RT Journal Article
SR Electronic
T1 Paracetamol: not as safe as we thought? A systematic literature review of observational studies
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 552
OP 559
DO 10.1136/annrheumdis-2014-206914
VO 75
IS 3
A1 Roberts, Emmert
A1 Delgado Nunes, Vanessa
A1 Buckner, Sara
A1 Latchem, Susan
A1 Constanti, Margaret
A1 Miller, Paul
A1 Doherty, Michael
A1 Zhang, Weiya
A1 Birrell, Fraser
A1 Porcheret, Mark
A1 Dziedzic, Krysia
A1 Bernstein, Ian
A1 Wise, Elspeth
A1 Conaghan, Philip G
YR 2016
UL http://ard.bmj.com/content/75/3/552.abstract
AB 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.