OBJECT DRUGS

Opioid Analgesics:

• Alfentanil (Alfenta)
• Fentanyl (Sublimaze, etc.)
• Methadone (Dolophine, etc.)
• Oxycodone (Percocet, etc.)
• Sufentanil (Sufenta)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Amprenavir (Agenerase)
• Aprepitant (Emend)
• Atazanavir (Reyataz)
• Cimetidine (Tagamet, etc.)
• Conivaptan (Vaprisol)
• Cyclosporine (Neoral, etc.)
• Darunavir (Prezista)
• Delavirdine (Rescriptor)
• Diltiazem (Cardizem, etc.)
• Dronedarone (Multaq)
• Fluvoxamine (Luvox, etc.)
• Grapefruit
• Indinavir (Crixivan)
• Nefazodone
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)
• Verapamil (Isoptin, etc.)

Comment:

These enzyme inhibitors may inhibit the elimination of these opioids via CYP3A4 metabolism and possibly other pathways. Excessive opioid effects have been reported. The magnitude of the interaction may vary considerably depending on the inhibitor. Some inhibitors (e.g., cyclosporine, nefazodone) are more potent than weaker inhibitors such as cimetidine. Nonetheless, cimetidine produced a large increase in alfentanil half-life and large reduction in alfentanil clearance.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Calcium channel blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit CYP3A4.
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have minimal effects on drug metabolism. In one study, ranitidine had no effect on alfentanil pharmacokinetics.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.
• Antidepressants: Sertraline (Zoloft), citalopram (Celexa), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4 than fluvoxamine, and much less likely than nefazodone. Fluoxetine (Prozac) appears to be a weak inhibitor of CYP3A4.
• Monitor: Monitor for evidence of excessive and/or prolonged opioid effects, including sedation and respiratory depression.