OBJECT DRUGS

• Tamoxifen (Nolvadex)

PRECIPITANT DRUGS

Enzyme Inhibitors (CYP2D6):

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

* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Tamoxifen is a prodrug that is converted to active metabolites by CYP2D6. Evidence from studies in patients with breast cancer have suggested that patients on potent CYP2D6 inhibitors have reduced concentrations of active tamoxifen metabolites, and reduced survival. People with "normal" CYP2D6 activity ("Rapid Metabolizers") would be at the greatest risk of these interactions. There is recent evidence suggesting that CYP2D6 activity may not be as important as earlier thought, but given the potential severity of the interaction it would be prudent to avoid CYP2D6 inhibitors in patients on tamoxifen until conclusive evidence is available. 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:
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have minimal effects on drug metabolism.
• Diphenhydramine: Other antihistamines such as desloratadine (Clarinex), fexofenadine (Allegra), loratadine Claritin), and cetirizine (Zyrtec) are not known to inhibit CYP2D6.
• Monitor: If CYP2D6 inhibitors are used with tamoxifen, be alert for evidence of reduced tamoxifen effect.