OBJECT DRUGS

Ergot Alkaloids:

• Dihydroergotamine (D.H.E. 45, etc.)
• Ergotamine (Cafergot)
• Methysergide (Sansert)

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

Comment:

Ergotamine (and probably dihydroergotamine and methysergide) undergo first-pass metabolism by CYP3A4, and several reports of ergotism have appeared when CYP3A4 inhibitors were given concurrently. Theoretically non-oral routes of ergot administration would interact much less than the oral route. Some of these combinations are listed as contraindicated in the product information (e.g., amprenavir or mifepristone with ergot alkaloids).

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: If possible, select an alternative to the CYP3A4 inhibitor for patients receiving concomitant ergot alkaloids.
• Calcium channel blocker: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of ergot alkaloids.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: If the combination is used, monitor carefully for evidence of ergotism such as ischemia of extremities (pain, tenderness, cyanosis, and low skin temperature), hypertension, and tongue ischemia.