ELIGLUSTAT TARTRATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELIGLUSTAT TARTRATE (ELIGLUSTAT TARTRATE).
Eliglustat is a glucosylceramide synthase inhibitor that reduces the biosynthesis of glucocerebroside, a glycolipid that accumulates in Gaucher disease. It acts as a substrate reduction therapy by decreasing the rate of production of glucocerebroside to a level that allows the residual enzyme activity to clear accumulated substrate.
| Metabolism | Primarily metabolized by CYP2D6, with minor contribution from CYP3A4. |
| Excretion | Renal: 41.4% (unchanged drug and metabolites); fecal: 55.4% (mostly as metabolites). Approximately 2% of the dose is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 6.1 to 8.4 hours. In patients with hepatic impairment (Child-Pugh class B or C), half-life may be prolonged (up to 14-22 hours), requiring dose adjustment. |
| Protein binding | Approximately 89% bound to plasma proteins, predominantly to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 67.5 L (0.9 L/kg for a 75 kg adult), indicating extensive distribution into tissues, including lysosomes where the target enzyme glucocerebrosidase is located. |
| Bioavailability | Oral bioavailability is approximately 70% (range 60-80%) under fasting conditions. Food decreases the rate but not the extent of absorption; however, it may reduce peak plasma concentrations. |
| Onset of Action | Oral: Onset of clinical effect (reduction in glucosylceramide levels) occurs within 2-4 weeks of starting therapy, with maximal substrate reduction achieved by 6-12 months. |
| Duration of Action | Duration of action is 12 hours, supporting twice-daily dosing. Continuous therapy is required to maintain substrate reduction; discontinuation leads to gradual return of glucosylceramide to pretreatment levels over several weeks to months. |
100 mg orally three times daily, at regular intervals (every 8 hours).
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (GFR <30 mL/min) or end-stage renal disease. |
| Liver impairment | Child-Pugh A (mild): No adjustment. Child-Pugh B (moderate): 100 mg twice daily. Child-Pugh C (severe): Not recommended. |
| Pediatric use | Pediatric use not established; safety and efficacy in patients under 18 years have not been studied. |
| Geriatric use | No specific dose adjustment recommended based on age; clinical studies did not include sufficient numbers to determine differences in response. Use with caution due to potential comorbidities and concurrent medications. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELIGLUSTAT TARTRATE (ELIGLUSTAT TARTRATE).
| Breastfeeding | Unknown whether eliglustat is excreted in human milk. No M/P ratio available. Because many drugs are excreted in human milk and the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, eliglustat tartrate was associated with fetal developmental toxicity at doses similar to human exposures. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit justifies potential risk to fetus. First trimester: Theoretical risk of teratogenicity based on mechanism of action (sphingolipid metabolism disruption). Second and third trimesters: Potential for fetal harm; avoid unless clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["CYP2D6 ultra-rapid metabolizers (due to insufficient efficacy).","Concomitant use with strong CYP2D6 inhibitors in CYP2D6 poor metabolizers (risk of increased exposure).","Concomitant use with strong CYP3A4 inhibitors in CYP2D6 intermediate metabolizers and poor metabolizers.","Moderate to severe hepatic impairment (Child-Pugh class B or C).","Pre-existing cardiac disease including prolonged QTc interval, myocardial infarction, heart failure, or arrhythmias."]
| Precautions | ["Cardiac effects: Avoid use in patients with pre-existing cardiac disease (e.g., myocardial infarction, angina, heart failure, arrhythmias, QT prolongation).","ECG monitoring required before and during treatment.","Drug interactions: Use with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) or strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may increase drug exposure and risk of adverse effects.","Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment."] |
| Food/Dietary | Administer with food to enhance bioavailability. Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition. No other significant food interactions reported. |
Loading safety data…
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST, bilirubin) every 3 months during pregnancy. Perform fetal ultrasound for skeletal anomalies and growth restriction if used in second/third trimester. Monitor for maternal ECG abnormalities (QT prolongation risk); baseline and periodic ECGs recommended, especially during dose titration or if interacting drugs are used. |
| Fertility Effects | In animal studies, no impairment of fertility or reproductive performance in male or female rats at exposures up to 11 times the human AUC at maximum recommended dose. No human data on fertility effects. |
| Clinical Pearls | Eliglustat tartrate is a glucosylceramide synthase inhibitor used for Gaucher disease type 1. CYP2D6 poor metabolizers require dose reduction; genotyping recommended before starting. Monitor for bradycardia, QTc prolongation, and conduction abnormalities. Avoid concurrent use with strong or moderate CYP2D6 inhibitors in extensive metabolizers due to increased exposure. |
| Patient Advice | Take with food to improve absorption and reduce gastrointestinal side effects. · Do not change your dose or stop taking without consulting your doctor. · Report symptoms such as dizziness, fainting, palpitations, or slow heart rate. · Inform your healthcare provider about all medications you are taking, especially those affecting heart rhythm. · Avoid grapefruit and grapefruit juice during treatment. · If you miss a dose, skip it and take the next dose at the scheduled time; do not double the dose. |