Public health and WHODrugs withdrawn from the market — why were they considered safe for years?
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- Henryk Różański — Dwunitrofenol (dinitrophenolum) i tusza ciała
- Jerzy Jaśkowski — Czego nie wiemy o statynach?
- Drug Withdrawal Due to Safety: A Review of the Data Supporting Withdrawal Decision. · Curr Drug Saf 2020
- Safety data and withdrawal of hepatotoxic drugs. · Therapie 2021
- Data-driven in silico toxicity profiling of marketed drugs and retrospective analysis of post-marketing withdrawal risk. · Toxicol Mech Methods 2026
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Jerzy Zięba says that Vioxx was withdrawn only after about 100,000 deaths, and that after the drug was introduced, patients began to get sicker or die more often.
- According to Zięba, the manufacturer analyzed the study results itself and submitted them to the FDA without independent external verification.
- Piotr Witczak points out that Vioxx was described as “effective and safe,” and was later linked to more than 140,000 heart attacks and over 55,000 deaths.
What the authors write
The manufacturer analyzed the study results itself and submitted them to the FDA without independent external verification.
After the drug was introduced, patients began to get sicker or die more often, and Vioxx was withdrawn only after about 100,000 deaths.
Vioxx was described as “effective and safe,” and was later linked to more than 140,000 heart attacks and over 55,000 deaths.
DNP was quickly withdrawn from medical use after it was found to damage multiple organs and eyesight.
Curantyl was withdrawn from the market less than four years later because of the large number of heart attacks among people who took it.
Research from PubMed · Europe PMC
We selected 3 studies with the best, positive results. This is a selection, not a full review of all research.
Total number of studies on this topic in PubMed: 8 639.
The analysis found that drugs were withdrawn after an average of more than 20 years, and that decisions were most often based on spontaneous reports or case reports.
Aim of the study: Several drugs were withdrawn from the market due to safety. 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.
Results: A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the market due to safety reasons in the period reviewed (1990 - 2010).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). 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.
“Not stated” does not mean nobody paid — the database does not always record it.
The review indicated that the risk of liver damage may have been overlooked because of limitations in studies and insufficient attention to rare adverse effects.
Aim of the study: The occurrence of drug induced liver injury (DILI) is the most common reason of post-marketing withdrawals. DILI in humans is difficult to predict using in vitro cytotoxicity screening and animal studies. A review of hepatotoxicity data was performed with the aim of identifying relevant factors that could have predicted the occurrence of serious DILI.
Results: From 1997 to 2016, eight drugs were withdrawn from the market for hepatotoxicity reason: tolcapone, troglitazone, trovafloxacin, bromfenac, nefazodone, ximelagatran, lumiracoxib and sitaxentan. The safety data suggest that while liver test abnormalities have been detected during clinical trials, other relevant factors leading to the discontinuation of these drugs have been identified: lack of predictability of animal models, inappropriate liver function test, non-compliance with drug treatment, less attention paid to rare adverse drug reactions, unpredictable occurrence and irreversible outcome of liver toxicity. Several relevant factors may contribute to an inadequate risk management leading to the discontinuation of the drugs. Preclinical safety data are not sufficient to allow early prediction of DILI in humans and post-marketing safety monitoring and signal detection still should be used to identify potential serious cases of DILI.
“Not stated” does not mean nobody paid — the database does not always record it.
The analysis suggests that the limited size and duration of pre-approval studies make it difficult to detect rare or delayed adverse effects.
Aim of the study: Drug safety remains a central challenge in drug development and post-marketing surveillance, as the limited size and duration of pre-approval trials constrain detection of rare or delayed adverse effects, leaving patients exposed to residual risk after launch.
Results: Using ProTox 3.0 in silico toxicity predictions and statistical modeling, we analyzed an observational cohort of nearly 2,000 historically marketed small-molecule drugs and identified hepatotoxicity as a robust and consistent determinant of pharmaceutical post-marketing withdrawal probability after adjustment for therapeutic context. Other organ toxicities and structural descriptors of the drug molecules exhibited additional, indication-specific associations with withdrawal status, indicating that ex-ante toxicity liability is heterogeneous across therapeutic areas. While our analysis does not establish causality, the stable correlations observed across toxicity profiles, structural characteristics, and clinical indications suggest that a substantial fraction of withdrawal risk is statistically predictable.
“Not stated” does not mean nobody paid — the database does not always record it.
Perspectives and opinion materials
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