Drug Interaction:
Imiglucerase-
coadminstration of miglustat appeared to increase the clearance of imigluerase . Results are not
conclusive. Combination therapy with Imiglucerease and miglustat is not indicated
Indication:
Gaucher Disease
Gaucher disease is a glucosylceramide lipidosis caused by deficiency of glucosylceramidase.
An infantile form is characterised by early onset , marked hepatomegaly , and severe neurological
progression to early death.
A juvenile form with milder neurological involvement exists.
Adverse Reaction:
CNS- headache 21% leg cramps 4% parathesia 6% tremor 10%
GI- abdominal pain 17% anorexia 7% diarrhea 85% dyspepsia 6%
flatulence 28% nausea 14% vomiting 4%
Hematologic - thromboctopenia 7%
Metabolic/nutritional - weight decrease 39%
Contra-Indications:
If this drug is administred to a woman with reproductive potential, the patient should be apparaised
of the potential hazard to the fetus.
Special Precautions-
Peripheral neuropathy- patients who develop symptoms such as numbness and tingling should
have a careful re-assesment of the risk /benefit of miglustat therapy and cessation of treatment
considered.
Administration- therapy should be directed by physicians knowledgeable in the management of
patients with Gaucher disease.
Tremor- tremor usually began within the first month of therapy and in many cases resolved between
1 to 3 months during treatment. Dose reduction may ameliorate the tremor ( usualy within 3 days)
but discontinuation with treatment may sometimes be required
Diarrhea and weight loss- patients may be instructerd to avoid high carbohydrate content foods
during treatment with migulustat if they present with diarrhea. The incident of weight loss was evident
in the first 12 months of treatment.
Male fertility- It is adviced that before seeking to conceive ,male patients should cease migulustat
and maintain reliable contraceptive methods for 3 months thereafter.
Renal failure imparment- elderly patients are more likely to have decreased renal function, care
should be taken in dose selection and it may be useful to monitor renal function.
Pregnancy- miglustat should not be used during pregnancy
Lactation- a decision should be taken whether to continue nursing or discontinue the drug , taking
into account the importance of drug to the lactating woman.
Children- the effects of miglustat on growth and development in children have not been evaluated
Dosages/ Overdosage Etc:
Indication-
Gaucher Disease
Dosage-
One 100mg capsule administered orally 3 times a day and at regular intervals
It may necessary to reduce the dose to 1 capsule once ot twice daily in some patients if adverse
effects such as tremor or diarrhea occur.
Patient Information:
1. Patients should be informed of the potential and benefits of miglustat and of altrenative
modes of therapy
2. Patients should be advised that diarrhea, GI complaints, and weight loss are common side
effects of miglustat therapy and to adhere to dietary instructions
3. Patients should be adviced to promptly report any numbness, pain, or burning in the
hands and feet, and the development of tremor or worsening in an existing tremor
Pharmacology/ Pharmacokinetics:
Pharmacolgy-
Gaucher Disease- patients with mild to moderate type I Gaucher disease for whom enzyme
replacement therapy is not an therapeutic option (eg. because of constraints such as allergy,
hypersensitivity or poor venous access.)
Miglustat functions as a competitive and reversible ihibitor of the enzyme glucosylceramide
synthasase , the initial enzyme in a series of reactions which results in the synthesis of most
glycophingolipids .
The goal of treatment is to reduce the rate of glycophngolipid biosynthesis so that the amount
of glycosphingolipids substrate is reduced to a level which allows the residual activity of the
deficient glucocerebrosidase enzyme to be more effective ( substrate reduction therapy).
Pregnancy and lactation:
Pregnancy-
Miglustat should not be used during pregnancy
Lactation-
A decision should be taken whether to continue nursing or discontinue the drug , taking
into account the importance of drug to the lactating woman.
Children-
The effects of miglustat on growth and development in children have not been evaluated
Manufacturer Details