GALAFOLD Hard capsule Ref.[9249] Active ingredients: Migalastat

It is advised to periodically monitor renal function, echocardiographic parameters and biochemical markers (every 6 months) in patients initiated on or switched to migalastat. In case of meaningful clinical deterioration, further clinical evaluation or discontinuation of treatment with Galafold should be considered.

Galafold is not indicated for use in patients with non-amenable mutations (see section 5.1).

No reduction in proteinuria was observed in patients treated with Galafold.

Galafold is not recommended for use in patients with severe renal insufficiency, defined as estimated GFR less than 30 mL/min/1.73m² (see section 5.2).

Limited data suggest that co-administration of a single dose of migalastat and a standard enzyme replacement therapy infusion results in an increased exposure to agalsidase of up to 5-fold. This study also indicated that agalsidase has no effect on the pharmacokinetics of migalastat. Galafold is not intended for concomitant use with enzyme replacement therapy.

Paediatric population

123 mg migalastat capsules are not for children (≥ 12 years) weighing less than 45 kg, (see section 5.2).

Based upon in vitro data, migalastat is not an inducer of CYP1A2, 2B6, or 3A4. Furthermore, migalastat is not an inhibitor or a substrate of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4/5. Migalastat is not a substrate for MDR1 or BCRP, nor is it an inhibitor of BCRP, MDR1, or BSEP human efflux transporters. In addition, migalastat is not a substrate for MATE1, MATE2-K, OAT1, OAT3, or OCT2, nor is it an inhibitor of OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2-K human uptake transporters.

Effect of other drugs on migalastat

Co-administration of migalastat with caffeine decreases migalastat systemic exposure (AUC and C_max) which may reduce Galafold efficacy (see section 5.2). Avoid co-administration of Galafold with caffeine at least 2 hours before and 2 hours after taking Galafold (see section 4.2).

Women of childbearing potential/Contraception in males and females

Galafold is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are limited data from the use of Galafold in pregnant women. In rabbits, developmental toxicity was observed only at maternally toxic doses (see section 5.3). Galafold is not recommended during pregnancy.

Breast-feeding

It is not known whether Galafold is secreted in human milk. However, migalastat has been shown to be expressed in the milk of lactating rats. Accordingly, a risk of migalastat exposure to the breast-feeding infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue Galafold, taking into account the benefit of breast-feeding for the child relative to the benefit of therapy for the mother.

Fertility

The effects of Galafold on fertility in humans have not been studied. Transient and fully reversible infertility in male rats was associated with migalastat treatment at all doses assessed. Complete reversibility was seen after 4 weeks off-dose. Similar findings have been noted pre-clinically following treatment with other iminosugars (see section 5.3). Migalastat did not affect fertility in female rats.

Galafold has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most common adverse reaction was headache, which was experienced by approximately 10% of patients who received Galafold.

Tabulated list of adverse reactions

Frequencies are defined as: 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 the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing frequency within each System Organ Class.

Table 1. Adverse reactions with Galafold:

^* Reported from post-marketing data

Adolescent population

The safety assessment in 21 adolescents (12 to <18 years of age and weighing ≥45 kg) is based on 1-year safety data from the open label AT1001-020 study in which subjects received the same dosage regimen as adults (see section 5.2). No age-specific differences in adverse reactions were observed between adolescent and adult subjects. The frequency, type and severity of adverse reactions in adolescents are expected to be the same as in adults based on these data.

Reporting of suspected adverse reactions

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.