OBJECT DRUGS

Antiarrhythmics (CYP2D6 Substrates):

• Flecainide (Tambocor)
• Mexiletine (Mexitil)
• Propafenone (Rythmol, etc., etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors

• Abiraterone (Zytiga)
• Amiodarone (Cordarone, etc.)
• Cinacalcet (Sensipar)
• Clobazam (Onfi)
• Diphenhydramine (Benadryl, etc.)
• Haloperidol (Haldol)
• Mirabegron (Myrbetriq)
• Propafenone (Rythmol)
• Propoxyphene^*
• Quinidine (Quinidex)
• Ritonavir (Norvir)
• Terbinafine (Lamisil, etc.)
• Thioridazine (Mellaril)

^* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Drugs that inhibit CYP2D6 can lead to accumulation of flecainide, mexiletine, and propafenone, and increase the risk of toxicity. People with "normal" CYP2D6 activity (Extensive Metabolizers) are 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 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Diphenhydramine: Other antihistamines such as desloratadine (Clarinex), fexofenadine (Allegra), loratadine Claritin), and cetirizine (Zyrtec) are not known to inhibit CYP2D6.
• Monitor: Be alert for an increased effect of the antiarrhythmic if CYP2D6 inhibitors are coadministered. Monitoring of the antiarrhythmic plasma concentration is warranted.