OBJECT DRUGS

Antidiabetic Agents (CYP3A4 Substrates):

• Nateglinide (Starlix)
• Pioglitazone (Actos)
• Repaglinide (Prandin)
• Saxagliptin (Onglyza)
• Sitagliptin (Janumet)

PRECIPITANT DRUGS

Antimicrobials:

• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Isoniazid (INH)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Quinupristin (Synercid)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

Some antimicrobials can reduce oral hypoglycemic metabolism and produce hypoglycemic episodes. Pioglitazone and repaglinide are also metabolized by CYP2C8, and people taking a CYP2C8 inhibitor in addition to a CYP3A4 inhibitor may have large interactions. For example, patients taking repaglinide with both gemfibrozil (CYP2C8 inhibitor) and itraconazole (CYP3A4 inhibitor) may have 20-fold increases in repaglinide plasma concentrations. (See CYP Table at front of book for other CYP2C8 inhibitors.)

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: Azithromycin (Zithromax) and dirithromycin^* do not appear to inhibit CYP3A4 and are unlikely to interact. (^* not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic should be considered.
• Monitor: Monitor for hypoglycemic episodes during azole antifungal or macrolide coadministration.