Basic Information
ID DDInter1951 and DDInter76
Interaction Amiodarone may increase the pharmacologic effects of warfarin by inhibiting CYP450 2C9 hepatic metabolism of S-warfarin. Similar effects may also occur with other oral anticoagulants, resulting in significant hypoprothrombinemia and bleeding. When amiodarone is added to an anticoagulant regimen, increased anticoagulant effects may become apparent within one to several weeks and may persist for months after the amiodarone is discontinued. The effects of this interaction are highly variable - while some patients are asymptomatic, serious and life-threatening bleeding complications have been reported in others. Patients who are poor CYP450 2C9 metabolizers may have a higher risk of bleeding and a faster onset of the interaction.
Management An empiric 30% to 50% reduction in anticoagulant dosage has been recommended, in addition to frequent monitoring of the patient and the prothrombin time or International Normalized Ratio (INR). Patients should be advised to notify their physician promptly if they experience any signs of excessive anticoagulation such as unusual or prolonged bleeding, bruising, vomiting, change in stool or urine color, headache, dizziness, or weakness.
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Alternative for Warfarin B01A
Reteplase Cangrelor Desirudin Enoxaparin Protein C Treprostinil
Bivalirudin Ticlopidine Dipyridamole Eptifibatide Lepirudin
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Alternative for Amiodarone C01B
Tocainide Ibutilide Bretylium
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.