OBJECT DRUGS

Antidiabetic Agents (CYP3A4 Substrates):

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

PRECIPITANT DRUGS

Calcium Channel Blockers:

• Diltiazem (Cardizem, etc.)
• Verapamil (Isoptin, etc.)

Comment:

Diltiazem and verapamil (both are CYP3A4 inhibitors) could 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:
• Calcium channel blockers: Agents other than diltiazem and verapamil are unlikely to inhibit the metabolism of these antidiabetic agents.
• Monitor: Monitor for hypoglycemic episodes during calcium channel blocker coadministration.