WHO DRUG

INFORMATION

VOLUME 10 • NUMBER 3 • 1996

RECOMMENDED INN LIST 36 INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES

WORLD HEALTH ORGANIZATION • GENEVA Volume 10, Number 3, 1996 World Health Organization, Geneva

WHO Drug Information

Contents

General Policy Topics WHO and harmonization of pharmaceutical HIV protease inhibitors and spontaneous regulations 125 bleeding 135 Terbinafine: surprising number of reports 136 Personal Perspectives Withdrawal of topical products containing gentamicin 136 Prevention of medication errors: vaccines 127 Emergency contraceptives recommended for over-the-counter (OTC) use? 136 Reports on Individual Drugs Conjugated estrogens and generic Combined oral contraceptives and stroke 131 pharmaceuticals 137 Azithromycin: a new opportunity for control Chlormezanone withdrawn following skin of trachoma 132 reactions 137 Marketing authorization of fixed combination Regulatory Matters medicinal products 137 Alendronic acid-induced oesophageal ulcers 134 Oral contraceptives containing desogestrel Recommended International or gestodene: updated position statement 134 Temazepam now a controlled drug 135 Nonproprietary Names: List 36 139

i WHO Drug Information Vol. 10, No. 3, 1996

General Policy Topics

WHO and harmonization of Work on The International Pharmacopoeia dates back to the First World Health Assembly in 1948, pharmaceutical regulations when WHO was requested to "set up within its Secretariat a section on the unification of pharma- As an intergovernmental organization with some copoeias." The preparation of monographs for The 190 Member States, the World Health Organization International Pharmacopoeia is carried out in has an explicit responsibility to promote normative consultation with an international panel of experts initiatives directed towards international harmoniza- and with reference to current pharmacopoeias. tion of standards wherever and whenever this is Emphasis is placed on the use of methods which appropriate within the health sector. Article 2 (u) of are accessible to modestly equipped quality control the WHO Constitution — with particular reference laboratories in countries with limited resources. to pharmaceutical products — requires the Organization to "develop, establish and promote The aim of the WHO Certification Scheme on the international standards with respect to food, quality of pharmaceutical products moving in biological, pharmaceutical and similar products". international commerce is to provide a normative These standards, norms, guidelines, guiding instrument and channel for the exchange of principles and codes of good practice are prepared information between the competent authorities in by the WHO Secretariat in close collaboration with importing and exporting countries. It provides Member States. The consultations, advisory information on the regulatory status of a product in meetings and WHO Expert Committee meetings the exporting country, the manufacturer's com- which take place involve drug regulators, scientists, pliance with WHO good manufacturing practices representatives of the pharmaceutical industry and (GMP), and approved product information in the other interested parties. Subsequently, the WHO exporting country. governing bodies discuss and, if appropriate, endorse these normative recommendations with a More recently, harmonization activities have view to implementation by Member States. focused on good manufacturing practices (GMP). Revised WHO GMP Guidelines were published in Since its very inception in 1948, WHO has been 1992, and these have been complemented with involved in several long-standing normative guidelines on the inspection of manufacturers, activities that have direct relevance to drug validation of manufacturing processes, and GMP regulators, the pharmaceutical industry and public for investigational pharmaceutical products and health worldwide, and it is now engaged in several biological products. As local production of pharma- new areas of harmonization that have immediate ceuticals and biologicals increases and spreads impact on new drug development, production and into the new manufacturing countries, these trade, and the regulatory control of pharmaceutical guidelines will become more and more relevant in products. underpinning the internationally recognized standards which form the basis of quality As an example of WHO's long-standing normative assurance. activities, the designation of International Non- proprietary Names (INNs) for Pharmaceutical Since its creation in 1975, the WHO Model List of Substances has been ongoing since 1953, and Essential Drugs has been updated every two years. between 120 and 140 new INNs are currently More recently, it has been supplemented with selected and published each year. INNs identify WHO Model Prescribing Information. The Model pharmaceutical substances by unique, globally List provides a rational basis not only for the recognized names. A single internationally selection and procurement of essential drugs at recognized name for an active drug substance is national level, but also for establishing priority drug vital for safe prescribing and dispensing and for requirements within the health care system. ease of communication among scientists and health professionals worldwide.

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Guidelines for Good Clinical Practice (GCP) for in this forum is vital if it is to remain fully informed of trials on pharmaceutical products have also been progress made and to provide a communication prepared, in consultation with representatives of and consultation bridge between the 17 ICH drug regulatory authorities, academia and the countries and the remaining non-participating WHO pharmaceutical industry. The purpose of the Member States. This point was re-emphasized by Guidelines is to set globally applicable, ethical and the World Health Assembly in resolution WHA45.28 scientific standards for the conduct of biomedical in 1992 when it noted the progress made in ICH research on human subjects. and recognized WHO's intergovernmental role within the harmonization process. The same Other areas of activity within the harmonization resolution endorsed the International Conferences process are: the drafting of Model national of Drug Regulatory Authorities (ICDRA) as an legislation for pharmaceuticals; Guidance to institution, and invited the pharmaceutical industry prevent antimicrobial resistance; Guidelines for the to continue to collaborate with drug regulatory prevention of distribution and sale of counterfeit authorities and with WHO, where appropriate, in drugs; and the WHO model formulary for essential order to ensure that harmonization is of benefit to drugs. Work also continues on the selection of all concerned. international reference products or "comparators" for use in equivalence studies, and on Guiding If successful, harmonization of pharmaceutical principles for regulatory approval of inter- requirements will result in substantial savings in changeable multisource (generic) pharmaceutical both time and cost involved in the development and products. investigation of new drugs. Animal testing will be more rational and unnecessary duplication of The biologicals area is one of expansion and preclinical studies will be eliminated. Harmonization increasing diversity, and this is particularly reflected will enhance regulatory assessment and approval by the latest trends in biotechnology. This sector is by simplifying and unifying scientific documentation. evolving rapidly, not only in developed countries, This means that new treatments can be introduced but also in an increasing number of developing more quickly, to the benefit of all concerned. countries. It is important that activities within this Agreement on common core documentation and area are supported and strengthened and that dossiers for efficacy, safety and quality will facilitate globally agreed standards are applied on a timely regulatory reviews and international recognition of basis to these products. It is foreseeable that new drug approvals. innovative technologies and scientific break- throughs will soon provide us with products different For norms and standards to be, firstly, applicable from anything known to us today, raising new and then, effectively implemented, all partners critical issues of how to deal with safety, efficacy concerned must be involved in the negotiation and quality. Such issues require internationally process as early and as fully as possible. As a agreed and written physical standards, together member of this partnership, WHO is ready to meet with a global exchange of both information and the challenge of harmonization in all areas of experience on the development and use of rapidly advancing modern technology. biologicals. Juhana E. Idänpään-Heikkilä, M.D., DMSc., WHO has been invited as an observer to the Director, working groups for quality, safety and efficacy of Division of Drug Management & Policies, the International Conference of Harmonisation World Health Organization, Geneva. (ICH) since its inception in 1990. WHO's presence

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Personal Perspectives

Prevention of medication A standard approach to classifying errors is to create categories such as: wrong patient, wrong errors: vaccines drug, wrong dose. However, this method does little to pinpoint where improvements in the delivery John D. Grabenstein, system can be made. Army Medical Department University of North Carolina, USA, Instead, we suggest classifying errors according to & Susan M. Proulx and Michael R. Cohen, severity (3). This helps concentrate quality- Institute for Safe Medication Practices (ISMP) improvement efforts where risks are greatest. It will Warminster, PA, USA. also help identify where: e mail: [email protected] ¥ the system failed to catch the error, and how this Vaccines are no more or less likely to be involved in affected the patient; medication errors than other drugs. Nevertheless, it is helpful to consider this group of medicinal ¥ the system worked and stopped the error before it products in isolation, especially in light of the affected the patient; and consequences of immunological reactions to a ¥ the system identified an uncorrected risk, which medication error. can be defined as "someone will be harmed if a change is not made". From the disciplines of engineering and aerospace research, medication error experts have borrowed Next, the component of the system that failed must the term "failure mode and effects" and have be categorized (4). A single incident can involve created an analysis system (FMEA). This technique multiple failures of a system. The following recognizes the inevitability of human error and illustrative examples serve to show how this works. encourages the development of systems to Most are actual cases; others are accidents that anticipate, prevent and recover from human error. could happen. The goal of FMEA is to identify mistakes that could happen before they happen, and determine 1. Paediatric-strength diphtheria-tetanus toxoids whether the consequences of such errors are (DT) have been confused with adult-strength tolerable or intolerable. When FMEA indicates that tetanus-diphtheria toxoids (Td) because of the an error would be intolerable, "safety layers" are similarity in label wording and print-type styles and added to the procedures involved. The more layers because official titles of the products are so similar. or error traps that are added, the safer the system This error can be averted through clearer labelling. — albeit cumbersome — and the less likely it will be for the patient to suffer injury (1). By planning 2. An obsolete colloquial term for rubella in the ahead, health professionals can strengthen their United States is German measles. The wrong error-detection system and minimize the potential vaccine has been given when health workers for error, or at least its consequences. The following confuse vaccines against measles and German is a summary and discussion of some reports of measles. Alternative terms for the two are no better: errors involving vaccines, as well as anecdotal rubeola and rubella. In this case, use of the words reports known to the authors (2). By agreement measles and rubella should be encouraged and use with the United States Pharmacopeia, the Institute of the other terms should be actively discouraged. for Safe Medication Practices (ISMP) is notified of This can be achieved through training and the all voluntary reports submitted by practitioners to cooperation of industry and regulatory authorties. the USP's Medication Errors Reporting Programme. The ISMP also reviews medication error reports 3. Several sound-alike or look-alike names involve submitted to the US Food & Drug Administration vaccines: varicella and vaccinia; hepatitis A and MedWatch programme. hepatitis B; Haemophilus influenzae type B (HiB)

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and viral influenza; HiB and hepatitis (hep) B. A question frequently arises concerning intra- These names can easily be confused in verbal or muscular injections that are inadvertently written communication. administered subcutaneously. Subcutaneous injections, in general are absorbed more slowly 4. Abbreviations are another major source of error than the equivalent volume injected intramuscularly. (5, 6). DTP is commonly understood in English to This has resulted in reduced antibody titres in some refer to diphtheria-tetanus-pertussis vaccine. But it cases (7). has also been used in the United States as short- hand for a sedative cocktail of Demerol (meperi- Perhaps the most frequently reported errors dine, pethidine), Thorazine (chlorpromazine) and involving vaccines concern improper dose Phenergan (promethazine). Several cases have measurements. The main culprit within the USA occurred where a child was vaccinated rather than may be hepatitis B vaccine, where a wide variety of receiving the sedative mixture. No doubt analogous doses are recommended, depending on the situations exist in other countries. patient's age and the brand of the vaccine. If health care institutions change from one brand to the 5. What does the abbreviation MR mean? Some other, or from paediatric to adult formulations, people will guess measles-rubella vaccine, while vaccine administrators need to be alerted to the others will assume mumps-rubella vaccine. There is change in dose volumes. When this error occurred no single correct answer and the listener or reader recently at a hospital, some 1400 newborns were can infer a different product than the one intended. left vulnerable to hepatitis B over a 2-year period. It is the speaker's or writer's responsibility to be After changing brands, the pre-printed order forms clear. that listed the old volume of hepatitis B vaccine were not updated with the correct volume for the 6. Reliance on brand names is helpful only if all new brand. To address the error, the hospital workers fully understand the ingredients involved. pharmacy involved switched to dispensing pre-filled Suffixes attached to a brand name are a special single-dose syringes and expanded its educational source of confusion. An error occurred when programmes (8). Imovax ID for pre-exposure rabies immunization was inadvertently substituted for Imovax for pre- The complexity of products and schedules for HiB and post-exposure treatment. The error was caught vaccines presents more opportunities for error. after an exposed patient received pre-exposure Workers are often accustomed to vaccines being vaccine for two of the five post-exposure doses. available from only one manufacturer or, Luckily, the patient suffered no ill effects. occasionally, prophylactically equivalent vaccines being available from a short-list of manufacturers 7. Other sources of miscommunication involve bad with comparable instructions for use. Several non- handwriting. Many errors have occurred when a equivalent protein-conjugated HiB vaccines present health worker misunderstood a written order. Using an entirely different situation — one disease with abbreviations such as "u" for units can lead to fatal many unique vaccines used on several distinct overdoses when mistaken for a zero or the figure schedules: Act HIB (SmithKline & Connaught), four. The word "units" should never be abbreviated. HibTITER (Wyeth-Lederle), PedvaxHIB (Merck) Trailing zeros after a decimal point have led to ten- and ProHIBiT (Connaught). fold overdoses when the decimal point is over- looked. To prevent this error always use 4 mg Ð not If adult-strength tetanus-diphtheria toxoids (Td) are 4.0 mg. On the other hand, use a zero preceding a prescribed, but DTP is delivered, the error is in the decimal point for amounts less than one. Write, for drug distribution system. Was there no Td on hand, example 0.2 ml and not .2 ml. The US Pharmaco- and was DTP erroneously provided? Or were both peia insists on this within the USA. products in the refrigerator, but placed in the wrong locations? Or did the person who took the DTP out Not having enough information about the patient is of the proper bin in the refrigerator not understand another factor in vaccine mishaps. For example, the distinction between the two products? Whatever failure can occur when charts or computerized the answer, the way to prevent future errors of this patient profiles are not marked adequately; when sort lies in correct purchasing and drug storage patients or parents are not queried about reactions methods, and in education. after a previous dose; or when clinicians do not use the proper diagnostic process to identify true In another case, health workers reached into a adverse events after immunization. refrigerator and somehow pulled out the neuro-

128 WHO Drug Information Vol. 10, No. 3, 1996 Personal Perspectives

muscular blocker pancuronium bromide instead of agenda for discussion wherever this is a relevant influenza vaccine. This error was repeated for five issue. To receive ISMP's biweekly safety alerts and or six patients before it was discovered. Fortunate- error reduction tips, send your e-mail address to ly, in this case no harm came to the patients at the [email protected]. 0.5 ml dose but it was found that similarly coloured labels were at the root of the mix-up. Among the greatest risks are the silent errors which go unrecognized. Not only can they do harm to This phenomenon is called "confirmation bias" and individual patients, but they can be repeated again happens when practitioners rely too often on and again (10). Hospitals and health institutions familiar evidence — the colour and shape of the need open systems where preventing future errors vials for instance — while missing the drug names takes precedence over blaming or punishing on the containers. Health workers easily confuse employees. Talented, creative employees must look-alike packaging and one way to reduce error have an opportunity to communicate their ideas on potential of this type is to repeat the name of the error prevention. People are much more likely to drug to yourself and then read the container label share ideas if they feel that action will be taken to (9). address the problems.

Another report describes the case of two people While computers can speed delivery of medications reporting to a clinic. One was to be vaccinated to patients and provide a basis for information against hepatitis B and the other with Td. Instead, retrieval and storage, they can also contribute to both people received a dose of hepatitis B vaccine. errors. A hospital's computer system is only as A cause for the error was not found, but it is easy to good as the people who use it. Orders entered into speculate that it could have been caused by a the computer must be double-checked against the telephone call or a visitor distracting the nurse. original order before filling. Alternatively, the mistake may have resulted from a lapse in attention, stress, or miscommunication. Because so many vaccines are identified by their Personnel turnover or other forms of inadequate abbreviations, the potential for error using computer staffing can place health workers in a situation mnemonics for their names is great. So-called where they are insufficiently prepared. "short codes" can be interpreted in many different ways. Mumps skin test antigen (MSTA) and mumps vaccine have been confused over the years, in both We all expect vaccines to perform minor miracles in directions. MSTA has been administered in a futile just one or a few doses. If a decade or more of attempt to immunize and mumps vaccine has been protection results from these doses, vulnerability to given in a fruitless effort to assess cell-mediated a preventable infection as a result of vaccine failure immunity. In many cases, these errors result from may persist for a long term, and may even prove rapid staff turnover that places inadequately trained fatal. personnel in decision-taking positions. This particular error is abetted by related system failures According to studies, at least one error occurs for involving nomenclature and distribution. every patient hospitalized (10). Professionals should therefore take the following precautions: Any quality improvement system needs a means of evaluating errors and averting future ones. One of ¥ Be involved in the selection of vaccines used at the most effective methods of safety evaluation is your practice site. often overlooked: that is, to discuss reports of errors from elsewhere. ¥ Consider the potential for product mix-ups when storing vaccines and other injectables. Professional groups, including the Institute for Safe Medication Practices in the USA, publish accounts ¥ Keep reference information which is up-to-date for of errors in journals and newsletters to alert health each vaccine and educate health workers on workers to the problems. Efforts are also under way proper use. by the FIP (Féderation internationale pharma- ceutique) and ISMP to stimulate such programmes ¥ Double-check your work. Ask others to do the worldwide. Risk-management should be on the same.

