WHO DRUG INFORMATION VOLUME 19 NUMBER 4 • 2005 PROPOSED INN LIST 94 INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES WORLD HEALTH ORGANIZATION - GENEVA WHO Drug Information Vol 19, No. 4, 2005 World Health Organization WHO Drug Information Contents Drug Management Regulatory Action and News Avian influenza: impact on health Safety update on paediatric use of programmes 273 oseltamivir 301 Influenza antiviral medicinal products for Influenza virus composition for 2006 potential use during a pandemic 274 southern hemisphere winter 301 International biosafety guidelines for Safety and Efficacy Issues influenza vaccine production 301 Veralipride: withdrawal following review of Safety challenges of preventing malaria risk/benefit 302 during pregnancy 286 Pemoline: liver injury risk and market WHO International Drug Monitoring withdrawal 302 Programme: 28th meeting 287 Nelarabine approved for leukaemia and Statins and memory loss 288 lymphoma 303 New safety information on long-acting EMEA proposes new, faster scientific beta-2 agonists 289 advice procedure 303 Meningococcal vaccine and Guillain Barre Withdrawal of Infanrix HepB® 303 syndrome 290 Precautionary suspension of Hexavac®: Trastuzumab and possible cardiotoxicity 291 lowered immunogenicity 304 Trastuzumab: interim treatment Environmental risk assessment for human recommendations 291 and veterinary medicinal products 304 Oseltamivir paediatric adverse events 291 Duloxetine hydrochloride and hepatic effects 292 Intrathecal baclofen: incidents with implantable Recent Publications, drug pump system 292 Information and Events Ibritumomab tiuxetan therapeutic regimen: Promoting drug use in the community 306 cutaneous reactions 293 Interactions with implantable medical Registration of fixed dose combinations 306 devices 293 Sources and prices of HIV medicines and Liquid chemical polymer and serious adverse diagnostics 306 events 294 Screening guidelines for women exposed Atomoxetine and suicidal thinking in children to DES in utero 307 and adolescents 294 The Blue Guide on advertising 307 Paroxetine: first trimester exposure and Chronic airways disease guide 308 congenital malformations 295 Priority medicines for Europe and the world 308 International Pharmacopoeia Access to Medicines Monograph for oral powders 309 Canada and the “Jean Chrétien Pledge to Africa” 296 Launch of new medicines website 312 Proposed International Nonproprietary Names: List 94 315 271 World Health Organization WHO Drug Information Vol 19, No. 4, 2005 WHO Drug Information e-mail table of contents and subscriptions available at: http://www.who.int/druginformation 272 WHO Drug Information Vol 19, No. 4, 2005 Drug Management Avian influenza: impact including subtypes from different species, can swap or “reassort” genetic materials and merge. on health programmes This reassortment process, known as antigenic “shift”, results in a novel subtype different from Avian influenza is an infectious disease of birds both parent viruses. As populations will have no caused by type A strains of the influenza virus. immunity to the new subtype, and as no existing The disease, which was first identified in Italy vaccines can confer protection, antigenic shift has more than 100 years ago, occurs worldwide. historically resulted in highly lethal pandemics. For this to happen, the novel subtype needs to All birds are thought to be susceptible to infection have genes from human influenza viruses that with avian influenza, though some species are make it readily transmissible from person to more resistant to infection than others. Infection person for a sustainable period. causes a wide spectrum of symptoms in birds, ranging from mild illness to a highly contagious Conditions favourable for the emergence of and rapidly fatal disease resulting in severe antigenic shift have long been thought to involve epidemics. The latter is known as “highly patho- humans living in close proximity to domestic genic avian influenza”. This form is characterized poultry and pigs. Because pigs are susceptible to by sudden onset, severe illness, and rapid death, infection with both avian and mammalian viruses, with a mortality that can approach 100%. including human strains, they can serve as a “mixing vessel” for the scrambling of genetic Fifteen subtypes of influenza virus are known to material from human and avian viruses, resulting infect birds, thus providing an extensive reservoir in the emergence of a novel subtype. Recent of influenza viruses potentially circulating in bird events, however, have identified a second populations. To date, all outbreaks of the highly possible mechanism. Evidence is mounting that, pathogenic form have been caused by influenza A for at least some of the 15 avian influenza virus viruses of