OBJECT DRUGS
Tyrosine Kinase Inhibitors (CYP3A4 Substrates):
- Crizotinib (Xalkori)
- Dasatinib (Sprycel)
- Erlotinib (Tarceva)
- Gefitinib (Iressa)
- Imatinib (Gleevec)
- Lapatinib (Tykerb)
- Nilotinib (Tasigna)
- Pazopanib (Votrient)
- Sorafenib (Nexavar)
- Sunitinib (Sutent)
PRECIPITANT DRUGS
Enzyme Inhibitors:
- Amiodarone (Cordarone, etc.)
- Amprenavir (Agenerase)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Darunavir (Prezista)
- Delavirdine (Rescriptor)
- Diltiazem (Cardizem, etc.)
- Dronedarone (Multaq)
- Grapefruit
- Indinavir (Crixivan)
- Nelfinavir (Viracept)
- Ritonavir (Norvir)
- Saquinavir (Invirase)
- Telaprevir (Incivek)
- Verapamil (Isoptin, etc.)
Comment:
Although data are limited, these enzyme inhibitors may increase the plasma levels of tyrosine kinase inhibitors. Toxicity including skin rashes, anemia, hemorrhage, and gastrointestinal symptoms could result. Assume that all CYP3A4 inhibitors interact until proven otherwise.
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 tyrosine 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.