OBJECT DRUGS

• Pimozide (Orap)

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

Comment:

Pimozide alone can prolong the QT interval, and it has been associated with ventricular arrhythmias (torsades de pointes). Drugs that inhibit CYP3A4 may increase pimozide serum concentrations and increase the risk of ventricular arrhythmias. Orap product information states that pimozide is contraindicated with indinavir, nelfinavir, ritonavir, saquinavir, and other CYP3A4 inhibitors. The mifepristone product information states that concurrent use of pimozide is contraindicated.

Class 1: Avoid Combination

• Avoid: CYP3A4 inhibitors should not be given to patients receiving pimozide due to the risk of life-threatening ventricular arrhythmias. Use an alternative drug to the CYP3A4 inhibitor if possible.
• Use Alternative:
• Antidepressants: Citalopram (Celexa), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4 than fluvoxamine. Fluoxetine (Prozac) appears to be a weak inhibitor of CYP3A4, and could increase pimozide concentrations.
• Calcium channel blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit CYP3A4.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.