OPFOLDA

Treatment should be supervised by a physician experienced in the management of patients with Pompe disease or other inherited metabolic or neuromuscular diseases. Miglustat 65 mg hard capsules must be used in combination with cipaglucosidase alfa.

The summary of product characteristics (SmPC) for cipaglucosidase alfa should be consulted before taking miglustat. Posology The recommended dose is to be taken every other week in adults aged 18 years and older and is based on body weight: • For patients weighing ≥ 50 kg, the recommended dose is 260 mg (4 capsules of 65 mg).

• For patients weighing ≥ 40 kg to < 50 kg, the recommended dose is 195 mg (3 capsules of 65 mg). Miglustat 65 mg hard capsules should be taken orally approximately 1 hour but no more than 3 hours before the start of the cipaglucosidase alfa infusion.

Figure 1. Dose timeline Miglustat 65 mg hard capsules should be taken approximately 1 hour but no more than 3 hours before the start of the cipaglucosidase alfa infusion. Patient response to treatment should be routinely evaluated based on a comprehensive evaluation of all clinical manifestations of the disease.

In case of an insufficient response or intolerable safety risks, discontinuation of miglustat 65 mg hard capsules in combination with cipaglucosidase alfa treatment should be considered. Both medicinal products should either be continued or discontinued.

Missed dose If the miglustat dose is missed, treatment should occur as soon as possible. If it is not taken, do not start the cipaglucosidase alfa infusion. Cipaglucosidase alfa infusion can start 1 hour after miglustat is taken. Special populations Renal and hepatic impairment The safety and efficacy of miglustat in combination with cipaglucosidase alfa therapy have not been evaluated in patients with renal and/or hepatic impairment.

When administering every other week, increased plasma miglustat exposure as a result of moderate or severe renal or hepatic impairment is not expected to appreciably impact cipaglucosidase alfa exposures and is not anticipated to affect efficacy and safety of cipaglucosidase alfa in a clinically meaningful manner.

No dose adjustment is required in patients with renal or hepatic impairment. Elderly There is limited experience with the use of miglustat in combination with cipaglucosidase alfa therapy in patients above the age of 65 years old. There is no dose adjustment required in elderly patients.

3%). Tabulated list of adverse reactions 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.

0 months. Adverse reactions 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 (≥ 1/1000 to < 1/100), rare (≥ 1/10 000 to < 1/1000), very rare (< 1/10 000), and not known (cannot be estimated from available data).

Table 1:

Summary of adverse reactions of miglustat-treated patients System organ class (SOC) Frequency Adverse reaction (preferred term) Common Anaphylactic reaction7 Immune system disorders Uncommon Hypersensitivity Very common Headache Common Tremor, dysgeusia, paraesthesia Nervous system disorders Uncommon Balance disorder, migraine4 Common Tachycardia6 Common Hypotension Cardiac disorders Uncommon Pallor Common DyspnoeaRespiratory, thoracic and mediastinal disorders Uncommon Asthma Common Diarrhoea, nausea, abdominal pain1, flatulence, abdominal distension, vomiting, constipation† Gastrointestinal disorders Uncommon Abdominal discomfort†, oesophageal spasm, oral pain Common Urticaria3, rash2, pruritus, hyperhidrosisSkin and subcutaneous tissue disorder Uncommon Skin discolouration Common Muscle spasms, myalgia, arthralgia, muscular weakness Musculoskeletal and connective tissue disorders Uncommon Flank pain, muscle fatigue, musculoskeletal stiffness Common Fatigue, pyrexia, chills, peripheral swelling General disorders and administration site conditions Uncommon Asthenia, facial pain, feeling jittery†, non-cardiac chest pain System organ class (SOC) Frequency Adverse reaction (preferred term) Common Blood pressure increased5 Investigations 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.

Miglustat 65 mg hard capsules must be used in combination with cipaglucosidase alfa. Because of this, the summary of product characteristics (SmPC) for cipaglucosidase alfa should be consulted in relation to its safety profile before taking miglustat.

8).

1. • Contraindication to cipaglucosidase alfa.