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¥ Use single-dose injections wherever possible. The 3. American Society of Hospital Pharmacists. Guidelines added cost is far outweighed by the increased on preventing medication errors in hospitals. American safety to the patient. Journal of Hospital Pharmacy, 50: 305Ð314 (1993). 4. Cohen, M.R. Risk management of medication errors ¥ Counsel the patient on the medication being used. must include careful look at the specific systems involved. Educated patients notice errors. Hospital Pharmacy, 31: 454, 458, 461Ð462 (1996). ¥ Recognize that children are more vulnerable to 5. Cohen, M.R. Play it safe. Don't use these abbrevia- the effects of errors because of pharmacokinetic tions. Nursing, 87: 46Ð47 (1987). and dose-related factors. ¥ Consider using pre-printed forms, but revise them 6. Davis, N.M. Medical abbreviations: 10 000 conven- iences at the expense of communications and safety. 7th periodically, as required. edition. Huntingdon Press 1995. Professionals are requested to compile data on errors to educate health workers and prevent 7. Grabenstein, J.D. ImmunoFacts: vaccines and immunologic drugs. Facts & Comparisons Inc., St. Louis, subsequent repetition. By informing others, the USA, 1996. chance of error recurrence can be eliminated. 8. Cohen, M.R. Insufficient dose of hepatitis B vaccine References given to 1400 newborns. Hospital Pharmacy, 30: 938Ð939 (1995). 1. Cohen, M., Senders, J., Davis, N.M. Failure mode and effects analysis: a novel approach to avoiding dangerous 9. Cohen, M.R. To prevent mix-ups, learn to talk to medication errors and accidents. Hospital Pharmacy, 29: yourself. Hospital Pharmacy, 31: 184, 187Ð188 (1996). 319Ð324 (1994). 10. Allen, E.L., Barker, K.N. Fundamentals of medication 2. Grabenstein, J.D., Proulx, S.M., Cohen, M.R. Recogniz- error research. American Journal of Hospital Pharmacy, ing and preventing errors with immunologic drugs. Hospi- 47: 555Ð571 (1990) tal Pharmacy, 31: 7 (1996).

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Reports on Individual Drugs

Combined oral estrogen dose of OCs was interpreted to be due to the different prevalence of cardiovascular risk contraceptives and stroke factors in users of higher-dose and low dose OCs in the two groups of countries. No significant increase The risk of venous thromboembolism associated of the risk estimates was observed with increasing with low-dose combined oral contraceptives (OCs) duration of OC use among current users, and the containing the progestogens desogestrel and risks were not significantly increased after cessa- gestodene has been under review by drug tion of use of OCs. regulatory authorities in the last year as a result of findings from the WHO Collaborative Study of Haemorrhagic stroke Cardiovascular Disease and Steroid Hormone The WHO study included 1068 cases of haemor- Contraception (1). The WHO study (2, 3) and other rhagic stroke and 2910 age-matched controls. In studies reported an approximate doubling of the women of less than 35 years of age currently using risk of venous thromboembolic events among users OCs, the relative risk estimate of haemorrhagic of these so-called third-generation OCs compared stroke was not elevated in either group of countries, with similar low-dose OCs containing, for example, while in women aged 35 years or more, the risk levonorgestrel. Many drug regulatory agencies, estimates were 2.17 and 2.46 in Europe and including now New Zealand (4), have revised their developing countries, respectively. In women with a prescription recommendations for low-dose OCs history of hypertension, the OC-associated risk containing desogestrel or gestodene. WHO estimates were substantially elevated (ten to continues to publish findings from the large fifteen-fold), and in both groups of countries the multicentre, hospital-based case-control study risks were elevated to about three in women using carried out in 21 centres in 17 countries in Africa, OCs who also smoked. The dose of estrogen and Asia, Europe and Latin America. The most recent dose or type of progestogen were not found to publications report findings on ischaemic and modify the risk estimates, which were not haemorrhagic stroke, and overall risk of stroke significantly increased among women who had associated with use of modern oral contraceptives previously used OCs. (5, 6). Overall risk of stroke Ischaemic stroke The evaluation of risk of ischaemic and haemor- The association between ischaemic stroke and use rhagic stroke separately is of scientific and clinical of OCs was examined in 697 cases and 1962 age- importance since the two diseases have different matched hospital controls in Africa, Asia, Europe etiology, clinical course and prognosis. However, and Latin America. Overall, the estimated relative for women choosing a contraceptive method, and risk of ischaemic stroke for current use of OCs was medical staff giving counselling and advice, the 2.99 (95% CI 1.65Ð5.40) in Europe, and 2.93 overall risk of stroke associated with use of OCs (2.15Ð4.00) in developing countries. The risk appears to be a more relevant consideration. In the estimates were lower in younger women and those WHO study, the overall risk of stroke for low-dose who did not have hypertension, and less than 2 in and higher-dose OCs was respectively 1.41 and women who did not have hypertension and who 2.71 in Europe, and 1.86 and 1.92 in the developing reported that their blood pressure had been countries. checked before the current episode of OC use. In women with a history of hypertension, the relative The incidence of stroke in women of reproductive risk was 10.7 in Europe and 14.5 in developing age is low. From data from the Oxford Centre in the United Kingdom which participated in the study, the countries. In Europe, OCs containing 50 µg or more of ethinylestradiol were associated with higher risk overall incidence rate of stroke in women aged 20Ð44 years not using OCs was estimated to be 4.8 estimates than OCs containing 30Ð35 µg or less ethinylestradiol. In developing countries, there was per 100 000 women-years; for women using low- no significant difference between the overall dose OCs the estimate was 6.7, and for higher- estimates of risk associated with use of higher-dose dose OCs it was 12.9 per 100 000 women-years. and low-dose OCs. This differential effect of Thus the excess risk associated with use of OCs

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can be estimated to be 2 per 100 000 women-years 7. Petitti, D.B., Sidney, S., Bernstein, A. et al. Stroke in of low-dose OCs and 8 for higher-dose OCs. users of low-dose oral contraceptives. New England Journal of Medicine, 335: 8Ð15 (1996). Results similar to those from the WHO study were also recently reported from a population-based case-control study in the United States which used Azithromycin: a new opportunity data from the California Kaiser Permanente Medical for control of trachoma Care Programme (5). The overall incidence of stroke in women of reproductive age (15Ð44 years) Trachoma is still the leading cause of preventable was estimated at 11.3 per 100 000 women-years in blindness globally, despite several decades of this population. On the basis of data from 295 control efforts. Progress in the medical treatment of women with stroke and their controls, the adjusted trachoma has been slow, and in the absence of relative risk estimate for ischaemic stroke in women socioeconomic improvements in the communities using low-dose OCs was 1.18 and for haemor- concerned, the disease tends to remain an rhagic stroke it was 1.14. For women who used important cause of visual loss. Currently, it is OCs and smoked, the risk estimate for haemor- estimated that there are some 146 million cases of rhagic stroke was 3.64. In the USA study, there active trachoma, with an additional 5.9 million blind were few women with hypertension who were or severely visually disabled persons (1). current users of OCs and only a small proportion of women aged 35 years or older were using OCs. Trachoma is caused by Chlamydia trachomatis, a microorganism that exists as different variants; The results indicate that women with cardiovascular some of these are responsible for eye disease in risk factors such as smoking or hypertension, parti- the form of trachoma, whereas other strains lead to cularly if they are in the later half of the reproductive venereal disease and related complications. age-span, will have some increased risk of stoke if they choose to use OCs. However, use of low-dose Trachoma is typically a disease of the poorest-of- OCs by carefully screened healthy women is asso- the-poor, with foci of blinding disease in under- ciated with, at most, a small excess risk of stroke. served rural communities or urban slums. Trachoma was endemic in many European References countries well into this century, but it disappeared 1. Oral contraceptives and thromboembolism. WHO Drug as a result of improved standards of living and Information, 9: 221Ð222 (1995). hygiene, mainly before the era of antibiotics. Today, trachoma is found in underprivileged communities 2. WHO Collaborative Study of Cardiovascular Disease where there is little hope of rapid economic and Steroid Hormone Contraception. Venous thrombo- development, which makes the need for medical embolic disease and combined oral contraceptives: intervention imperative, to break the trend of results of an international multicentre case-control study. increasing poverty due to blindness, with its Lancet, 346; 1575Ð1582 (1995). socioeconomic consequences. 3. WHO Collaborative Study of Cardiovascular Disease The treatment of trachoma can be either pre- and Steroid Hormone Contraception. Effect of different ventive/suppressive or curative. The latter is more progestogen in low oestrogen oral contraceptives on difficult, because of the extensive treatment venous thromboembolic disease. Lancet, 346: 1582Ð1588 (1995). schedules needed. These are therefore usually reserved for severe, potentially blinding, cases. 4. Prescriber update. Ministry of Health, New Zealand. Based on a series of field studies in the 1950s and Number 4, pp. 1Ð6 (1996). 1960s, the treatment recommended by WHO has long been topical application of 1% tetracycline eye 5. WHO Collaborative Study of Cardiovascular Disease ointment (2). This regimen can either be applied and Steroid Hormone Contraception. Ischaemic stroke twice daily for six weeks, or as an intermittent and combined oral contraceptives: results of an inter- treatment twice daily for five consecu-tive days national, multicentre, case-control study. Lancet, 348: each month for at least six consecutive months per 498Ð505 (1996). year. However, this treatment can only be 6. WHO Collaborative Study of Cardiovascular Disease considered as suppressive. It reduces the intensity and Steroid Hormone Contraception. Haemorrhagic of inflammation in the conjunctiva, and breaks the stroke, overall stroke risk, and combined oral contra- vicious circle of bacterial conjunctivitis and ceptives: results of an international, multicentre, case- trachoma reinfection — which often occurs as control study. Lancet, 348: 505Ð510 (1996). seasonal epidemics. This topical suppressive

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treatment must be maintained systematically during application of a single 1g dose for treatment of childhood to prevent the development of severe urethritis caused by this organism (5). inflammatory disease, which leads to trichiasis and entropion later in life, with subsequent ensuing So far, azithromycin has been used against blindness. This long-term topical regimen inevitably trachoma in a few field trials, with very promising leads to a problem of compliance, which is a major results (6, 7). Research is still needed to determine obstacle to the community public health control of the optimal application of azithromycin against the disease. trachoma; it seems clear, though, that this drug carries the potential for large-scale treatment Curative single-patient treatment has been ad- schemes based on an annual, or possibly six- ministered in the form of sulfonamides or antibiotics monthly, dose which appears to reduce inflam- since the 1950s. However, large-scale treatment matory trachoma to non-blinding intensity. The with sulfonamides was abandoned after a few years target groups for such treatment would be children, because of the difficulty of dealing with serious from the age of 2Ð3 years, and to some extent side-effects such as Stevens-Johnson syndrome. women. The antibiotics commonly used have included The use of azithromycin in field programmes will tetracycline or, recently, doxycycline, and require careful planning particularly with regard to erythromycin. Whichever antibiotic is chosen, it contraindications, post-treatment surveillance, and must be administered for a minimum of 15 days. monitoring of both the results and possible This again leads to a problem of compliance and antibiotic resistance. For individual cases of tracho- the ensuing operational difficulties in large-scale ma, azithromycin is at present clearly the drug of treatment schemes. Furthermore, the use of choice, but use in large-scale public health pro- systemic tetracycline with its potential teratogenic grammes will require urgent and careful considera- and bone-growth inhibitory effects, makes its use in tion, not least in assuring that the drug is both women of child-bearing age and children difficult. accessible and affordable to those most in need. As a rule, systemic antibiotics have therefore only been used in cases of severe inflammatory Dr B. Thylefors, Programme for Prevention of trachoma, not responding to the ordinary topical Blindness and Deafness, WHO treatment with tetracycline eye ointment (3). It is in this perspective that a new antibiotic which is References potent against trachoma may represent a break- 1. Thylefors, B., Negrel, A.D., Pararajasegaram, R., through in terms of possible control. Azithromycin, Dadzie, K.Y. Global data on blindness. Bulletin of the an azalide derived from the macrolide class of World Health Organization, 73: 115Ð121 (1995). antibiotics carries the hope of particular efficacy 2, Dawson, C.R., Jones, B.R., Tarizzo, M.L. Field guide against Chlamydia trachomatis. Azithromycin is for trachoma control. World Health Organization, Geneva, active against a wide variety of Gram-positive and 1981. Gram-negative bacteria by the inhibition of bacteria protein synthesis. Furthermore, azithromycin has 3. Strategies for the prevention of blindness in national particular pharmacokinetic properties; it is rapidly programmes. World Health Organization, Geneva 1985. and widely distributed throughout the body, and it 4. Dunn, C.J., Barradell, L.B. Azithromycin— A review of shows markedly high concentrations in tissue as its pharmacological properties and use as 3-day therapy compared to plasma. Thus, the drug is heavily in respiratory tract infections. Drugs, 51: 483Ð505 (1996). tissue-bound, with up to 150 times higher levels in some tissues in relation to plasma concentrations 5. Hoepelman, I.M., Schneider, M.M.E. Azithromycin: the (4). This, together with its relatively slow elimination first of the tissue-selective azalides. International Journal and a tissue depletion half-life of 2 to 4 days, of Antimicrobial Agents, 5: 145Ð167 (1995). makes azithromycin an ideal drug for treatment of several infectious disorders. In the case of 6. Bailey, R.L., Arullendran, P., Whittle, H.C., Mabey, D.C. Randomized controlled trial of single-dose azithromycin in trachoma, the high tissue affinity is of great treatment of trachoma. Lancet, 342: 453Ð456 (1993). importance in reducing the conjunctival infection with follicle formation: a particular feature of 7. Tabbara, K.F., Abu El-Asrar, A.M., Al-Omar, O., azithromycin is that it rapidly penetrates the phago- Choudhury, A.H., Al-Faizal, Z. Single-dose azithromycin in cyte cells. Its outstanding effect on Chlamydia the treatment of trachoma: a randomized, controlled trachomatis is also documented in the effective study. Ophthalmology, 103: 842Ð846 (1996).

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Regulatory Matters

Alendronic acid-induced Venous thromboembolism is a serious but rare risk associated with the use of oral contraceptives. oesophageal ulcers Because this complication is rare it is difficult to United States of America — Alendronic acid is the study, and estimates of its incidence are not first non-hormonal therapy to be approved in a precise. number of countries for the treatment of All studies hitherto presented to the CPMP indicate osteoporosis in postmenopausal women; it is also that the risk for venous thromboembolism is higher indicated for the treatment of Paget disease. in users of desogestrel or gestodene-containing Since introduction of the product onto the market, oral contraceptives than in users of levonorgestrel- the manufacturer has received a number of case containing oral contraceptives. The impact of reports of oesophagitis and oesophageal ulceration biases and confounders on the difference still where patients have presented with retrosternal cannot be fully evaluated. pain, and difficulty or pain in swallowing. Data from studies of haemostatic factors indicate As a result, the manufacturer has circulated a letter differences between levonorgestrel-containing oral to doctors and other health professionals stating contraceptives (so-called second generation) and that oesophageal reactions have been reported that desogestrel or gestodene-containing oral contra- are of a greater severity than those observed during ceptives (so-called third generation), but these are controlled clinical trials. The manufacturer has duly of unknown clinical relevance as yet. revised the package labelling and patient insert to emphasize that reactions such as oesophageal The requested pooled analyses of acute myocardial erosion, ulceration or oesophagitis may be avoided infarction have not yet been performed and cur- or reduced by carefully following the instructions for rently available data do not allow a conclusion that use as set out in the new recommendations. desogestrel or gestodene-containing oral contra- ceptives have an advantage over levonorgestrel- Each tablet should be swallowed with a full glass of containing oral contraceptives in this respect. plain water immediately on rising in the morning and at least 30 minutes before the first food, There is no evidence that from a public health point beverage or medication of the day. Patients should of view the other major benefits or risks (e.g. be instructed not to lie down for at least 30 minutes reliability of contraception) are different from deso- after taking the tablet, and not to take the drug at gestrel or gestodene-containing oral contraceptives. bedtime or before rising for the day. For the individual there may, however, be benefits in quality of life. Source: From the FDA. Journal of the American Medical Association, 278: 1534 (1996). Factors other than the "generation" of pill used, such as heredity and immobilization, also have an Oral contraceptives containing important role for the occurrence of venous thromboembolic events. desogestrel or gestodene: updated position statement To further evaluate to what extent biases and confounding factors have contributed to the differ- European Union — The Committee for Proprietary ence in risk of venous thromboembolic events in Medicinal Products (CPMP) held a meeting in April users of desogestrel or gestodene-containing oral 1996 to discuss further the risks of thrombo- contraceptives and levonorgestrel-containing oral embolism associated with combined oral contra- contraceptives respectively, and to clarify whether ceptives containing desogestrel or gestodene. In there are differences in effect on myocardial addition to the previous statement published in infarction rates, the CPMP will request further October 1995 (1) the following position statement analysis of the data presented, and carefully keep has now been issued by the CPMP. the ongoing studies under review.

134 WHO Drug Information Vol. 10, No. 3, 1996 Regulatory Matters

The previous message to doctors/users is still ¥ Temazepam will become subject to a set of safe relevant and in addition doctors/users are reminded custody requirements, and the drug will be kept in of the following: locked controlled-drug cabinets;

¥ Discontinuation of oral contraceptives should be ¥ Additional documentation will be required when a seriously considered in situations that are person other than a doctor supplies the drug, and associated with an increased risk of venous will require persons who are not already thromboembolic events, such as immobilization, authorized to possess, supply or produce major trauma or major surgery. schedule 3 drugs to obtain an appropriate written authority; ¥ Due to the vague symptomatology of many venous thromboembolic events, discontinuation of ¥ Supply on prescription will be more carefully oral contraceptives should be considered in cases undertaken; and of suspected thrombosis in patients on oral contraceptives, while diagnostic interventions are ¥ Containers in which the drug is supplied will be being pursued. suitably marked. ¥ In cases of an uncertain diagnosis of venous Existing requirements which apply to schedule 4 thromboembolic events, alternative contraceptive drugs, such as keeping of records of the quantities strategies should be discussed with the patient, produced, imported and exported, will remain in since the event may represent a first signal of oral effect. contraceptive-associated thrombophilia. References Source: Position statement of the CPMP on oral contraceptives containing desogestrel or gestodene. 1. Communication from the Home Office, London, United CPMP/374/96, EMEA, 17 April 1996. Kingdom, 16 April 1996.

