MIGLUSTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIGLUSTAT (MIGLUSTAT).
Miglustat is a glucosylceramide synthase inhibitor that reduces the synthesis of glucosylceramide, a precursor in the biosynthesis of glycosphingolipids. It acts as a competitive inhibitor of the enzyme glucosylceramide synthase, thereby decreasing the accumulation of glucosylceramide and other glycosphingolipids.
| Metabolism | Miglustat undergoes minimal metabolism; it is primarily excreted unchanged in the urine. A small fraction is metabolized via glucuronidation (UGT2B7) to inactive metabolites. |
| Excretion | Primarily renal excretion of unchanged drug. Following oral administration, approximately 80% of the dose is excreted unchanged in urine, with less than 5% recovered in feces. |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 5–10 hours) in patients with normal renal function; half-life is prolonged in renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 10–20% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is about 1.5 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 80–90% (based on absorption from the gastrointestinal tract). |
| Onset of Action | Clinical effect (reduction in glucosylceramide levels) is observed within 2–4 weeks of continuous oral dosing. |
| Duration of Action | Duration of action with repeated dosing is sustained as long as drug is taken regularly; after discontinuation, glucosylceramide levels begin to rise within days. |
100 mg orally three times daily, at regular intervals.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 30-70 mL/min/1.73m²: 100 mg twice daily. For GFR <30 mL/min: Not recommended. |
| Liver impairment | No formal Child-Pugh based adjustments; use with caution in severe hepatic impairment. |
| Pediatric use | For patients aged ≥12 years: Same as adult dose (100 mg three times daily). For <12 years: Not established. |
| Geriatric use | No specific dose adjustments; monitor renal function and dose accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIGLUSTAT (MIGLUSTAT).
| Breastfeeding | It is unknown if miglustat is excreted in human milk. In lactating rats, miglustat was present in milk. Due to potential for adverse effects in nursing infants, breastfeeding is not recommended while on miglustat therapy. M/P ratio: not determined in humans. |
| Teratogenic Risk | Miglustat is teratogenic in animals at doses similar to human exposure. There are no adequate human studies. In rats, embryotoxicity, reduced fetal weight, and increased incidence of skeletal variations were observed. In rabbits, increased post-implantation loss and fetal abnormalities. There is a potential risk for fetal harm; use only if benefit justifies risk and patient is counseled. First trimester: highest risk due to organogenesis. Second and third trimesters: potential for developmental toxicity. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe renal impairment (creatinine clearance <30 mL/min)"]
| Precautions | ["Peripheral neuropathy: Monitor for onset or worsening of paresthesia, weakness, or pain; perform neurological evaluation at baseline and periodically.","Tremors: Often reversible upon dose reduction or discontinuation.","Gastrointestinal disturbances: Diarrhea, flatulence, weight loss, and abdominal discomfort are common; may be managed with dietary modifications, antidiarrheals, and/or dose adjustments.","Renal impairment: Dose adjustment required for mild to moderate impairment; not recommended in severe impairment (CrCl <30 mL/min)."] |
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| Fetal Monitoring | Monitor for maternal gastrointestinal adverse effects, peripheral neuropathy, and tremor. No specific fetal monitoring established; however, consider regular ultrasound for fetal growth and development. Monitor for signs of thrombocytopenia or other hematologic effects in mother. Pre- and post-treatment neurologic exams recommended. |
| Fertility Effects | In animal studies, miglustat decreased fertility in male rats, with reduced sperm count and motility. In female rats, estrous cycle irregularities and reduced fertility at high doses. Human data limited; potential for reversible impaired fertility in both sexes. Advise patients of potential reproductive risks. |