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They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC\/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC\/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta\u2010analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English\u2010language reports on combination use of rifamycins and AC\/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a017), direct oral anticoagulants (DOACs) (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a08), and antiplatelet agents (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a04) combined with rifampin (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a028) or rifabutin (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a01). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin\u2010warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%\u201374%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3\u20135 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%\u201367%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC\/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC\/AP drugs.\n                  <\/jats:p>","DOI":"10.1002\/phar.2672","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T11:58:06Z","timestamp":1644753486000},"page":"343-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Systematic review of drug\u2013drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8690-5796","authenticated-orcid":false,"given":"Conan","family":"MacDougall","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy University of California San Francisco School of Pharmacy  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theora","family":"Canonica","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy San Francisco Veterans' Affairs Medical Center  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Keh","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binh An","family":"P. 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