OBJECT DRUGS
Anticoagulants, Oral:
- Acenocoumarol
- Phenprocoumon
- Warfarin (Coumadin, etc.)
PRECIPITANT DRUGS
Enzyme Inducers:
- Azathioprine (Imuran, etc.)
- Barbiturates
- Bosentan (Tracleer)
- Carbamazepine (Tegretol, etc.)
- Cloxacillin (Cloxapen)
- Dabrafenib (Tafinlar)
- Dicloxacillin (Dynapen)
- Griseofulvin (Grisactin, etc.)
- Nafcillin (Unipen)
- Oxcarbazepine (Trileptal, etc.)
- Phenytoin (Dilantin, etc.)
- Primidone (Mysoline)
- Rifabutin (Mycobutin)
- Rifampin (Rifadin, etc.)
- Rifapentine (Priftin)
- St. John's Wort
Comment:
Enzyme inducers gradually reduce the anticoagulant response to oral anticoagulants. Phenytoin may actually increase warfarin effect initially—possibly by competitively inhibiting CYP2C9 activity and displacement of warfarin from plasma protein binding—but the initial increase is followed by reduced anticoagulant effect due to enzyme induction. Consider the increased risk of impaired anticoagulant control, and the increased monitoring cost, especially if the enzyme inducer will not be used chronically in a stable dose. Azathioprine appears to inhibit the anticoagulant effect of warfarin, but the mechanism for this effect is not clear. Theoretically, mercaptopurine may produce a similar effect on warfarin.
Class 2: Use Only if Benefit Felt to Outweigh Risk
- Use Alternative:
- General: Suitable alternatives with equivalent efficacy are not available for most enzyme inducers. In patients stabilized on chronic therapy with the anticoagulant and an enzyme inducer, it may be better to maintain current therapy, making sure the patient knows not to stop or change the dose of the enzyme inducer without consulting the prescriber of the anticoagulant.
- St. John's wort: Given the limited evidence of efficacy, St. John's wort should generally be avoided in patients taking oral anticoagulants.
- Monitor: If it is necessary to use enzyme inducers and oral anticoagulants concurrently, monitor for altered response if the inducer is initiated, discontinued, or changed in dosage. Note that enzyme induction is often gradual; it can take up to 1 to 2 weeks or more for maximal effects, and from 1 to 4 weeks for the effect to dissipate (depending on which inducer is used).