OBJECT DRUGS

Antidiabetic Agents: (CYP2C9 Substrates):

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

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Capecitabine (Xeloda)
• Ceritinib (Zykadia)
• Co-trimoxazole (Septra)
• Delavirdine (Rescriptor)
• Efavirenz (Sustiva)
• Etravirine (Intelence)
• Fluorouracil (Adrucil)
• Fluoxetine (Prozac, etc.)
• Fluvastatin (Lescol, etc.)
• Fluvoxamine (Luvox, etc.)
• Metronidazole (Flagyl, etc.)
• Sulfinpyrazone (Anturane)

Comment:

Oral hypoglycemic drugs that are metabolized by CYP2C9 may produce enhanced hypoglycemic effects when administered with a CYP2C9 inhibitor. Nateglinide and rosiglitazone both have additional pathways of metabolism and may be less affected by inhibitors of only one pathway. Co-trimoxazole, however, inhibits two pathways for rosiglitazone metabolism; the trimethoprim component inhibits CYP2C8, and the sulfamethoxazole component inhibits CYP2C9. Single doses of metronidazole would be unlikely to produce hypoglycemia when combined with these antidiabetic agents.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Fluvastatin: Atorvastatin (Lipitor), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor) do not appear to inhibit CYP2C9.
• Fluoxetine / Fluvoxamine: Other SSRI antidepressants would not be expected to interact.
• Monitor: Monitor for hypoglycemic episodes during coadministration of CYP2C9 inhibitors.