OBJECT DRUGS

Antidepressants, Tricyclic:

• Amitriptyline (Elavil)
• Amoxapine (Asendin)
• Clomipramine (Anafranil)
• Desipramine (Norpramin)
• Doxepin (Sinequan, etc.)
• Imipramine (Tofranil, etc.)
• Nortriptyline (Vivactil, etc.)
• Protriptyline (Anafranil)
• Trimipramine (Surmontil)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Abiraterone (Zytiga)
• Amiodarone (Cordarone, etc.)
• Atazanavir (Reyataz)
• Cimetidine (Tagamet, etc.)
• Cinacalcet (Sensipar)
• Clobazam (Onfi)
• Conivaptan (Vaprisol)
• Diphenhydramine (Benadryl, etc.)
• Haloperidol (Haldol)
• Mirabegron (Myrbetriq)
• Propafenone (Rythmol, etc.)
• Propoxyphene*
• Quinidine (Quinidex)
• Ranolazine (Ranexa)
• Ritonavir (Norvir)
• Terbinafine (Lamisil, etc.)
• Thioridazine (Mellaril)

* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

CYP2D6 inhibitors (and to a lesser extent inhibitors of CYP1A2 and CYP3A4) can increase tricyclic antidepressant (TCA) serum concentrations possibly leading to toxicity (e.g., dry mouth, urinary retention, blurred vision, tachycardia, constipation, and postural hypotension). Both bupropion and tricyclic antidepressants can lower the seizure threshold, so theoretically the combination may increase the risk of seizures. Note that because terbinafine has an extraordinarily long terminal half-life, the inhibitory effect of terbinafine on CYP2D6 may last for many weeks after terbinafine is discontinued.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Cimetidine: Other acid suppressors are unlikely to interact. Consider using famotidine (Pepcid), nizatidine (Axid), ranitidine (Zantac), dexlansoprazole (Kapidex), esomeprazole (Nexium), omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), or pantoprazole (Protonix).
• Diphenhydramine: Nonsedating antihistamines are unlikely to inhibit CYP2D6.
• Monitor: Monitor for altered TCA response if an enzyme inhibitor is initiated, discontinued, or changed in dosage.