Ifosfamide (Specialist drug)

Source: UK SPC (eMC) 4.2 for Ifosfamide Injection 1g (https://www.medicines.org.uk/emc/product/1834/smpc). VERBATIM: 'A guide to the dosage regimens used for most indications is given below: a) 8 - 12 g/m2 equally fractionated as single daily doses over 3 - 5 days every 2 - 4 weeks. b) 5 - 6 g/m2 (maximum 10 g) given as a 24 hour infusion every 3 - 4 weeks.' SPC gives two guide regimens for most indications: (a) 8-12 g/m2 equally fractionated as single daily doses over 3-5 days every 2-4 weeks; (b) 5-6 g/m2 (maximum 10 g) as a 24-hour infusion every 3-4 weeks (for this, made up in 3 x 1 litre sodium chloride 0.9%, each litre over 8 hours). Dosage must be individualised - dose, duration and interval depend on indication, the combination regimen, general health, organ function and laboratory monitoring; dose reduction or longer therapy-free intervals may be needed with other agents of similar toxicity. Frequency of dosing is determined by degree of myelosuppression and time to bone marrow recovery. Usual number of courses is 4, but up to 7 (6 by 24-hour infusion) have been given. Must be given only under the direction of a specialist oncology service, by physicians experienced with this drug, with facilities for clinical, biochemical and haematological monitoring. Mesna must be co-administered to prevent urothelial toxicity (increased mesna doses recommended in children, previously damaged urothelium, or inadequate protection with standard mesna doses when given as IV bolus). Force diuresis with adequate fluid during/immediately after administration; fluid intake at least 2 litres/24 h on the intermittent regimen; a diuretic may be needed as ifosfamide can have an antidiuretic effect. Withhold treatment if leucocytes <4,000/mm3 or platelets <100,000/mm3 until counts return to normal; no signs of urothelial toxicity or renal/hepatic impairment should be present before each course. Hepatic impairment (particularly severe) may reduce activation of ifosfamide and increase formation of a nephrotoxic metabolite - consider when selecting dose. Elderly: dose selection should be cautious. PAEDIATRIC (SPC 'Use in Paediatric Patients', by body surface area, not per kg): dosage and administration determined by tumour type and stage, general condition, previous cytotoxic therapy and concurrent chemo/radiotherapy; clinical trials have involved doses of (a) 5 g/m2 over 24 hours, (b) 9 g/m2 equally fractionated as single daily doses over 5 days, (c) 9 g/m2 as a continuous infusion over 72 hours repeated at three-weekly intervals. Verify any paediatric regimen against a children's formulary and local protocol. NOTE: the source SPC sections were truncated at the fetch limit - the full posology and safety text has not been fully captured; verify against the complete SPC.