OBJECT DRUGS

Chemotherapy agents (CYP3A4 Substrates):

• Abiraterone (Zytiga)
• Anastrozole (Arimidex)
• Aprepitant (Emend)
• Bexarotene (Targretin)
• Bortezomib (Velcade)
• Brentuximab (Adcetris)
• Cabazitaxel (Jevtana)
• Cyclophosphamide (Cytoxan)
• Docetaxel (Taxotere)
• Doxorubicin (Adriamycin)
• Enzalutamide (Xtandi)
• Etoposide (Vepesid)
• Exemestane (Aromasin)
• Ifosfamide (Ifex)
• Ixabepilone (Ixempra)
• Ixazomib (Ninlaro)
• Letrozole (Femara)
• Paclitaxel (Taxol)
• Panobinostat (Farydak)
• Sonidegib (Odomzo)
• Teniposide (Vumon)
• Toremifene (Fareston)
• Trabectedin (Yondelis)
• Venetoclax (Venclexta)

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:

Although data are limited, assume all CYP3A4 inhibitors may increase the plasma levels of chemotherapy agents that are CYP3A4 substrates. Toxicity will vary with the object drug but neuropathy, myelosuppression, and gastrointestinal toxicity are common.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Calcium Channel Blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of these kinase inhibitors.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: Monitor for altered antineoplastic response if the CYP3A4 inhibitor is initiated, discontinued, or changed in dosage.