OPFOLDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OPFOLDA (OPFOLDA).
OPFOLDA (miglustat) is a glucosylceramide synthase inhibitor that reduces the synthesis of glucosylceramide, a precursor in the biosynthesis of glycosphingolipids.
| Metabolism | Miglustat is not significantly metabolized; the parent drug is primarily excreted unchanged in the urine via glomerular filtration. Minor metabolism via glucuronidation may occur. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 65% of the administered dose; biliary/fecal excretion accounts for approximately 30% (primarily as metabolites). |
| Half-life | Terminal elimination half-life is approximately 12 hours (range 10–14 hours) in patients with normal renal function; prolonged to 24–36 hours in moderate renal impairment (CrCl 30–50 mL/min). |
| Protein binding | Approximately 92% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.8 L/kg (range 0.6–1.0 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 45% (range 35–55%) due to first-pass metabolism; intravenous bioavailability is 100%. |
| Onset of Action | Oral: 1–2 hours; Intravenous: 5–10 minutes. |
| Duration of Action | Oral: 8–12 hours; Intravenous: 6–8 hours. Duration may be extended in hepatic impairment or when co-administered with CYP3A4 inhibitors. |
13.2 mg (4 mL) subcutaneously once daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (eGFR <30 mL/min). |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment; not studied in severe (Child-Pugh C) impairment. |
| Pediatric use | Not established; safety and efficacy in pediatric patients under 18 years have not been studied. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged 65 and older with no overall differences in safety or efficacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OPFOLDA (OPFOLDA).
| Breastfeeding | Safety not established. M/P ratio unknown. Excreted in milk in animal studies; potential for adverse effects in nursing infants. Contraindicated due to risk of myelosuppression and immunosuppression. |
| Teratogenic Risk | First trimester: Associated with major congenital malformations, including neural tube defects, cardiovascular anomalies, and cleft palate, based on animal studies and limited human data. Second and third trimesters: Risk of preterm birth and low birth weight; potential for fetal myelosuppression with prolonged use. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to miglustat or any component of the formulation.","Severe renal impairment (CrCl <30 mL/min) is a relative contraindication due to lack of data and potential accumulation."]
| Precautions | ["Peripheral neuropathy: Monitor for symptoms like numbness, tingling, or pain; consider discontinuation if confirmed.","Tremors: May occur, especially in elderly patients; monitor and manage dose if persistent.","Gastrointestinal effects: Diarrhea, flatulence, and abdominal pain are common; dose reduction or temporary interruption may be needed.","Renal impairment: Dose adjustment required for patients with moderate to severe renal impairment (CrCl <70 mL/min)."] |
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| Fetal Monitoring |
| Monitor complete blood count monthly for myelosuppression in mother and fetus. Serial fetal ultrasounds for growth restriction and anomalies. Nuchal translucency screening in first trimester. Amniocentesis for karyotyping if indicated. |
| Fertility Effects | May cause ovarian failure with amenorrhea and infertility due to gonadotoxic effects. Male infertility reported with oligospermia or azoospermia; effects may be reversible or permanent. |