OBJECT DRUGS
PRECIPITANT DRUGS
Calcium Channel Blockers:
- Diltiazem (Cardizem, etc.)
- Verapamil (Isoptin, etc.)
Comment:
Eliglustat is a CYP3A4 substrate, and CYP3A4 inhibitors such as diltiazem or verapamil may increase the risk of 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: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit the metabolism of eliglustat, and are also less likely to increase the risk of eliglustat-induced bradycardia. The product information for eliglustat states that concurrent use of diltiazem and verapamil should be avoided.
- Circumvent/Minimize: In IMs or PMs, "moderate" CYP3A4 inhibitors such as diltiazem or verapamil are not recommended. 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 CYP2D6 inhibitors are coadministered. Monitoring the ECG for evidence of QTc prolongation may be useful.