Comparative risks of non-prescription analgesics: a structured topic review and research priorities

The aims of this report are to quantify and compare competing risks associated with the use of non-prescription analgesics (daily doses of acetaminophen ≤ 4000 mg, aspirin ≤ 4000 mg, ibuprofen ≤ 1200 mg, naproxen ≤ 660 mg and ketoprofen ≤ 75 mg) and identify research needs.

Literature was searched and organized by medication, adverse effect and direction of effect. Causality was determined using structured consensus, using IOM and GRADE nomenclature. Magnitude of risk data were extracted from primary sources. Structured consensus were used to construct a list of research priorities.

The available data favor acceptance of a causal relationship between each of the five analgesics studied and at least one specific form of harm. Dosing in excess of the non-prescription limits is associated with increased risk. Existing data do not support precise estimates of population or individual patient attributable risks for most analgesic and organ system combinations, and as a result competing risks cannot be adequately assessed. The highest priority research needs included understanding 'real world' dosing and how co-morbidities and prodromal symptoms modify exposure.

Although generally safe, all non-prescription analgesics are associated with some harm, particularly when recommended dosing limits are exceeded. Research to quantify the competing risks of different analgesic strategies is urgently needed.