OBJECT DRUGS
PRECIPITANT DRUGS
Enzyme Inhibitors:
- Amiodarone (Cordarone, etc.)
- Amprenavir (Agenerase)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Boceprevir (Victrelis)
- Ceritinib (Zykadia)
- Cobicistat (Stribild)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Darunavir (Prezista)
- Delavirdine (Rescriptor)
- Diltiazem (Cardizem, etc.)
- Dronedarone (Multaq)
- Grapefruit
- Imatinib (Gleevec)
- Indinavir (Crixivan)
- Lapatinib (Tykerb)
- Lomitapide (Juxtapid)
- Mifepristone (Korlym)
- Nelfinavir (Viracept)
- Ritonavir (Norvir)
- Saquinavir (Invirase)
- Telaprevir (Incivek)
- Verapamil (Isoptin, etc.)
Comment:
Rifabutin serum concentrations can be markedly increased by CYP3A4 inhibitors; toxicity is often manifested by uveitis but rash, bone marrow suppression, and increased hepatic enzymes can also occur. Also, the plasma concentrations of some of the enzyme inhibitors listed above (e.g., cyclosporine, diltiazem, verapamil) are likely to be substantially reduced due to the ability of rifabutin to act as an enzyme inducer.
Class 2: Use Only if Benefit Felt to Outweigh Risk
- Use Alternative:
- Enzyme Inhibitor: Use an alternative to the enzyme inhibitor if possible.
- Calcium Channel Blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of rifabutin. But most calcium channel blockers are highly susceptible to enzyme induction, so rifabutin is likely to substantially reduce their plasma concentrations.
- Grapefruit: Orange juice does not appear to inhibit CYP3A4.
- Circumvent/Minimize: Rifabutin dose may require reduction if used with CYP3A4 inhibitors. In patients on ritonavir, the use of rifabutin once or twice weekly has been successful in some patients.
- Monitor: If CYP3A4 inhibitors are used with rifabutin, monitor for rifabutin toxicity.