Replagal

Replagal treatment should be supervised by a physician experienced in the management of patients with Fabry Disease or other inherited metabolic diseases. 2 mg/kg body weight every other week by intravenous infusion over 40 minutes.

Special populations Elderly patients Studies in patients over the age of 65 years have not been performed and no dosage regimen can presently be recommended in these patients as safety and efficacy have not yet been established. Patients with hepatic impairment No studies have been performed in patients with hepatic impairment.

Patients with renal impairment No dose adjustment is necessary in patients with renal impairment. 3 The presence of extensive renal damage (eGFR < 60ml/min) may limit the renal response to enzyme replacement therapy. Limited data are available in patients on dialysis or post-kidney transplantation, no dose adjustment is recommended.

Paediatric population The safety and efficacy of Replagal in children aged 0-6 years has not yet been established. 1 but no recommendation on posology can be made. 1). 6. Administer the infusion solution over a period of 40 minutes using an intravenous line with an integral filter.

Do not infuse Replagal concomitantly in the same intravenous line with other agents. Replagal home infusion, and administration by the patient in presence of a responsible adult or administration by the patient’s caregiver (self-administration), may be considered for patients who are tolerating their infusions well.

The decision to have a patient move to home infusion and/or self-administration should be made after evaluation and recommendation by the treating physician. Appropriate training should be given by the treating physician and/or nurse to the patient and/or caregiver prior to initiation of self-administration.

Dose and infusion rate should remain constant while at home, and not be changed without supervision of a healthcare professional. Self-administration should be closely followed by the treating physician. Any patients experiencing adverse events during the home infusion/self-administration need to immediately stop the infusion process and seek the attention of a healthcare professional.

Subsequent infusions may need to occur in a clinical setting.

7% of adult patients treated with Replagal in clinical trials. Most undesirable effects were mild to moderate in severity. Tabulated list of adverse reactions Table 1 lists adverse reactions reported for the 344 patients treated with Replagal in clinical trials, including 21 patients with history of end stage renal disease, 30 paediatric patients (≤ 18 years of age) and 98 female patients, and from post-marketing spontaneous reports.

Information is presented by system organ class and frequency (very common ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon ≥ 1/1 000 to < 1/100). The adverse reactions categorized as incidence “not known (cannot be estimated from the available data)” are derived from post-marketing spontaneous reports.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The occurrence of an event in a single patient is defined as uncommon in view of the number of patients treated. A single patient could be affected by several adverse reactions.

4. 4) may include cardiac events such as cardiac arrhythmias (atrial fibrillation, ventricular extrasystoles, tachyarrhythmia), myocardial ischemia, and heart failure in patients with Fabry disease involving the heart structures. The most common infusion related reactions were mild and include rigors, pyrexia, 7 flushing, headache, nausea, dyspnoea, tremor, and pruritus.

Infusion-related symptoms may also include dizziness, hyperhidrosis, hypotension, cough, vomiting and fatigue. Hypersensitivity, including anaphylaxis, has been reported. Paediatric population Adverse drug reactions reported in the paediatric population (children and adolescents) were, in general, similar to those reported in adults.

However, infusion related reactions (pyrexia, dyspnoea, chest pain) and pain exacerbation occurred more frequently. Other special populations Patients with renal disease Adverse drug reactions reported in patients with history of end stage renal disease were similar to those reported in the general patient population.

Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. 7% of adult patients treated with Replagal in clinical trials have experienced idiosyncratic infusion related reactions.

5 years of treatment (mean duration of approx. 4 years). 2 years. The most common symptoms have been rigors, headache, nausea, pyrexia, flushing and fatigue. Serious infusion reactions have been reported uncommonly; symptoms reported include pyrexia, rigors, tachycardia, urticaria, nausea/vomiting, angioneurotic oedema with throat tightness, stridor, and swollen tongue.

Other infusion-related symptoms may include dizziness and hyperhidrosis. A review of cardiac events 4 showed that infusion reactions may be associated with hemodynamic stress triggering cardiac events in patients with pre-existing cardiac manifestations of Fabry disease.

The onset of infusion related reactions has generally occurred within the first 2-4 months after initiation of treatment with Replagal although later onset (after 1 year) has been reported as well. These effects have decreased with time.

If mild or moderate acute infusion reactions occur, medical attention must be sought immediately, and appropriate actions instituted. The infusion can be temporarily interrupted (5 to 10 minutes) until symptoms subside and the infusion may then be restarted.

Mild and transient effects may not require medical treatment or discontinuation of the infusion. In addition, oral or intravenous pre-treatment with antihistamines and/or corticosteroids, from 1 to 24 hours prior to infusion may prevent subsequent reactions in those cases where symptomatic treatment was required.

Hypersensitivity reactions Hypersensitivity reactions have been reported. If severe hypersensitivity or anaphylactic reactions occur, the administration of Replagal should be discontinued immediately and appropriate treatment initiated.

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