2. Martindale — The extra pharmacopoeia. Royal Temazepam now a controlled drug Pharmaceutical Society, London. Thirty-first edition. 1996. United Kingdom — The Secretary of State for Health has announced that temazepam, a short- HIV protease inhibitors and acting benzodiazepine, is to be transferred from schedule 4 of the Misuse of Drugs Regulations spontaneous bleeding 1985 to schedule 3, which will mean tighter controls on its availability. These measures are being taken France — The Medicines Agency has reported 9 in an attempt to prevent misuse (1). It is also cases of haematoma in haemophiliac patients with announced that gel-filled capsules of the drug will AIDS who are being treated with the HIV protease no longer be prescribed on the National Health inhibitors indinavir, ritonavir and saquinavir. An Service. inquiry is in progress (1). It should be noted that factor VIII infusion in these patients has had to be Liquid-filled temazepam capsules have been widely increased since the beginning of treatment. abused on the illicit drugs market, the liquid gel lending itself to intravenous administration. This United States of America & Canada — The FDA formulation was replaced in the United Kingdom by has learned of 15 case reports of spontaneous tablets and capsules containing semi-solid gel, bleeding episodes in HIV-positive patients with which it was considered difficult to inject. In spite of haemophilia receiving protease inhibitors in Europe. this there has still been evidence of abuse (2). Of these cases, 11 have involved haematomas and 5 haemarthroses. None involved serious injury or The rescheduling means that: death. The majority of patients, who are on multiple drug therapy, have continued taking the HIV ¥ Simple possession of the drug without authority protease inhibitors despite the bleeding event. No will be an offence; events have been reported within the United States. To date, there is no conclusive evidence to ¥ Import and export of the drug are required to be establish that this class of drugs is the cause of licensed; spontaneous bleeding episodes. However, the FDA

135 Regulatory Matters WHO Drug Information Vol. 10, No. 3, 1996

will continue to keep close watch on the situation There are two prominent groups of adverse since the three products in question have been reactions. Those involving the gastrointestinal tract, given marketing approval under the FDA's which include taste perversion or loss, and those accelerated approval mechanism for treatment of involving the skin, suggestive of hypersensitivity or life-threatening illness. photosensitivity. So far, ADRAC has received 2 reports describing suspected neutropenia and one The FDA and manufacturers of the products in case of agranulocytosis. Finally, there are 11 question recommend that health-care providers reports of adverse hepatic reactions. monitor haemophiliac patients for spontaneous bleeding episodes whenever any protease While all the above reactions are mentioned in the inhibitors are used as part of HIV treatment. product information, careful prescribing and close However, patients with haemophilia and HIV monitoring must be encouraged. infection who are currently on protease inhibitor therapy should not discontinue treatment, but Source: Australian Adverse Drug Reactions Bulletin. Volume 15, number 1, 1996. consult with their health care providers if they have any concerns (2). Withdrawal of topical products The Canadian Health Protection Branch is also closely monitoring the situation and, in addition to containing gentamicin the above-mentioned cases, has received a report of one Canadian patient affected by spontaneous Malaysia — In view of the fact that long-term use of bleeding. HPB states that all of the reports involved topical antibiotics can lead to development of patients with haemophilia and advanced HIV infec- hypersensitivity and widespread use can lead to a tion who were receiving multiple drug treatment. risk of emergence of resistant strains, the Drug Clinical studies using HIV protease inhibitors have Control Authority has withdrawn marketing of not so far reported an increased incidence of either topical cream or ointment products containing bleeding or coagulation abnormalities in patients gentamicin. Out of 28 products available for topical with or without haemophilia (3). use in Malaysia, 16 contained gentamicin as the sole active substance, while the other 12 References preparations were combinations of gentamicin with a corticosteroid. 1. Notice from Medicines Agency, France dated 20 June Source: Newsletter of the Drug Control Authority of 1996. Malaysia, 10: 4 (1996). 2. Letter to US health-care providers from the Department of Health & Human Services, sent on 17 July 1996. Emergency contraceptives 3. Notice to health care providers in Canada sent by the recommended for over-the-counter Health Protection Branch on 18 July 1996. (OTC) use? Terbinafine: surprising New Zealand — The Medicines Classification Committee (MCC) has recommended that number of reports emergency contraceptive tablets be sold by pharmacists over-the-counter. These will be Australia — Terbinafine is a new antifungal drug supplied in a special pack which contains with activity against infections due to dermato- instructions approved by the Ministry of Health. phytes and Candida albicans. The product was first Meanwhile, the recommendation cannot be marketed in Australia in late 1993, and since that implemented until approval has been given by the time the Adverse Drug Reactions Advisory Cabinet to amend the Medicines Regulations. Committee (ADRAC) has received 168 reports documenting a total of 323 suspected adverse Source: New Zealand Prescriber. Update No. 12, July reactions. ADRAC is concerned by the number and 1996. nature of these reports, considering that the drug is often used for minor conditions and for a prolonged period.

136 WHO Drug Information Vol. 10, No. 3, 1996 Regulatory Matters

Conjugated estrogens It is generally used as adjunctive therapy for the treatment of lumbago, torticollis or pain caused by and generic pharmaceuticals minor injuries. United States of America — Natural conjugated Results of the study show that the incidence of estrogens excreted by pregnant mares are used for Stevens-Johnson syndrome is estimated at 1 to 6 estrogen replacement to treat symptoms of the cases per million person-years and toxic epidermal menopause and allied disorders such as necrolysis at 0,4 to 1,2 cases per million person- postmenopausal osteoporosis, atrophic vaginitis, years. Although these conditions are rather kraurosis vulvae and atrophic urethritis. Discussion infrequent, they may kill or severely disable is now centred on which active hormonal ingredient previously healthy people and they are frequently contributes to the effectiveness and safety of the associated with drug use. When skin detachment is brand product, Premarin¨, Wyeth Ayerst, and very extensive, prognosis is poor, with death rates which of these components should be included in of 30 to 40 per cent. Documentation of a causal the generic version of the product. relationship with medication requires widespread population studies because of the low frequency of Two estrogen ingredients — estrone sulfate and disorders. This explains the fact that drugs may equilin sulfate — have been regarded as Premarin's have been used for many years before such data main active substances. Despite the company's on adverse reactions become available. The petition, the contribution made to the product's present study began in 1989 and included about safety and effectiveness by the remaining 120 million people in France, Germany, Italy and estrogens (which include estrogen-8, 9- Portugal. dehydroestrone sulfate Ð delta-8-DHES) has been questioned by generic companies. The US Food The continued reporting and monitoring of adverse and Drug Administration has prepared a document drug reactions has once again proven crucial in the entitled Preliminary analysis of scientific data on the benefit/risk assessment of treatment. Whenever composition of conjugated estrogens, and has safer alternative drugs or therapy become included this as part of the public docket for the available, older therapies are subject to reassess- petition. A Federal Register notice providing an ment . The present withdrawal should thus be opportunity for public comment on this preliminary appreciated as a sign of improvement and analysis will soon be published. appropriateness of available treatment. Reference: FDA Talk Paper, T96-73, 1996. References 1. Agence du Médicament. Pharmacovigilance. 14 Chlormezanone withdrawn October 1996. following skin reactions 2. Roujeau, J.C., Kelly, J.P., Naldi, L. et al. Medication use and the risk of Stevens-Johnson syndrome or toxic France — In agreement with the French Medicines epidermal necrolysis. New England Journal of Medicine, Agency, the manufacturers of chlormezanone- 333: 1600Ð1607 (1995). containing products (Trancopal¨, Trancogesic¨, Sanofi Winthrop and Alinam¨, Therabel Lucien 3. SCRIP. No. 2176, p. 16. 1996. Pharma) have decided to stop marketing the product and recall batches immediately (1). The Marketing authorization of fixed decision was based on findings of a recently published multicountry case-control study on the combination medicinal products risk of Stevens-Johnson syndrome and toxic epidermal necrolysis (2). Based on these European Union— The Committee for Proprietary developments, Sanofi Winthrop has decided to Medicinal Products (CPMP) has approved guide- withdraw the drug worldwide (3). lines for submission of an application for marketing authorization of fixed-dose combination medicinal Chlormezanone is a mild tranquillizer with muscle- products. The guidance comes into effect for relaxant properties and a sedative effect which has European Union countries in October 1996. been available since the 1960s in a single formulation, and later in combination with either Pharmaceutical companies submitting an applica- analgesics or nonsteroidal anti-inflammatory drugs. tion are now required to justify the particular

137 Regulatory Matters WHO Drug Information Vol. 10, No. 3, 1996

combination of active substances proposed. Fixed- ¥ the addition of the different adverse reactions combination products will only be considered specific to each substance. acceptable if the proposed combination is based on valid therapeutic principles. The guidline points out that fixed combinations, in principle, may not be considered rational if the For any individual fixed combination, it is necessary duration of action of the substances differ to assess the potential advantages in a clinical significantly. This may not apply where it can be setting against possible disadvantages in order to shown that the combination is clinically valid determine whether the product meets the despite differences in this respect, i.e. if one requirements of efficacy and safety. substance is intended to enhance absorption of the other or where the substances are intended to exert Potential advantages of fixed combinations should their effects successively. include one of the following: Each substance of the fixed combination must have (a) An improvement of the benefit/risk assessment a justified action. The inclusion of a substance to due to: counteract an adverse reaction of another sub- stance may be considered justified, but only if the 1. Addition or potentiation of therapeutic activities adverse reaction is a serious or commonly of their substances, which results in: occurring one. However, the inclusion of a sub- stance intended to produce unpleasant adverse ¥ a level of efficacy similar to the one achievable effects as a means of preventing abuse is by each active substance used alone at higher undesirable. It is considered that substances having doses than in combination, but associated with a a critical dosage range or a narrow therapeutic better safety profile; or index are inappropriate for inclusion in fixed ¥ a level of efficacy above the one achievable by combinations. a single substance with an acceptable safety profile. The guidline goes on to discuss indications, drug interactions and dosage levels of each of the 2. The counteracting by one substance of an substances, and the need for pharmacodynamic adverse reaction produced by another. and pharmacokinetic studies, and clinical trials to prove efficacy and safety of fixed combinations. It (b) A simplification of therapy which improves also points out that safety studies in animals should patient compliance. (When it is the only claim, it be conducted, but may not be required if all the would be restricted to a particular situation such as substances concerned have been extensively used non-prescription products). in humans in identical or very similar combinations and if their safe long-term use has been well Disadvantages of fixed combinations include: documented.

¥ the fact that even a combination which meets the Reference: European Agency for the Evaluation of needs of the average patient is unlikely to be Medicinal Products. Note for guidance on fixed combina- ideally adjusted for the needs of each individual tion medicinal products. CPMP/EWP/240/95. patient; and

138 WHO Drug Information. Vol. 10, No. 3, 1996 Recommended INN: List 36

International Nonproprietary Names for Pharmaceutical Substances (INN)

Recommended International Nonproprietary Names (Rec. INN): List 36 Notice is hereby given that, in accordance with paragraph 7 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances [Off. Rec. Wld Health Org., 1955, 60, 3 (Resolution EB15.R7); 1969, 173, 10 (Resolution EB43.R9)]. the following names are selected as Recommended International Nonproprietary Names. The inclusion of a name in the lists of Recommended International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1-73) and Recommended (1-35) International Nonproprietary Names can be found in Cumulative List No. 9, 1996.

Dénominations communes internationales des Substances pharmaceutiques (DCI)

Dénominations communes internationales recommandées (DCI Rec): Liste 36 Il est notifié que, conformément aux dispositions du paragraphe 7 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques [Actes off. Org. mond. Santé, 1955. 60, 3 (résolution EB15.R7); 1969, 173, 10 (résolution EB43.R9)] les dénominations ci-dessous sont mises à l'étude par l'Organisation mondiale de la Santé en tant que dénominations communes internationales proposées. L'inclusion d'une dénomination dans les listes de DCI proposées n'implique aucune recommandation en vue de l'utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d'autres listes de Dénominations communes internationales proposées (1-73) et recommandées (1-35) dans la Liste récapitulative No. 9, 1996.

Denominaciones Comunes Internacionales para las Sustancias Farmacéuticas (DCI)

Denominaciones Comunes Internacionales Recomendadas (DCI Rec): Lista 36 De conformidad con lo que dispone el párrafo 7 del Procedimiento de Selección de Denominaciones Comunes Internacionales Recomendadas para las Sustancias Farmacéuticas [Act. Of. Mund Salud, 1955, 60. 3 (Resolución EB15.R7); 1969, 173, 10 (Resolución EB43.R9)]. se comunica por el presente anuncio que las denominaciones que a continuación se expresan han sido seleccionadas como Denominaciones Comunas Internacionales Recomendadas. La inclusión de una denominación en las listas de las Denominaciones Comunes Recomendadas no supone recomendación alguna en favor del empleo de la sustancia respectiva en medicina o en farmacia. Las listas de Denominaciones Comunes Internacionales Propuestas (1-73) y Recomendadas (1-35) se encuentran reunidas en Cumulative List No. 9, 1996

139 Recommended INN: List 36 WHO Drug Information, Vol. 10, No. 3, 1996

Recommended INN Chemical name or description and Molecular formula (Latin, English, French, Spanish) DCI Recommandée Nom chimique ou description et Formule brute DCI Recomendada Nombre químico o descripción y Fórmula empírica

abirateronum 17-(3-pyridyl)androsta-5,16-dien-3β-ol abiraterone 17-{3-pyndyl)androsta-5,16-dién-3β-ol abiratérone 17-(3-piridil)androsta-5,16-dien-3β-ol abiraterona

C24H31NO

abitesartanum 1 -[[N-[p-(o-1 H-tetrazol-5-y1phenyl)benzyl]valeramido] methyl]-1 -cyclopentane- abitesartan carboxylic acid acide 1 -[[pentanoyl[4-[2-(1 H-tétrazol-5-yl)phényl]benzyl]amino]rnéthyl]= abitésartan cyclopeníane-1-carboxylique ácido 1 -[[N-[p-(o-1 H-Metrazol-5-ilfenil)bencil]valeramido]metil]- abitesartán 1 -ciclopentancarboxílico

C26H31N5O3 acídum ranelicum 5-[bis(carboxymethyl)amino]-2-carboxy-4-cyano-3-thiopheneacetic acid ranelic acid acide [5-carboxy-4-(carboxyméthyl)-3-cyano-2-thiényl]iminodiacétique acide ranélique ácido 5-[bis[carboximetil)amino]-2-carboxi-4-ciano-3-tiofenoacético ácido ranélico

C12H10N2O8S almurtidum 2-acetamido-3-O-[[[(1 S)-1 -[[(1 R)-1 -carbamoyl-3-carboxypropyl]carbamoyl]- almurtíde elhyl]carbamoyl]methyl]-2-deoxy-D-glucopyranose acide (4R)-5-amino-4-[[(2S)-2-[[2-[[2-(acétylamino)-2-désoxy- alrnurtide D-glucopyranos-3-yl]oxy]acétyl]amino]propanoyl]amino]-5-oxopentanoique 2-acetamido-3-O-[[[(1S)-1-[[(1R)-1-carbamoil-3-carboxipropil]carbamoil]etil]= almurtida carbamoil]metil]-2-desoxi-D-gIucopiranosa

C18H30N4O11 amelometasonum (+)-9-fluoro-11β, 17-dihydroxy-21-methoxy-16β-methylpregna-1,4-diene- amelometasone 3, 20-dione 17-propionate (+)-17-propanoate de 9-fluoro-11β, 17-dihydroxy-21-méthoxy- amélométasone 16β-méthylprégna-1,4-diène-3,20-dione 17-propionato de (+)-9-fluoro-11β,17-dihidroxi-21-metoxi-16β-metilpregna-1,4- amelometasona dien-3,20-diona

C26H35FO6

140 WHO Drug Information. Vol. 10, No. 3, 1996 Recommended INN: List 36

apafluranum 1,1,1,2,3,3,3-heptafluoropropane apaflurane 1.1,1,2,3,3,3-heptafluoropropane apaflurane 1,1.1,2.3,3.3-heptafluoropropano apaflurano

C3HF7 arcitumomabum arcitumomab immunoglobulin G 1 (mouse monoclonal IMMU-4 Fab' fragment γ-cham anti- human antigen CEA), disulfide with mouse monoclonal IMMU-4 light chain

immunoglobuline G 1 (chaîne γ du fragment Fab' de l'anticorps monoclonal arcitumomab de souris IMMU-4 anti-antigène CEA humain), disulfure avec la chaîne légère de l'anticorps monoclonal de souris IMMU-4

inmunoglobulina G 1 (cadena γ del fragmento Fab' del anticuerpo monoclonal arcitumomab de ratón IMMU-4 anti-antigeno CEA humano) disulfuro con la cadena ligera del anticuerpo monoclonal de ratón IMMU-4 asimadolinum asimadoline N-[(αS)-α-[[(3S)-3-hydroxy-1-pyrrolidinyl]methyl]benzyl]-N-methyl- 2,2-diphenylacetamide asimadoline N-[(1S)-2-[{3S)-3-hydroxypyrrolidin-1-yl]-1-phényléthyl]-N-méthyl- 2,2-diphénylacétamide asimadolina N-[(αS)-α-[[(3S)-3-hidroxi-1-pirrolÍdinil]metil]bencil]-N-metil- 2,2-difenilacetamida

