a
child.
423 DDNS TI Interactions of Ibuprofen, Influenza and Hyperammonemia in Reye's
Syndrome.
424 EMZZ TI Juvenile rheumatoid arthritis - a review
425 DDNS TI Factors i n the Duration and Discontinuation of Treatment with
Nonsteroidal Anti-Inflammatory Medications.
426 BIZZ TI OPTIMAL ANTI PYRESIS IN CHILDREN
427 EMZZ TI Improved high-performance liquid chromatographic assay of ibuprofen in
plasma.
428 DDNS TI Nonsteroidal Anti-Inflammatory Drugs and the Risk for Chronic Renal
Disease.
129 BIZZ TI ZPdL ATJT: P:'DE'T!C THERAPY EVALC'AT!ON OF !P,LI?P,OFEF!,
430 EMZZ TI Ibuprofen in children with infective disorders - antipyretic efficacy.
431 DDNS TI Drug Use During Breast-Feeding,
432 EMZZ TI Fever: To treat or not to treat
433 DDNS TI Allergic Drug Reactions: Identification and Management.
434 EMZZ TI Antipyretic activity of ibuprofen and paracetamol in children with
pyrexia.
435 DDNS TI Upper Gastrointestinal Lesions in Elderly Patients Presenting for
Endoscopy: Relevance oi"SA1D Usage.
436 EMZZ TI Non-steroidal anti-inflammatory drugs i n podiatric medicine and surgery
437 EMZZ TI Analgesic-antipyretic choices for children with asthma: A review of
safety and risk for common preparations.
438 DDNS TI Pattern and Prevalence of Non-Steroidal Anti-Inflammatory Drug Use in
Elderly Patients with Complicated Peptic Ulcer Disease.
439 DDNS TI Antipyretic Drug Disposition in Febrile Children.
440 EMZZ
with pyrexia.
441 DDNS
TI A comparative study of two dosage levels of ibuprofen syrup in children
TI A Case of Severe Pancytopenia Caused by Ibuprofen.
442 EMZZ TI Optimum management ofjuvenile chronic polyarthritis.
443 DDNS TI Nonsteroidal Anti-Inflammatorv Drug Use and Increased Risk for Peptic -
Ulcer Disease in Elderly Persons.
444 EMZZ T T X i - L r e - : * I I luunirleuluaroL"~iL uses 0f::SA:DS.
445 DDNS TI Naproxen-Associated Pulmonary Infiltrates with Eosinophilia (PIE
Syndrome).
446 EMZZ TI Antipyretic analgesics for children.
441 DDNS TI Determination of Ibuprofen in Plasma by High Performance Liquid
Chromatography.
448 EMZZ TI Comparative study of the antipyretic effect of ibuprofen (oral
suspension) and paracetamol (suppositories) in paediatrics.
449 DDNS TI Ketorolac, an Injectable Nonnarcotic Analgesic.
450 DDNS TI An Assessment of Drug Related Admissions to a Medicine for the Elderly
Unit.
451 EMZZ TI Clinical pharmacology of antipyretics in children.
452 DDNS TI Naproxen-Induced Pseudoporphyria: A Distinctive Photodermatitis
453 EMZZ T1 Treatment of fever in 1982: A review.
454 DDNS TI Aplastic Anaemia Associated with a Non-Steroidal Anti-Inflammatory Drug:
Relapse after Exposure to Another Such Drug.
455 EMZZ TI Analgesics and antipyretics in paediatric medicine
456 DDNS TI Transplacental Cardiovascular Effects of Four Popular Analgesics in
Rats.
457 EMZZ TI Arthritis & rheumatism
458 DDNS TI Nephrotic Syndrome Associated with Nonsteroidal Anti-Inflammatory Drug
Use in Two Children.
459 DDNS TI Pharmacokinetics of Misoprostol in the Elderly, in Patients with Renal
Failure and When Coadministered with NSAID or Antipyrine, Propranolol or Diazepam.
