OBJECT DRUGS

Antidiabetic Agents (CYP2C9 Substrates):

• Chlorpropamide (Diabinese)
• Glimepiride (Amaryl)
• Glipizide (Glucotrol, etc.)
• Glyburide (DiaBeta, etc.)
• Nateglinide (Starlix)
• Rosiglitazone (Avandia)
• Tolbutamide (Orinase)

PRECIPITANT DRUGS

Azole Antifungals:

• Fluconazole (Diflucan)
• Miconazole (Monistat, etc.)
• Voriconazole (Vfend)

Comment:

Oral hypoglycemic drugs that are metabolized by CYP2C9 may produce enhanced hypoglycemic effects when administered with azole antifungal agents that inhibit the enzyme. Nateglinide and rosiglitazone both have additional pathways of metabolism and may be less affected by inhibitors of only one pathway.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative: Itraconazole (Sporanox) and terbinafine (Lamisil) are antifungals that do not inhibit CYP2C9. Ketoconazole (Nizoral) has been reported to increase the plasma concentrations of rosiglitazone and tolbutamide.
• Monitor: Diabetic patients taking CYP2C9-inhibiting antifungals should be warned that hypoglycemic episodes may occur more frequently and should monitor their blood glucose concentrations.