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Replagal (agalsidase alfa) Prescribing Information: Please consult the Summary of Product Characteristics (SmPC) before prescribing. Presentation: Concentrate solution for IV infusion. 1ml of concentrate for solution for infusion contains 1mg of agalsidase alfa. Indication: Long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (agalactosidase A deficiency) Dosage and administration: Replagal 0.2mg/kg body weight by IV infusion over 40 min every other week. No dosage regimen in children (0-6 years) can presently be recommended as safety and efficacy have not yet been sufficiently established. Because no unexpected safety issues were encountered in the 6 month study with Replagal administered at 0.2mg/kg, this dose regimen is suggested for children between 7–18 years of age. Contraindications: Hypersensitivity to the active substance or any of the excipients. Warnings and precautions: 13.7% of adult patients receiving Replagal in clinical trials had idiosyncratic infusion-related reactions (generally within 2–4 months of starting treatment although later onset [after 1 year] has been reported as well). Four of 17 paediatric patients >7 years of age and 3 of 8 paediatric patients <7 years experienced at least one infusion reaction over a period of approx. 4 years of treatment. These effects have decreased with time. If mild or moderate acute infusion reactions occur, seek medical attention immediately. The infusion can be temporarily interrupted (for 5–10 minutes) until symptoms subside. If severe allergic or anaphylactic-type reactions occur, discontinue Replagal immediately and initiate appropriate treatment. A review of cardiac events showed that infusion reactions may be associated with hemodynamic stress triggering cardiac events in patients with pre-existing cardiac manifestations of Fabry disease. Patients may develop IgG antibodies to the protein. A low titre antibody response was seen in approximately 24% of male patients; the remaining 76% remained antibody negative throughout. In paediatric patients >7 yrs of age, 1/16 male patients tested positive for IgG anti-agalsidase alfa antibodies. No increase in the incidence of adverse events was apparent for this patient. In paediatric patients <7 yrs of age, 0/7 male patients tested positive for IgG anti-agalsidase alfa antibodies. No IgE antibodies have been detected in any patient receiving Replagal. Extensive renal damage may limit the renal response to enzyme replacement therapy. Do not give Replagal together with chloroquine, amiodarone, benoquin or gentamicin because these substances can inhibit intracellular a-galactosidase activity. Caution should be exercised in pregnant or breast-feeding women. Side effects: Most reported adverse effects have been mild to moderate. Very common (>1/10 patients): headache, flushes, nausea, rigors, pyrexia, pain/discomfort, fatigue; common (>1/100, <1/10 patients): peripheral oedema, dizziness, dysgeusia, neuropathic pain, tremor, hypersomnia, hypoesthesia, paraesthesia, increased lacrimation, tinnitus, tinnitus aggravated, tachycardia, palpitations, hypertension, cough, hoarseness, throat tightness, dyspnoea, nasopharyngitis, pharyngitis, increased throat secretion, rhinorrhoea, diarrhoea, vomiting, abdominal pain/discomfort, acne, erythema, pruritus, rash, livedo reticularis, musculoskeletal discomfort, myalgia, back pain, limb pain, peripheral swelling, arthralgia, joint swelling, aggravated fatigue, feeling hot, feeling cold, asthenia, chest pain, chest tightness, influenza-like illness, injection-site rash, malaise, decreased corneal reflex; uncommon (>1/1000, <1/100 patients): parosmia, angioneurotic oedema, urticaria, sensation of heaviness, decreased oxygen saturation. Not known (since derived from post-marketing spontaneous reports): cardiac arrhythmias (atrial fibrillation, ventricular extrasystoles, tachyarrhythmia), myocardial ischaemia, heart failure, hypotension, hyperhidrosis. Infusion related reactions reported in the post marketing setting may also 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. Infusion-related symptoms may include dizziness, hyperhidrosis, and hypotension. The most frequent were mild infusion-related reactions that mainly included rigors, pyrexia, flushing, headache, nausea, and dyspnoea. Package quantity and price: Vials of 5ml (containing 3.5ml concentrate) in a pack size of 1 vial. Price: £1049.94 for one 5ml vial. Pharmaceutical precautions: Store in a refrigerator (2°C–8°C). Marketing authorisation number and holder: EU/1/01/189/001-006. Shire Human Genetic Therapies AB, Svärdvägen 11D, 182 33 Danderyd, Sweden. Legal category: POM. Further information is available in the Summary of Product Characteristics (SmPC), or on request from the marketing authorisation holder. Date of preparation: 30th March 2012 Item code: UK/HG/REP/12/0015 Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Shire Human Genetic Therapies on +44 (0)1256 894000 or faxed on +44 (0)1256 894715 or emailed to [email protected]