OBJECT DRUGS

Beta-Blockers (CYP2D6 Substrates):

• Carvedilol (Coreg, etc.)
• Metoprolol (Lopressor, etc.)
• Nebivolol (Bystolic)
• Propranolol (Inderal, etc.)
• Timolol (Blocadren, etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Cimetidine (Tagamet, etc.)
• Cinacalcet (Sensipar)
• Diphenhydramine (Benadryl, etc.)
• Haloperidol (Haldol)
• Propafenone (Rythmol, etc.)
• Propoxyphene^*
• Quinidine (Quinidex)
• Ritonavir (Norvir)
• Terbinafine (Lamisil, etc.)
• Thioridazine (Mellaril)

^* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Inhibitors of CYP2D6 can increase the concentration of beta-blockers, potentially resulting in bradycardia, hypotension or heart failure. Rapid metabolizers of CYP2D6 (over 90% of the population) will be at the greatest risk. 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).
• Beta-blocker: Select a beta-blocker that is not a CYP2D6 substrate such as atenolol (Tenormin) or nadolol (Corgard).
• Monitor: Monitor for altered beta-blocker effect if inhibitor is initiated, discontinued, or changed in dosage.