OBJECT DRUGS

Vinca Alkaloids:

• Vinblastine (Velban)
• Vincristine (Oncovin)
• Vinorelbine (Navelbine)

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)
• Dronedarone (Multaq)
• Fluvoxamine (Luvox, etc.)
• Grapefruit
• Imatinib (Gleevec)
• Indinavir (Crixivan)
• Lapatinib (Tykerb)
• Lomitapide (Juxtapid)
• Mifepristone (Korlym)
• Nefazodone
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)

Comment:

Vinca alkaloids appear to be metabolized by CYP3A4 and several reports have described severe vincristine toxicity in patients receiving CYP3A4 inhibitors. P-glycoprotein inhibition may also be involved in these interactions.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Use an alternative to the enzyme inhibitor if possible.
• Antidepressants: Sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4. Fluoxetine (Prozac) appears to be only a weak inhibitor of CYP3A4.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: Monitor for toxicity from vincristine (primarily peripheral neuropathy symptoms: paresthesias, neuritic pain, muscle pain, constipation sometimes progressing to paralytic ileus) or vinblastine and vinorelbine (primarily bone marrow suppression).