Page 1172 - Basic _ Clinical Pharmacology ( PDFDrive )

1158 SECTION X Special Topics

TABLE 66–1 Important drug interactions. (Continued)

Drug or Properties Promoting
Drug Group Drug Interaction Clinically Documented Interactions
Anticoagulants, Susceptible to induction and Drugs that may increase anticoagulant effect:
oral inhibition of CYP2C9 (warfarin),
CYP3A4 (apixaban, rivaroxaban), Acetaminophen: [NE] Impaired synthesis of clotting factors at higher doses.
and P-glycoprotein (apixaban, Amiodarone: [P] Inhibited anticoagulant elimination.
dabigatran, edoxaban, rivaroxaban).
Warfarin highly bound to plasma Anabolic steroids: [P] Altered clotting factor disposition?
proteins. Anticoagulation response Azole antifungals: [P] Ketoconazole, itraconazole, voriconazole, and posaconazole can
altered by drugs that affect clotting
factor synthesis or catabolism. decrease apixaban, dabigatran, edoxaban, rivaroxaban, and perhaps warfarin elimination.
Cimetidine: [HP] Decreased warfarin metabolism.
Clopidogrel: [NP] Decreased warfarin metabolism and inhibits platelet function.
Disulfiram: [P] Decreased warfarin metabolism.
Efavirenz: [NP] Decreased warfarin metabolism.
Fluconazole: [P] Decreased warfarin metabolism.
Fluoxetine: [P] Decreased warfarin metabolism.
Gemfibrozil: [NE] Mechanism not established.
Lovastatin: [NP] Decreased warfarin metabolism.
Macrolide antibiotics: [NP] Clarithromycin and erythromycin inhibit the metabolism
of oral anticoagulants.
Metronidazole: [P] Decreased warfarin metabolism.
Miconazole: [NE] Decreased warfarin metabolism.
Nonsteroidal anti-inflammatory drugs (NSAIDs): [HP] Inhibition of platelet function,
gastric erosions; some agents increase hypoprothrombinemic response (unlikely with
diclofenac, ibuprofen, or naproxen).
Propafenone: [NE] Probably decreases anticoagulant elimination.
Quinidine: [NP] Additive hypoprothrombinemia, decreased apixaban, dabigatran,
edoxaban, rivaroxaban elimination.
Ritonavir: [P] Decreased apixaban, dabigatran, edoxaban, rivaroxaban elimination.
Salicylates: [HP] Platelet inhibition with aspirin but not with other salicylates; [P] large
doses have hypoprothrombinemic effect.
Simvastatin: [NP] Decreased warfarin metabolism.
Sulfinpyrazone: [NE] Inhibited warfarin metabolism.
Sulfonamides: [NE] Inhibited warfarin metabolism.
Trimethoprim-sulfamethoxazole: [P] Decreased warfarin metabolism.
Verapamil: [P] Decreased apixaban, dabigatran, edoxaban, rivaroxaban elimination.
See also Alcohol; Allopurinol.
Drugs that may decrease anticoagulant effect:
Aminoglutethimide: [P] Increased metabolism of anticoagulant.
Barbiturates: [P] Increased metabolism of anticoagulant.
Bosentan: [P] Increased metabolism of anticoagulant.
Carbamazepine: [P] Increased elimination of anticoagulant.
Cholestyramine: [P] Reduced absorption of anticoagulant.
Nafcillin: [NE] Increased metabolism of anticoagulant.
E, Expected; HP, Highly predictable. Interaction occurs in almost all patients receiving the interacting combination; P, Predictable. Interaction occurs in most patients receiving the
combination; NP, Not predictable. Interaction occurs only in some patients receiving the combination; NE, Not established. Insufficient data available on which to base estimate
of predictability.
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