subtypes H5 and H7. subtypes circulating in bird populations, humans themselves can serve as the “mixing vessel”. A constantly mutating virus All type A influenza viruses, including those that Clinical course and treatment of human regularly cause seasonal epidemics of influenza cases of H5N1 avian influenza in humans, are genetically labile and well adapted Tests for diagnosing all influenza strains of to elude host defenses. Influenza viruses lack animals and humans are rapid and reliable. Many mechanisms for the “proofreading” and repair of laboratories in the WHO global influenza network errors that occur during replication. As a result of have the necessary high-security facilities and these uncorrected errors, the genetic composition reagents for performing these tests as well as of the viruses changes as they replicate in considerable experience (http://www.who.int/csr/). humans and animals, and the existing strain is Rapid bedside tests for the diagnosis of human replaced with a new antigenic variant. These influenza are also available, but do not have the constant, permanent and usually small changes in precision of the more extensive laboratory testing the antigenic composition of influenza A viruses that is currently needed to fully understand the are known as antigenic “drift”. most recent cases and determine whether human infection is spreading, either directly from birds or The tendency of influenza viruses to undergo from person to person. frequent and permanent antigenic changes Antiviral drugs, some of which can be used for necessitates constant monitoring of the global both treatment and prevention, are clinically influenza situation and annual adjustments in the effective against influenza A virus strains in composition of influenza vaccines. otherwise healthy adults and children, but have some limitations. Some of these drugs are also Influenza viruses have a second characteristic of expensive and supplies are limited. great public health concern: influenza A viruses, 273 Drug Management WHO Drug Information Vol 19, No. 4, 2005 Experience in the production of influenza vac- discussed in a workshop with European Experts cines is also considerable, particularly as vaccine held in February 2005. The review and its recom- composition changes each year to match mendations were submitted to the Commission in changes in circulating virus due to antigenic drift. March 2005. The consensus reached at that time However, at least four months would be needed is summarized below. to produce a new vaccine in significant quantities, capable of conferring protection against a new It should be noted that by no means should any of virus subtype. the following scientific guidance on the use of antivirals in a pandemic situation be regarded as introducing derogation(s) to the terms of existing Influenza antiviral medicinal marketing authorisation. products for potential use during a pandemic* Overview of available antivirals There are four potential antiviral agents for the Occasionally, emerging influenza A virus strains widespread use during an influenza pandemic, undergo major changes in their genes, especially M2 inhibitors amantadine and rimantadine as well in the neuraminidase (NA) and haemagglutinin as the neuraminidase inhibitors oseltamivir and (HA) genes. This may be due to an adaptation of zanamivir. an avian or porcine strain to the human host or to a genetic reassortment in a coinfection setting. The changes may provide the virus means for Adamantane class (M2 inhibitors) both increased infectivity and altered tissue distribution as well as a possibility to avoid Rimantadine detection by the host immune defence. Therefore, the new strains may have the capacity of causing Rimantadine inhibits the M2 membrane protein severe worldwide pandemics. It is also possible ion channel activity. This results in inhibition of the that the past pandemic strains will re-emerge after acidification of the virus interior which is required being dormant for decades. to promote fusion of the viral envelope with the endosome and for dissociation of the M1 matrix An influenza pandemic is a major acute threat to protein from the ribonucleoprotein complex public health and warrants a concerted action for (uncoating). Consequently, viral replication is pandemic preparedness within the European blocked at an early stage of infection. Other Union. A wider international collaboration under effects may occur at later stages of the virus the auspices of WHO is crucial for the proper replication cycle. surveillance and timely execution of pandemic plans. Influenza antiviral medicinal products and Amantadine and rimantadine differ significantly in pandemic influenza vaccines have a complemen- their pharmacokinetics, with rimantadine