C27H30N2O2 avorelinum avorelin 5-oxo-L-proIyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-2-methyl-D-tryptophyl- L-leucyl-L-arginyl-N-elhyl-L-prolinamide avoréline (5-oxo-L-prolyl)-L-histidy]-L-tryptophyl-L-séryl-L-tyrosyl-(2-méthyl-D-tryptophyl)- L-leucyl-L-arginyl-(N-éthyl-L-prolinamide) avorelina 5-oxo-L-prolil-L-histidil-L-triptofil-L-seril-L-tirosil-2-metil-D-triptofil-L-leucil- L-arginil-N-etil-L-prolinamida

C65H85N17O12 azalanstatum 1-[[(2S,4S)-4-[[(p-aminophenyl)thio]methyl]-2-(p-chlorophenethyl)- azalanstat 1,3-dioxolan-2-yl]methyI]imidazole 1-[[(2S,4S)-4-[[(4-aminophényl)sulfany[]méthyl]-2-[2-(4-chIorophényl)éthyl]- azalanstat 1,3-dioxolan-2-yl]méthy]]-1 H-imidazole 1-[[(2S,4S)-4-[[(p-aminofeniI]tio]metil]-2-(p-clorofenetil)- azalanstat 1,3-dioxolan-2-il]metil]imidazol

C22H24CIN3O2S becaplerminum becaplermin recombinant human platelet-derived growth factor B

facteur de croissance B d'origine plaquettaire humain obtenu par génie bécaplermine génétique

factor B de crecimiento derivado de plaquetas (humano recombinante) becaplermina

141 Recommended INN: List 36 WHO Drug Information, Vol. 10, No. 3, 1996

bisnafidum bisnafide N,N'-[ethylenebis[iminoI[(R)-1-methylethylene]]]bis[3-nitronaphthalimide] 2,2'-[éthylènebis[imino[(R)-1-méthyléthylène]]bis[5-nitro-2H-benzo[de]- bisnafide isoquinoléine-1,3-dione] N,N'-[etilenbis[imino[(R)-1-metiletilen]]]bis[3-nitronaftalimida] bisnafida

C32H28N6O8 cariporidum N-(diaminomethylene)-4-isopropyl-3-(methylsulfonyl)benzamide cariporide N-(diaminométhylène)-4-(1-méthyléthyl)-3-(méthylsulfonyl)benzamide canporide N-(diaminometilen)-4-isopropil-3-(rnetilsulfonil)benzarnida cariporida

C12H17N3O3S cellacefatum cellacefate a mixed acetate and hydrogen phthalate ester of cellulose (about 50% of the hydroxyl groups are acetylated and about 25% are esterified with one of the carboxyl groups of phthalic acid) cellacefate mélange partiel d'esters acétique et phtalique de cellulose (50% environ des groupes hydroxyl sont acétylés et 25% sont estérifiés par l'un des groupes carboxyl de l'acide phtalique) cellacefato mezcla de acetato y biftalato de celulosa en la que alrededor del 50% de los hidroxilos están acetilados y alrededor del 25% están esterificados por uno de los carboxilos del ácido itálico cerivastatinum cerivastatin (3R,5S,6E)-7-[4-(p-fluorophenyl)-2,6-diisopropyl-5-(methaxymethyl)- 3-pyridyl]-3,5-dihydroxy-6-heptenoic acid cérivastatine acide (6E)-(3R,5S)-7-[4-{4-fluorophényl)-5-(méthoxyméthyl)- 2,6-bis(1-méthyléthyl)-3-pyridyl]-3,5-dihydroxyhept-6-énoïque cerivastalina ácido (3R,5S,6E)-7-[4-(p-fluorofenil)-2,6-diisopropil-5-(metoximetil)- 3-piridil]-3,5-dihidroxi-6-heplenoico

C26H34FNO5 ciaftalanum zincum (SP-4-1)-[phthalocyaninato(2-)-N29, N30, N31, N32]zinc ciaftalan zinc (SP-4-1)-[29H,31H-phtalocyaninato(2-)-N29, N30, N31, N32]zinc ciaftalane zinc (SP-4-1)-[ftalocianínato(2-)-N29,N30, N31, N32]zinc ciaftalán zinc

C32H16N8Zn cisatracurii besilas cisatracurium besilate (1 R,2R)-2-(2-carboxyethyl )-1,2,3,4-tetrahydro-6,7-d¡methoxy-2-methyl-1 - veratrylisoquinolimum benzenesulfonate, pentamethylene ester

dibenzènesulfonate de 2,2'-[pentane-1,5-diylbis(oxycarbonyléthylène)]- bésilate de cisatracurium bis[(1R,2R)-1-(3,4-dimétrioxybenzyl)-6,7-diméthoxy-2-méthyl- 1,2,3,4-tétrahydroisoquinolémium]

bencenosulfonato del [1 R[1α, 2α (1'R*,2'R*)]]-2,2'-[1,5-pentanodiilbis [oxi(3- besilato de cisatracurio oxo-3,1-propanodiil)]]bis[1-[(3,4-dimetoxifenil)metil]-1,2,3,4-tetrahidro-6,7- dimetoxi-2-metilisoquinolinio]

C65H82N2O18S2

142 WHO Drug Information, Vol 10, No. 3, 1996 Recommended INN: List 36

colestilanum 2-methylimidazole polymer with 1-chloro-2,3-epoxypropane colestilan copolymère de 2-méthylimidazole et de 1-chloro-2,3-époxypropane colestilan polímero de 2-metilimidazol con 1-cloro-2,3-epoxipropano colestilan

(C4H6N2C3H5CIO)n dabelotinum (±)-1,2,3,4-tetrahydro-1-methyl-a-(2-morpholinylmethoxy)quinohne dabelotine (±)-1-méthyl-8-[(2RS)-morpholin-2-yl]méthoxy]-1,2,3.4-tétrahydroquinoiéine dabélotine (±)-1,2,3.4-tetrahidro-1-melil-8-(2-morfolinilmetoxi)quinolina dabelotina

C15H22N2O2 danaparoidum natricum danaparoid sodium mixture of: mucopolysaccarides derived from hog intestinal mucosa consisting of sodium salts of heparan sulfate (major component), dermatan sulfate, and chondroitin sulfate danaparoide sodique mélange de: mucopolysaccharides extraits de la muqueuse intestinale de porc, constitue par les sels de sodium du sulfate d'héparan (principal composant), du sulfate de dermatan et du sulfate de chondroitine danaparoide sódico mezcla de: mucopolisacaridos de mucosa intestinal de cerdo consistentes en sales sódicas de haparan sulfato (componente principal), dermatan sulfato y condroitin sulfato)

dapitantum (3aS,4S,7aS)-hexahydro-2-[(αS)-o-methoxyhydratropoyl]- dapitant 4-(o-methoxyphenyl)-7,7-diphenyl-4-isoindollnol (3aS,4S,7aS)-4-hydroxy-4-(2-méthoxyphényl)-2-[(2S)-2-(2-méthoxyphenyl)= dapitant propanoyl]-7.7-diphényloctahydro-1H-isoindoIe (3aS.4S,7aS)-hexahidro-2-[(αS)-o-metoxihidratropoil]-4-(o-metoxifenil)- dapitant 7 7-difenil-4-isoindolinol

C37H39NO4 darsidominum 3-(cis-2.6-d[methylpiperidino)sydnone imine darsidomine 3-(cis-2,6-diméthylpipérIdin-1-yl)sydnone imine darsidomine 3-(cis-2,6-dimetilpiperidino)sidnona imina darsidomina

C9H16N4O

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delequaminum (8aR,12aS,13aS)-5,8,8a,9,10,11,12.12a,13,13a-decahydro-3-methoxy- delequamine 12-(methylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine (8aR,12aR,13aS}-3-méthoxy-12-(méthylsulfonyl)- déléquamme 5,8,8a,9,10,11,12,12a,13,13a-décahydro-6H-isoquino[2,1-g][1,6]naprityridine (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahídro-3-metoxi- delecuamina 12-(metilsulfonil)-6H-isoquino[2,1-g][1,6]naftiridina

C18H26N2O3S dexecadotrilum (+)-N-[(R)-α-(mercaptomethyl)hydrocinnamoyl]glycine,benzyl ester, acetate dexecadotril (ester) (+)-(R)-2-[[2-[(acétylsulfanyl)méthyl]-3-phénylpropanoyl]amino]acétate de dexecadotril benzyle (+)-N-[(R)-α-(mercaptometil)hidrocinamoil]glicina, éster bencílico, acetato dexecadotrilo (éster)

C21H23NO4S dexsotalolum dexsotalol (+)-(S)-4'-[1-hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide dexsotalol (+)-N-[4-[(1S)-1-hydroxy-2-[(1-méthyléthyl)amino]éthyl]phényl]= methanesulfonamide dexsotalol (+)-(S)-4'-[1-hidroxi-2-(isopropilamino)etil]metanosulfonanilida

C12H20N2O3S dimadectinum dimadectin mixture of (2aE,4E,5'S.6S,6'R,7S.8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-(S)-sec- butyl-3',4',5',6,6',7,10.11,14,15,17a,20,20a,20b-tetradecahydro-20 ,20b- dihydroxy-7-[(2-methoxyethoxy)methoxy]-5',6,8,19-tetramethylspiro[11,15- methano-2H,13H, 17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'- [2H[pyran]-17-one (major component) and (2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)- 3',4',5',6,6',7.10,11,14,15.17a,20,20a,20b4etradecahydro-20,20b-dihydroxy- 6'-isopropyl-7-[(2-methoxyethoxy)methoxy]-5',6,8,19-tetramethylspiro[11, 15-methano-2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'- [2H]pyran]-17one dimadectine mélange de: (2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13R,15S,17aR,20R,20aR,20bS)-20,20b- dihydroxy-7-[(2-méthoxyéthoxy)méthoxy]-5', 6,8,19-tétraméthyl-6'-[(1 S)-1 - méthylpropyl]-3',4',5',6,6',7,10,11,14,15,17a.20,20a,20b-tétradéca= hydrospiro[11,15-méthano-2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclo^ octadécène-13,2'-2H]pyran]-17-one (constituant principal) et de (2aE,4E,8E)-{5'S,6S,6'R,7S,l1R,13R,15S,17aR,20R,20aR,20bS)-20,20b- dihydroxy-7-[(2-méthoxyétrioxy)méthoxy]-5', 6,8,19-tétraméthyl-6'- (1-méthyléthyl)-3',4',5',6,6',7,10,11,14,15,17a,20,20a,20b- tétradécahydrospiro[11,15-methano-2H,13H,17H-furo[4,3,2- pq][2,6]benzodioxacyclooctadécène-13,2'-[2H]pyran]-17-one

144 WHO Drug Information, Vol. 10, No. 3, 1996 Recommended INN. List 36

dimadectina mezcla de (2aE,4E,5'S,6S,6'R,7S.8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-(S)-sec- butil-3',4',5',6,6',7,10,11,14,15,17a,20,20a,20b-tetradecahidro-20,20b- dihidroxi-7-[(2-metoxietoxi)metoxi]-5',6,8,19-tetrametilespiro[11.15-metano- 2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacicIooctadecin-13,2'-[2H]piran]-17- ona (constituyente principal) y (2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)- 3',4',5',6,6',7,10,11,14,15,17a,20,20a,20b-tetradecahidro-20,20b-dihidroxi-6'- isopropil-7-[(2-metoxietoxi)metoxi]-5',6,8,19-tetrametilespiro[11,15-metano- 2H,13H17H-furo[4,3,2-pq][2,6]benzodioxaciclooctadecin-13,2'-[2H]piran]-17- one

C38H58O10 + C37H58O10 droxinavirum 3-tert-butyl-1-[(2R,3S)-3-[(2S)-3,3-dimethy[-2-[2-(methylarnino)acetamido]= droxinavir butyramido]-2-hydroxy-4-phenylbutyl]1-isopentylurea 3-(1,1-diméthyléthyl)-1-[(2R,3S)-3-[[(2S)-3,3-diméthyl-2-[[(méthylamino)= droxinavir acétyl]amino]butanoyl]amino]-2-hydroxy-4-phénylbutyl]-1-(3-méthylbutyl)urée 3-terc-buti[-1-[(2R,3S)-3-[(2S)-3,3-dimetil-2-[2-(metilamino)acetamido] = droxinavir butiramida]-2-hidroxi-4-fenilbutil]-1-isopentilurea

C29H51N5O4 edaravonum 3-methy[-1-phenyl-2-pyrazolin-5-one edaravone 5-méthy[-2-phényl-2,4-dihydro-3H-pyrazol-3-one édaravone 3-metil-1-fenil-2-pirazolin-5-ona edaravona

C10H10N2O edrecolomabum edrecolomab immunoglobulin G 2a (mouse monoclonal 17-1A γ-chain anti-human colon cancer tumor-associated antigen), disulfide with mouse monoclonal 17-1A light chain, dimer

édrécolomab immunoglobulin G 2a (chaîne γ de l'anticorps monoclonal de souris 17-1A anti-antigène tumoral associé au cancer du colon humain), dimère du disulfure avec la chaîne legère de l'anticorps monoclonal de souris 17-1A edrecolomab inmunoglobulina G 2a (cadena γ del anticuerpo monoclonal de ratón 17-1A anti-antigeno tumoral asociado al cáncer de colon humano), dimero del disulfuro con la cadena ligera del anticuerpo monoclonal de ratón 17-1A eletriptanum 3-[[(R)-1-methyl-2-pyrrolidinyl]methyl]-5-[2-(phenylsulfonyl)ethyl]indole eletriptan 3-[(2R)-(1-méthylpyrrohdin-2-yl)méthyl]-5-[2-(phénylsulfonyI)éthyl]-1H-indole élétriptan 3-[[(R)-1-metil-2-pirrolidiml]metiI]-5-[2-(fenilsulfonil)etil]indol eletriptán

C22H26N2O2S emoctakinum interleukin 8 (human) emoctakin interleukin 8 humaine émoctakine irterleuquina 8 humana emoctakin

C372H600N106O186S4

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epoetinum omega epoetin omega 1-165-erythropoietin (human clone λHEPOFL13 protein moiety), glycoform ω

1-165-érythropoïétine (partie proteique de la substance issue du clone de époétine oméga cellules humaines λHEPOFL13), forme glycosylée ω

1-165-eritropoietina (fracción protéica del clon humano λHEPOFL13) epoetina omega glicoforma ω

C809H1301N229O210S5

eprinomectinum eprinomectin mixture of: (2aE,4E,5'S,6S,6'R,7S,8E,11R,13S,15S,17aR,20R,20aR,20bS)-6'-(S)-sec- butyl-5',6,6',7,10,11,14,15,17a,20, 20a,20b-dodecahydro-20,20b-dihydroxy- 5',6,8,19-tetramethyl-17-oxospiro[11,15-methano-2H,13H17H-furo[4,3,2- pq][2,6]benzodioxacyclooctadecin-13,2'-[2H]pyran]-7-yl 4-O-(4-acetamido- 2,4,6-trideoxy-3-O-methyl-α-L-lyxo-hexopyranosyl)-2,6-dideoxy-3-O-methyl-α- L-arabino-hexopyranoside (major component) and (2aE,4E,5'S,6S,6'R,7S,8E,11R,13S,15S,17aR,20R,20aR,20bS)- 5',6,6',7,10,11,14,15,17a,20,20a,20b-dodecahydro-20,20b-dihydroxy-6'- isopropyl-5',6,8,19-tetramethyl-17-oxospiro[11,15-methano-2H,13H,17H- furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'-[2H]pyran]-7-yl 4-O-(4- acetamido-2,4,6-trideoxy-3-O-methyl-α-L-lyxo-hexopyranosyl)-2,6-dideoxy-3- O-methyl-α-L-arabino-hexopyranoside

éprinomectine mélange de: (2aE,4E,8E)-(5'S.6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-7-[[4-O-[4- (acétyiamino)-3-0-méthyl-2,4,6-tridésoxy-α-L-lyxo-hexopyranosyl]-3-O- méthyi-2,6-didésoxy-α-L-arabino-hexopyranosyl]oxy]-20,20b-dihydroxy- 5',6,8,19-tétraméthyl-6'-[(1S)-1-méthylpropyl]- 5',6.6' ,7,10,11,14,15,17a, 20,20a,20b-dodecahydrospiro[11,15-méthano- 2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadécène-13,2'-[2H|pyran]- 17-one (constituant principal) et de (2aE,4E,8E)-(5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-7-[[4-O-[4- (acétylamino)-3-O-méthyl-2,4,6-tridésoxy-α-L-lyxo-hexopyranosyl]-3-O- méthyl-2,6-didésoxy-α-L-arabino-hexopyranosyl]oxy]-20,20b-dihydroxy- 5',6,8,19-tétraméthyl-6'-(1-méthyléthyl)-5',6,6',7,10,11,14,15,17a,20,20a,20b- dodécahydrospiro[11,15-méthano-2H,13H,17H-furo[4,3.2- pg][2,6]benzodioxacyclooctadécène-13,2'-[2H]pyran]-17-one

eprinomectina mezcla de: (2aE,4E,5'S,6S,6'R,7S,8E,11R,13S,15S,17aR,20R,20aR,20bS)-6'-(S}-sec- butil-5',6.6',7,10,11,14,15,17a,20,20a,20b-dodecahidro-20,20b-dihidroxi- 5',6,8,19-tetrametil-17-oxospiro[11,15-metano-2H,13H,17H-furo[4.3,2- pq][2,6]benzodioxaciclooctadecin-13,2'-[2H]piran]-7-il 4-O-(4-acetamido- 2,4,6-tridesoxi-3-O-metil-α-L-lixo-hexopiranosil)-2,6-didesoxi-3-O-metil-a-L- arabino-hexopiranósido (constituyente principal) y (2aE,4E,5'S,6S,6'R7S,8E,11R,13S,15S,17aR,20R,20aR, 20bS)- 5',6,6',7,10,11,14,15,17a,20,20a,20b-dodecahidro-20,20b-dihidroxi-6'- isopropil-5',6,8.19-tetrametil-17-oxospiro[11,15-metano-2H,13H,17H- furo[4,3,2-pq][2,6]benzodioxaciclooctadecin-13,2'-[2H]piran]-7-il 4-O-(4- acetamido-2,4,6-tridesoxi-3-O-metil-α-L-lixo-hexopiranosil)-2,6-didesoxi-3-O- metil-α-L-arabino-hexopiranósido

