PMID- 33769581 OWN - NLM STAT- MEDLINE DCOM- 20211207 LR - 20211214 IS - 1365-2125 (Electronic) IS - 0306-5251 (Linking) VI - 87 IP - 11 DP - 2021 Nov TI - Drug-drug interactions with warfarin: A systematic review and meta-analysis. PG - 4051-4100 LID - 10.1111/bcp.14833 [doi] AB - AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death. CI - (c) 2021 British Pharmacological Society. FAU - Wang, Mei AU - Wang M AUID- ORCID: 0000-0001-5974-1450 AD - Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. AD - Clinical Pharmacology & Toxicology, Research Institute, St Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6, Canada. FAU - Zeraatkar, Dena AU - Zeraatkar D AD - Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. FAU - Obeda, Michael AU - Obeda M AD - Department of Family Medicine, Queen's University, 220 Bagot St, Kingston, Ontario, K7L 3G2, Canada. FAU - Lee, Munil AU - Lee M AD - Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada. FAU - Garcia, Cristian AU - Garcia C AD - Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. FAU - Nguyen, Laura AU - Nguyen L AD - Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, K1H 8M5, Canada. FAU - Agarwal, Arnav AU - Agarwal A AD - Department of Medicine, University of Toronto, 27 King's College Circle, Toronto, Ontario, M5S 1A, Canada. FAU - Al-Shalabi, Farah AU - Al-Shalabi F AD - Clinical Pharmacology & Toxicology, Research Institute, St Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6, Canada. FAU - Benipal, Harsukh AU - Benipal H AD - Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. FAU - Ahmad, Afreen AU - Ahmad A AUID- ORCID: 0000-0002-7757-2141 AD - Bachelor Health Sciences Program, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. FAU - Abbas, Momina AU - Abbas M AD - Bachelor Arts & Science Program, Faculty of Arts & Science, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. FAU - Vidug, Kristina AU - Vidug K AD - Clinical Pharmacology & Toxicology, Research Institute, St Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6, Canada. FAU - Holbrook, Anne AU - Holbrook A AD - Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. AD - Clinical Pharmacology & Toxicology, Research Institute, St Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, L8N 4A6, Canada. AD - Division of Clinical Pharmacology & Toxicology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1, Canada. LA - eng GR - 365834/CIHR/Canada PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20210516 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 0 (Anticoagulants) RN - 0 (Pharmaceutical Preparations) RN - 5Q7ZVV76EI (Warfarin) SB - IM MH - Anticoagulants/adverse effects MH - Drug Interactions MH - Gastrointestinal Hemorrhage MH - Humans MH - *Pharmaceutical Preparations MH - Randomized Controlled Trials as Topic MH - *Warfarin/adverse effects OTO - NOTNLM OT - drug interaction OT - meta-analysis OT - systematic review OT - warfarin EDAT- 2021/03/27 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/03/26 12:59 PHST- 2021/03/07 00:00 [revised] PHST- 2020/09/03 00:00 [received] PHST- 2021/03/10 00:00 [accepted] PHST- 2021/03/27 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/03/26 12:59 [entrez] AID - 10.1111/bcp.14833 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2021 Nov;87(11):4051-4100. doi: 10.1111/bcp.14833. Epub 2021 May 16.