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| __NOTOC__
| | #REDIRECT [[Rivaroxaban#Drug Interactions]] |
| {{Rivaroxaban}}
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| {{CMG}}; {{AE}} {{AZ}}
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| | | [[Category: Cardiovascular Drugs]] |
| ==Drug Interactions==
| | [[Category: Drug]] |
| Rivaroxaban is a substrate of [[CYP3A4]]/[[CYP3A5|5]], [[CYP2J2]], and the P-gp and ATP-binding cassette G2 (ABCG2) transporters. Inhibitors and inducers of these CYP450 enzymes or transporters (e.g., P-gp) may result in changes in rivaroxaban exposure.
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| === Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems===
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| In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and [[CYP3A4]] inhibitors ([[ketoconazole]], [[ritonavir]], [[clarithromycin]], [[erythromycin]] and [[fluconazole]]), increases in rivaroxaban exposure and pharmacodynamic effects (i.e., [[factor Xa]] inhibition and [[PT]] prolongation) were observed. The increases in exposure ranged from 30% to 160%. Significant increases in rivaroxaban exposure may increase bleeding risk [see [[Rivaroxaban clinical pharmacology |Clinical Pharmacology]]].
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| When data suggest a change in exposure is unlikely to affect bleeding risk (e.g., [[clarithromycin]], [[erythromycin]]), no precautions are necessary during coadministration with drugs that are combined P-gp and [[CYP3A4]] inhibitors.
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| Avoid concomitant administration of XARELTO with combined P-gp and strong CYP3A4 inhibitors [see [[Rivaroxaban warnings and precautions |Warnings and Precautions]]].
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| === Drugs that Induce Cytochrome P450 3A4 Enzymes and Drug Transport Systems===
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| Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of XARELTO with a combined P-gp and strong [[CYP3A4]] inducer (e.g., [[rifampicin]], [[phenytoin]]) decreased rivaroxaban exposure by up to 50%. Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to rivaroxaban may decrease efficacy [see [[Rivaroxaban clinical pharmacology |Clinical Pharmacology]]].
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| Avoid concomitant use of XARELTO with drugs that are combined P-gp and strong CYP3A4 inducers (e.g., [[carbamazepine]], [[phenytoin]], [[rifampin]], [[St. John's wort]]) [see [[Rivaroxaban warnings and precautions |Warnings and Precautions]]].
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| === Anticoagulants and NSAIDs/Aspirin===
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| Single doses of [[enoxaparin]] and XARELTO given concomitantly resulted in an additive effect on anti-[[factor Xa]] activity. Single doses of [[warfarin]] and XARELTO resulted in an additive effect on [[factor Xa]] (FXa) inhibition and [[PT]]. Concomitant [[aspirin]] use has been identified as an independent risk factor for major bleeding in efficacy trials. [[NSAIDs]] are known to increase bleeding, and bleeding risk may be increased when NSAIDs are used concomitantly with XARELTO. Coadministration of the platelet aggregation inhibitor [[clopidogrel]] and XARELTO resulted in an increase in bleeding time for some subjects [see [[Rivaroxaban clinical pharmacology |Clinical Pharmacology]]].
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| Avoid concurrent use of XARELTO with other anticoagulants due to increased bleeding risk unless benefit outweighs risk. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with [[aspirin]], other platelet aggregation inhibitors, or [[NSAIDs]] [see [[Rivaroxaban warnings and precautions |Warnings and Precautions]]].
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| === Drug-Disease Interactions with Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems===
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| Results from a pharmacokinetic trial with [[erythromycin]] indicated that patients with [[renal impairment]] coadministered XARELTO with drugs classified as combined P-gp and moderate [[CYP3A4 ]]inhibitors (e.g., [[diltiazem]], [[verapamil]], [[dronedarone]], and [[erythromycin]]) have increased exposure compared with patients with normal renal function and no inhibitor use. Significant increases in rivaroxaban exposure may increase bleeding risk.
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| While increases in rivaroxaban exposure can be expected under such conditions, results from an analysis in the ROCKET AF trial, which allowed concomitant use with combined P-gp and weak or moderate CYP3A4 inhibitors (e.g., [[amiodarone]], [[diltiazem]], [[verapamil]], [[chloramphenicol]], [[cimetidine]], and [[erythromycin]]), did not show an increase in bleeding in patients with CrCl 30 to <50 mL/min [Hazard Ratio (95% CI): 1.05 (0.77, 1.42)] [see [[Rivaroxaban use in specific populations |Use in Specific Populations]]].
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| XARELTO should not be used in patients with CrCl 15 to 80 mL/min who are receiving concomitant combined P-gp and moderate [[CYP3A4]] inhibitors unless the potential benefit justifies the potential risk [see [[Rivaroxaban clinical pharmacology|Clinical Pharmacology]]].<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = XARELTO (RIVAROXABAN) TABLET, FILM COATED [JANSSEN PHARMACEUTICALS, INC.] |url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=10db92f9-2300-4a80-836b-673e1ae91610 | publisher = | date = | accessdate = }}</ref>
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| ==References==
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| {{Reflist}}
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| {{FDA}}
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| [[Category:Drugs]] | |