9.1.2 Drugs used in megaloblastic anaemias

Megaloblastic anaemia is usually due to vitamin B12 or folate deficiency; the specific deficiency and underlying cause must be identified. Treatment is usually only started once a firm diagnosis is made. In emergencies, where delayed treatment may be dangerous, both folate and vitamin B12 may be required initially, until assay results are known. Folate must not be used alone in undiagnosed megaloblastic anaemia due to the risk of B12 deficiency leading to peripheral neuropathy.

Vitamin B12 deficiency

ChoiceDrugDosage
First choiceHydroxocobalamin injection 1mg/1ml

Dose:
By intramuscular injection

Pernicious anaemia and other macrocytic anaemias without neurological involvement, initially 1 mg 3 times a week for 2 weeks then 1 mg every 3 months

Pernicious anaemia and other macrocytic anaemias with neurological involvement, initially 1 mg on alternate days until no further improvement, then 1 mg every 2 months. Prophylaxis of macrocytic anaemias associated with vitamin B12 deficiency, 1 mg every 2–3 months

Prescribing Notes

  • Apart from dietary deficiency, all other causes of vitamin B12 deficiency are attributable to malabsorption.
  • There is little place for the use of low-dose vitamin B12 orally (insufficient absorption).
  • There is no justification for prescribing multiple ingredient vitamin preparations containing vitamin B12 or folic acid.

Folate deficiency

ChoiceDrugDosage
1st choiceFolic acid 5mg tablets

Dose:
Folate-deficient megaloblastic anaemia, 5mg daily for 4 months (until term in pregnant women); up to 15mg daily may be required in malabsorption states

Prescribing Notes

  • Folic acid has few indications for long-term therapy since most causes of folate deficiency are self-limiting or will yield to a short course of treatment.
  • Do not use in undiagnosed megaloblastic anaemia unless vitamin B12 is administered concurrently otherwise neuropathy may be precipitated.
  • For prophylaxis in pregnancy, see Supplementations in pregnancy.
  • Where folic acid is prescribed to reduce methotrexate toxicity, the 5mg tablet should be used, not 400microgram. The usual dose is folic acid 5mg weekly, one to two days after methotrexate.