OBJECT DRUGS
Ergot Alkaloids:
- Dihydroergotamine (D.H.E. 45, etc.)
- Ergotamine (Cafergot)
- Methysergide (Sansert)
PRECIPITANT DRUGS
Antimicrobials:
- Ciprofloxacin (Cipro, etc.)
- Clarithromycin (Biaxin, etc.)
- Erythromycin (E-Mycin, etc.)
- Fluconazole (Diflucan)
- Itraconazole (Sporanox, etc.)
- Ketoconazole (Nizoral, etc.)
- Posaconazole (Noxafil)
- Quinupristin (Synercid)
- Telithromycin (Ketek)
- Troleandomycin (TAO)
- Voriconazole (Vfend)
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.
Class 2: Use Only if Benefit Felt to Outweigh Risk
- Use Alternative:
- Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4, and would not be expected to interact with ergot alkaloids.
- Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4. (*not available in US)
- Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
- 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.