WHO DRUG INFORMATION VOLUME 3 • NUMBER 4 • 1989 PROPOSED INN LIST 62 INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES WORLD HEALTH ORGANIZATION • GENEVA WHO Drug Information WHO Drug Information provides an cerned with the rational use of overview of topics relating to drug drugs. In effect, the journal seeks development and regulation that to relate regulatory activity to are of current relevance and im­ therapeutic practice. It also aims to portance, and will include the lists provide an open forum for debate. of proposed and recommended In­ Invited contributions will portray a ternational Nonproprietary Names variety of viewpoints on matters of for Pharmaceutical Substances general policy with the aim of (INN). Its contents reflect, but do stimulating discussion not only not present, WHO policies and ac­ in these columns but wherever tivities and they embrace socio­ relevant decisions on this subject economic as well as technical mat­ have to be taken. ters. 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ISSN 1010-9609 WHO Drug Information Vol. 3, No. 4, 1989 World Health Organization, Geneva WHO Drug Information Contents General Policy Topics Ethylene oxide: a potential carcinogen? 183 Hair restorers on prescription only 184 Reserve antibiotics 165 Mefloquine: restrictive labelling 184 Metamizole: withdrawal of combination Personal Perspectives products 184 Counterfeit medicines: a problem Sulfonamides: suppository formulations of today 167 withdrawn 185 L-Tryptophan supplements Reports on Individual Drugs and eosinophilia-myalgia syndrome 185 Vasodilator therapy following myocardial infarction 169 Advisory Notices Praziquantel: are there brand differences? 169 Delayed shock and low osmolar Progestational contraceptives: radiocontrast media 186 also a risk factor for breast cancer? 170 Counterfeit dermatological products 186 Plasma substitutes and renal failure 171 Counterfeit Fansidar® 186 Haemopoietic growth factors as Flunarizine and extrapyramidal symptoms 186 adjuvants in cancer chemotherapy 171 Minoxidil and contact dermatitis 186 Haemophilia: the therapeutic dilemma 172 Retinoids and necrotizing vasculitis 187 Calcium channel blockers: a need Steroid aerosols and cataract 187 for reassessment? 173 Oral contraceptives and older women 188 Antimalarials and pruritus 174 Xamoterol: inappropriate for severe heart failure 188 General Information Zidovudine: carcinogenic potential 188 Should antimalarials be given to all Zidovudine-induced neutropenia 188 pregnant women at risk? 175 Cost-effective health care delivery 176 Cost-conscious prescribing 176 Essential Drugs Hazards of herbal medicines 177 WHO Model List: Sixth Revision 191 Generic drug products: is interchangeability still an issue? 178 204 Drugs in donated blood 179 Newly Registered Products Adverse reaction reporting: engaging commitment 179 DNA probes: a new generation Recent Publications of diagnostic tools 180 The role and function of the pharmacist How often are drugs really taken? 181 in Europe 205 Asthma: inadequacies in concepts Clandestinely produced drugs, and management 181 analogues and precursors 205 Naming organic compounds 205 Regulatory Matters The business of pharmaceutical inspection 206 Aminoglycoside antibiotics: restrictive measures 183 Aphrodisiac activity: no more claims 183 Proposed International Non­ Cosmetics: disclosure of ingredients 183 proprietary Names: List 62 207 i WHO Drug Information Vol. 3, No. 4, 1989 General Policy Topics Reserve antibiotics with the emergence of multiresistant staphylococci Few would contest that antibiotics have contributed (many of which are now sensitive only to vanco­ more to the advancement of medical care over the mycin), has shown that the evolution of resistance past half-century than virtually any other class of constantly threatens to outstrip innovative capacity. therapeutic substances. Where they are readily available and effectively used, bacterial disease Great harm has similarly resulted, to quote but one has long ceded its former dominance as a primary further example, from widespread incursions of cause of mortality. But there are no grounds for resistant beta-lactamase-producing strains of complacency because pathogenic bacteria are Haemophilus influenzae (7) and gonococci (8). Now constantly posing new therapeutic challenges. fears are being expressed that multiresistant strains Earlier editions of institutional and national formu­ of such major and ubiquitous pathogens as laries provide a salutory reminder that, twenty years Streptococcus pyogenes (9) and Streptococcus ago, all but the most exceptional needs were pneumoniae (10) threaten to become more widely satisfied by 20 to 30 substances. Today, the same distributed. As yet, there is no means of determin­ handbooks list at least three times as many. Costs ing the likely extent of such trends since they follow are also escalating: it is claimed that, in many no established pattern. health-care settings, antibiotics now account for 15 to 30 per cent of the total drug budget (1). What is certain is that these and many other manifestations of resistance are genetically In some measure, these developments are forced determined and that the diverse cytoplasmic by the degree to which the effectiveness of long- transposons and plasmids that carry many of the established, relatively cheap antibiotics has been responsible genes sometimes migrate to other eroded by resistant strains of pathogenic bacteria strains and species of bacteria (3). The potential for (2, 3). It is inevitable that any use of antibiotics will transfer of one, or even of several genes encoding tend to generate selection pressure favouring the for specific mechanisms of resistance is conse­ emergence of resistant strains. However, this quently limitless and largely unpredictable. Inevita­ pressure has been intensified, gratuitously and bly, the outcome is that the resulting emergence of sometimes recklessly, firstly, by the prodigious resistance often makes the cheaper, long-estab­ scale on which these substances are now used — lished antibiotics unreliable for use in serious not only within medicine but in livestock farming (4) infections. — and, secondly, by irrational prescribing practices often inspired by the promotion of broad spectrum This reality has led a WHO Expert Committee, antibiotics as panaceas which dispose of the need meeting in Geneva in December 1989, to consider for diagnostic precision (5, 6). how the situation might best be reflected in the latest biennial revision of the Model List of Essential Too often in the past such complacency has been Drugs (set out on page 191 of this issue). It has fuelled by expectation that the pharmaceutical decided that the concept and purpose of the List industry can be confidently relied upon to produce would be unacceptably compromised simply by yet another generation of effective and safe incorporating into it a range of relatively new and substances to replace those compromised by resis­ expensive antibiotics. Instead, it proposed the con­ tance, and that the prevalence of resistant strains cept of "reserve antibiotics" — substances which can, in any case, be reduced simply by adjusting are useful for a wide range of infections, but which prevailing prescribing policies to relieve the are inappropriate for unrestricted use because of selection pressure. Neither of these assumptions is the need to reduce the risk of development of resis­ warranted. The performance of the research-based tance to them and because of their relatively high pharmaceutical industry in the innovation of cost. It identified the third generation cefalosporins, antibiotics has, indeed, been spectacular. However, the quinolones, and vancomycin as being illustra­ experience over the past two decades, particularly tive of such products in the following situations: 165 General Policy Topics WHO Drug Information Vol. 3, No. 4, 1989 "Several third generation cefalosporins are suitable ment and use of antibiotics everywhere and