460 EMZZ TI Chronic juvenile arthritis. A study of 46 patients,
461 EMZZ TI Comparative efficacy of aspirin and acetaminophen in the reduction of
fever in children.
462 DDNS TI Non-Steroidal Anti-Inflammatory Drugs and Gastrointestinal Bleeding in
the Elderly.
463 EMZZ TI Mycoplasma pneumoniae infection with arthritis and a varicella-like
eruption
464 DDNS TI Elderly People Taking Uon-Steroidal Anti-Inflammatory Drugs are llnlikely
to Have Excess Renal Impairment.
465 EMZZ TI Ibuprofen and flurbiprofen.
466 DDNS TI Hematologic and Renal Safety of Choline Magnesium Trisalicylate
467 EMZZ TI Antipyretic analgesics for young children
468 EMZZ Ti Oral antipyretic therapy evaluation of the propionic acid derivatives
ibuprofen, ketoprofen, fenoprofen and naproxen.
469 DDNS Ti Immunological Effects of Antiinflammatory Drugs: Testing in MLC
470 EMZZ TI Brufen in the complex treatment of rheumatic fever in children
471 DDNS TI Liquid Chromatographic Method for Indomethacin and Other Inflammatory
Drugs.
472 EMZZ TI Rheumatic disease in children and adolescents
473 DONS -7 T T I I updaic on NSAiDs ill tile Elderly
414 EMZZ TI Optimal antipyresis in children
475 DDNS Ti Ibuprofen Antipyresis and Pharmacokinetics in Children
416 EMZZ TI Evolution ofjuvenile rheumatoid arthritis. A review of 101 patients.
477 DDNS Ti Revised Pharmacokinetic Constants for Use Under Systeme international
478 EMZZ TI Juvenile rheumatoid arthritis
479 DDNS TI Problem of Aspirin lnduced Asthma.
4S0 EhlZZ TI Lymphopenia and hepatic toxicity with ibuprofen
481 DDNS TI Death from Undiagnosed Peptic Ulcer Complications: A Continuing
Chsllenge.
452 EMZZ TI Pyrexia and antipyrexial treatment in children
463 DDNS TI Adenosine and Leukotrienes have a Regulatory Role in Lung Surfnctant
Secretion in the Newborn Rabbit.
484 EMZZ TI Oral antipyretic therapy. Evaluation of ibuprofen.
485 DDNS TI Choice of Non-Steroidal Anti-Inflammatory Drug in Persons Treated for
Dyspepsia.
486 EMZZ TI Drug therapy in juvenile rheumatoid arthritis, with a study of
azathioprine (Norwegian).
487 DDNS TI A Single-Blind Parallel Group Study Investigating the Antipyretic
Properties of Ibuprofen Syrup versus Acetylsalicylic Acid Syrup in Febrile Children.
455 EMZZ __ -. I I I ne use of ibuprofen in the controi of rheumalic [ever cases
489 DDNS TI Steady State Pharmacokinetics of Naproxen in Elderly Rheumatics Compared
with Young Volunteers.
490 DDNS TI The Use of Digoxin in 55 Residential Homes for Elderly People.
491 DDNS TI A Scoring System for Selection of Essential Drugs.
492 DDNS TI Hyponatremic Hypervolemia Caused by a Drug-Drug Interaction Mistaken for
Syndrome of Inappropriate ADH.
493 DDNS TI Evaluation of Renal Function in Elderly Patients Receiving "SAID'S
194 DDNS TI Repeat Prescribing ot"on-Steroidal Anti-Inflammatory Drugs.
495 DDNS TI Nonsteroidal Anti-inflammatory Drugs and Hospitalization for
Gastroesophageal Bleeding in the Elderly.
496 DDNS TI Human Fetal Ductus Arteriosus Constriction from Nonsteroidal
Antiinflammatory Drugs.
497 DDNS TI Cyclooxygenase Inhibition Reduces Placental Transfer: Reversal by
Carbacyclin.
