BNF for Children 2011-2012

432 8.2.1 Antiproliferative immunosuppressants BNFC 2011–20128 Malignant disease and immunosuppressionbone marrow suppression e.g. inexplicable bruising orbleeding, infectionContra-indications hypersensitivity to mercaptopurineHepatic impairment reduce dose; monitor liver function;see also CautionsRenal impairment reduce dose; see also CautionsPregnancy see section 8.2; treatment should not normallybe initiated during pregnancyBreast-feeding present in milk in low concentration;no evidence of harm in small studies—use if potentialbenefit outweighs riskSide-effects hypersensitivity reactions (includingmalaise, dizziness, vomiting, diarrhoea, fever, rigors,myalgia, arthralgia, rash, hypotension and interstitialnephritis—calling for immediate withdrawal); doserelatedbone marrow suppression (see also Cautions);liver impairment, cholestatic jaundice, hair loss andincreased susceptibility to infections and colitis inpatients also receiving corticosteroids; nausea; rarelypancreatitis, pneumonitis, hepatic veno-occlusivedisease, lymphomaIndication and doseSuppression of transplant rejection. By mouth, or (if oral route not possible) byintravenous infusion (see also note below)Consult local treatment protocol for detailsChild 1 month–18 years maintenance, 1–3 mg/kg once daily, adjusted according to response; totaldaily dose may alternatively be given in 2 divideddosesSevere ulcerative colitis and Crohn’s diseasesection 1.5.3Systemic lupus erythematosus, vasculitis,auto-immune conditions when corticosteroidtherapy alone has proved inadequate section10.1.3Administration Consult local treatment protocol fordetailsFor intravenous injection, reconstitute 50 mg with 5–15 mL Water for Injections; give over at least 1 minuteFor intravenous infusion, reconstitute 50 mg with 5–15 mL Water for Injections; dilute requisite dose to aconcentration of 0.25–2.5 mg/mL in Glucose 5% orSodium Chloride 0.9%Note Intravenous injection is alkaline and very irritant.Intravenous route should therefore be used only if oral routenot feasible and discontinued as soon as oral route can betolerated. To reduce irritation flush line with infusion fluidAzathioprine (Non-proprietary) ATablets, azathioprine 25 mg, net price 28-tab pack =£6.67; 50 mg, 56-tab pack = £5.56. Label: 21Brands include Azamune cImuran c (Aspen) ATablets, both f/c, azathioprine 25 mg (orange), netprice 100-tab pack = £10.99; 50 mg (yellow), 100-tabpack = £7.99. Label: 21Injection, powder for reconstitution, azathioprine (assodium salt), net price 50-mg vial = £15.38Extemporaneous formulations available seeExtemporaneous Preparations, p. 6MYCOPHENOLATE MOFETILCautions full blood counts every week for 4 weeksthen twice a month for 2 months then every month inthe first year (consider interrupting treatment if neutropeniadevelops); active gastro-intestinal disease(risk of haemorrhage, ulceration and perforation);delayed graft function; increased susceptibility to skincancer (avoid exposure to strong sunlight); possibledecreased effectiveness of vaccination—avoid livevaccines; interactions: Appendix 1 (mycophenolatemofetil)Bone marrow suppression Children and their carers shouldbe warned to report immediately any signs or symptoms ofbone marrow suppression e.g. infection or inexplicablebruising or bleedingRenal impairment manufacturer advises considerdose reduction if estimated glomerular filtration rateless than 25 mL/minute/1.73 m 2Pregnancy manufacturer advises avoid—congenitalmalformations reported; effective contraceptionrequired before treatment, during treatment, and for 6weeks after discontinuation of treatmentBreast-feeding manufacturer advises avoid—presentin milk in animal studiesSide-effects taste disturbance, gingival hyperplasia,nausea, constipation, flatulence, anorexia, weightloss, diarrhoea, vomiting, abdominal pain, gastrointestinalinflammation, ulceration, and bleeding,hepatitis, jaundice, pancreatitis, stomatitis, ileus,pleural effusion, oedema, tachycardia, hypertension,hypotension, vasodilatation, cough, dyspnoea,insomnia, agitation, confusion, depression, anxiety,convulsions, paraesthesia, myasthenic syndrome,tremor, dizziness, headache, influenza-like syndrome,infections, hyperglycaemia, renal impairment, malignancy(particularly of the skin), blood disorders(including leucopenia, anaemia, thrombocytopenia,pancytopenia, and red cell aplasia—see notes above),disturbances of electrolytes and blood lipids, arthralgia,alopecia, acne, skin hypertrophy, and rash; alsoreported intestinal villous atrophy, progressive multifocalleucoencephalopathy, interstitial lung disease,pulmonary fibrosisLicensed use not licensed for use in children under 2years for the prophylaxis of acute rejection in renaltransplantation; not licensed for use in children forthe prophylaxis of acute rejection in hepatic transplantationIndication and doseProphylaxis of acute rejection in renal transplantationin combination with a corticosteroidand ciclosporin. By mouthConsult local treatment protocol for detailsChild 1 month–18 years 600 mg/m 2 twice daily(max. 2 g daily)Prophylaxis of acute rejection in renal transplantationin combination with a corticosteroidand tacrolimus. By mouthConsult local treatment protocol for detailsChild 1 month–18 years 300 mg/m 2 twice daily(max. 2 g daily)