Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review

ABSTRACT

Introduction: Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed.

Areas covered: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler’s Side Effects of Drugs; Stephens’ Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions.

Expert opinion: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

KEYWORDS:

• Adverse reactions
• analgesics
• drug withdrawal
• systematic review

Article highlights

• 47 analgesic medicinal products have been withdrawn from the market because of adverse reactions

• Case reports are most commonly cited as evidence for making the withdrawal decisions

• The pattern of post-marketing withdrawal of analgesics suggests inadequate assessment of harms in pre-marketing phases

• COX-2 selective inhibitors are more likely to be withdrawn because of cardiovascular

• adverse reactions compared with the non-selective COX-inhibitors

• Analgesic products are more likely to be withdrawn in Europe than the USA when serious adverse reactions are attributed to their use

This box summarizes key points contained in the article.

Declaration of interest

IJO receives scholarship funding from the Clarendon Fund for the DPhil programme in Primary Health Care at the University of Oxford. CJH is supported by the National Institute for Health Research School for Primary Care Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Funding

This paper was not funded.