498 DDNS TI Case Report Naproxen-Induced Pseudoporphyria.
499 DDNS TI Time-Dependent Inhibition of Platelet Cyclo-Oxygenase by Indomethacin is
Slowly Reversible.
500 DDNS TI Clinical Pharmacology of Pediatric Antipyretic Drugs.
501 DDNS TI Arachidonic Acid Metabolites Stimulate Phosphatidylcholine Secretion in
Primary Cultures of Type I1 Pneumocytes.
502 DDNS TI First-Trimester Drug Use and Congenital Disorders
5% DDNS TI Prostaglandin Synthesis in Rat Embryo Tissue; The Effect ofNon -
Steroidal Anti-Inflammatory Drugs In Vivo and Ex Vivo.
504 DDNS TI Juvenile Chronic Arthritis in Black and Indian South African Children.
505 DDNS TI Consumption Coagulopathy Associated with Systemic Juvenile Rheumatoid
Arthritis.
506 DDNS TI Familial Palindromic Rheumatism: A Possible Association with HLA.
507 DDNS TI The Hypermobility Syndrome.
508 DDNS TI Constriction of Fetal Ductus Arteriosus by Nan-Steroidal Anti -
Inflammatory Drugs.
509 DDNS
TI ,A. New Eereditary Type of Affection of Skin and Bones. (Russ.).
L
Application for Inclusion of Oral Ibuprofen Suspension To The WHO Model List of Essential Medicines
APPENDIX 11 STATEMENTS OF SUPPORT
Guy's and S t Thomas' NHS Foundation Trust
20''' October 2004
The Secretary Expert Committee Department of Essential Drugs and Medicines Policy (EDM) WHO Essential Medicine List World Health Organisation CH-I211 GENEVA 27 Switzerland
Dear Colleague
Ibuprofen for fever and pain management in children
For a number of years. I have. as a practising paediatrician and academic teacher at the above institution. been involved in the care of children who require safe and
agcd 6 months to 16 years.
I n this context, I have been very impressed by the relative safety and efficacy of Ibuprofen. compared with other available drugs; and we have gradually moved in our own practice to recorninend its use. In this context, and particularly in the context of llie very advantageous Therapeutic Index of Ibuprofen, I w-odd recommend its inclusion in the WIHO Essential Medicines List for the inaiiagement of pyrexial illnesses of childhood.
The reasons for my proposal to your esteemed committee are as follows:
'The literature supports the effect on childhood pyrexia is dose dependent for both ibuprofen and paracetamol and comparative studies with regard lo the rate o f recluction in temperature. degree and the duration of the reducrion. indicate that both the drugs have comparable antipyretic activity'.'.'. The acceptability and tolerability iix hot11 medicines are also hroactly similar ', however. there is some indicalion that Ihuprot'en may have a longer duration of effect'.
i l l .iiiclition. illere are instaii~es \+liere paracetamol may noi LicIiie\:e thc desired ;in1i!3yretic effect nilti o r the dowse recommendations may have been cscerded and ~ot i ie have concluded that ihiiprotkn ma! he p ~ ~ i c ~ i i a r l y iiseliii i n ii child \\lie c:iiiiinI
ui;e nor achieve satisfacrory antipyresis n i t h paracetamol alone
ii'iiplc ^.-* ^*. . -. C1^.^ "A,,... 1"..'.. f-.. 'L. :. a,.... ~~ ._.. I. I .I a ~ A p ~ & *i,a:p&. p u & u u u y UI UK intciLaici1i vii,il diseases ofcliiidreii
4
'l'lial is nor to say that paracetamol is ineffective and there is 110 evidcnce to my Iknowledge that oiie preparation is superior to another in terms of adverse effects Inowever. a large clinical trial involving 84 191 children aged 6 months to I7 years. receiving either paracetainol or ibuprofen revealed few serious adverse effects. giving a11 estimated popiilation risk o f less than 7.7 adverse events per 100,000 patients for the development of gastrointestinal bleeding, acute renal failure. anaphylaxis. or lie ye's s y tidro me5.
