WHO DRUG INFORMATION VOLUME 18 • NUMBER 4 • 2004 PROPOSED INN LIST 92 INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES WORLD HEALTH ORGANIZATION • GENEVA WHO Drug Information Vol 18, No. 4, 2004 World Health Organization WHO Drug Information Contents Drug Management Long-term use of Depo-Provera® and Cost containment and generic substitution 269 bone density loss 286 Generic substitution in Finland 269 Duloxetine approved for neuropathic pain associated with diabetes 286 Aripiprazole approved for acute bipolar Safety and Efficacy Issues mania 287 Australian experience with pneumococcal conjugate vaccine 272 HIV Medicines Overdose and tricyclic antidepressants 272 Terbinafine and blood dyscrasias 273 3 by 5 strategy: improving access to Cholinesterase inhibitors and cardiac paediatric HIV medicines 288 arrhythmias 273 Urgent need for paediatric antiretroviral Lamotrigine: hormonal contraceptives formulations 288 decrease serum levels 274 WHO prequalification: implications Transdermal fentanyl and respiratory arrest of delisting 290 in adolescents 275 Combining TB and HIV treatment to save Infliximab and etanercept: serious infections lives 292 and tuberculosis 275 Medication error alert 277 Recent Publications and Sources of Information Current Topics International Conference on Improving International standard for genetic testing 278 Use of Medicines 294 Selective reporting and clinical trial Three new quality assurance guidelines registration 278 endorsed by WHO Expert Committee 294 Trials registration policy 279 WHO Medicines Bookshelf 295 National Library of Medicine trials International network on HIV/AIDS registration 280 for pharmacists 295 Managing pharmaceuticals internationally 295 Regulatory and Safety Action New brochure on adverse reaction reporting 296 International chemical reference substances Antidepressants and suicidality in children for malaria 296 and adolescents 281 New physician guidelines on commercial Withdrawal of rofecoxib 282 relationships 296 Regulations for COX-2 inhibitors 283 COHRED and Research into Action 297 Southern hemisphere influenza vaccines Evaluation of medicinal products in children 297 2005 283 Procurement of medicines in HIV 297 European regulation for paediatric New antimicrobial resistance website for medicinal products 284 the public 297 Ephedrine and pseudoephedrine to Therapeutic guidelines on dermatology 298 become controlled drugs 284 International Pharmacopoeia available Epoetin alfa and blood clot formation in on CD-ROM 298 cancer patients 285 Safety monitoring of herbal medicines 298 Mifepristone labelling changes 285 Medicinal plant guidelines translated 298 TNF-blocking agents and serious infections 286 .../... 267 World Health Organization WHO Drug Information Vol 18, No. 4, 2004 Contents (continued) Consultation Documents Isoniazid and ethambutol hydrochloride tablets (1st draft) 311 The International Pharmacopoeia: Rifampicin, isoniazid, pyrazinamide and monographs for antiretrovirals hydrochloride tablets (1st draft) 313 Saquinavir mesilate (1st draft) 299 Rifampicin tablets (1st draft) 317 Saquinavir (1st draft) 302 Rifampicin and isoniazid tablets (1st draft) 320 Ritonavir (1st draft) 305 The International Pharmacopoeia: monographs for tuberculosis medicines Proposed International Rifampicin, isoniazid and pyrazinamide Nonproprietary Names: tablets (1st draft) 308 List 92 323 WHO Drug Information and e-mail table of contents subscriptions available at: http://www.who.int/druginformation 268 WHO Drug Information Vol 18, No. 4, 2004 Drug Management Cost containment and generic substitution Expenditure on medicines accounts for a major proportion of public health costs and governments increasinlgly focus on ways to reduce the burden on public spending. Overall, generic drugs are substantially less expensive than branded products and their promotion can lead to a reduction in drug costs and increased availability. Generic substitution is a cost-effective strategy for containing drug expenditure and has considerable potential for contributing to cost savings. The aim of generic substitution is to provide an economic incentive for countries with health insurance schemes to pro- mote the use of low/cost generic equivalents. Recent experience in Finland shows how substitution with a cheaper alternative increased competition between pharmaceutical companies and lead to substantial cost savings amounting to nearly 40 million in six months. The amount saved in one year was approximately 5% of the total cost of all reimbursed medicines. Generic substitution in Finland Generic substitution operates within a price Generic substitution aims at promoting cost- “corridor”. Prescribed products are replaced with effective medical treatment. Savings are made