Miglustat
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From MedlinePlus, U.S. National Library of Medicine
Enzyme Stabilizer, Glucosylceramide Synthase Inhibitor
Dosing in kidney impairment
Recommended Dosage in Patients with Renal Impairment The recommended dosage of OPFOLDA in patients with moderate or severe renal impairment is shown in Table 1 [see Clinical Pharmacology ] . Table 1. Recommended OPFOLDA Dosage in Patients with Moderate or Severe Renal Impairment [See table below.] 130 mg For patients with mild renal impairment (creatinine clearance based on the Cockcroft-Gault equation, CLcr 60-89 mL/minute), the recommended OPFOLDA dosage is the same as for patients with normal renal function.
| ∗ Renal function classified by CLcr (creatinine clearance) based on the Cockcroft-Gault equation. | ||
| Patient Weight | Moderate Renal Impairment∗(CLcr 30-59 mL/minute) | Severe Renal Impairment∗ (CLcr 15-29 mL/minute) |
| ≥50 kg | 195 mg | 195 mg |
| ≥40 kg to <50 kg | 130 mg | 130 mg |
Preparation and administration
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Recommended Dosage and Administration OPFOLDA must be administered in combination with Pombiliti (see Figure 1 for the dosing timeline). Refer to the Pombiliti Prescribing Information for Pombiliti dosage and administration recommendations. The recommended dosage of OPFOLDA is based on actual body weight. For patients weighing: ≥50 kg, the recommended dosage is 260 mg orally every other week. ≥40 kg to <50 kg, the recommended dosage is 195 mg orally every other week.
Start OPFOLDA in combination with Pombiliti 2 weeks after the last ERT dose. Take OPFOLDA approximately 1 hour before intravenous administration of Pombiliti. Swallow the OPFOLDA capsules whole only with unsweetened beverages (e.g., water, tea or coffee with no cream, sugar, or sweeteners). Do not consume other beverages or food for at least 2 hours prior to and 2 hours after administration of OPFOLDA.
Missed Dose If the OPFOLDA dosage is missed, Pombiliti should not be administered and treatment should be rescheduled at least 24 hours after OPFOLDA was last taken. If OPFOLDA in combination with Pombiliti are both missed, re-start treatment as soon as possible. Figure 1. Dosing Timeline Figure 1
Contraindications
4 CONTRAINDICATIONS OPFOLDA in combination with Pombiliti is contraindicated in Pregnancy [see Use in Specific Populations (8.1 )] Pregnancy. ( 4, 5.1, 8.1 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Miglustat is an oral inhibitor of glucosylceramide synthase which is used in the therapy of type 1 Gaucher disease. Clinical experience with miglustat is limited, but it has not been linked to serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, OPFOLDA in combination with Pombiliti may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy. In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with miglustat in combination with cipaglucosidase alfa-atga at 3-fold and 16-fold, respectively, the MRHD of OPFOLDA and Pombiliti based on plasma AUC exposure. A No Observed Adverse Effect Level (NOAEL) was not identified for the combination.
In a pre- and post-natal development study in rats, increases in pup mortality were seen following maternal treatment with miglustat in combination with cipaglucosidase alfa-atga (400 mg/kg), or with cipaglucosidase alfa-atga (400 mg/kg) alone. The NOAEL for cipaglucosidase alfa-atga alone is 150 mg/kg (5-fold the Pombiliti MRHD margin). A NOAEL for the combination was not identified. Margins at the lowest observed adverse effect level (LOAEL), relative to exposures at the MRHD of OPFOLDA and Pombiliti were 4-fold and 20-fold, respectively, based on plasma AUC exposure ( see Data ).
There are no available human data on OPFOLDA in combination with Pombiliti use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Data Animal Data Reproductive toxicity studies of cipaglucosidase alfa-atga in rats and rabbits included pretreatment with diphenhydramine (DPH) to prevent or minimize hypersensitivity reactions. In a rabbit embryo-fetal development study, 25 mg/kg oral miglustat alone, or in combination with intravenous cipaglucosidase alfa-atga 175 mg/kg, was administered every other day to pregnant females during organogenesis (Gestation Day [GD] 7 through GD 19).
Additional experimental groups received cipaglucosidase alfa-atga (30, 70, or 175 mg/kg) with the same dosing frequency during organogenesis. Clusters of great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with the combination of miglustat and cipaglucosidase alfa-atga at 3-fold and 16-fold the MRHD of OPFOLDA and Pombiliti, respectively, based on plasma AUC exposure. A NOAEL for the combination was not identified. One fetus treated with miglustat alone (25 mg/kg) and one fetus treated with cipaglucosidase alfa-atga alone (175 mg/kg), each showed a similar cluster of these great vessel and cardiac malformations.
In a rat embryo-fetal development study, 60 mg/kg oral…
Breastfeeding (LactMed)
No published experience exists with miglustat during breastfeeding. Because of the lack of information and its side effect profile, most sources, including the manufacturer, consider breastfeeding to be contraindicated during maternal miglustat therapy.
- Alglucerase
- Imiglucerase
- Taliglucerase Alfa
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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