Drug Withdrawal Due to Safety: A Review of the Data Supporting Withdrawal Decision.

INTRODUCTION: Several drugs were withdrawn from the market due to safety. OBJECTIVE: The aim of this study was to describe data supporting drug withdrawal from the market due to safety reasons in countries belonging to the World Health Organization. METHODS: We analyzed drugs withdrawn from the market between 1990 and 2010. All medicine agencies of the countries belonging to the Program for International Drug Monitoring of the World Health Organization were contacted. To complete data, Medline, reference books and available drug databases were also searched. Information sources on which authorities based their withdrawal were categorized and the average time between the first date of exposure and withdrawal was calculated and stratified. RESULTS: A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the market due to safety reasons in the period reviewed (1990 - 2010). Hepatotoxicity (n=36, 27.1%), cardiac disorders (n=25, 18.8%), hypersensitivity (n=17, 12.8%) and nephrotoxicity (n=14, 9.8%) were the major reasons responsible for 69.2% of all drugs withdrawn. In most cases, Information Sources for drug withdrawal were spontaneous reports and/or case reports (n=86, 64.7%), followed by clinical trials (n=24, 18.0%). The average time between the introduction of a drug and its withdrawal due to safety reasons was 20.3 years (SD±13.8). CONCLUSION: According to available and published evidence, there is no gold standard to identify risks associated with drug exposure. These findings strengthen the role of different information sources within the drug safety review process.

L-TRUST: Long-term risk of cancer in patients under statins therapy. A systematic review and meta-analysis.

INTRODUCTION: Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins. METHODS: Medline, Cochrane library, and clinicaltrials.gov were searched in order to identify studies with a minimum average follow-up of 10 years of exposure to statins and a cancer-related outcome reported. Relative risk (RR) of the primary outcomes and the combined effect was presented using a random-effects model. In the selected randomized control trials (RCT), statin exposure was compared with placebo, and in the selected observational studies, it was compared with no exposure to statins. RESULTS: We retrieved 1627 studies, of which 15 full-papers were included for final review, five RCT, two cohort studies (CSs), and eight case-control studies (CCs), representing a total of 358 544 patients. Five RCT, two cohort studies (CSs), and eight case-control studies (CCs). No significant differences were found regarding risk of cancer occurrence (RR = 1.08, 0.96-1.21) or cancer mortality (RR = 0.91, 0.80-1.04) due to long-term statin exposure. Regarding all-cause mortality, a protective effect was found (RR = 0.93, 0.90-0.97). CONCLUSIONS: According to available and published evidence, statins are not associated with an increased risk of cancer after prolonged exposure. These findings strengthen the role of statins in the primary and secondary prevention of cardiovascular events.