Chemical formula: C₁₀H₂₁NO₄ Molecular mass: 219.278 g/mol PubChem compound: 51634
Miglustat interacts in the following cases:
Pharmacokinetic data indicate increased systemic exposure to miglustat in patients with renal impairment. In patients with an adjusted creatinine clearance of 50–70 ml/min/1.73 m², administration should commence at a dose of 100 mg twice daily in patients with type 1 Gaucher disease and at a dose of 200 mg twice daily (adjusted for body surface area in patients below the age of 12) in patients with Niemann-Pick type C disease.
In patients with an adjusted creatinine clearance of 30–50 ml/min/1.73 m², administration should commence at a dose of 100 mg once daily in patients with type 1 Gaucher disease and at a dose of 100 mg twice daily (adjusted for body surface area in patients below the age of 12) in patients with Niemann-Pick type C disease.
Use in patients with severe renal impairment (creatinine clearance <30 ml/min/1.73 m²) is not recommended.
There are no adequate data from the use of miglustat in pregnant women. Studies in animals have shown reproductive toxicity, including dystocia. The potential risk for humans is unknown. Miglustat crosses the placenta and should not be used during pregnancy.
There are no clinical data from the use of miglustat in combination with cipaglucosidase alfa in pregnant women. Miglustat crosses the placenta. Animal studies with miglustat alone as well as in combination with cipaglucosidase alfa have shown reproductive toxicity. Miglustat in combination with cipaglucosidase alfa therapy is not recommended during pregnancy.
It is not known if miglustat is secreted in breast milk. Miglustat should not be taken during breast-feeding.
It is not known if miglustat and cipaglucosidase alfa are secreted in human breast milk. Available pharmacodynamic/toxicological data in animals have shown secretion/excretion of miglustat and cipaglucosidase alfa in milk. A risk to new-borns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from miglustat in combination with cipaglucosidase alfa therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Studies in the rat have shown that miglustat adversely affects sperm parameters (motility and morphology) thereby reducing fertility.
There are no clinical data on the effects of miglustat in combination with cipaglucosidase alfa therapy on fertility. Preclinical data in rats have shown that miglustat adversely affects sperm parameters (motility and morphology), thereby reducing fertility. However, no effects on sperm concentration, motility, or morphology were seen in 7 healthy adult men who received miglustat 100 mg, orally, twice daily for 6 weeks.
Contraceptive measures should be used by women of child-bearing potential. Reliable contraceptive methods should be maintained while male patients are taking miglustat and for 3 months following discontinuation.
Reliable contraceptive measures must be used by women of childbearing potential during treatment with miglustat in combination with cipaglucosidase alfa, and for 4 weeks after discontinuing treatment. The medicinal product is not recommended in women of childbearing potential not using reliable contraception.
Miglustat has negligible influence on the ability to drive and use machines. Dizziness has been reported as a common adverse reaction, and patients suffering from dizziness should not drive or use machines.
The most common adverse reactions reported in clinical studies with miglustat were diarrhoea, flatulence, abdominal pain, weight loss and tremor. The most common serious adverse reaction reported with miglustat treatment in clinical studies was peripheral neuropathy.
In 11 clinical trials in different indications 247 patients were treated with miglustat at dosages of 50-200 mg t.i.d. for an average duration of 2.1 years. Of these patients, 132 had type 1 Gaucher disease, and 40 had Niemann-Pick type C disease. Adverse reactions were generally of mild to moderate severity and occurred with similar frequency across indications and dosages tested.
Adverse reactions from clinical trials and spontaneous reporting, occurring in >1% of patients, are listed in the table below by system organ class and frequency (very common: ≥1/10, common: ≥1/100 <1/10, uncommon: ≥1/1,000 to <1/100, rare: ≥1/10,000 to <1/1,000, very rare: <1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
| Blood and lymphatic system disorders | |
| Common | Thrombocytopenia |
| Metabolism and nutrition disorders | |
| Very common | Weight loss, decreased appetite |
| Psychiatric disorders | |
| Common | Depression, insomnia, libido decreased |
| Nervous system disorders | |
| Very common | Tremor |
| Common | Peripheral neuropathy, ataxia, amnesia, paraesthesia, hypoaesthesia, headache, dizziness |
| Gastrointestinal disorders | |
| Very common | Diarrhoea, flatulence, abdominal pain |
| Nausea, vomiting, abdominal distension/discomfort, constipation, dyspepsia | |
| Musculoskeletal and connective tissue disorders | |
| Common | Muscle spasms, muscle weakness |
| General disorders and administration site reactions | |
| Common | Fatigue, asthenia, chills and malaise |
| Investigations | |
| Common | Nerve conduction studies abnormal |
Weight loss has been reported in 55% of patients. The greatest prevalence was observed between 6 and 12 months.
Miglustat has been studied in indications where certain events reported as adverse reactions, such as neurological and neuropsychological symptoms/signs, cognitive dysfunction and thrombocytopenia could also be due to the underlying conditions.
The most commonly reported adverse reaction only attributable to miglustat 65 mg was constipation (1.3%).
The assessment of adverse reactions was informed by subjects treated with miglustat in combination with cipaglucosidase alfa therapy from the pooled safety analysis across the 3 clinical trials. The total mean duration of exposure was 17.2 months.
Adverse reactions from the clinical trials are listed by MedDRA system organ class in the following table. The corresponding frequency categories are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), and not known (cannot be estimated from available data).
Summary of adverse reactions from clinical trials with miglustat-treated subjects:
| System organ class (SOC) | Frequency | Adverse reaction (preferred term) |
|---|---|---|
| Immune system disorders | Uncommon | Hypersensitivity |
| Nervous system disorders | Very common | Headache |
| Common | Tremor, dysgeusia | |
| Uncommon | Balance disorder, migraine4 | |
| Cardiac disorders | Common | Tachycardia6 |
| Vascular disorders | Uncommon | Hypotension, pallor |
| Respiratory, thoracic and mediastinal disorders | Common | Dyspnoea |
| Uncommon | Asthma | |
| Gastrointestinal disorders | Common | Diarrhoea, nausea, abdominal pain1, flatulence, abdominal distension, vomiting, constipation† |
| Uncommon | Abdominal discomfort†, oesophageal spasm, oral pain | |
| Skin and subcutaneous tissue disorder | Common | Urticaria3, rash2, pruritus, hyperhidrosis |
| Uncommon | Skin discolouration | |
| Musculoskeletal and connective tissue disorders | Common | Muscle spasms, myalgia, muscular weakness |
| Uncommon | Arthralgia, flank pain, muscle fatigue, musculoskeletal stiffness | |
| General disorders and administration site conditions | Common | Fatigue, pyrexia, chills |
| Uncommon | Asthenia, facial pain, feeling jittery†, non-cardiac chest pain, peripheral swelling | |
| Investigations | Common | Blood pressure increased5 |
| Uncommon | Lymphocyte count decreased, platelet count decreased† |
† Reported with miglustat only
1 Abdominal pain, abdominal pain upper, and abdominal pain lower are grouped under abdominal pain.
2 Rash and rash erythematous are grouped under rash.
3 Urticaria, urticaria rash, and mechanical urticaria are grouped under urticaria.
4 Migraine and migraine with aura are grouped under migraine.
5 Hypertension and blood pressure increased are grouped under blood pressure increased.
6 Tachycardia and sinus tachycardia are grouped under tachycardia.
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