OBJECT DRUGS
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* Propoxyphene (Darvon) was withdrawn from the US market.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:
Tamoxifen is a prodrug that is converted to active metabolites by CYP2D6. Studies in patients with breast cancer have shown that patients on potent CYP2D6 inhibitors have reduced concentrations of active tamoxifen metabolites, and reduced survival. People with "normal" CYP2D6 activity ("Rapid Metabolizers") will be at the greatest risk from these interactions. 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.