In a further randomised controlled study by Lesko et ai. ibuprofen was found to be less likely to exacerbate asthma symptoms when compared to paracetamol (children with known hypersensitivity to paracetamol or NSAIDS being excluded) '.
Ihuprofen also has the advantage that it can be ~ised for mild to moderate pain and reduction of inflammation, although I am aware that this latter property is weaker than its analgesic effect. Considering that children with pyrexia also have concurrent pain, iund [nay have an infective or inflammatory basis for their pyrexia. I can readily see the clinical advantage of using this agent in preference to paracetamol.
Other indications in my paediatric practice include the relief of pain due to headache including migraine, postoperative pain, musculoskeletal, joint and rheumatoid disorders, dental pain and dysmenorrhoea in teenagers.
I note that there is presently no disease / clinical indication heading for antipyretics in EMLib and would recommend that sucli a provision be made with the posology:
Ibuprofen liquid preparation: 5 - 10 mg /kg given 6 - Shourly (with a maximum daily dosz of40 mg / I& d a y ) and &.;en for a maximL:m o f 3 ~ 5 days.
Thank you for your kind consideration.
Yours sincerely
Dr Dipak Kanabar Consultant Paediatrician
References
I . Van Esch 4 . Van Steensel-Moll IHA> et al. Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures. Arch Pediutr Ado/ Mcd 1995. 149 : 632 - 637.
3. Sidler .I. Frey B, Baerlocher K. A double-blind comparison of ibuprofen and paracetamol in juvenile pyrexia. Br .JC/in Pract. 1990: 44 (suppl. 70): 22 - 25.
3 . Aindekar YK. Desai RZ: Antipyretic activity o f ibuprofen and paracetamol in children with pyrexia. Br. J. Clin. Pracf. 1985; 41: 140- 143.
4. Kauffinaii RE, Sawyer LA, Sclieinbautn ML. Antipyretic efficacy of ibuprofen vs acetaminophen. A.JDC 1992; 146: 622 - 625.
5. Lesko SM, Mitchell AA. An assessment of the safety ofpaediatric ibuprofen: a practitioner-based randomised clinical trial. J A M 1995; 273: 929 - 933.
6. Lesko SM, Louik C, Vezina RM, et al. Asthma morbidity after short-term use of ibuprofen i n children. Pediatrics 2002; 109: e20
THE UNIVERSITY OF QUEENSLAND A U S T R A L I A
School of Medicine
Discipline of Paediatrics and Child Health HEAD OF DISCIPLINE Professor Geoff Clegharn 3365 5329
Professor John Pearn 3365 5323 Assoc Pmf Pe!er Oa'?!es 3365 5305 Assoc Prof James Nixon 3365 5322 Or Roy Kimble 3365 5315 Dr Michael Nissen 3365 5021 Or Jane Peake 3365 5333
The University of Quaensland Level 3, RCH Foundation Bullding Royal Children's Hospital Herston Qld 4029 Australia Telephone +61 7 3365 5338 / 3365 5479 Facsimile +61 7 3365 5455
7"' October. 2004,
The Co-ordinator, WHO Essential Medicine List, World Health Organisation, Geneva, SWITZERLAND.
Dear Colleague,
Ibuprofen
For a number of years I have: as a practising paediatrician and academic teacher, been involved in the care of children who require safe and simple antipyretic amlgesia, p a r t i c ~ l d j j hi thz inisiiusent viral diseases of iliildhood.
In this context I have been very impressed by the relative safety and efficacy of Ibuprofen, coinpared with other available drugs; and we have gradually moved in our own practice to recommend its use. In this context, and partic.ularly in the context of the very advantageous Therapeutic hdes of Ibuprofen, I would recommend its inc!usion in the WHO Essential Medicines List.
Thank you for your kind consideration, 1
.m '--
Professor John Peam. Professor of Paediatrics & Child Health.