|Trade names||Zavesca, Brazaves|
|Other names||OGT 918, 1,5-(butylimino)-1,5-dideoxy-D-glucitol, N-butyl-deoxynojirimycin|
|Drug class||Glucosylceramide synthase inhibitor|
|Main uses||Gaucher disease type 1 (GD1), Niemann–Pick disease type C (NPC)|
|Side effects||Weight loss, shaking, diarrhea, increased intestinal gas, abdominal pain|
|Typical dose||100 mg TID|
|Elimination half-life||6–7 hours|
|Chemical and physical data|
|Molar mass||219.281 g·mol−1|
|3D model (JSmol)|
Common side effects include weight loss, shaking, diarrhea, increased intestinal gas, and abdominal pain. Other side effects may include peripheral neuropathy and low platelets. Safety in pregnancy is unclear. It is a glucosylceramide synthase inhibitor.
Miglustat was approved for medical use Europe in 2002 and the United States in 2003. It is available as a generic medication. In the United Kingdom 4 weeks of medication costs the NHS about £3,400 as of 2021. This amount in the United States costs about 23,000 USD.
Miglustat is used to treat adults with mild to moderate type I Gaucher disease for whom enzyme replacement therapy is unsuitable.
It is typically taken at a dose of 100 mg three times per day; though 100 mg once to twice a day may be used if side effects are too great.
Miglustat is contraindicated for people with neurological conditions, kidney problems, women who are pregnant, and men and women planning to conceive a child.
Serious side effects include pain, burning, numbness or tingling in the hands, arms, legs, or feet; shaking hands that cannot be controlled; changes in vision; and easy bruising or bleeding. Common side effects include gastrointestinal effects (including diarrhea, stomach pain or bloating, gas, loss of appetite, weight loss, upset stomach, vomiting, constipation), dry mouth, muscular effects (including weakness, muscle cramps, especially in the legs, feeling of heaviness in the arms or legs, unsteadiness when walking), back pain, dizziness, nervousness, headache, memory problems, and difficult or irregular menstruation (period).
Mechanism of action
Type I Gaucher's disease is an autosomal recessive disorder; parents are generally healthy carriers with one functional and one mutated (nonfunctioning) copy of the Gaucher disease gene, GBA. People with type I Gaucher have a defect in the enzyme called glucocerebrosidase (also known as acid β-glucosidase). Glucocerebrosidase is an enzyme, and its function is to convert glucocerebroside (also known as glucosylceramide) into ceramide and glucose. When this enzyme doesn't work, glucocerebroside accumulates, which in turn causes liver and spleen enlargement, changes in the bone marrow and blood, and bone disease. It functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids.
Earlier treatments on the market (imiglucerase (approved in 1995), velaglucerase (approved in 2010), taliglucerase alfa (Elelyso) (approved in 2012)) are enzyme replacement therapy - they are functioning versions of the enzyme that doesn't work. Miglustat works differently - it prevents the formation of the substance that builds up when the enzyme doesn't work; this is called substrate reduction therapy.
Society and culture
Miglustat has been approved in the EU, Canada, and Japan for treating progressive neurological complications in people with Niemann–Pick disease, type C (NPC). Miglustat has not received approval for this indication outside of these countries and use for this disease, including the US, is off-label.
In July 2004, Actelion started a clinical trial of miglustat to treat Tay–Sachs disease, particularly late-onset Tay–Sachs with an estimated enrollment of 10 subjects; the trial ended August 2007.
In November 2007, Actelion initiated a clinical trial with miglustat in people with cystic fibrosis (CF) who have the ΔF508 in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene; the study ended in March 2008. The cystic fibrosis trial showed no effect.
- Migalastat, a drug for the treatment of Fabry disease, with a similar structure
- Miglitol, an oral antidiabetic drug with a similar structure
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- Staff, The Pharma Letter. 4 April 2012. Actelion drops setipiprant, gets miglustat approval in Japan
- Kevin Grogan for PharmaTimes. 10 March 2010. FDA rejects Actelion's Zavesca for rare NP-C disease Archived 2014-09-03 at the Wayback Machine
- Actelion Press Release. 23 March 2010 Zavesca (Miglustat) First Treatment Available in Canada for Rare Progressive Niemann-Pick Type C Disease
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- Clinicaltrials.gov Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses Accessed 1 September 2014
- Clinicaltrials.gov Miglustat / OGT 918 in the Treatment of Cystic Fibrosis Accessed 1 September 2014
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