OBJECT DRUGS
Calcium Channel Blockers:
- Amlodipine (Norvasc)
- Bepridil (Vascor)
- Diltiazem (Cardizem, etc.)
- Felodipine (Plendil)
- Isradipine (DynaCirc, etc.)
- Nicardipine (Cardene, etc.)
- Nifedipine (Procardia, etc.)
- Nimodipine (Nimotop)
- Nisoldipine (Sular)
- Nitrendipine (Baypress)
- Verapamil (Isoptin, etc.)
PRECIPITANT DRUGS
Antimicrobials:
- 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:
Calcium channel blockers (CCBs) are metabolized by CYP3A4, so CYP3A4 inhibitors may substantially increase their serum concentrations. Not all combinations of CCBs and CYP3A4 inhibitors have been studied; assume they interact until proven otherwise. Note, however, that the magnitude of interaction can vary considerably depending on the CCB involved. For example, felodipine undergoes extensive first pass metabolism by CYP3A4 and is markedly affected by CYP3A4 inhibition, while amlodipine undergoes considerably less first pass metabolism by CYP3A4 and is much less affected by CYP3A4 inhibition. Short-term use of an azole antifungal (1-2 days) is unlikely to result in a clinically important interaction.
Class 3: Assess Risk & Take Action if Necessary
- Consider Alternative:
- Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4; but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
- 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 should be considered.
- Monitor: If alternatives are not appropriate, consider reducing CCB dose and monitor for altered CCB response if inhibitor is initiated, discontinued, or changed in dosage.