Regulatory agencies rarely resort to truly effective measures, such as market withdrawal, in order to protect patients. They are too often more concerned with protecting companies’ financial interests, and simply withdraw certain indications, modify the summary of product characteristics (SPC) or information concerning risks.

Market withdrawals: too few in 2008
Three products were withdrawn from the French market for safety reasons:

• aprotinin, an antifibrinolytic drug associated with excess mortality (Prescrire International 97);

• fentanyl iontophoretic transdermal system, an unreliable delivery system for this opiate (Prescrire International 95 and 96);

• rimonabant, a cannabinoid derivative used as an appetite suppressant, with numerous and sometimes fatal psychological effects (Prescrire International 100).

This is too little, considering that many drugs, including some very old drugs, remain on the market despite unfavourable risk-benefit balances.

Restricted indications: far less effective than simple market withdrawal
The restrictions placed on the indications for piroxicam, a nonsteroidal antiinflammatory drug (NSAID) used in rheumatology, are insufficient. Patients continue to be exposed to this drug’s adverse effects, while other safer NSAIDs are available (la revue Prescrire 294 p. 257).

The indication for "hypertriglyceridaemia" was removed from the benfluorex summary of product characteristics, but it is unacceptable that diabetic patients should still be exposed to this amphetamine (la revue Prescrire 291 p. 19).

SPC modifications: too little stress placed on adverse effects
Risks identified after market release are sometimes added to the SPC. However, these changes can be difficult for healthcare professionals to detect, and regulatory agencies fail to publicise them adequately. Examples include: patent blue V and anaphylaxis (in a coming issue); ethinylestradiol-etonorgestrel vaginal rings that may be accidentally expelled (la revue Prescrire 292 p. 103); hydrochlorothiazide, indapamide and photosensitisation (la revue Prescrire 300 p. 738); manidipine and gingival hyperplasia (la revue Prescrire 295 p. 341); and trospium and QT prolongation (la revue Prescrire 295 p. 346).

Regulatory agencies provide limited information about riskd
Regulatory agencies have a responsibility to inform users of the risks associated with specific drugs. Some of the safety information disseminated by the European and French agencies was presented in these pages in 2008. Examples include: oseltamivir and gastrointestinal bleeding (la revue Prescrire 293 p. 186); sirolimus and tuberculosis (la revue Prescrire 294 p. 266); topical tacrolimus and cancer (la revue Prescrire 301 p. 828); and varenicline and gastrointestinal, psychiatric and cardiovascular disorders (la revue Prescrire 294 p. 266). The limited safety information that does trickle down from regulatory agencies to the public is often inadequate. Prescrire had to ask the EMEA for access to important data that had been kept from the public. Examples include: exenatide and renal failure (la revue Prescrire 299 p. 664), sitagliptin and allergies (la revue Prescrire 302 p. 907), and sorafenib and gastrointestinal perforation (la revue Prescrire 299 p. 664).

©Prescrire April 2009

Source: Prescrire Int 2009 18 (100) 84-88.