C50H75NO14 + C49H73NO14

146 WHO Drug Information, Vol. 10, No 3, 1996 Recommended INN List 36

fabesetronum (+)-(R)-8,9-dihydro-10-methyl-7-[{5-methyIimidazol-4-yl)methyl]pyrido= fabesetron [1,2-a]indol-6(7H)-one (+)-(7R)-10-méthyl-7-[(5-méthy]-1H-imidazol-4-yl)méthyl]- fabésétron 8,9-dihydropyndo[1,2-a]indol-6(7H)-one (+)-(R)-8,9-dihidru-10-metil-7-[(5-metilimidazo]-4-il)metil]pirido= fabesetron [1,2-a]indol-6(7H)-ona

C18H19N3O falecalcitriolum (+)-(5Z,7E)-26,26,26,27,27,27-hexafluoro-9,10-secocholesta-5,7.10(19)- falecalcitriol triene-1α,3β,25-triol (+)-(5Z,7E)-26,26,26,27,27,27-hexafluoro-9,10-sécocholesta-5,7,10(19)- falécalcitriol triène-1α,3β,25-triol (+)-(5Z,7E)-26,26,26,27,27,27-hexafluoro-9,10-secocolesta-5,7,10(19)-trien- falecalcitriol 1a,3β,25-triol

C27H38F6O3 fasidotrilum N-[(S)-α-(mercaptomethyl)-3,4-(methylenedioxy)hydrocinnamoyl]-L-alanine. fasidotril benzyl ester, acetate (ester) (2S)-2-[[(2S)-2-[(acétylsulfanyl)méthyl]-3-(1,3-benzodioxol- fasidotril 5-yl)propanoyl]amrno]propanoate de benzyle N-[(S)-α-(mercaptometil)-3,4-(metilenodioxi)hidrocinamoil]-L-alanina, éster fasidotril bencílico, acetato (éster)

C23H25NO6S fexofenadinum (±)-p-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidino]butyl]- fexofenadine α-methylhydratropic acid acide 2-[4-[(1 RS)-1 -hydroxy-4-[4-(hydroxydiphénylméthyl)pipéridin- fexofénadine 1-yl]butyl]phényl]-2-méthyipropanoïque ácido (±)-p-[1-hidroxi-4-[4-(hidroxidifenilmetil)piperidino]butil]- fexofenadina α-metilhïdratropico

C32H39NO4 forasartanum 5-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyI]-2-(o-1H-tetrazol- forasartan 5-ylphenyl)pyndine 5-[(3,5-dibutyl-1 H-1,2,4-triazol-1 -yl)méthyl]-2-[2-(1 H-tétrazol- forasartán 5-yl)phényl]pyridine 5-[(3,5-dibutil-1H-1,2,4-triazol-1-il)metil]-2-(o-1H-tetrazoi-5-ilfenil)piridine forasartan C23H28N8

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fozivudinum tidoxilum (2RS)-2-(decyloxy)-3-(dodecylthio)propyl hydrogen 3'-azido-3'-deoxy-5'- fozivudine tidoxil thymidylate hydragéno(3'-azido-3'-désoxy-5'-thymidylate) de (2RS)-2-(décyloxy)- fozivudine tidoxil 3-(dodécylsulfanyl)propyle 3'-azido-3'-desoxi-5'-timidilato de (2RS)-2-(deciloxi)-3-(dodeciltio)propil fozivudina tidoxilo hidrógeno

C35H64N5O8PS

gatifloxacinum (±)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazLnyl)-4- gatifloxacin oxo-3-quinolinecarboxylic acid acide 1-cyclopropyl-6-fluoro-8-méthoxy-7-[(3RS)-3-méthylpipérazin-1-yl]- gatifloxacine 4-oxo-1,4-dihydroquinoléine-3-carboxylique ácido (±)-1-ciclopropil-6-fluoro-1,4-dihidro-8-metoxi-7-(3-metil-1-piperazinil)-4- gatifloxacino oxo-3-quinolinacarboxílico

C19H22FN3O4

glaspimodum N2,N2'-[(2S,7S)-2,7-bis[(2S)-3-carboxy-2-[(2S)-4-carboxy-2-[(2S)-5-oxo- glaspimod 2-pyrrolidinecarboxamido]butyramido]propionamido]octanedioyl]di-L-lysine N2,N3'-[(2S,7S)-2,7-bis[[(5-oxo-L-prolyl)-L-glutamyl-L-aspartyl]amino]= glaspimod octanedioyl]di-L-lysine N2,N2'-[(2S,7S)-2,7-bis[(2S)-3-carboxi-2-[(2S)-4-carboxh2-[(2S)-5-oxo- glaspimod 2-pirrolidinacarboxamido]butiramido]propionamido]octanodioil]di-L-lisina

C48H74N12O22

igovomabum

igovomab immunoglobulin G 1 (mouse monoclonal OC125 F(ab')2 fragment anti-human ovarian cancer antigen CA 125), disulfide with mouse monoclonal OC125

F(ab')2 light chain igovomab immuoglobuline G1 fragment F(ab')2 de l'anticorps monoclonal OC 125 anti­ antigène CA 125 associé à certaines tumeurs ovariennes igovomab inmunoglobulin G1 fragmento F(ab')2 del anticuerpo monoclonal OC 125 anti- antígeno CA 125 asociado a ciertos tumores ováricos ilomastatum (R)-N'-hydroxy-N-[(S)-2-indol-3-yl-1-(methylcarbamoyl)ethyl]- ilomastat 2-isobutylsuccinamide (2R)-N1-hydroxy-N4-[(1S)-1-[(1H-indol-3-yl)méthyl]-2-(méthylamino)- ilomastat 2-oxoéthyl]-3-(2-méthylpropyl)butanediamide (R)-N'-hidroxi-N-[(S)-2-indol-3-il-1-(metilcarbamoil)etil]-2-isobutilsuccinamida ilomastat C20H28N4O4

148 WHO Drug Information, Vol 10, No. 3, 1996 Recommended INN: List 36

indinavirum indinavir (αR,γS,2S)-a-benzyl-2-(tert-butylcarbarnoyl)-γ-hydroxy-N-[(1S,2R)- 2-hydroxy-1-indanyl]-4-(3-pyridyImethyl)-1-piperazinevaleramide indinavir (2R,4S)-2-benzyl-5-[(2S)-2-[(1,1-diméthyléthyl)carbamoyl]-4-(3-pyridyl= méthyl)pipérazin-1-yl]-4-hydroxy-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-indén- 1-yl]pentanamide indinavir (αR,γS,2S}-a-bencil-2-(terc-butiIcarbamoiI)-γ-hidroxi-N-[(1S,2R)-2-hidrox¡- 1-indanil]-4-(3-pindi[metil)-1-piperazinavaIeramida

C36H47N5O4 iolopridum (123l) iolopride (123l) N-[[(2fí)-1-ethyl-2-pyrrolidinyl]methy[]-6-hydroxy-5-([123l]iodo)-o-anisamide

123 123 (S)-N-[(1-éthy]pyrrol¡dm-2-yl}méthyl]-2-hydroxy-3-[ ]]iodo- iolopride ( l) 6-méthoxybenzamide

N-[[(2S)-1-etil-2-pirrolidinil]metil]-6-hidraxi-5-([123l]iodo)-o-anisamida ioloprida (123l) 123 C15H21 IN2O3 ipidacrinum 9-amino-2,3,5,6,7,8-hexahydro-1H-cycIopenta[b]quinoIine ipidacrine (2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoléin-9-yl) amine ipidacrine 9-amino-2,3,5,6,7,8-hexahidro-1H-ciclopenta[b]quinolina ipidacrina

C12H16N2 iroplactum N-L-methionylbIood platelet factor 4 (human subunit) iroplact N-L-méthionylfacteur plaquétaire 4 sanguin (sous-unité humaine) iroplact N-L-metionilfactor plaquetario 4 (subunidad humana) iroplact

C346H585N97O102S5 lenaperiemum lenapenem (+)-(4R,5S,6S)-6-[(R)-1-hydroxyethyI]-3-[[(3S,5S)-5-[(R)-1-hydroxy- 3-(methylamino)propyl]-3-pyrrohdinyl]thio]-4-methyl-7-oxo- 1-azabicyclo[3 2 0]hept-2-ene-2-carboxyIic acid iénapénem acide (+)-(4R,5S,6S)-6-[(1 R)-1-hydroxyéthyl]-3-[[(3S,5S)-5-[(1 R)-1 -hydroxy-3- (méthylamino)propyl]pyrrolidin-3-yl]sulfanyl]-4-méthyl-7-oxo- 1 -azabicyclo[3.2 0]hept-2-ène-2-carboxylique lenapenem ácido (+)-(4R,5S,6S)-6-[(R)-1 -hidroxietil]-3-[[(3S,5S)-5-[(R)-1 -hidroxi- 3-(metilam[no)propil]-3-pirrolidini]]tio]-4-metiI-7-oxo- 1-azabiciclo[3.2.0]hept-2-en-2-carboxíhco

C18H29N3O5S

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lepirudinum 1-L-leucine-2-i_-threonine-63-desulfohirudin [Hirudo medicinalis isoform HV1) lepirudin 1 -L-leucine-2-L-thréonine-63-désuifohirudine (Hirudo medicinalis, variant HV1 ; lépirudine 1-L-leucina-2-L-treonina-63-desulfohirudina (Hirudo medicinalis, isoforma lepirudina HV1)

C287H440N80O111S6 levobupivacainum (S)-1-butyl-2'.6'-pipecoloxylidide levobupivacaine (2S)-1-butyl-N-(2,6-diméthylphényl)pipéridine-2-carboxamide lévobupivacaine (S)-1-butil-2',6'-pipecoloxilidida levobupivacaina

C18H28N2O levormeloxifenum (-)-1-[2-[p-(trans-7-methoxy-2,2-dimethyl-3-phenyl-4-chromanyl)phenoxy]= levormeloxifene ethyl]pyrrohdine (-)-1-[2-[4-[(3R,4H)-7-méthoxy-2,2-diméthyl-3-phénylchroman-4-yl]phénoxy]= levormeloxifene éthyl]pyrrolidine (-)-1-[2-[p-(trans-7-metoxi-2,2-dimetil-3-fenil-4-cromanil)fenoxi]etil]pirrolidina levormeloxifeno C30H35NO3 linetastinum linetastine (2E,4E)-N-[2-[4-(diphenylmethoxy)piper¡dino]ethyl]-5-(4-hydroxy- 3-methoxyphenyl)-2,4-pentadienamide ethyl carbonate (ester) linétastine carbonate de 4-[(1E,3E)-5-[[2-[4-(diphénylméthoxy)pipéridin- 1-yl]éthyl]amino]-5-oxopenta-1,3-diényl]-2-méthoxyphényle et d'éthyle linetastina etilcarbonato de (2E,4E)-N-[2-[4-(difenilmetoxi}pipendino]etil]-5-(4-hidroxi- 3-metoxifenil)-2,4-pentadienarnida

C35H40N2O6 lintitriptum 2-[[4-{o-chlarophenyl)-2-thiazolyl]carbamoyl]indole-1 -acetic acid lintitript acide 2-[2-[[4-(2-chlorophényl)thiazol-2-yl]carbamoyl]-1 H-indol-1 -yl]acétique lintitript ácido 2-[[4-(o-clorofenil)-2-tiazolil]carbamoil]indol-1-acético lintitript

C20H14CIN3O3S lirexapridum 4-amino-5-chloro-a-cyclopropyl-N-[(1R,2R)-2-[(4-methylpipend¡no)methyl]= lirexapride cyclohexyl]-o-anisamide 4-amino-5-chIoro-2-(cyclopropylméthoxy)-N-[(1R,2R)-2-[(4-méthylp¡péridin- lirexapride 1-yl)méthyl]cyclohexyl]benzamide 4-amino-5-clora-a-ciclopropil-N-[(1R,2R)-2-[(4-metilpiperidino)metil]= lirexaprida ciclohexil]- o-anisamida

C24H36CIN3O2

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lurtotecanum lurtotecan (8S)-8-ethy]-2,3-dihydro-8-hydroxy-15-[(4-methyl-1-piperazinyl)methyl]-11H- p-dioxino[2,3-g]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12(8H,14H)-dione lurtotécan (8S)-8-éthyl-8-hydroxy-15-[(4-méthylpípérazin-1-y])méthyl]- 2,3.11.14-tétrahydro-12H-1,4-dioxino[2.3-g]pyrano[3',4':6,7]indolizino- [1,2-b]quinoléin-9,12(8H)-dione lurtotecán (8S)-8-etil-2,3-dihidro-8-hidroxi-15-[(4-metil-1-piperazinil)metiI]-11H- p-dioxino[2,3-g-]pirano[3',4':6,7]indolízino[1,2-b]quinolina-9,12(8H,14H)-diona

C28H30N4O5 melagatranum N-[(R)-[[(2S)-2-[(p-amidinobenzyl)carbamoyl]-1-azetidinyl]carbonyl]- melagatran cyclohexylmethyl]glycine acide 2-[[(1R)-2-[(2S)-2-[(4-carbamirnidoylbenzyl)carbamoyl]azétidin-1-yl]- mélagatran 1-cyclahexyl-2-oxoéthyl]amino]acétique N-[(R)-[[(2S)-2-[(p-amidinobencil)carbamoil]-1-azetidinil]carbonil]= melagatrán ciclohexilmetil]glicina

C22H31N5O4 milamelinum 1,2,5,6-tetrahydro-1-methylnicotinaldehyde (E)-O-methyloxime milameline (E)-1 -méthyl-1 2,5,6-tétrahydropyndine-3-carbaldéhyde O-méthyloxime milaméline 1,2,5,6-tetrahidro-1-metilnicotinaldehide (E)-O-metiloxima milamelina

C8H14N2O milodistimum milodistim 23-L-leucine-27-L-aspartie acid-39-L-glutamic acidcolony-stimulating factor 2 (human clone pHG25 protein moiety reduced), (127-9')-protein with 9-glycine-10-glycine-11-glycine-12-glycine-13-L-serine-14-g!ycine-15-glycine- 16-glycine-18-glycine-19-L-serine-34-L-aspartic acid-89-L-aspartic acid- 9-152-interleukin 3 (human clone D11 precursor protein moiety reduced) milodistim [23-L-leucine-27-acide L-aspartique-39-acide L-gIutamique]facteur 2 de stimulation des colonies (clone humain pHG25, partie protéique réduite), (127-9')-protéine avec la [9-glycine-10-glycine-11-glycine-12-glycine-13- L-sérine-14-glycine-15-glycine-16-glycine-18-glycine-19-L-sérine-34-acide L-aspartique-89-acide L-aspartique]-9-152-interleukin 3 (clone humain D11 précurseur de la partie protéique réduite) milodistim 23-L-leucina-27-ácido L-aspártico-39-ácido L-glutámico-factor 2 estimulante de colonias (clon humano pHG25 fraccion proteica reducida), (127-9')-proteina con 9-glicina-10-glicina-11 -glicina-12-glicina-13-L-serma-14-glicina-15-glicma- 16-gliclna-18-glicina-19-L-serina-34-ácido L-aspártico-89-ácido L-aspártico-9-152-interleuquina 3 (clon humano D11 precursor de la fracción proteica reducida)

C1336H2116N362O410S13

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minolteparinum natricum minolteparin sodium Sodium salt of depolymerized heparin obtained by nitrous acid degradation of heparin from pork intestinal mucosa, the majority of the componants have a 2-O-sulfo-α-L- idopyranosuronic acid structure at the non-reducing end and a 6-O-suIfo-2,5-anhydro-D-mannitol structure at the reducing end of their chain; the average relative molecular mass is between 1700 and 3300, 90 per cent of which ranging between 1000 and 8000; the degree of sulfatation is about 2,1 per disaccharidic unit

minoltéparine sodique Sel de sodium d'héparine dépolymérisée obtenue par fragmentation au moyen d'acide nitreux d'héparine de muqueuse intestinale de porc. La majorité des composants présentent une structure acide 2-O-sulfo-α-L- idopyranosuronique à l'extrémité non réductrice et une structure 6-O-sulfo- 2,5-anhydro-D-mannitol à l'extrémité réductrice de leur chaîne. La masse moléculaire relative moyenne est de 1700 à 3300. 90% de celle-ci se situant entre 1000 et 8000. Le degré de sulfatation est d'environ 2,1.

