Emmert Roberts 1 , Vanessa Delgado Nunes 2 , Sara Buckner 2 , Susan Latchem 2 , Margaret Constanti 2 , Paul Miller 2 , Michael Doherty 3 , Weiya Zhang 3 , Fraser Birrell 4 , Mark Porcheret 5 , Krysia Dziedzic 6 , Ian Bernstein 7 , 8 , Elspeth Wise 9 , Philip G Conaghan 10
2 March 2015
We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.
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.
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).