Cerestel

Cerestel Uses, Dosage, Side Effects, Food Interaction and all others data.

Cerestel, marketed by Genzyme as CERDELGA, is a glucosylceramide synthase inhibitor indicated for the long-term treatment of type 1 Gaucher disease. Patients selected for treatment with Cerestel undergo an FDA approved genotype test to establish if they are CYP2D6 EM (extensive metabolizers), IM (intermediate metabolizers), or PM (poor metabolizers), as the results of this test dictate the dosage of Cerestel recommended. There are no recommended dosing guidelines for CYP2D6 ultra-rapid or indeterminate metabolizers. Cerestel was approved for use by the FDA in August 2014.

According to pharmacokinetic and pharmacodynamic modelling, plasma concentrations of 500ng/mL of eliglustat are predicted to increase mean concentration in the PR, QRS, and QTcF intervals of 22, 7, and 13 msec, respectively. (Taken from Cerdelga prescribing information).

Trade Name Cerestel
Availability Prescription only
Generic Eliglustat
Eliglustat Other Names Eliglustat, éliglustat, Eliglustatum
Related Drugs miglustat, VPRIV, Cerezyme, Elelyso, imiglucerase, velaglucerase alfa
Type
Formula C23H36N2O4
Weight Average: 404.551
Monoisotopic: 404.267507647
Protein binding

76 to 83%.

Groups Approved
Therapeutic Class
Manufacturer
Available Country Russia
Last Updated: September 19, 2023 at 7:00 am
Cerestel
Cerestel

Uses

Cerestel is a glucosylceramide synthase used to treat type 1 Gaucher disease in patients who are CYP2D6 extensive, intermediate, or poor metabolizers, based on the FDA-approved test.

Cerestel is indicated for the long-term treatment of type 1 Gaucher disease in adult patients who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test.

Cerestel is also used to associated treatment for these conditions: Gaucher Disease, Type 1

How Cerestel works

Cerestel is a glucosylceramide synthase (IC50 = 10 ng/mL) specific inhibitor that acts as a substrate inhibitor of glucosylceramide.

Toxicity

In rats, eliglustat increased pre-implantation loss at 30 and 100 mg/kg/day. In male mature rats, eliglustat showed reversible adverse affects on sperm morphology, germ cell necrosis, and sloughed cells in the epididymis.

Food Interaction

  • Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of eliglustat, which may increase its serum concentration.
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of eliglustat and may reduce its serum concentration.
  • Take with or without food.

[Major] GENERALLY AVOID: Grapefruit juice may significantly increase the systemic exposure to eliglustat.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Because eliglustat is predicted to cause prolongation of the PR, QTc, and QRS cardiac intervals at substantially elevated plasma concentrations, consumption of grapefruit juice during treatment may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes.

MANAGEMENT: Patients treated with eliglustat should avoid consumption of grapefruit and grapefruit juice.

Volume of Distribution

835 L in CYP2D6 EMs (extensive metabolizers).

Elimination Route

In CYP2D6 EMs (extensive metabolizers), median time to reach maximum plasma concentrations (tmax) occurs at 1.5 to 2 hours following multiple doses of eliglustat 84 mg twice daily.

Half Life

6.5 hours in EM (extensive metabolizers) and 8.9 hours in PM (poor metabolizers).

Clearance

88 L/h (8.8%) in CYP2D6 EM (extensive metabolizers).

Elimination Route

Urine (41.8%) and feces (51.4%), mainly as metabolites after oral administration.

Innovators Monograph

You find simplified version here Cerestel

*** Taking medicines without doctor's advice can cause long-term problems.
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