minoltepanna sodica Sal sódica de la heparina despohmerizada obtenida por fragmentación con ácido nitroso de la heparina de la mucosa intestinal del cerdo; la mayoría de los componentes tienen una estructura de ácido 2-O-sulfo-α-L- idopiranosurónico en el extremo no reductor y una estructura de 6-O-sulfo- 2,5-anhidro-D-manitol en el extremo reductor de la cadena, la masa molecular relativa media está entre 1700 y 3300, con 90% entre 1000 y 8000, el grado de sulfatación es aproximadamente de 2,1 por unidad de disacárido.

mipitrobanum 6-chloro-3-(p-chlorobenzyl)-β,β-dimethyl-3H-imidazo[4,5-b]pyridine-2-butync mipitroban acid acide 4-[6-chloro-3-(4-chlorobenzyl)-3H-imidazo[4,5-b]pyridin-2-yI]- mipitroban 3,3-diméthylbutanoique ácido 6-cloro-3-(p-clorobencil)-β,β-dimetil-3H-imidazo[4,5-b]piridina-2-butírico mipitroban C19H19Cl2N3O2

miproxifenum miproxifene (Z)-α-[p-[2-(dimethylamino)ethoxy]phenyl]-α'-ethyl-4'-isopropyl-4-stilbenol

4-[(12)-1-[4-[2-(díméthylamino)éthoxy]phényl]-2-[4-(1-méthyléthyl)phényl]but- miproxifène 1 -ényl]phénol

(Z)-α-[p-[2-(dimetilamino)eloxi]fenil]-α'-etil-4'-isopropil-4-estilbenol miproxifeno

C29H35NO2 montelukastum 1-[[[(R)-m-[(E)-2-(7-chloro-2-quinolyl)vinyl]-α-[o-(1-hydroxy- montelukast 1-methylethyl)phenethyl]benzyl]thio]methyl]cyclopropaneacetic acid acide 2-[1-[[[(R)-1-[3-[(E)-2-(7-chloroqumoléin-2-yl)éthényl]phényl]-3-[2-(1- montélukast hydroxy-1-méthyléthyl)phényl]propyl]sulfanyl]méthyl]cyclopropyl]acétique ácido 1-[[[(R)-m-[(E)-2-{7-cloro-2-quinolil)vinil]-α-[o-(1-hidroxi- montelukast 1-metiletil)fenetil]bencil]tio]metil]cicloprapanacético

C35H36CINO3S

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napitanum (±)-(3R*)-3-phenyl-1 -[[(6R*)-6,7,8,9-tetrahydronaphtho[1,2-d]-1,3-dioxol- napitane 6-yl]methyl]pyrrolidine

(3RS)-3-phényl-1-[[(6RS)-6,7,8,9-tétrahydronaphto[1,2-d]-1,3-dioxol- napitane 6-yl]méthyl]pyrroIidine

(±)-(3R*)-3-fenil-1-[[(6R*)-6,7,8,9-tetrahidronafto[1,2-d]-1,3-dioxol- napitano 6-il]metil]pirrolidina

C22H25NO2 nateplasum nateplase mixture of. N-[N2-(N-glycyl-L-alanyl)-L-arginyljpIasminogen activator (human tissue-type 1-chain form, protein moiety), glycoform β (major component) and plasminogen activator (human tissue-type 1-chain form, protein moiety), glycoform β natéplase mélange de. N-[N2-(N-glycyl-L-alanyl)-L-arginyl]activateur du plasminogène (type tissulaire humain constituté d'une chaîne, partie protéique), forme glycosylee β (constituant principal) et d'activateur du plasminogène (type tissulaire humain constituté d'une chaîne, partie protéique), forme glycosylee β nateplasa mezcla de N-[N2-(N-glicil-L-alanil)-L-arginil]activador del plaminógeno (tipo tisular humano forma monocatenaria, fracción proteica), forma glicosilada β (constituyente principal) y activador del plasminógeno (tipo tisular humano forma monocatenaria, fracción proteica), forma glicosilada β nepaprazolum (±)-(9R*)-9-[(SS*)-2-benzimidazolylsulfÍnyl]-6,7,8,9-tetrahydro-4-methoxy- nepaprazole 5H-cyclohepta[b] pyridine (9RS)-9-[(SR)-1H-benzimidazol-2-ylsulfinyl]-4-méthoxy-6,7,8,9-tétrahydro-5H- népaprazole cyclohepta[b]pyhdine (±)-(9H*)-9-[(SS*)-2-benzimidazolilsulfinil]-6,7,8,9-tetrahidro-4-metoxi-5H- nepaprazol ciclohepta[b]piridina

C18H19N3O2S octocogum alfa octocog alfa blood-coagulation factor VIII (human), glycoform α octocog alfa facteur VIII de coagulation sanguine (humain), forme glycosylée α octocog alfa factor de coagulación VIII (humano) forma glicosilada α

odulimomabum odulirnomab immunoglobulin G1 (mouse monoclonal 25.3 heavy chain anti-human antigen CD 11 α-chain), disulfide with mouse 25.3 light chain, dimer odulimomab immunoglobuline G1 (chaîne lourde de l'anticorps monoclonal de souris 25 3 anti-chaîne α de l'antigène CD11 humain), dimère du disulfure avec la chaîne légère de l'anticorps monoclonal de souris 25 3 odulimomab mmunoglobulin G1 (cadena pesada del anticuerpo monoclonal de ratón 25 3 anti-cadena α del antigeno CD11 humano), dímero del disulfuro con la cadena ligera del anticuerpo monoclonal de raton 25 3

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osanetantum N-[1-[3-[(R)-1-benzoyl-3-(3,4-dichlorophenyl)-3-piperidyl]propyl]-4-phenyl- osanetant 4-piperidyl]-N-methylacetamide N-[1-[3-[(3H)-1-benzoyl-3-(3,4-dichlorophényl)pipéridin-3-yl]propyl]- osanétant 4-phénylpipéridin-4-yl]-N-iméthylacétamide N-[1-[3-[(R)-1-bencil-3-(3,4-diclorofenil)-3-piperidil]propil]-4-fenil-4-piperidil]-N- osanetant metilacetamida

C35H41Cl2N3O2 pagoclonum pagoclone (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexy])phthahmidine

(+)-2-(7-chloro-1,8-naphtyridm-2-yl)-3-(5-méthyl-2-oxohexyl)-2,3-dihydro- pagoclone 1H-isoindol-1-one

(+)-2-(7-cloro-1,8-naftiridin-2-il)-3-{5-metil-2-oxohexil)ftalimidina pagoclona C23H22CIN3O2

pallnavirum palinavir N-[(1S)-1-[[1S,2R)-1-benzyl-3-[(2S,4R)-2-(tert-butylcarbamoyl)- 4-(4-pyridylmethoxy)pipendino]-2-hydroxypropyl]carbamoyl]- 2-methylpropyl]quinaldamide palinavir N-[(1S)-1-[(1S,2R)-1-benzyl-3-[(2S,4R)-2[(1,1-diméthyléthyl)carbamoyl]- 4-(4-pyridylméthoxy)pipéridín-1-yl]-2-hydoxypropyl]carbamoyl]-2-méthyl= propyl]quínoléine-2-carboxamide palinavir N-[(1S)-1-[[(1S,2R)-1-bencil-3-[(2S,4R)-2-(terc-butilcarbamoit)- 4-(4-piridilmetoxi)piperidino]-2-hidroxipropil]carbamoil]- 2-metilpropil]quinaldamida

C41H52N6O5 palonosetronum palonosetron 2,4,5,6-tetrahydro-2-[(3S)-3-quinuclidinyl]-1H-benz[de]isoquinolin-1-one

2-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-2,4,5,6-tétrahydro- palonosétron 1 H-benzo[de]isoquinoléin-1 -one

2,4,5,6-tetrahidro-2-[(3S)-3-quinuclidinil]-1H-benz[de]isoquinolin-1-ona palonosetron C19H22N2O pamaquesidum 11-oxo-(25R)-5α-spirostan-3β-yl 4-O-β-D-glucopyranosyl- pamaqueside p-D-glucopyranoside 3β-[(4-O-β-D-glucopyranosyl-β-D-gIucopyranosyl)oxy]-(25R)-5α-spirostan- pamaquéside 11-one 11-oxo-{25R)-5α-espirostan-3β-il 4-O-β-D-glucopiranosil-β-D-glucopiranósido pamaquesida C39H62O14

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panamesinum (5S)-5-[[4-hydroxy-4-[3,4-(methylenedioxy)phenyl]piperidino]metriyl]- panamesine 3-(p-methoxyphenyl)-2-oxazolidinone (-)-(5S)-5-[[4-(1,3-benzodioxol-5-yl)-4-hydroxypipéndin-1-yl]méthyl]- panamésine 3-(4-méthoxyphényl)oxazolidin-2-one (5S)-5-[[4-Hidroxi-4-[3,4-(rnetilenodioxi)fenil]piperidino]metil]- panamesina 3-(p-metoxifenil)-2-oxazolidinona

C23H26N2O6 piclamilastum 3-(cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-p-anisamide piclamilast 3-(cycIopentyloxy)-N-(3,5-dichioropyndin-4-yl)-4-méthoxybenzamide piclarnilast 3-(ciclopentiloxi)-N-(3,5-dicloro-4-píridíl)-p-anisamida piclamilast

C18H18Cl2N2O3 plusonerminum plusonermin mixture of tumor necrosis factor proteins (human): 1-157-tumor necrosis factor, 3-157-tumor necrosis factor (major component), and 5-157-tumor necrosis factor plusonermine mélange de protéines de facteur de nécrose tumorale (humain) 1-157-facteur de nécrose tumorale, 3-157-facteur de nécrose tumorale (constituant principal) et 5-157-facteur de nécrose tumorale plusonermina mezcla de factor de necrosis tumoral proteínas: 1-157-factor de necrosis tumoral, 3-157-factor de necrosis tumoral (constituyente principal) y 5-157-factor de necrosis tumoral pomisartanum 4'-[[2-ethyl-4-methyl-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyndm-2-yl)- pomisartan 1 -benzimidazolyl]methyl]-2-biphenylcarboxylic acid acide 4'-[[2-éthyl-4-méthyl-6-(5,6,7,8-tétrahydroimidazo[1,2-a]pyridin-2-yl)-1H- pomisartan benzimidazol-1-yl]methyl]biphényle-2-carboxylïque ácido 4'-[[2-etiI-4-metil-6-(5,6,7,8-tetrahidroimidazol[1,2-a]pindin-2-il)- pomisartán 1-benzimidazolil]metil]-2-bifenilcarboxilico

C31H30N4O2 povidonum povidone 1-vinyl-2-pyrrolidinone polymer, linear povidone poly[l-(2-oxopyrrolidin-1-yl)éthylène] linéaire povidone polímero lineal de 1-vinil-2-pirrolidonona

(C6H9NO)n

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pramlintidum pramlintide L-lysyl-L-cysteinyi-L-asparaginyl-L-threonyl-L-alanyl-L-threonyl-L-cysteinyl- L-alanyl-L-threonyl-L-glutaminyl-L-arginyl-L-leucyl-L-alanyl-L-asparaginyl- L-phenylalanyl-L-leucyl-L-valyl-L-histidyl-L-seryl-L-seryl-L-asparaginyl- L-asparaginyl-L-phenylalanylglycyl-L-prolyl-L-isoleucyl-L-leucyl-L-prolyl-L-prolyl- L-threonyl-L-asparaginyl-L-valylglycyl-L-seryl-L-asparaginyl-L-threoriyl- L-tyrosmamide, cyclic (2-7)-disulfide

pramlintide (2-7)-disufure cyclique de L-lysyl-L-cystéinyl-L-asparaginyl-L-thréonyl- L-alanyl-L-thréonyl-L-cystéinyl-L-alanyl-L-thréonyl-L-glutaminyl-L-arginyl- L-leucyl-L-alanyl-L-asparaginyl-L-phénylalanyl-L-leucyl-L-valyl-L-histidyl-L-séryl- L-séryl-L-asparaginyl-L-asparaginyl-L-phénylalanyl-glycyl-L-prolyl-L-isoleucyl- L-leucyl-L-prolyl-L-prolyl-L-thréonyl-L-asparaginyl-L-valyl-glycyl-L-séryl- L-asparaginyl-L-thréonyl-L-tyrosinarnide

pramlintida (2-7)-disulfuro cíclico de L-lisil-L-cisteinil-L-asparaginil-L-treonil-L-alanil- L-treonil-L-cisteiml-L-alanil-L-treonil-L-glutaminil-L-arginil-L-leucil-L-alanil- L-asparaginil-L-fenilalanil-L-leucil-L-valil-L-histidil-L-seril-L-seril-L-asparaginil- L-asparaginil-L-fenilalanilglicil-L-prolil-L-isoleucil-L-leucil-L-prolil-L-prolil- L-treonil-L-asparaginil-L-valilglicil-L-seril-L-asparaginil-L-treonil-L-tirosinamida

C171H267N51O53S2

propacetamolum N,N-diethylglycine, ester with 4'-hydroxyacetanilide propacetamol 2-(diéthylamino)acétate de 4-(acélylamino)phényle propacétamol éster de la N,N-dietilglicina con la 4'-hidroxiacetanilida propacetamol

C14H20N2O3

quetiapinum 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]etrianol quetiapine 2-[2-[4-(dibenzo[b,f][1,4]thiazépin-11-yl)pipérazin-1-yl]éthoxy]éthanol quétiapine 2-[2-(4-dibenzo[b,f][1,4]tiazepin-11 -il-1 -piperazinil)etoxi]etanol quetiapina

C21H25N3O2S racecadotrilum racecadotril (±)-N-[a-(mercaptomethyl)hydrocinnamoyl]glycine, benzyl ester, acetate (ester) racécadotril (RS)-2-[[2-[(acétylsulfanyl)méthyl)-3-priénylpropanoyl]amino]acétate de benzyle

racecadotrilo (±)-N-[α-(mercaptometil)hidrocinamoil]glicina,éster bencílico, acetato (éster)

C21H23NO4S raltitrexedum N-[5-[[(3.4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]methylamino]- raltitrexed 2-thenoyl]-L-glutamic acid acide (2S)-2-[[[5-[méthyl[(2-méthyl-4-oxo-3,4-dihydroquinazo[in- raltitrexed 6-yl)méthyl]amino]-2-thiényl]carbonyl]arnino]pentanedioïque ácido N-[5-[[(3,4-dihidro-2-metil-4-oxo-6-quinazo[inil)metil]metilamino]- raltitrexed 2-tenoil]-L-glutámico

C21H22N4O6S

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ramatrobanum (+)-(3R)-3-(p-fluorobenzenesulfonamido)-1,2,3,4-tetrahydrocarbazole-9- ramatroban propionic acid

acide (+)-3-[(3R)-3-[[(4-fluorophényl)sulfonyl]amino]-1,2,3,4-tétrahydo- ramatroban 9H-carbazol-9-yl]propanoïque

àcido (+)-(3R)-3-(p-fluorobencensu[fonamido)-1,2,3,4-tetrahidrocarbazol- ramatroban 9-propiónico

C21H21FN2O4S resocortolum 11β,17α-dihydroxy-17-propionylandrost-4-en-3-one resocortol 11β,17α-dihydroxy-17-propanoylandrast-4-én-3-one résocortol 11β,17α-dihidroxi-17-propionilandrost-4-et-3-ona resocortol

C22H32O4 revatropatum revatropate (R)-3-quinuclidinyl (S)-β-hydroxy-α-[2-(R)-methylsulfinyl]ethyl]hydratropate

(2S)-2-(hydroxymethyl)-4-[(R)-méthyisulfinyl]-2-phénylbutanoate de révatropate (3R)-1 -azabicyclo[2 2.2]oct-3-yle

(2S)-2-(hidroximetil)-4-[(R)-metilsulfinil]-2-fenilbutanoato de revatropato (3R)-1-azabiciclo[2 2 2]oct-3-ilo

C19H27NO4S ripisartanum 5-methyi-7-propyl-8-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]-s-triazolo= ripisartan [1,5-c]pyrimidin-2(3H)-one 5-méthyl-7-propyl-8-[4-[2-(1H-tétrazai-5-yl)phényl]benzyI][1,2,4]triazoIo= npisartan [1,5-c]pyrimidin-2(3H)-one 5-metil-7-propil-8-[p-(o-1H-tetrazol-5-ilfenil)bencil]-s-triazolo= ripísartán [1,5-c]pirimidin-2(3H)-ona

C23H22N8O rismorelinum rismorelin 1-(p-methylhippuric acid)-9-L-asparagine-12-L-arginine-15-L-threonine-21-L- arginine-27-L-leucine-51-L-leucine-56-L-arginine- 58-L-leucineprosomatohberin (pig) rismoréline [1-[N-(4-méthylbenzoyl)glycine]-9-L-asparagine-12-L-arginine-15-L-thréonine- 21-L-arginine-27-L-Ieucine-51-L-leucine-56-L-arginine- 58-L-leucine]prosornatolibérine (de porc) rismorelina 1 -(ácido p-metilhipúnco)-9-L-asparagina-12-L-arginina-15-L-treonina- 21-L-arginina-27-L-leucina-51-L-leucina-56-L-arginina- 58-L-leucinaprosomatoliberina (cerdo)

