OBJECT DRUGS
Antidiabetic Agents (CYP3A4 Substrates):
- Nateglinide (Starlix)
- Pioglitazone (Actos)
- Repaglinide (Prandin)
- Saxagliptin (Onglyza)
- Sitagliptin (Janumet)
PRECIPITANT DRUGS
Antimicrobials:
- Ciprofloxacin (Cipro, etc.)
- 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 (a substrate of CYP3A4, CYP2C8, and OATP) with both gemfibrozil (an inhibitor of both CYP2C8 and OATP) and itraconazole (CYP3A4 inhibitor) may have 20-fold increases in repaglinide plasma concentrations. (See CYP Table at front of book for other CYP2C8 and OATP 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 other than ciprofloxacin should be considered.
- Monitor: Monitor for hypoglycemic episodes during azole antifungal or macrolide coadministration.