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Paracetamol: not as safe as we thought? A systematic literature review of observational studies

Lookup NU author(s): Professor Fraser Birrell

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Abstract

Objectives We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.Methods We searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome.Results Of 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of >= 30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43).Discussion Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.

Publication metadata

Author(s): Roberts E, Nunes VD, Buckner S, Latchem S, Constanti M, Miller P, Doherty M, Zhang WY, Birrell F, Porcheret M, Dziedzic K, Bernstein I, Wise E, Conaghan PG

Publication type: Review

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2016

Volume: 75

Issue: 3

Pages: 552-559

Online publication date: 02/03/2015

Acceptance date: 13/01/2015

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ PUBLISHING GROUP

URL: http://dx.doi.org/10.1136/annrheumdis-2014-206914

DOI: 10.1136/annrheumdis-2014-206914

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