C379H623N127O118 ritonavirum ritonavir 5-thiazolylmethyl [(αS)-α-[(1S,3S)-1 -hydroxy-3-[(2S)-2-[3-[(2-isopropyl- 4-thiazolyl)methy]]-3-methylureido]-3-methylbutyramido]- 4-phenylbutyl]phenethyl]carbamate

157 Recommended INN: List 36 WHO Drug Information, Vol. 10, No 3, 1996

ritonavir [(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-3-méthyl-2-[3-méthyl- 3-[[2-(1-méthyléthyl)thiazol-4-yl]méthyl]uréido]butanoyl]amino]- 5-phénylpentyl]carbamate de thiazol-5-ylméthyle ritonavir [(αS)-α-[(1S,3S)-1-hidroxi-3-[(2S)-2-[3-[(2-isopropil-4-tiazolil)metil]- 3-metilureido]-3-metilbutiramido]-4-fenilbutil]fenetil]carbamato de 5-tiazolilmetil

C37H48N6O5S2

rufinamidum 1-(2,6-difluorobenzyl)-1H-1,2,3-tnazole-4-carboxamide rufinamide 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide rufinamide 1-(2,6-difluorobencil)-1H-1,2,3-triazol-4-carboxamida rufinamida

C10H8F2N4O rupatadinum 8-chloro-6,11 -dihydro-11 -[1 -[(5-methyl-3-pyridyl)methyl]-4-piperidylidene]- rupatadine 5H-benzo[5,6]cyclohepta[1,2-b]pyridine 8-chloro-11-[1-[(5-méthyl-3-pyndyl)métriyl]pipéridin-4-ylidène]-6,11-dihydro- rupatadine 5H-benzo[5,6]cyclohepta[1,2-b]pyridine 8-cloro-6,11-dihidro-11-[1-[(5-metil-3-piridil)metil]-4-piperidiliden]- rupatadina 5H-benzo[5,6]ciclohepta[1,2-b]piridina

C26H26CIN3 salnacedinum N-acetyl-L-cysteine salicylate (ester) salnacedin acide (2R)-2-(acétylamino)-3-[(2-hydroxybenzoyl)sulfanyl]propanoique salnacédine salicilato de N-acetil-L-cisteina (éster) salnacedina

C12H13NO5S samarii (153Sm) lexidronamum pentahydrogen (OC-6-21}-[[[ethylenebis(nitriIodimethylene)]= p p p'' p'' 153 samarium (153Sm) lexidronam tetraphosphonato] (8-)-N,N',O ,O ',O ,O samarate(5-)- Sm pentahydrogéno (OC-6-21H[éthylènebis(nitrilodiméthylène)]= p p p P 153 samarium (153Sm) lexidronam tetraphosphonato] (8-)- N,N',O ,O ',O ",O ''']samarate(5-)- Sm pentahidrógeno (OC-6-21)-[[[etilenbis(nitrilodimetilen)]tetrafosfonato]- P p p'' P'' 153 samario (153Sm) lexidronam (8-)-N,N',O ,O ',O ,O ]samarato(5-)- Sm 153 C6H17N2O12P4 Sm sampatrilatum sampairilat N-[1-[(S)-3-[(S)-6-amino-2-methanesulfonamidohexanamido]- 2-carboxypropyl]cyclopentyl]carbonyl]-L-tyrosine sampatrilate acide (2S)-2-[[[1-[(2S)-3-[[(2S)-6-amino-2-[(méthylsulfonyl)amino]= hexanoyl]amino]-2-carboxypropyl]cyclopentyl]carbonyl]amino]- 3-(4-hydroxyphényl)propanoïque sampatrilat N-[[1-(S)-3-[(S)-6-amino-2-metansulfonarnidohexanamido]- 2-carboxipropil]ciclopentil]carbonil]-L-tirosina

C28H40N4O9S

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sildenafilum 1-[[3-{6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)- sildenafil 4-ethoxyphenyl]sulfonyl]-4- methylpiperazine

1-[[4-éthoxy-3-[1-méthyl-7-oxo-3-propyl-6,7-dihydro-1H- sildénafil pyrazolo[4,3-d]pynmidin-5-yl]phényl]sulfonyl]-4-méthylpipérazine

1-[[3-(6,7-dihidro-1-metil-7-oxo-3-propil-1H-pirazolo[4,3-d]pirimidin-5-il)- sildenafilo 4-etoxifeniI]sulfonil]-4- metilpiperazina

C22H30N6O4S sinitrodilum 2,3-dihydro-3-{2-hydroxyethyI)-4H-1,3-benzoxazin-4-one nitrate (ester) sinitrodil nitrate de 2-[4-oxo-2H-1,3-benzoxazin-3(4H)-yl]éthyle sinitrodil nitrato de 2-(4-oxo-2H-1,3-benzoxazin-3(4H)-il)etilo sinitrodil

C10H10N2O5 sipatriginum 4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3.5-trichlorophenyl)pyrimidine sipatrigine [2-(4-méthylpipérazin-1-yl)-5-(2,3,5-trichlorophényl)pyrimidin-4-yl]amine sipatrigine 4-amino-2-(4-metil-1-piperazinil)-5-(2,3,5-triclorofenil)pirimidina sipatrigina

C15H16CI3N5 stacofyllinum N,N-diethyl-4-[3-(1,2,3,6-tetrahydro-1,3,7-trimethyl-2,6-dioxopurin- stacofylline 8-yl)propyl]-1-piperazinecarboxamide N,N-diéthyl-4-[3-(1,3,7-triméthyl-2,6-dioxo-2,3,6,7-tétrahydro-1H-purin- stacofylline 8-yl)propyl]pipérazine-1-carboxamide N,N-dietil-4-[3-{1,2,3,6-tetrahidro-1,3,7-tnmetil-2,6-dioxopurin-8-il)propil]- estacofilina 1 -piperazinacarboxamida

C20H33N7O3 susalimodum susalimod 5-[[p-[(3-methyl-2-pyndyl)sulfamoyl]phenyl]ethynyl]salicylic acid susalimod acide 2-hydroxy-5-[2-[4-[(3-méthylpyridin-2-yl)sulfamoyl]phényl]= éthynyl]benzoïque susalimod ácido 5-[[p-[[3-metil-2-piridil)sulfamoil]fenil]etinil]salicílico

C21H16N2O5S tamibarotenum tamibarotene N-(5,6,7 8-tetrahydro-5,5,8,8-tetramethyI-2-naphthyl)terephthalamic acid tamibarotène acide 4-[(5,5,8,8-tétramélhyl-5,6,7,8-tétrahydronaphtalén-2-yl)carbamoyl= benzoïque tamibaroteno ácido N-(5.6.7,8-tetrahidro-5,5,a,8-tetrametil-2-naftil)terefíalámico

C22H25NO3

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tazofelonum (±)-5-(3,5-di-tert-butyl-4-riydroxybenzyl)-4-thiazolidinone tazofelone (RS)-5-[3,5-bis(1,1-diméthyléthyl)-4-hydroxybenzyl]thiazolidin-4-one tazofélone (±)-5-(3,5-di-terc-butil-4-hidroxibencil)-4-tiazolidinona tazofelona

C18H27NO2S telinavirum (2S)-N-[(1S,2R)-1-benzyl-3-(3-fer(-butyl-1-isobutylureido)-2-riydroxypropyl]- telinavir 2-quinaldamidosuccinamide (2S)-N1-[(1S,2R)-1-benzyl-3-[3-(1-1-diméthyléthyl)-1-(2-méthylpropyl)uréido]- télinavir 2-hydroxypropyl]-2-[(quinoléin-2-ylcarbonyl)amino]butanediamíde (2S)-N-[(1S,2R)-1-bencil-3-(3-terc-butil-1-isobutilureido)-2-hidroxipropil]- telinavir 2-quinaldamidosuccinamida

C33H44N6O5 thymalfasinum thymalfasin N-acetyl-L-seryl-L-α-aspartyl-L-alanyl-L-alanyl-L-valyhL-α-aspartyl-L-threonyl-L- seryl-L-seryl-L-α-glutamyl-L-isoleucyl-L-threonyl-L-threonyl-L-lysyl- L-α-aspartyl-L-leucyl-L-lysyl-L-α-glutamyl-L-lysyl-L-lysyl-L-α-glutamyl-L-valyl-L- valyl-L-α-glutamyl-L-α-glutamyl-L-alanyl-L-α-glutamyl-L-asparagine thymalfasine N-acéty-L-séryl-L-α-aspartyl-L-alanyl-L-alanyl-L-valyl-L-α-aspartyl-L-thréonyl-L- séryl-L-séryl-L-α-glutamyl-L-isoleucyl-L-thréonyl-L-thréonyl-L-lysyl- L-α-aspartyl-L-leucyl-L-lysyl-L-α-glutamyl-L-lysyl-L-lysyl-L-α-glutamyl-L-valyl-L- valyl-L-α-glutamyl-L-α-glutamyl-L-alanyl-L-α-glutamyl-L-asparagine timalfasina N-acetil-L-senl-L-α-aspartil-L-alanil-L-alanil-L-valil-L-α-aspartil-L-treonil-L-seril- L-seril-L-α-glutamil-L-isoleucil-L-treonil-L-treonil-L-lisil-L-α-aspartil-L-leucil- L-lisil-L-α-glutamil-L-listl-L-lisil-L-α-glutamil-L-valil-L-valíl-L-α-glutamil- L-α-glutamil-L-alanil-L-α-glutamil-L- asparagina

C129H215N23O56 tilnoprofenum arbamelum (±)-α,2-dimethyl-5H-[1]-benzopyrano[2,3-b]pyridine-7-acetic acid, ester with tilnoprofen arbamel N,N-dimethylglycolamide (2RS)-2-[2-méthyl-5H-[1]benzopyrano[2,3-b]pyridin-7-yl]prapanoate de tilnoprofène arbamel 2-(diméthylamino)-2-oxoéthyle ácido (±)-α,2-dimetil-5H-[1]-benzopirano[2,3-b]piridina-7-acético, ester con tilnoprofeno arbamel N,N-dimetilglicolamida

C20H22N2O4 tirofibanum tirofiban N-(butylsulfonyl)-4-[4-(4-piperidyl)butoxy]-L-phenylalanine tirofiban acide (2S)-2-[(butylsulfonyl)amino]-3-[4-[4-(pipéridin-4-yl)butoxy]phényl]- propanoïque tirofibán N-(butilsulfonil)-4-[4-(4-piperidil)butoxi]-L-fenilalanina

C22H36N2O5S tivirapinutn tivirapine (S)-8-chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo= [4,5,1-jk][1,4]benzodiazepine-2(1H)-thione

160 WHO Drug Information, Vol 10, No. 3, 1996 Recommended INN: List 36

tivirapine (-)-(5S)-8-chloro-5-méthyl-6-(3-méthylbut-2-ényl)-4,5,6,7-tétrahydro= imidazo[4,5,1-jk][1,4]benzodiazépine-2(1H)-thione tivirapina (S)-8-cloro-4,5,6,7-tetrahidro-5-metil-6-(3-metil-2-butenil)imidazo= [4,5,1-jk][1,4]benzodiazepina-2(1H)-tiona

C16H20CIN3S traferminum trafermin 2-155-basic fibroblast growth factor (human clone λKB7/λHFL1 precursor reduced) trafermine 2-155-facteur de croissance des fibroblastes basiques (forme réduite du précurseur issu du clone humain λKB7/λHFL1 ) trafermina 2-155-factor de crecimiento de los fibroblastos básicos (forma reducida del precursor procedente del clon humano λKB7/λHFL1)

C764H1201N217O219S6 trifosminum tris(3-methoxyprapyl)phosphine trifosmin tris(3-mélhoxypropyl)phosphane trifosmine tris(3-metoxipropil)fosfina trifosmina

C12H27O3P trovafloxacinum 7-[(1R,5S,6s)-6-amino-3-azablcyclo[3.1.0]hex-3-yl]-1-(2,4-difluorophenyI)- trovafloxacin 6-fluoro-1,4-dihydro-4-oxo-1,3-naphthyridine-3-carboxyhc acid acide 7-[(1 R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]-1-(2,4- trovafloxacine difluorophényl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphtyridine-3-carboxylique ácido 7-[(1R,5S,6s)-6-amino-3-azabiciclo[3.1.0]hex-3-il]-1-(2,4-difluorofenil)-6- trovafloxacino fluoro-1,4-dihidro-4-oxo-1,8-naftiridina-3-carboxilico

C20H15F3N4O3 trovirdinum 1-(5-bromo-2-pyridyi)-3-[2-(2-pyridyl}ethyI]-2-thiourea trovirdine 1-(5-bromopyridin-2-yl)-3-[2-(pyridin-2-yl)éthyl]thiourée trovirdine 1-(5-bromo-2-piridil)-3-[2-(2-piridil)etil]-2-tiourea trovirdina

C13H13BrN4S valnemulinum valnemulin [[2-[(r)-2-amino-3-methylbutyramido]-1,1-dimethylethyl]thio]acetic acid, 8-ester with (3aS,4R,5S,6S,8H,9H,9aR,10R)-octahydro-5,8-dihydroxy- 4,6,9,10-tetramethyl-6-vinyl-3a,9-propano-3aH-cyclopentacycloocten-1(4H)- one valnemuline 2-[[2-[[(2R)-2-amino-3-méthylbutanoyl]amino]-1,1-diméthyléthyl]= sulfanyl]acétate de (1 S,2R,3S,4S,6R,7R,8R,14R)-4-éthényl-3-hydroxy- 2,4,7,14-tétraméthyl-9-oxotricyclo[5.4.3.01,8]tétradéc-6-yle valnemulina acido [[2-[(R)-2-amino-3-metilbutiramido]-1.1 -dimetiletil]tio]acético, 8-éster con (3aS,4R,5S,6S,8R,9R,9aR,10R)-octahidro-5,8-dihidroxi- 4,6,9,10-tetrametíl-6-vinil-3a,9-propano-3aH-ciclopentacicloocten-1(4H)-ona

C31H52N2O5S

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voriconazolum (αR,βS)-α-(2,4-difluorophenyl)-5-fluoro-β-methyl-a-{1H-1,2,4-triazol- voriconazole 1-ylmethyl)-4-pyrimidineethanol (2R,3S)-2-(2,4-difluorophényl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol- voriconazole 1-yl)butan-2-ol (αR,βS)-α-(2,4-difluorofenil-5-fluoro-β-metil-α-(1H-1,2,4-triazol-1-ilmetil)- voriconazol 4-pinmidinetanol

C16H14F3N5O xemilofibanum xemilofiban ethyl (3S)-3-[3-[(p-amidinophenyl)carbamoyl]propionamido]-4-pentynoate xémilofiban (3S)-3-[[4-[(4-carbamimidoylphényl)amino]-4-oxobutanoyl]amino]pent- 4-ynoate d'éthyle xemilofiban (3S)-3-[3-[(p-amidinofenil)carbamoil]propionamido]-4-pentinoato de etilo

C18H22N4O4 zinostatinum stimalamerum zinostatin stimalamer substance produced by combining two parts of styrene-alt-maleic acid copolymer that is partially butyl esterized with one part of zinostatin (neocarzinostatm) zinostatine stimalamère substance obtenue par combinaison de deux parties d'un copolymére alterné de styrène et d'acide maléique partiellement estérifié par de l'alcool butylique avec une partie de zinostatine (néocarzinostatine) zinostatina estimalámero sustancia producida por combinación de una parte de zinostatina y los partes de copolímero de estireno-alt-ácido maléico parcialmente esterficado con butilio zolmitriptanum (S)-4-[[3-[2-(dÍmethyiammo)ethyl]indol-5-yl]methyl]-2-oxazolidinone zolmitriptan (4S)-4-[[3-[2-(diméthylamino)éthyl]-1H-indol-5-yl]méthyl]oxazolidin-2-one zolrnitriptan (S)-4-[[3-[2-(dimetilamino)etil]indol-5-il]metil]-2-oxazolidinona zolmitriptan

C16H21N3O2

AMENDMENTS TO PREVIOUS LISTS

Recommended International Nonproprietary Names (Rec. INN): List 19 (WHO Chronicle Vol. 33, No. 10, 1979) p. 8 zinostatinum replace the description by the following: zinostatin (4S, 6R,11R,12R)-1 1 -[(α-D-2,6-dideoxy-2-methylaminogalactopyranosyl)oxy]- 12-[[(2-hydroxy-7-methoxy-5-methyl-1-naphtyl)carbonyl]oxy]-4-((4R)-2-oxo- 1,3-dioxolan-4-yl}-5-oxatricyclo[8 3.0.04,6]tridec-9,13-dien-2,7-diyne and apoprotein

162 WHO Drug Information, Vol. 10, No. 3, 1996 Recommended INN: List 36

Recommended International Nonproprietary Names (Rec. INN): List 25 (WHO Chronicle Vol. 39, No. 5, 1985) p.14 interferonum beta replace the description by the following: interferon beta A secreted protein known previously as fibroblast interferon, that is produced according to the information coded by a specis of interferon gene. Sub species of human beta gene produce protein variants designated by the hyphenated addition of a number, e g. interferon beta-1 The numbers conform with the recommendations of the Interferon Nomen­ clature Committee. Human interferon beta has the following amino acid sequence*

* glycosylation site

In the case of interferon beta-1 it is necessary to qualify the number by a letter depending on the amino-acid residues at positions 1 and 17 in the protein chain and to whether or not glycosylation is present at a specified glycosylation site

Amino acid structure Glycosylation Positions 1(X) 17(Y) 80

beta-1 a Met Cys Asn beta-1 b Ser

Mixtures of interferon beta proteins will be designated as interferon beta-n1, interferon beta-n2 etc.

