OBJECT DRUGS

• Alfuzosin (Uroxatral)

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:

Alfuzosin is primarily metabolized by CYP3A4, and these antimicrobial agents are inhibitors of CYP3A4. Based on a more than 3-fold increase in alfuzosin AUC with ketoconazole, the alfuzosin labeling states that combined use of alfuzosin with potent CYP3A4 inhibitors is contraindicated. Although not all of these antimicrobials have equal potency as CYP3A4 inhibitors, they all would be expected to produce substantial increases in alfuzosin plasma concentrations.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4 than itraconazole or ketoconazole, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, other macrolides such as 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 alfuzosin is used with a CYP3A4 inhibitor, monitor blood pressure for evidence of hypotension. Placing the patient in the supine position or additional measures (intravenous fluids, vasopressors) may be necessary if hypotension occurs.