OBJECT DRUGS

• Eliglustat (Cerdelga)

PRECIPITANT DRUGS

Antimicrobials:

• Ciprofloxacin (Cipro, etc.)
• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Quinupristin (Synercid)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

Eliglustat is metabolized by CYP3A4, and antimicrobials that are CYP3A4 inhibitors may increase the risk of eliglustat toxicity. Since eliglustat is also a CYP2D6 substrate, the effect of CYP3A4 inhibitors is likely to be greater in patients who also receiving CYP2D6 inhibitors, or who have genotypes leading to reduced CYP2D6 activity. Testing for CYP2D6 genotype is required prior to eliglustat treatment, and the management recommendations are different depending on whether the patient is an extensive metabolizer (EM), intermediate metabolizer (IM) or poor metabolizer (PM). See below. Also, the eliglustat label (2014) 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:
• Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4, but it is a CYP2D6 inhibitor and would be expected to increase eliglustat concentrations.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4. (*not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
• Circumvent/Minimize: In IMs or PMs, "moderate" CYP3A4 inhibitors are not recommended, and "stong" CYP3A4 inhibitors are contraindicatd. All of the antimicrobials listed above are either strong or moderate, and given that there is often overlap between strong and moderate, it would be best to avoid all of these antimicrobials if possible. In EMs it is recommended to reduce the eliglustat dose to 84 mg once daily if strong or moderate CYP3A4 inhibitors are given concurrently.
• Monitor: Be alert for evidence of increased eliglustat plasma concentrations if CYP3A4 inhibitors are coadministered. Monitoring the ECG for evidence of QTc prolongation may be useful.