BNF for Children 2011-2012

446 9.1.2 Drugs used in megaloblastic anaemias BNFC 2011–20129 Nutrition and bloodadminister both substances after the bone marrow testwhile plasma assay results are awaited. Normally, however,appropriate treatment should not be instituteduntil the results of tests are available.Vitamin B 12 is used in the treatment of megaloblastosiscaused by prolonged nitrous oxide anaesthesia, whichinactivates the vitamin, and in the rare disorders ofcongenital transcobalamin II deficiency, methylmalonicacidaemia and homocystinuria (see section9.8.1).Vitamin B 12 should be given prophylactically after totalileal resection.Apart from dietary deficiency, all other causes of vitaminB 12 deficiency are attributable to malabsorption. Thereis little place for the use of low-dose vitamin B 12 orallyand none for vitamin B 12 intrinsic factor complexesgiven by mouth. Vitamin B 12 in large oral doses [unlicensed]may be effective.Hydroxocobalamin has completely replaced cyanocobalaminas the form of vitamin B 12 of choice fortherapy; it is retained in the body longer than cyanocobalaminand thus for maintenance therapy can begiven at intervals of up to 3 months. Treatment isgenerally initiated with frequent administration of intramuscularinjections to replenish the depleted bodystores. Thereafter, maintenance treatment, which isusually for life, can be instituted. There is no evidencethat doses larger than those recommended provide anyadditional benefit in vitamin B 12neuropathy.Folic acid has few indications for long-term therapysince most causes of folate deficiency are self-limiting orwill yield to a short course of treatment. It should not beused in undiagnosed megaloblastic anaemia unless vitaminB 12is administered concurrently otherwise neuropathymay be precipitated (see above).In folate-deficient megaloblastic anaemia (e.g. becauseof poor nutrition, pregnancy, or treatment with antiepileptics),daily folic acid supplementation for 4months brings about haematological remission andreplenishes body stores; higher doses may be necessaryin malabsorption states. In pregnancy, folic acid 5 mgdaily is continued to term.For prophylaxis in chronic haemolytic states, malabsorptionor in renal dialysis, folic acid is given dailyor sometimes weekly, depending on the diet and the rateof haemolysis.Folic acid is also used for the prevention of methotrexate-inducedside-effects in juvenile idiopathic arthritis(see also section 10.1.3, p. 508), severe Crohn’sdisease (see section 1.5.3, p. 54), and severe psoriasis(see section 13.5.3, p. 572).For prophylaxis in pregnancy, see Prevention of NeuralTube Defects below.Folic acid is actively excreted in breast milk and is wellabsorbed by the infant. It is also present in cow’s milkand artificial formula feeds but is heat labile. Serum andred cell folate concentrations fall after delivery andurinary losses are high, particularly in low birth-weightneonates. Although symptomatic deficiency is rare inthe absence of malabsorption or prolonged diarrhoea, itis common for neonatal units to give supplements offolic acid to all preterm neonates from 2 weeks of ageuntil full-term corrected age is reached, particularly ifheated breast milk is used without an artificial formulafortifier.Folinic acid is also effective in the treatment of folatedeficientmegaloblastic anaemia but it is normally onlyused in association with cytotoxic drugs (see section8.1); it is given as calcium folinate.Prevention of neural tube defects Folic acid supplementstaken before and during pregnancy can reducethe occurrence of neural tube defects. The risk of aneural tube defect occurring in a child should beassessed and folic acid given as follows:Women at a low risk of conceiving a child with aneural tube defect should be advised to take folicacid as a medicinal or food supplement at a dose of400 micrograms daily before conception and untilweek 12 of pregnancy. Women who have not beentaking folic acid and who suspect they are pregnantshould start at once and continue until week 12 ofpregnancy.Couples are at a high risk of conceiving a child witha neural tube defect if either partner has a neuraltube defect (or either partner has a family history ofneural tube defects), if they have had a previouspregnancy affected by a neural tube defect, or if thewoman has coeliac disease (or other malabsorptionstate), diabetes mellitus, sickle-cell anaemia, or istaking antiepileptic medicines (see also section4.8.1).Women in the high-risk group who wish to becomepregnant (or who are at risk of becoming pregnant)should be advised to take folic acid 5 mg daily andcontinue until week 12 of pregnancy (women withsickle-cell disease should continue taking their normaldose of folic acid 5 mg daily (or increase thedose to 5 mg daily) and continue this throughoutpregnancy).There is no justification for prescribing multipleingredientvitamin preparations containing vitaminB 12or folic acid.HYDROXOCOBALAMINCautions should not be given before diagnosis fullyestablished but see also notes above; interactionsAppendix 1 (hydroxocobalamin)Breast-feeding present in milk but not known to beharmfulSide-effects nausea, headache, dizziness; fever,hypersensitivity reactions (including rash and pruritus);injection-site reactions; hypokalaemia andthrombocytosis during initial treatment; chromaturiaLicensed use licensed for use in children (age notspecified by manufacturers); not licensed for use ininborn errors of metabolismIndication and doseMacrocytic anaemia without neurologicalinvolvement. By intramuscular injectionChild 1 month–18 years initially 250 micrograms–1mg 3 times a week for 2 weeks then250 micrograms once weekly until blood countnormal, then 1 mg every 3 months