163 Recommended INN: List 36 WHO Drug Information, Vol. 10, No. 3, 1996

Recommended International Nonproprietary Names (Rec. INN): List 26 (WHO Chronicle Vol. 40, No. 6, 1936)

p.13 interferonum alfa replace the description by the following: interferon alfa A family of secreted proteins, known previously as leucocyte interferon or lymphoblastoid interferon, that is produced according to the information coded by multiple interferon alfa genes Sub-species of human alfa gene are variants designated by the hyphenated addition of a number, e.g interferon alfa-2 The numbers conform with the recommendations of the Interferon Nomen­ clature Committee. Human interferon alfa-2 has the following amino acid sequence:

In the case of interferon alfa-2 it is necessary to qualify the number by a letter depending on the amino-acid group occupying positions 23 and 34 respectively in the protein chain:

Amino acid structure Positions 23(X) 34(Y) alfa-2a Lys His alfa-2b Arg His alfa-2c Arg Arg

Mixtures of interferon alfa proteins will be designated as interferon alfa-n1 interferon alfa-n2 etc.

164 WHO Drug Information. Vol 10, No. 3, 1996 Recommended INN List 36

p.13 interferonum gamma replace the description by the following: interferon gamma A secreted protein known previously as immune interferon, that is produced according to the information coded by a specis of interferon gene. Sub-species of human gamma gene produce protein variants designated by the hyphenated addition of a number, e.g. interferon gamma-1a The numbers conform with the recommendations of the Interferon Nomen­ clature Committee. Human interferon gamma has the following amino acid sequence:

In the case of interferon gamma-1 it is necessary to qualify the number by a letter depending on the nature of the termini X and Y at positions 1 and 139 in the protein chain:

Amino acid structure Glycosyiation terminal group terminal group X(1) Y (139)

gamma-1a H-Cys-Tyr-Cys Arg-Ala-Ser-Gln-OH gamma-1b* H-Met OH gamma-1c H-Met Arg-Ala-Ser-Gln-OH

*formerly interferon gamma-2a

Mixtures of interferon gamma proteins will be designated as interferon gamma-n1, interferon gamma-n2 etc.

P 9 sometribovum replace the molecular formula by the following: sometribove C978H1537N265O236S9

p. 9 sometriporum replace the molecular formula by the following: sometripor C979H1527N265O287S8

165 Recommended INN: List 36 WHO Drug Information, Vol. 10, No 3, 1996

Recommended International Nonproprietary Names (Rec. INN): List 27 (WHO Drug information, Vol. 1, No. 4, 1987) p.10 sornatropinum replace the chemical name: somatropin growth hormon (human), r-DNA derived

Recommended International Nonproprietary Names (Rec. INN): List 30 (WHO Drug Information, Vol. 4, No. 3, 1990) p. 3 ciclesonidum replace the chemical name by the following: ciclesonide (R)-11β,16α,17,21 -tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17- acetal with cyclohexanecarboxaldehyde, 21-isobutyrate p. 4 dosmalfatum replace the chemical name and the molecular formula by the following:

dosmalfate [u7-[[diosmin heptasulfato](7-)]]tetracontahydroxytetradecaaluminium C28H60Al14O71S7

Recommended International Nonproprietary Names (Rec. INN): List 33 (WHO Drug information, Vol 7, No. 3, 1993) p. 6 pegaldesleukinum replace the chemical name by the following: pegaldesleukin 125-L-serine-2-133-interleukin 2 (human reduced), reaction product with glutaric anhydride, esters with polyethylene glycol monomethyl ether

Recommended International Nonproprietary Names (Rec. INN): List 35 Dénominations communes internationales recommandées (DCI Rec): Liste 35 Denominaciones Comunes Internacionales Recomendadas (DCI Rec): Lista 35 (WHO Drug information, Vol. 9, No. 3, 1995) p.16 mangafodipirum mangafodipir sustituyase la descripción por la siguiente: hexahidrógeno (OC-6-13H[N,N'-etilenbis[N:-[[3-hidroxi-5-(hidroximetil)- 2-metil-4-pindil]metil]glicina] 5,5'-bis(fosfato)](8-)]manganato(6-) p.18 muplestimum replace the description and molecular formula by the following: muplestim interleukin 3 (human protein moiety) remplacer la description et la formule brute par muplestim interleukine 3 (partie protéique humaine) reemplácense la descripción y la fórmula empírica por muplestim interleukina 3 (fracción proteica humana)

C670H1074N186O199S5

166 WHO Drug Information, Vol. 10 No 3. 1996 Recommended INN: List 36

MODIFICATIONS APPORTEES AUX LISTES ANTERIEURES

Dénominations communes Internationales recommandées (DCI Rec.): Liste 19 (Supplément à la Chronique OMS, Vol. 33, No. 10, 1979) p. 8 zinostatinum remplacer la description par: zinostatin combinaison de 2-hydroxy-7-méthoxy-5-méthylnaphtaiène-1 -carboxylate de (4S,6R11R12R)-11-[[2-(méthylamino)-2,6-didésoxy-α-D galactopyranosyl]oxy]-4-[(4R)-2-oxo-1,3-dioxalan-4-yl]-5- oxatricyclo[8.3.0.04,6]tridéca-1(13),9-diène-2,7-diyn-12-yle avec l'apoproptéine dont la structure suit

Dénominations communes internationales recommandées (DCI Rec.): Liste 25 (Supplément à la Chronique OMS, Vol. 39, No. 5, 1985) p.14 interferonum beta remplacer la description par: interféron bêta Protéine diffusible, antérieurement connue sous le nom d'interferon fibroblastoide, produite selon l'information codée par une espèce de gène interféron Des sous-espèces du gène bêta humain produisent des variants de la protéine désignés par l'adjonction d'un nombre relié par un tiret, par exemple interféron bêta-1. Les nombres sont conformes aux recommandations du Comité de nomen­ clature pour l'interféron. L'interféron bêta humain présente la séquence d'acides aminés suivante :

* site de glycosylation

167 Recommended INN: List 36 WHO Drug Information, Vol. 10, No. 3, 1996

Dans le cas de l'interféron bêta-1, il est nécessaire de faire suivre le nombre par une lettre selon les restes d'acides aminés qui occupent respectivement les positions 1 et 17 dans la chaîne peptidique et selon qu'une glycolysation est présente ou non à un site de glycosylation spécifié

Nature des acides aminés Glycosylation Positions 1(X) 17(Y) 80

bêta-1 a Met Cys Asn bêta-1 b Ser

Les mélanges des protéines d'interféron bêta seront désignés comme interféron bêta-n1, interféron bêta-n2, etc.

Dénominations communes internationales recommandées (DCI Rec.): Liste 26 (Supplément à ta Chronique OMS, Vol. 40, No. 6, 1986) p13 interferonum alfa remplacer la description par: interferon alfa Famille de protéines diffusibles, antérieurement connue sous le nom d'interíéron leucocytaire ou lymphoblastoide, produites selon l'information codée par plusieurs gènes interferon alfa. Des sous-espèces du gène alfa humain produisent des variants de la protéine désignés par l'adjonction d'un nombre relié par un tiret, par exemple interféron alfa-2 Les nombres sont conformes aux recommandations du Comité de nomen­ clature pour l'interféron. L'interféron alfa-2 humain présente la sequence d'acides aminés suivante :

Dans le cas de l'interféron alfa-2, il est nécessaire de faire suivre le nombre par une lettre selon les restes d'acides aminés qui occupent respectivement les positions 23 et 34 dans la chaîne peptidique

168 WHO Drug Information. Vol. 10, No. 3, 1996 Recommended INN List 36

Nature des acides aminés Positions 23(X) 34(Y) alfa-2a Lys His alfa -2b Arg His alfa-2c Arg Arg

Les mélanges des protéines d'interféron alfa seront désignés comme interféron alfa-n1, interféron alfa-n2. etc. p.13 interferonum gamma remplacer la description par: interféron gamma Protéine diffusible, antérieurement connue sous le nom d'interféron immun, produite selon l'information codée par une espèce de gène interféron. Des sous-espèces du gène gamma humain produisent des variants de la protéine désignés par l'adjonction d'un nombre relié par un tiret, par exemple interféron gamma-1 Les nombres sont conformes aux recommandations du Comité de nomen­ clature pour l'interféron. L'interféron gamma humain présente la séquence d'acides aminés suivante

Dans le cas de l'interféron gamma-1, il est nécessaire de faire suivre le nombre par une lettre selon la nature des acides aminés qui composent les groupes terminaux X et Y fixés respectivement sur les positions 1 et 139 de la chaîne peptidique Nature des acides aminés Glycosylation Groupe terminal Groupe terminal X(1) Y (139)

gamma- 1a H-Cys-Tyr-Cys Arg-Ala-Ser-GIn-OH gamma-1b* H-Met OH gamma-1c H-Met Arg-Ala-Ser-GIn-OH

*précédemment interféron gamma-2a

169 Recommended INN: List 36 WHO Drug Information, Vol 10, No. 3, 1996

Les mélanges des protéines d'interféron gamma seront désignés comme interféron gamma-n1, interféron gamma-n2, etc.

p. 9 sometribovum remplacer la formule brute par: sométribove C978H1537N265O286S9

p. 9 sometriporum remplacer la formule brute par: sométripor C979H1527N265O287S8

Dénominations communes internationales recommandées (DCI Rec): Liste 27 (Informations pharmaceutiques OMS, Vol. 1, No. 4, 1987) p.10 somatropinum remplacer la description : somatropine hormone de croissance (humaine), obtenue par génie génétique

Dénominations communes internationales recommandées (DCI Rec.): Liste 30 (Informations pharmaceutiques OMS, Vol. 4, No. 3, 1990) p 3 ciclesonidum remplacer le nom chimique par ciclésonide 21-(2-méthylpropanoate) de 16α,17-[[(R)-cyclohexylméthyléne]bis(oxy)]- 11β,21-dihydroxyprégna-1,4-diéne-3,20-dione p. 5 dosmalfatum remplacer le nom chimique et la formule brute par:

dosmalfate [µ7-[[diosmine heptasulfato](7-)]]tétracontahydroxytétradécaaluminiurn

C28H60Al14O71S7

Pour toutes modifications apportées aux Dénominations communes internationales recommandées (DCI Rec.): Liste 35 voir page 166, séction AMENDMENTS TO PREVIOUS LISTS.

MODIFICACIONES A LAS LISTAS ANTERIORES

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 19 (Suplemento de Crónica de la OMS, Vol. 33, No. 10, 1979) p. 8 zinostatinum sustituyase la descripción por la siguiente: zinostatina (4S, 6R,11R,12R)11-[(α-D-2,6-didesoxi-2-metilaminogalactopiranosil)oxi]-12- [[(2-hidroxi-7-metoxi-5-metil-1-naftil)carbonil]oxi]-4-((4R)-2-oxo-1,3-dioxolan- 4-iI)-5-oxatriciclo[8 3 0.04,6]tridec-9,13-dien-2,7-dime y apoproteins

170 WHO Drug Information Vol 10. No. 3. 1996 Recommended INN: List 36

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 25 (Suplemento de Crónica de la OMS, Vol. 39, No. 10, 1985) p.14 interferonum beta sustituyase la descripción por la siguiente: interféron beta: Una proteina secretada, previamente conocida como interferón fibroblástico, que está producida de acuerdo con la información codificada por un tipo gen de interferón . Las subespecies del gen beta humano constituyen vanantes, que se designan añadiendo un número precedido de un guión, p ej. interferon beta-1. Los números se ajustan a las recomendaciones del Comité para la Nomenclatura de interferones. El interferón beta humano tiene la siguiente secuencia de aminoácidos:

* posición de glicosilación

En el caso del interferón beta-1 sera necesario añadir ai número una letra, dependiendo del aminoácido que ocupe las posiciones 1 y 17, respectivamente, en la cadena de proteina:

Estructura de aminoácidos Glicosilación Posiciones 1(X) 17(Y) 8C

beta-1a Met Cys Asn beta-1b Ser

Las mezclas de interferones beta se designaran como interferón beta-n1, interferón beta-n2 etc

171 Recommended INN: List 36 WHO Drug Information, Vol. 10, No. 3, 1996

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 26 (Suplemento de Crónica de la OMS, Vol. 40, No. 6, 1986) p.13 interferonum alfa sustituyase la descripción por la siguiente: interferón alfa: Una familia de proteínas secretadas, previamente conocida como interferón leucocitario o linfoblastico producida de acuerdo con la información codificada por múltiples genes de interferón alfa. Las subespecies del gen alfa humano constituyen variantes, que se designan añadiendo un número precedido de un guión, p ej. interferón alfa-2. Los números se ajustan a las recomendaciones del Comité para la Nomenclatura de Interferones El interferon alfa-2 humano tiene le siguiente secuencia de aminoácidos.

En el caso del interferón alfa-2 será necesario añadir al número una letra, dependiendo de los aminoácidos que ocupen las posiciones 23 y 34, respectivamente, en la cadena de proteina:

Estructura de aminoácidos Posiciones 23(X) 34(Y) alfa-2a Lys His alfa-2b Arg His alfa -2c Arg Arg

Las mezclas de interferones alfa se designarán como interferón alfa-n1, interferón alfa-n2 etc.

172 WHO Drug Information, Vol. 10. No 3, 1996 Recommended INN List 36

p.13 interferonum gamma sustituyase la descripción por la siguiente: interferón gamma: Una proteína secrelada, previamente conocida como interferón inmune, que está producida de acuerdo con la información codificada por un tipo de gen de interferón Las subespecies del gen gamma humano producen variantes, que se designan añadiendo un número precedido de un guión, p.ej. interferon gamma-1a Los números se ajustan a las recomendaciones del Comité para la Nomenclatura de Interferones. El interferón gamma humano tiene la siguiente secuencia de aminoácidos:

En el caso del interferón gamma-1 será necesario añadir al número una letra, dependiendo de los aminoácidos que ocupen las posiciones 1 y 139, respectivamente, en la cadena de proteina:

Estructura de aminoácidos Glicosílación Grupo extremo Grupo extremo X(1) Y (139)

gamma- 1a H-Cys-Tyr-Cys Arg-Ala-Ser-GIn-OH gamma-1b* H-Met OH gamma-1c H-Met Arg-Ala-Ser-GIn-OH

*anteriormente interferon gamma-2a

Las mezclas de interferones gamma se designarán como interferón gamma-n1. interferón gamma-n2 etc.

173 Recommended INN. List 36 WHO Drug Information, Vol. 10, No. 3, 1996

p. 9 sometribovum sustituyase la fórmula molecular por la siguiente: sometribovo C978H1537N265O286S9

p. 9 sometriporum sustituyase la fórmula molecular por la siguiente: sometripor C979H1527N265O287S8

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 27 (Información Farmacéutica, OMS, Vol. 1, No. 4, 1987) p. 9 somatropinum sustituyase el nombre químico: somatropina hormona de crecimiento (humana), derivada de r-DNA

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 30 (Información Farmacéutica, OMS, Vol. 4, No. 3, 1990) p. 3 ciclesonidum sustituyase la fórmula empírica por la siguiente: ciclesonida (R)-11β,16α,17,21-tetrahidroxipregna-1,4-dieno-3,20-diona 16,17-acetal cíclico con cicloclohexanocarboxaldehído, 21-isobutirato p. 4 dosmalfatum sustituyanse el nombre químico y la fórmula empírica por los siguientes:

dosmalfato [µ7-[[diosmin heptasulfato](7-)]]tetracontahidroxitetradecaaluminio

C28H60Al14O71S7

Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 33 (Información Farmacéutica, OMS, Vol. 7, No. 3, 1993) p. 6 pegaldesleukinum sustituyase el nombre químico por el siguiente: pegaldesleukina 125-L-serina-2-133-interleuquina 2 (humana reducida), producto de la reacción con anhídrido glutárico, esterificado con éter monometílico de polietilenglicol

Para cualquier modificación de las Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Listas 35 vease página 166, sección AMENDMENTS TO PREVIOUS LISTS

The Use of Common Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances

1996, iv +118 pages [E] WHO/PHARM S/NOM 15 Rev 32 Sw fr. 18 -/US $1620 In developing countries Sw fr 12 60 Order no 1930083

Lists common stems for international nonproprietary names (INN) for pharmaceutical substances for which chemical or pharmacological categories have been established. These stems and their definitions are intended to guide the selection of new INNs (generic names) lor substances that belong to an established series of related compounds The list aims to encourage consistency in the designation of generic drug names while also protecting the principle that INNs are public property Produced as a working document, the list is of interest to manufacturers engaged in research and development, trade-mark officers, and national regulatory authorities, teachers of pharmaceutical chemistry and pharmacology The document has two main parts. The first, presented in tabular form, gives common stems and their definitions for 23 categories of drugs, moving from CNS depressants and stimulants, through cardiovascular agents and anti-infectives, to vitamins and hormone preparations The second and most extensive part provides an alphabetical list of recommended stems and the corresponding family of INNs Information on each stem includes a succinct definition, chemical formula where appropriate, and the relevant series of related INNs Each entry also includes a reference to the list where the proposed name was published, and where more comprehensive information can be obtained Annexed to the document is an explanation of stem system adopted for use when selecting international nonproprietary names lor monoclonal antibodies

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