{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:22:13Z","timestamp":1791235333327,"version":"4.1.0"},"reference-count":110,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The objective of this paper is to systematically review the literature on drug\u2013drug interactions with warfarin, with a focus on patient\u2010important clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug\u2013drug 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 42\u2009013 citations identified, a total of 72 studies reporting on 3\u2009735\u2009775 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\u2009=\u20091.74; 95% CI 1.56\u20131.94), many antimicrobials (OR\u2009=\u20091.63; 95% CI 1.45\u20131.83), NSAIDs including COX\u20102 NSAIDs (OR\u2009=\u20091.83; 95% CI 1.29\u20132.59), SSRIs (OR\u2009=\u20091.62; 95% CI 1.42\u20131.85), mirtazapine (OR\u2009=\u20091.75; 95% CI 1.30\u20132.36), loop diuretics (OR\u2009=\u20091.92; 95% CI 1.29\u20132.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin\u2010related gastrointestinal (GI) bleeding (OR\u2009=\u20090.69; 95% CI 0.64\u20130.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2013drug interactions leading to thromboembolic outcomes or death.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14833","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T11:15:07Z","timestamp":1616757307000},"page":"4051-4100","source":"Crossref","is-referenced-by-count":107,"title":["Drug\u2013drug interactions with warfarin: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5974-1450","authenticated-orcid":false,"given":"Mei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact (HEI) McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"},{"name":"Clinical Pharmacology &amp; Toxicology, Research Institute St Joseph's Healthcare Hamilton  50 Charlton Avenue East Hamilton Ontario L8N 4A6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena","family":"Zeraatkar","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact (HEI) McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Obeda","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Queen's University  220 Bagot St Kingston Ontario K7L 3G2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munil","family":"Lee","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry Western University  London Ontario N6A 3K7 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods, Evidence, and Impact (HEI) McMaster University  1280 Main Street West Hamilton Ontario L8S 4K1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ottawa  451 Smyth Rd Ottawa Ontario K1H 8M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnav","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  27 King's College Circle Toronto Ontario M5S 1A Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Al\u2010Shalabi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; 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