Desferrioxamine mesilate

Product: UK SPC via MHRA Products - DESFERRIOXAMINE MESILATE 500 MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION (PL245980020), Noridem Enterprises Ltd; §2: each vial contains desferrioxamine mesilate 500 mg. §4.1: chronic iron overload (transfusional haemosiderosis in patients receiving regular transfusions e.g. thalassaemia major; primary and secondary haemochromatosis in patients in whom concomitant disorders e.g. severe anaemia, hypoproteinaemia, renal or cardiac failure preclude phlebotomy), acute iron poisoning, diagnosis of iron storage disease and certain anaemias, and aluminium overload in maintenance dialysis. SPC §4.2 section 2) Chronic Iron Overload (Adults and children), verbatim: 'The main aim of therapy in well-controlled patients is to maintain an iron balance and prevent haemosiderosis, whilst in overloaded patients a negative iron balance is desirable in order to deplete the increased iron stores and to prevent the toxic effects of iron.' 'Desferrioxamine Mesilate therapy should be commenced after the first 10-20 blood transfusions, or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1000 ng/mL). The dose and mode of administration should be individually adapted according to the degree of iron overload.' 'The lowest effective dose should be used. The average daily dose will probably lie between 20 and 60 mg/kg/day. Patients with serum ferritin levels of < 2000 ng/mL should require about 25 mg/kg/day, and those with levels between 2000 and 3000 ng/mL about 35 mg/kg/day. Higher doses should only be employed if the benefit for the patient outweighs the risk of unwanted effects. Patients with higher serum ferritin may require up to 55 mg/kg/day.' CEILING (SPC wording, no single maximum is printed so maxDose is left blank): 'It is inadvisable to regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in patients who have completed growth.' 'If ferritin values fall below 1000 ng/mL, the risk of Desferrioxamine Mesilate toxicity increases; it is important to monitor these patients particularly carefully and perhaps to consider lowering the total weekly dose.' DOSE-FINDING (SPC): 24 hour urinary iron excretion should initially be monitored daily; 'Starting with a dose of 500 mg daily the dose should be raised until a plateau of iron excretion is reached.' Once the appropriate dose is established, urinary iron excretion can be assessed at intervals of a few weeks. Alternatively the mean daily dose may be adjusted on ferritin to keep the therapeutic index below 0.025 (mean daily dose in mg/kg divided by serum ferritin in micro g/L) - a tool to protect against excess chelation, not a substitute for careful clinical monitoring. METHOD (SPC): slow subcutaneous infusion using a portable pump over 8-12 hours is effective and convenient for ambulant patients; a further increase in iron excretion may be achieved by infusing the same daily dose over 24 hours; normally used with the pump 5-7 times a week; 'Desferrioxamine Mesilate is not formulated to support subcutaneous bolus injection'; intramuscular injections are given only when subcutaneous infusions are not feasible; do not give s.c. in concentrations and/or doses higher than recommended (local irritation). Prepare preferably as a 10% solution (500 mg vial in 5 mL water for injection); further dilution with Sodium Chloride 0.9%, Dextrose 5%, Sodium Chloride 0.9% with Dextrose 5%, or Ringer's Lactate, which must not be used as the solvent for the dry substance; only clear pale yellow solutions; heparin is incompatible. Elderly (SPC): clinical studies did not include sufficient numbers aged 65 and over; dose selection should be cautious, usually starting at the low end of the dosing range. NOT COVERED: intramuscular and intravenous regimens for chronic overload, aluminium-overload dosing and diagnostic dosing - the retrieved §4.2 ends mid-sentence in the Elderly paragraph ('...other medicinal product therapy' (see sections') and nothing after it was retrieved. SECONDARY INDICATION ON THIS PAGE - ACUTE IRON POISONING (NOT the dose above; §4.2 section 1, 'Adults and children'): 'The continuous intravenous administration of Desferrioxamine Mesilate is the preferred route and the recommended rate for infusion is 15 mg/kg per hour and should be reduced as soon as the situation permits, usually after 4 to 6 hours so that the total intravenous dose does not exceed a recommended 80 mg/kg in any 24 hour period. However, if the option to infuse intravenously is not available and if the intramuscular route is used the normal dosage is 2 g for an adult and 1g for a child, administered as a single intramuscular dose.' It is an adjunct to standard measures and treatment should start as soon as possible; the decision to stop is clinical (SPC suggested criteria: free of signs and symptoms of systemic iron poisoning; corrected serum iron normal or low, below 100 micro g/dL; abdominal radio-opacities resolved; vin-rose urine returned to normal). §4.8 is cut off at source after the injection-site reactions.

THESE ARE THE LABEL'S OWN FIGURES (SPC §4.2 section 2, 'Adults and children'): 'Growth retardation may result from iron overload or excessive Desferrioxamine Mesilate doses. If chelation is started before 3 years of age growth must be monitored carefully and the mean daily dose should not exceed 40mg/kg.' §4.4: growth retardation is associated with inappropriately high doses in patients with low ferritin or young children (<3 years at start); 'Growth retardation from desferrioxamine use is rare if the dose is kept below 40 mg/kg'; if growth retardation has been associated with higher doses, dose reduction may restore growth velocity but predicted adult height is not attained; three-monthly checks on body weight and height are recommended in children. §4.8: growth retardation and bone disorder are common in chelated patients given 60 mg/kg, especially if started in the first three years of life; risk considerably reduced if doses are kept to 40 mg/kg or below. The SPC gives no age bands and no neonate-specific regimen - do not extend to neonates; verify against a children's formulary. ACUTE IRON POISONING in children (not the dose above): same continuous IV regimen, 15 mg/kg per hour reduced after about 4 to 6 hours so the total IV dose does not exceed 80 mg/kg in any 24 hour period; if IV infusion is not available the normal intramuscular dosage for a child is 1 g as a single intramuscular dose.