Migalastat

Migalastat is not recommended for use in patients with severe renal insufficiency, defined as estimated GFR less than 30 mL/min/1.73m².

The effects of migalastat 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. Migalastat did not affect fertility in female rats.

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

There are limited data from the use of migalastat in pregnant women. In rabbits, developmental toxicity was observed only at maternally toxic doses. Migalastat is not recommended during pregnancy.

It is not known whether migalastat 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 migalastat, taking into account the benefit of breast-feeding for the child relative to the benefit of therapy for the mother.

Women of childbearing potential/Contraception in males and females

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

Fertility

The effects of migalastat 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. Migalastat did not affect fertility in female rats.

Migalastat 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 migalastat.

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.

Adverse reactions with migalastat:

^* 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. 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.