Miglustat
Regulatory sources consulted
Approved indications
- Oral treatment of adult patients with mild to moderate type 1 Gaucher disease, only when enzyme replacement therapy is not suitable.
- Treatment of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick disease type C.
Contraindications
Absolute
- Hypersensitivity to the active substance or any excipient.
Clinical warnings
- Major warning · Diarrhoea is very common and may require temporary dose reduction; consider reducing sucrose, lactose and other carbohydrates, taking between meals, or antidiarrhoeals according to clinical assessment. — AEMPS CIMA, Miglustat Accord, ficha técnica 78987, sección 4.4
- Major warning · Monitor tremor, peripheral neuropathy and platelet count; perform baseline and periodic neurological assessment. — AEMPS CIMA, Miglustat Accord, ficha técnica 78987, sección 4.4
- Use with caution in hepatic impairment because it has not been evaluated in this population. — AEMPS CIMA, Miglustat Accord, ficha técnica 78987, sección 4.2
Drug interactions
- LowImiglucerase
Mechanism: In a small study, co-administration was associated with an approximately 22% reduction in miglustat Cmax and 14% reduction in AUC; the effect on imiglucerase pharmacokinetics was absent or limited.
Recommendation: If co-administered, monitor clinical response and do not infer additional combination efficacy from these limited data.
https://cima.aemps.es/cima/dochtml/ft/78987/FT_78987.html
Adverse events
Common (≥1%)
Diarrhoea · Flatulence · Abdominal pain · Weight loss · Tremor
Rare but serious
Peripheral neuropathy · Thrombocytopenia
Pregnancy and lactation
It should not be used during pregnancy. It is not recommended during breastfeeding. Women who may conceive should use contraception, and men should maintain it during treatment and for three months after stopping.
Recent literature (PubMed)
Pompe disease is a debilitating and life-threatening disease caused by aberrant accumulation of glycogen resulting from reduced acid alpha-glucosidase activity. The first treatment for Pompe disease, the enzyme replacement therapy, Myozyme® (recombinant human acid alpha-glucosidase, alglucosidase alfa), is a lifesaving treatment for the most severe form of the disease and provided clinically meaningful benefits to patients with milder phenotypes. Nonetheless, many patients display suboptimal responses or clinical decline following years of alglucosidase alfa treatment. The approval of avalglucosidase alfa (Nexviazyme®) and cipaglucosidase alfa (Pombiliti®) with miglustat (Opfolda®) represents a new generation of enzyme replacement therapies seeking to further improve patient outcomes beyond alglucosidase alfa. However, the emergence of a complicated new phenotype with central nervous system involvement following long-term treatment, coupled with known and anticipated unmet needs of patients receiving enzyme replacement therapy, has prompted development of innovative new treatments. This review provides an overview of the challenges of existing treatments and a summary of emerging therapies currently in preclinical or clinical development for Pompe disease and related lysosomal storage disorders. Key treatments include tissue-targeted enzyme replacement therapy, which seeks to enhance enzyme concentration in target tissues such as the central nervous system; substrate reduction therapy, which reduces intracellular glycogen concentrations via novel mechanisms; and gene therapy, which may restore endogenous production of deficient acid alpha-glucosidase. Each of these proposed treatments shows promise as a future therapeutic option to improve quality of life in Pompe disease by more efficiently treating the underlying cause of disease progression: glycogen accumulation.