Miglustat Brand Name– Zavesca
What is Miglustat
Miglustat is an oral therapy used for the treatment of adults with type 1 Gaucher disease.
Miglustat is a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme responsible in the synthesis of glucosylceramide.
In type 1 Gaucher disease, a genetic disease found most commonly among Ashkenazi Jews, patients are deficient in the enzyme glucocerebrosidase, which is responsible for degradation of glucosylceramide.
Glucosylceramide arises mainly from the breakdown of red and white blood cells and turnover of lipids during CNS myelin sheath formation.
As evident in type 1 Gaucher disease, excess storage of glucosylceramide occurs within the macrophage lysosyme, leading to progressive organ enlargement (liver, spleen, bone marrow), thrombocytopenia, anemia, recurrent infection, and skeletal weakening (e.g., osteonecrosis, osteopenia).
Rather than replacing glucocerebrosidase, which may be done in some patients with Gaucher disease via the use of drugs like imiglucerase, miglustat acts as a substrate reducer (by inhibiting glucosylceramide synthase) and allows the available glucocerebrosidase enzyme to be more effective.
Adverse reactions such as diarrhea, weight loss, and tremor are common with miglustat therapy and may necessitate a dosage reduction in some patients.
Indications
- Gaucher disease
For the treatment of mild to moderate type 1 Gaucher disease in patients for whom enzyme replacement therapy is not an option
Side Effects
- abdominal pain
- anorexia
- back pain
- constipation
- diarrhea
- dizziness
- dyspepsia
- flatulence
- headache
- infertility
- menstrual irregularity
- migraine
- muscle cramps
- nausea
- paresthesias
- peripheral neuropathy
- spermatogenesis inhibition
- thrombocytopenia
- tremor
- visual impairment
- vomiting
- weakness
- weight loss
- xerostomia
Monitoring Parameters
- neurologic function
- platelet count
- serum creatinine
- weight
Contraindications
- breast-feeding
- children
- dehydration
- diarrhea
- electrolyte imbalance
- geriatric
- infants
- infertility
- male-mediated teratogenicity
- neonates
- peripheral neuropathy
- pregnancy
- renal disease
- renal failure
- renal impairment
- tremor
Interactions
- Imiglucerase
Imiglucerase: (Major) Combination therapy with miglustat and imiglucerase is not indicated for Gaucher disease. Miglustat may increase the clearance of imiglucerase, although the clinical significance of this interaction is not yet known.
