Galafold · 4.1 Therapeutic indications · 1

HOS-097565 · has-adverse-reaction-information · PDF-Seite 5

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 System organ class Frequency Adverse reaction (preferred term) Psychiatric disorders Common Depression Nervous system disorders Very common Headache Common Paraesthesia, dizziness, hypoaesthesia Ear and labyrinth disorders Common Vertigo Cardiac disorders Common Palpitations Respiratory, thoracic, and Common Dyspnoea, epistaxis mediastinal disorders Gastrointestinal disorders Common Diarrhoea, nausea, abdominal pain, constipation, dry mouth, defaecation urgency, dyspepsia Skin and subcutaneous tissue Common Rash, pruritus disorders Uncommon Angioedema* Musculoskeletal and connective Common Muscle spasms, myalgia, torticollis, tissue disorders Pain in extremity Renal and urinary disorders Common Proteinuria General disorders and Common Fatigue, pain administration site conditions Investigations Common Blood creatine phosphokinase increased, weight increased * 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 ad

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097561 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-097560 · has-indication-information · PDF-Seite 2

Galafold is indicated for long-term treatment of adults and adolescents aged 12 years and older with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) and who have an amenable mutation (see the tables in section 5.1).

HOS-097563 · has-interaction-information · PDF-Seite 4

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 Cmax) 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).

HOS-097564 · has-pregnancy-information · PDF-Seite 4

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.

HOS-097562 · has-warning-information · PDF-Seite 3

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. 3 VV-LAB-003881 - V1.0 Paediatric population 123 mg migalastat capsules are not for children (≥ 12 years) weighing less than 45 kg, (see section 5.2).