11 December 2002

Inclusion of Paediatric Ibuprofen Formulations on the

WHO Essential Drugs List

Introduction

Paracetamol suspension and suppositories are included in the World Health Organisation Essential Drug List, indicated as an analgesic and antipyretic. These dosage forms are suitable for use by the paediatric population. Acetylsalicylic acid is included in the list in 100-500mg tablet and 50-150mg suppository form. Where licensed, the suppositories may be used for paediatric use. Ibuprofen is included in the list only in 200mg and 400mg tablet form as an analgesic and antipyretic. Generally, 200mg ibuprofen is indicated only in children above the age of twelve years. We believe there is a sufficient body of evidence to allow the inclusion of paediatric ibuprofen formulations for paediatric use in the WHO Essential Drugs List.

The following information relates to ibuprofen suspension and suppository and refers to its global regulatory status and to data comparing the efficacy of ibuprofen to paracetamol in paediatric use. A comparison to acetylsalicylic acid has not been included. The use of aspirin in the paediatric population is limited due toconcerns over the association with Reye’s syndrome.

Given the wealth and consistency of data, we would like to progress an “application” to include the paediatric formulations on the WHO Essential Drugs List.

Ibuprofen

Ibuprofen is a non-steroidal anti-inflammatory drug with established analgesic, anti-inflammatory and antipyretic properties. It is a propionic acid derivative and is licensed for adult and paediatric use in many countries. Ibuprofen was first approved in the UK in February 1969 and has been one of the most heavily prescribed non-steroidal anti-inflammatory drugs (NSAIDs) since then. It was launched in the UK as an over-the-counter (OTC) medicine, Nurofen, in 1983 and is now widely used in self-medication. A switch to General Sales List (GSL) status in the UK was obtained in January 1996.

A Boots Healthcare International (BHI) paediatric ibuprofen suspension was first approved as a prescription-only medicine (POM) in the UK in 1989. The product was launched in 1990 and obtained OTC status in 1994. Appendix 1 lists those countries where BHI have a licensed paediatric ibuprofen product.

Efficacy versus Paracetamol

Fever is one of the most common symptoms in children, responsible for 20-30% of visits to the GP or paediatrician. Symptomatic treatment with rapid onset may be required to avoid discomfort, dehydration and febrile seizures.

The efficacy of ibuprofen in the treatment of pyrexia has been studied in comparator and placebo-controlled studies. The comparator most frequently used is paracetamol. Licensed doses of ibuprofen vary between countries, as they do for paracetamol. For all licensed doses, ibuprofen has been shown to be at least as effective as paracetamol in treating fever. There is evidence that, at some licensed doses, ibuprofen is superior to paracetamol.

As a general analgesic for short-term use, the efficacy of ibuprofen is at least equivalent to that of paracetamol. In more long-term treatment, ibuprofen has anti-inflammatory properties which make it a more suitable analgesic than paracetamol in disorders such as chronic juvenile arthritis.

Safety

The tolerability of ibuprofen when used as a short-term antipyretic/analgesic is similar to that of paracetamol. A large safety study involving 84,000 children showed a similar safety profile for ibuprofen and paracetamol (Lesko & Mitchell, 1995).

The risk of asthma complications in a subset of 1,876 children with asthma was significantly lower among those children treated with ibuprofen who had no known sensitivity to this medication, compared to those treated with paracetamol (Lesko et al, 2002). Furthermore, the wide therapeutic index of ibuprofen confers an advantageous safety profile in overdose when compared to paracetamol.

References:

Lesko SM, Mitchell AA

An assessment of the safety of paediatric ibuprofen

JAMA 1995; 273 (12): 929-931

Lesko SM, Louik C, Vegina RM, Mitchell AA

Asthma morbidity after the short-term use of ibuprofen in children

Paediatrics 2002; 109 (2)

APPENDIX I

Regulatory and Marketing Status in EU countries

Territory / Trade Name / Status / Date of Approval / Date of Launch
France / Nureflex enfants et nourrissons / OTX / 20.12.93 / 06.94
Nureflex enfants et nourrissons sans sucre / OTX / 11.00 / 04.02
Belgium / Junifen / P / 13.11.95 / 12.95
Junifen suikervrij / P / 09.03.98 / 01.99
Luxembourg / Junifen / P / 05.06.96 / 07.96
Junifen suikervrij / P / 30.09.98 / 01.99
Denmark / Nurofen Junior Mikstur / POM / 05.08.96 / Not marketed
The Netherlands / Nurofen voor kinderen suikervrije suspensie / P / 15.07.97 / 08.99
United Kingdom / Nurofen for Children
Nurofen for Children Singles (sachets) / P
GSL / 11.03.98
12.04.02 / 04.98
Not yet launched
Greece / Nurofen for Children / POM / 24.09.98 / Not marketed
Ireland / Nurofen for Children / P / 21.12.98 / 03.99
Germany / Nurofen fur kinder fiebersaft / P / 20.04.99 / 06.99
Portugal / Junifen / POM / 16.10.99 / Not marketed
Austria / Junifen / POM / 19.10.99 / Not marketed
Spain / Junifen suspension / POM / 08.03.00 / 05.00
Italy / Nureflex Bambini Suspensione / POM / 30.08.00 / 26.10.00

Regulatory and Marketing Status in non EU countries

Territory / Trade Name / Status / Date of Approval / Date of Launch
South Africa / Nurofen Junior Suspension
Nurofen for Children Sugar Free / P
P / 01.06.90
28.06.00 / Unknown
Not launched
Botswana / Nurofen Junior Suspension / OTC / 01.06.90 / Unknown
Namibia / Nurofen Junior Suspension / OTC / 01.06.90 / Unknown
Thailand / Junifen / POM / 29.03.91 / 04.91
Saudi Arabia / Junifen / POM / Unknown / 04.93
Philippines / Nurofen syrup / POM / 04.05.95 / 08.95
Malaysia / Nurofen for Children / P / 05.01.98 / 07.99
Australia / Nurofen for Children / P / 03.02.98 / 09.99
Russia / Nurofen for children (in Russian) / OTC / 06.03.98 / 04.98
Romania / Nurofen pentru copii / OTC / 01.08.98 / 09.98
Hong Kong / Nurofen Syrup / P / 05.09.98 / 02.99
New Zealand / Nurofen for Children / P / 12.03.99 / 04.99
Hungary / Nurofen Szuszpenzio Gyermekeknek / P / 12.03.99 / Not launched
Singapore / Nurofen syrup / POM / 25.05.99 / 07.99
Cyprus / Nurofen for Children Sugar Free / OTC / 15.09.99 / 10.99
Israel / Nurofen for Children / POM / 27.10.99 / 04.00
Poland / Nurofen zawiesina dla dzieci / OTC / 16.11.99 / Not marketed
Czech Republic / Nurofen Pro Deti / OTC / 02.02.00 / 04.00
Slovak Republic / Nurofen for Children / OTC / 04.05.00 / 11.00
Bulgaria / Nurofen for Children / POM / 05.06.00 / Not launched

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