the cheapest or close to the cheapest inter- both by actually replacing products with less changeable generic or parallel import product. expensive alternatives, and by promoting tougher The lowest limit within this corridor is the lowest price competition between pharmaceutical price of a substitutable product and the upper companies. Beginning in April 2003, more than limit, achieved by adding 2 to the lowest price, if 700 000 patients in Finland have since found that the least expensive product costs less than 40; one or more of the refundable drugs they have or 3, if the least expensive product costs 40 been receiving have been replaced with a less or more. The price corridor for different groups of expensive generic counterpart. substitutable drugs is established quarterly following price notifications submitted by pharma- The drugs most frequently replaced included ceutical companies. antihistamines, antidepressants and lipid-reducing agents. Two-thirds of the cost savings have been During the first year of generic substitution — generated by reductions in the price of medicinal from April 2003 to March 2004 — there were a products considered appropriate for substitution. total of 12.4 million prescriptions filled for substi- The savings generated by generic substitution tutable medicines dispensed by pharmacies and have offset, in particular, the increase in drug refunded by the health insurance scheme. This is costs generated by growing use of new, more about 45% of all refunded prescriptions during costly drugs. that time, i.e. purchase of a medicine prescribed by a doctor. Generic substitution was introduced in Finland in April 2003. This new practice required the The proportionate cost of substitutable drugs pharmacies to replace the medicinal product among the total costs of all refunded drugs during prescribed by a doctor with a less expensive the year was about 34%. In April 2003, the generic counterpart unless the doctor forbids or proportion was 36% and in March 2004 it was the buyer declines the replacement. The National less than 33%. This fluctuating percentage can be Agency for Medicines decides which generic explained by the increasing use of more recently counterpart can be substituted for another drug, marketed expensive drugs and by price reduc- and maintains a list of approved substitutable tions affecting substitutable products. An increase medicines. may also be felt, of course, as more medicinal 269 Drug Management WHO Drug Information Vol 18, No. 4, 2004 Table 1. Presciptions, costs and savings of substitutable products reimbursed by the national health insurance scheme (1 April 2003 to 31 March 2004). Prescriptions Costs Cost savings 000s share% 000s share% 000s share% A Alimentary tract and metabolism 648 5.2 28 650 5.0 3650 4.1 B Blood and blood forming organs 45 0.4 1553 0.3 16 0.0 C Cardiovascular system 4604 37.1 197 790 41.0 46 941 53.2 D Dermatologicals 120 1.0 11 882 2.5 1225 1.4 G Genito urinary system and sex hormones 512 4.1 28 984 6.0 2376 2.7 H Systemic hormonal preparations 47 0.4 1215 0.3 5 0.0 J Antiinfectives for systemic use 2013 16.2 39715 8.2 7377 8.4 L Antineoplastics and immunomodulating agents 144 1.2 23 880 5.0 304 0.3 M Musculo-skeletal system 1508 12.2 34760 7.2 4443 5.0 N Nervous system j 1958 15.8 86 994 18.1 17 434 19.7 P Antiparasitic products. insecticides and repellants 20 0.2 268 0.1 23 0.0 R Respiratory system 680 5.5 23 914 5.0 3846 4.4 S Sensory organs 92 0.7 2214 0.5 660 0.7 All substitutable products 12 394 100.0 481 829 100.0 88 300 100.0 Source: Prescription Register at Kela substances become substitutable on patent drugs entitled to special reimbursement fall into expiry. Medicines used for cardiovascular dis- the category of generic substitution. Over half of eases accounted for about 40% of all prescrip- the total savings were generated by drugs used tions and costs of substitutable drugs (Table 1). for cardiovascular diseases (Table 1). The pro- Measured by the number of prescriptions, the portion of the total savings due to substitution was biggest groups thereafter were anti-infectives and about a third, 28.8 million. drugs for the treatment of the nervous system. Over half of the savings created by generic During the year, about one in eight prescriptions substitution came from substituting lipid-lowering for a substitutable drug was replaced by a agents and antidepressants (Table 2). The cost cheaper alternative by the pharmacy. The most saving for each substitution was on average common substitutions made were of antihista- 18.39. One substitution involving the product mines (30% of prescriptions), antidepressants citalopram saved almost 56, and that of the (27%) and lipid-lowering agents (23%). Substitu- product simvastatin about