Drugs List

Therapeutic Indications

Uses

Treatment of neurological manifestations in Niemann-Pick type C disease
Treatment of Type 1 Gaucher disease in patients for whom ERT is unsuitable

Contraindications

Children under 4 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30ml/minute/1.73m sq

Precautions and Warnings

Children under 18 years
Elderly
Hepatic impairment
Renal impairment - creatinine clearance between 30-70ml/minute/1.73m sq

Severe Gaucher's disease: Safety & efficacy not established
Advise patient dizziness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Pre-treatment neurological examination recommended
Monitor linear growth in children
Monitor platelets
Monitor vitamin B12 levels regularly
Periodic neurological examination
Reduce dose or discontinue treatment if tremor occurs or worsens
Female: Ensure adequate contraception during treatment
Male: Use barrier contraception during and for 3 months after treatment

Enzyme replacement therapy (ERT) is the standard of care in patients who require treatment for type 1 Gaucher disease. In treatment-naive patients with type 1 Gaucher disease there is no evidence of an efficacy or safety advantage of miglustat over ERT.

There is an increased risk of peripheral neuropathy in patients with type 1 Gaucher disease.

Animal studies have shown adverse effects on spermatogenesis and reduced fertility.

Incidents of gastrointestinal events, mainly diarrhoea, have been reported in more than 80% of patients taking miglustat, and the majority of cases would be expected to resolve spontaneously. In clinical practice, diarrhoea may respond to anti-diarrhoeal medicinal products (e.g. loperamide), taking miglustat away from meals, and/or diet modification (reduction of lactose and carbohydrate intake). Temporary dose reduction may be necessary. If patients with chronic gastrointestinal symptoms do not respond to interventions, investigate with accordance to clinical practice. Miglustat has not been evaluated in patents with a history of significant gastrointestinal disease e.g. inflammatory bowel disease.

The benefit of treatment for neurological function in patients with Niemann-Pick type C disease should be evaluated on a regular basis such as every 6 months. Continuation of miglustat should be re-appraised after at least 1 year of treatment.

Mild reductions in platelet counts without association with bleeding has been observed in some patients with Niemann-Pick type C disease and type 1 Gaucher disease. In Niemann-Pick type C disease patients included in the clinical trial, 40 to 50% of patients had platelet counts below the lower limit of normal at baseline.

Pregnancy and Lactation

Pregnancy

Miglustat is contraindicated during pregnancy.

The manufacturer does not recommend using miglustat during pregnancy. Animal studies have shown reproductive toxicity, including dystocia. At the time of writing there is no adequate data available from the use of miglustat during human pregnancy. Miglustat is known to cross the placenta. Risks are unknown.

Lactation

Miglustat is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding is discontinued during treatment with miglustat. It is unknown if miglustat is excreted in human breast milk. A risk to the neonate cannot be excluded.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Amnesia
Anorexia
Asthenia
Ataxia
Chills
Cognitive impairment
Constipation
Decreased appetite
Depression
Diarrhoea
Dizziness
Dyspepsia
Fatigue
Flatulence
Headache
Hypoaesthesia
Impaired co-ordination
Insomnia
Malaise
Muscle spasm
Muscle weakness
Nausea
Paraesthesia
Peripheral neuropathy
Reduced libido
Thrombocytopenia
Tremor
Vomiting
Weight loss

Presentation

Oral formulations of miglustat.

Drugs List

Therapeutic Indications

Uses

Treatment of neurological manifestations in Niemann-Pick type C disease
Treatment of Type 1 Gaucher disease in patients for whom ERT is unsuitable

Dosage

Therapy should be directed by physicians who are knowledgeable in the management of Gaucher disease or Niemann-Pick type C disease.

A dose reduction may be necessary in some patients if miglustat is not tolerated.

Adults

Children

Patients with Renal Impairment

Contraindications

Children under 4 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30ml/minute/1.73m sq

Precautions and Warnings

Children under 18 years
Elderly
Hepatic impairment
Renal impairment - creatinine clearance between 30-70ml/minute/1.73m sq

Severe Gaucher's disease: Safety & efficacy not established
Advise patient dizziness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Pre-treatment neurological examination recommended
Monitor linear growth in children
Monitor platelets
Monitor vitamin B12 levels regularly
Periodic neurological examination
Reduce dose or discontinue treatment if tremor occurs or worsens
Female: Ensure adequate contraception during treatment
Male: Use barrier contraception during and for 3 months after treatment

Enzyme replacement therapy (ERT) is the standard of care in patients who require treatment for type 1 Gaucher disease. In treatment-naive patients with type 1 Gaucher disease there is no evidence of an efficacy or safety advantage of miglustat over ERT.

There is an increased risk of peripheral neuropathy in patients with type 1 Gaucher disease.

Animal studies have shown adverse effects on spermatogenesis and reduced fertility.

Incidents of gastrointestinal events, mainly diarrhoea, have been reported in more than 80% of patients taking miglustat, and the majority of cases would be expected to resolve spontaneously. In clinical practice, diarrhoea may respond to anti-diarrhoeal medicinal products (e.g. loperamide), taking miglustat away from meals, and/or diet modification (reduction of lactose and carbohydrate intake). Temporary dose reduction may be necessary. If patients with chronic gastrointestinal symptoms do not respond to interventions, investigate with accordance to clinical practice. Miglustat has not been evaluated in patents with a history of significant gastrointestinal disease e.g. inflammatory bowel disease.

The benefit of treatment for neurological function in patients with Niemann-Pick type C disease should be evaluated on a regular basis such as every 6 months. Continuation of miglustat should be re-appraised after at least 1 year of treatment.

Mild reductions in platelet counts without association with bleeding has been observed in some patients with Niemann-Pick type C disease and type 1 Gaucher disease. In Niemann-Pick type C disease patients included in the clinical trial, 40 to 50% of patients had platelet counts below the lower limit of normal at baseline.

Pregnancy and Lactation

Pregnancy

Miglustat is contraindicated during pregnancy.

The manufacturer does not recommend using miglustat during pregnancy. Animal studies have shown reproductive toxicity, including dystocia. At the time of writing there is no adequate data available from the use of miglustat during human pregnancy. Miglustat is known to cross the placenta. Risks are unknown.

Lactation

Miglustat is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding is discontinued during treatment with miglustat. It is unknown if miglustat is excreted in human breast milk. A risk to the neonate cannot be excluded.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Amnesia
Anorexia
Asthenia
Ataxia
Chills
Cognitive impairment
Constipation
Decreased appetite
Depression
Diarrhoea
Dizziness
Dyspepsia
Fatigue
Flatulence
Headache
Hypoaesthesia
Impaired co-ordination
Insomnia
Malaise
Muscle spasm
Muscle weakness
Nausea
Paraesthesia
Peripheral neuropathy
Reduced libido
Thrombocytopenia
Tremor
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2020

Reference Sources

Summary of Product Characteristics: Yargesa (miglustat) 100mg Hard Capsules. Piramal Critical Care Ltd. Revised January 2020.

Summary of Product Characteristics: Zavesca (miglustat) 100mg Hard Capsules. Janssen-Cilag Ltd. Revised February 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 8 September 2020