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1 Examples from recent years include rofecoxib (Vioxx°) with fatal cardiovascular events, selective serotonin reuptake inhibitorantidepressan ts (fluoxetine (Prozac°), paroxetine (Deroxat°/ Seroxat°) and others) and rimonaban t (Acomplia°) with increased suiciderisk, olanzapine (Zypre xa°) with diabetes and metabolic disorders, and rosiglitazone (Avandia°) with fatal cardiac disorders.
2 proposed article 22a of the Directive and article 10a of the Regulation3 proposed articles 22a and 104a of the Directive4 There are no plans however to provide public access to the health authorities’ detailed requests or the drug companies’ responsesthat influence the confirma tion and final content of these requests. Yet these docu men ts are extrem ely informa tive, as illustra ted by theUS experience with paediatric studiesfor which requests are publicly accessible on the FDA website, acco mpanied by the modifications requeste d by the pharmace uticalcompanies.
5 proposed article 107(1) and (2)6 proposed article 107(1)7 proposed article 107(4)8 proposed article 107b which stipulates that the “ scientific evaluation of the risk- benefit balance of themedicinal product “ be produced by pharmaceutical companies in their periodic safety update reports(PSURs) 10 proposed article 107k(2) of the Directive11 proposed article 107c(6) point (c)12 proposed article 107b(3) 13 In the face of reports of adverse effects (increased suicide risk) and deaths after rimonabant (Acomplia°) was licensed (a drug forobesity granted a European marketin g authorisation on the basis of rather insubstan tial data and poorly elucidated risks), the agencies’response was initially confined to setting up a “risk manage men t syste m ”, which was not made public. After repeate d requests, theassessment report on the risk manage men t system, produced by the Swedish drug regulatory agency, was sent to the editorial staff ofPrescrire (an independent drug bulletin): 65 of a total of 68 pages had been completely obscured ! It took over 2 years after itsmarketing authorisa tion was granted for rimonaban t to be withdrawn from the market due to an unfavourable risk- benefit balance inobesity. Similarly varenicline (Chantix°/Champ ix°), for which a risk manage me nt system was put in place, has an unfavourable risk-benefit balance in smoking cessation (withdrawal sympto ms, psychia tric disorders including increased suicide risk, etc.).
14 As part of the consultation held on this subject in February 2008, the Commission had in fact presented this weakening of pre-authorisation evalua tionas a means of boosting drug companies’ compe titiveness: “earlier product authorisatio n provid es faster return on investm en t and, byreducing the cost of capital (through increased investor confidence), the total cost of product develop me nt is reduced ” (section 3.2.1 ofthe introduction to the consultation of February 2008).
15 proposed amendment of article 11 of the Directive 16 One example is diethylstilbestrol (DES), which is responsible for uterine cancers and malformations in women exposed to this drugin utero while their mothers were pregna nt. Its adverse effects were recognized 30 years later. Another example is valproic acid, whichwas recently discovered to cause neuropsychiatric disorders in children following in- utero exposure. A further example is all german der,a medicina l plant traditionally used for decades, but which has been established to be hepatoto xic. A final examp le is the combina tio ndextrop ro poxyph ene + parace ta m ol, which was withdrawn from the market in several countries in 2005 whereas its marketingauthorisation was originally gran te d in the mid- 1960s.

Source: http://www.epha.org/IMG/pdf/EPHA_BRIEFING_NOTE_final_draft.pdf