OBJECT DRUGS
Antidiabetic Agents (CYP3A4 Substrates):
- Nateglinide (Starlix)
- Pioglitazone (Actos)
- Repaglinide (Prandin)
- Saxagliptin (Onglyza)
- Sitagliptin (Janumet)
PRECIPITANT DRUGS
Enzyme Inhibitors:
- Amiodarone (Cordarone, etc.)
- Amprenavir (Agenerase)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Boceprevir (Victrelis)
- Ceritinib (Zykadia)
- Cobicistat (Stribild)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Darunavir (Prezista)
- Delavirdine (Rescriptor)
- Fluvoxamine (Luvox, etc.)
- Grapefruit
- Imatinib (Gleevec)
- Indinavir (Crixivan)
- Lapatinib (Tykerb)
- Lomitapide (Juxtapid)
- Mifepristone (Korlym)
- Nefazodone
- Nelfinavir (Viracept)
- Ritonavir (Norvir)
- Saquinavir (Invirase)
- Telaprevir (Incivek)
Comment:
Although data are limited, any CYP3A4 inhibitor 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:
- Antidepressants: ertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), desvenlafaxine (Pristiq), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4 than fluvoxamine. Fluoxetine (Prozac) appears to be a weak inhibitor of CYP3A4.
- Grapefruit: Orange juice does not appear to inhibit CYP3A4.
- Circumvent/Minimize: In one study, giving repaglinide either 1 hour before or 3 hours after cyclosporine minimized the increase in repaglinide concentrations. It is not known if separating doses would circumvent the interactions of other combinations listed above.
- Monitor: Monitor for hypoglycemic episodes during the coadministration of CYP3A4 inhibitors.