OBJECT DRUGS

• Carbamazepine (Tegretol, etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Amprenavir (Agenerase)
• Aprepitant (Emend)
• Atazanavir (Reyataz)
• Cimetidine (Tagamet, etc.)
• Conivaptan (Vaprisol)
• Cyclosporine (Neoral, etc.)
• Danazol (Danocrine)
• Darunavir (Prezista)
• Delavirdine (Rescriptor)
• Dronedarone (Multaq)
• Grapefruit
• Indinavir (Crixivan)
• Isoniazid (INH)
• Nelfinavir (Viracept)
• Propoxyphene^*
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)

^* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Inhibition of CYP3A4 may result in carbamazepine toxicity, usually within 2-3 days of starting the inhibitor. Adverse outcomes from these interactions are fairly predictable, and most patients who start a CYP3A4 inhibitor while on carbamazepine will develop clinical evidence of carbamazepine toxicity. The effect of danazol may be delayed by 1-2 weeks. Not all known CYP3A4 inhibitors have been studied with carbamazepine, but assume they interact until proven otherwise.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have minimal effects on drug metabolism.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Monitor: If alternatives are not appropriate, consider reducing the dose of carbamazepine. Monitor for altered carbamazepine effect if enzyme inhibitors are initiated, discontinued, or changed in dosage. Symptoms of carbamazepine toxicity include nausea, vomiting, dizziness, drowsiness, headache, diplopia, and confusion.