OBJECT DRUGS

• Tamoxifen (Nolvadex)

PRECIPITANT DRUGS

Antidepressants:

• Bupropion (Wellbutrin, etc.)
• Duloxetine (Cymbalta)
• Fluoxetine (Prozac, etc.)
• Paroxetine (Paxil, etc.)

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. Many antidepressants have little effect on CYP2D6 (see below).

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Antidepressant: Given the severity of the potential interaction, every effort should be made to avoid the above antidepressants in patients receiving tamoxifen. Alternative antidepressants have less effect on CYP2D6: citalopram (Celexa), desvenlafaxine (Pristiq), escitalopram (Lexapro), and sertraline (Zoloft), are weak inhibitors of CYP2D6, and fluvoxamine and venlafaxine (Effexor) have little or no effect on CYP2D6.
• Monitor: If CYP2D6 inhibitors are used with tamoxifen, be alert for evidence of reduced tamoxifen effect.