BNF for Children 2011-2012

418 8.1 Cytotoxic drugs BNFC 2011–20128 Malignant disease and immunosuppressionPregnancy manufacturer advises avoid—no informationavailableBreast-feeding manufacturer advises avoid—noinformation availableSide-effects fever; nausea, vomiting; less frequentlydiarrhoea, headache, hypersensitivity reactions(including rash, bronchospasm and anaphylaxis);haemolytic anaemia, methaemoglobinaemiaLicensed use not licensed for use in childrenIndication and doseProphylaxis and treatment of acute hyperuricaemiawith initial chemotherapy for haematologicalmalignancy. By intravenous infusionConsult local treatment protocol for detailsFasturtec c (Sanofi-Aventis) AIntravenous infusion, powder for reconstitution,rasburicase, net price 1.5-mg vial (with solvent) =£57.88; 7.5-mg vial (with solvent) = £241.20Methotrexate-induced mucositis andmyelosuppressionFolinic acid (given as calcium folinate) is used tocounteract the folate-antagonist action of methotrexateand thus speed recovery from methotrexate-inducedmucositis or myelosuppression (‘folinic acid rescue’).The calcium salt of levofolinic acid, a single isomer offolinic acid, is also used following methotrexate administration.The dose of calcium levofolinate is generallyhalf that of calcium folinate.The disodium salts of folinic acid and levofolinic acidare also used for rescue therapy following methotrexateadministration.The efficacy of high dose methotrexate is enhanced bydelaying initiation of folinic acid for at least 24 hours,local protocols define the correct time. Folinic acid isnormally continued until the plasma-methotrexate concentrationfalls to 45–90 nanograms/mL (100–200 nanomol/litre).In the treatment of methotrexate overdose, folinateshould be administered immediately; other measuresto enhance the elimination of methotrexate are alsonecessary.Indication and doseSee under preparationCalcium folinate(Calcium leucovorin)Calcium Folinate (Non-proprietary) ATablets, scored, folinic acid (as calcium salt) 15 mg,net price 10-tab pack = £39.20, 30-tab pack = £85.74Brands include Refolinon cNote Not all strengths and pack sizes are available from allmanufacturersInjection, folinic acid (as calcium salt) 3 mg/mL, netprice 1-mL amp = £4.00, 10-mL amp = £4.62; 7.5 mg/mL, net price 2-mL amp = £7.80; 10 mg/mL, net price5-mL vial = £19.41, 10-mL vial = £35.09, 30-mL vial =£94.69, 35-mL vial = £90.98Brands include Refolinon cNote Not all strengths and pack sizes are available from allmanufacturersInjection, powder for reconstitution, folinic acid (ascalcium salt), net price 15-mg vial = £4.46; 30-mg vial= £8.36DoseReduction of methotrexate-induced toxicity. By mouth, by intravenous injection or byintravenous infusionSee notes above. Consult local treatment protocol fordetailsMethotrexate overdose. By intravenous injection or by intravenous infusionSee notes above. Consult local treatment protocol fordetailsMegaloblastic anaemia due to folate deficiency. By mouthChild up to 12 years 250 microgram/kg once dailyChild 12–18 years 15 mg once dailyMetabolic disorders leading to folate deficiency. By mouth or by intravenous infusionChild up to 18 years 15 mg once daily; larger doses maybe required in older childrenFOLINIC ACIDCautions avoid simultaneous administration ofmethotrexate; not indicated for pernicious anaemia orother megaloblastic anaemias due to vitamin B 12deficiency; interactions: Appendix 1 (folates)Safe PracticeIntrathecal injection contra-indicatedPregnancy not known to be harmful; benefit outweighsriskBreast-feeding presence in milk unknown but benefitoutweighs riskSide-effects rarely pyrexia after parenteral use; gastro-intestinaldisturbances, insomnia, agitation, anddepression after high dosesLicensed use consult product literature for licensingstatus of individual preparationsPrevention of megaloblastic anaemia associated withpyrimethamine and sulfadiazine treatment of congenitaltoxoplasmosis. By mouthNeonate 5 mg 3 times a week (increased up to 20 mg 3times a week if neutropenic)Child 1 month–1 year 10 mg 3 times a weekDisodium folinateSodiofolin c (Medac) AInjection, folinic acid (as disodium salt) 50 mg/mL,net price 2-mL vial = £35.09, 8-mL vial = £126.25, 18-mL vial = £284.07DoseAntidote to methotrexate. By intravenous injection or by intravenous infusionConsult local treatment protocols for details