OBJECT DRUGS

• Thioridazine (Mellaril)

PRECIPITANT DRUGS

Enzyme Inhibitors (CYP2D6):

• Abiraterone (Zytiga)
• Bupropion (Wellbutrin, etc.)
• Chloroquine
• Cimetidine (Tagamet, etc.)
• Cinacalcet (Sensipar)
• Clobazam (Onfi)
• Diphenhydramine (Benadryl, etc.)
• Duloxetine (Cymbalta)
• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)
• Mirabegron (Myrbetriq)
• Paroxetine (Paxil, etc.)
• Propoxyphene*
• Ritonavir (Norvir)
• Terbinafine (Lamisil, etc.)

* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Thioridazine can prolong the QT interval. Inhibitors of CYP2D6 may increase the risk of ventricular arrhythmias such as torsades de pointes. The product information for thioridazine states that concurrent use with known CYP2D6 inhibitors (or fluvoxamine) is contraindicated. 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: Use an alternative to the enzyme inhibitor if possible.
• Antidepressants: Citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), and desvenlafaxine (Pristiq), venlafaxine (Effexor) have less effect on CYP2D6 than fluoxetine and paroxetine, and would not be expected to have a large effect on thioridazine metabolism.
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have no known effects on CYP2D6 activity.
• Thioridazine: Most other phenothiazines produce less QT prolongation than thioridazine. Pimozide (Orap) can substantially prolong the QT interval and would not be a suitable substitute for thioridazine.
• Monitor: If combined therapy is necessary, monitor carefully for signs of delayed ventricular repolarization (prolonged QT interval) and symptoms of torsades de pointes including palpitations and syncope.