OBJECT DRUGS

• Irinotecan (Camptosar)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Amprenavir (Agenerase)
• 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:

CYP3A4 inhibitors may increase serum concentrations of irinotecan and its active metabolite (SN-38). Ketoconazole, for example, increased SN-38 AUC by 109%. Part of the effect of ketoconazole may be due to inhibition of the glucuronidation of SN-38 to SN-38G by UGT1A1, so it is not clear that all CYP3A4 inhibitors would necessarily interact with irinotecan. Nonetheless, the product information for irinotecan states that strong CYP3A4 inhibitors should not be used concurrently.

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 irinotecan.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: Monitor for altered irinotecan effect if CYP3A4 inhibitors are initiated, discontinued, or changed in dosage. Changes in irinotecan dosage may be necessary.