OBJECT DRUGS

• Eliglustat (Cerdelga)

PRECIPITANT DRUGS

Antidepressants:

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

Comment:

These antidepressants inhibit CYP2D6, and can lead to accumulation of eliglusatat, with increased risk of eliglustat toxicity. Since eliglustat is also metabolized by CYP3A4, the risk of eliglustat toxicity from concurrent CYP2D6 inhibitors is likely to be greater in patients also receiving CYP3A4 inhibitors. (See CYP Table) The eliglustat label states that concurrent use of CYP2D6 inhibitors and CYP3A4 inhibitors is contraindicated in patients taking eliglustat.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Antidepressant: 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.
• Circumvent/Minimize: In IMs or EMs, it is recommended to reduce the eliglustat dose to 84 mg once daily if CYP2D6 inhibitors such as these antidepressants are given concurrently. In PMs the use of CYP2D6 inhibitors is not likely to have much effect on CYP2D6 activity.
• Monitor: Be alert for evidence of increased eliglustat plasma concentrations if CYP2D6 inhibitors are coadministered. Monitoring the ECG for evidence of QTc prolongation may be useful.