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

Antimicrobials:

• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Isoniazid (INH)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Quinupristin (Synercid)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

Although data are limited, these antimicrobials 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:
• Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4; but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
• Macrolide Antibiotics: Azithromycin (Zithromax) and dirithromycin^* do not appear to inhibit CYP3A4 and are unlikely to interact. (^* not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic should be considered.
• Monitor: Monitor for altered antineoplastic response if the CYP3A4 inhibitor is initiated, discontinued, or changed in dosage.