Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Amicus Therapeutics Europe Limited, Block 1, Blanchardstown Corporate Park, Ballycoolin Road, Blanchardstown, Dublin, D15 AKK1, Ireland e-mail: info@amicusrx.co.uk
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Contraindication to cipaglucosidase alfa.
Adverse drug reactions may occur upon the use of miglustat in combination with cipaglucosidase alfa (see section 4.8).
No interaction studies have been performed related to the use of miglustat.
Miglustat is known to have a direct effect on the enzymatic function of major disaccharidases of the intestinal epithelium. Specifically, miglustat inhibits disaccharidases with alpha-glycosidic linkages including sucrase, maltase, and isomaltase. The strength of potential interactions can immediately interfere with digestive activity of sucrose, maltose and isomaltose leading to maldigestion, osmotic influx of water, increased fermentation, and production of irritating metabolites. Patients should fast for 2 hours before and for 2 hours after taking miglustat.
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 (see section 5.3). The medicinal product is not recommended in women of childbearing potential not using reliable contraception.
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 (see section 5.3). Miglustat in combination with cipaglucosidase alfa therapy is not recommended during pregnancy.
It is not known if miglustat and cipaglucosidase alfa are secreted in human breast milk (see section 5.3). 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.
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 (see section 5.3). 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.
Miglustat has no or negligible influence on the ability to drive or to use machines.
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 Table 1. 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).
Table 1. 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.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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