Eliglustatum
Eliglustatum Uses, Dosage, Side Effects, Food Interaction and all others data.
Eliglustatum, 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 Eliglustatum 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 Eliglustatum recommended. There are no recommended dosing guidelines for CYP2D6 ultra-rapid or indeterminate metabolizers. Eliglustatum 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 | Eliglustatum |
| 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 | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Eliglustatum 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.
Eliglustatum 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.
Eliglustatum is also used to associated treatment for these conditions: Gaucher Disease, Type 1
How Eliglustatum works
Eliglustatum 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.
Eliglustatum Drug Interaction
Major: sotalolModerate: tramadolUnknown: sulfamethoxazole / trimethoprim, ubiquinone, copper gluconate, ethanol, glycerin, heparin, arginine, levocarnitine, cysteine, lithium, bioflavonoids, vitamin a topical, bioflavonoids, valproic acid, thiamine, cyanocobalamin, pyridoxine, cholecalciferol
Eliglustatum Disease Interaction
Major: renal disease, hepatic dysfunction, preexisting heart conditions
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
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