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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. Where there is neurological involvement, seek urgent specialist advice from a haematologist. 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.

 For further information refer to NICE CKS Anaemia – B12 and folate deficiency

Vitamin B12 deficiency

First choiceHydroxocobalamin injection 1mg/1ml

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

  • Non diet-related vitamin B12 deficiencies are attributable to malabsorption, therefore there is little place for the use of low-dose oral vitamin B12.
  • In cases of dietary deficiency (without neurological symptoms or anaemia) an alternative option for maintenance treatment following initial correction is oral cyanocobalamin 50-150 micrograms daily (dose to be taken between meals). This may be purchased over the counter or prescribed if necessary. Reserve prescribing for medically diagnosed deficiency, including for those patients who may have a lifelong or chronic condition or have undergone surgery that results in malabsorption
  • There is no justification for prescribing multiple ingredient vitamin preparations containing vitamin B12 or folic acid.

Folate deficiency

1st choiceFolic acid 5mg tablets

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 below
  • 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.

Supplementations in Pregnancy / Pre-conception

Folic acid for prevention of neural tube defects
for all women who could become pregnant

Folic acid 400 microgram tablets

Advise to purchase OTC

Dose: Women at low risk of neural tube defects, 400micrograms daily until week 12 of pregnancy
high risk neural tube defectsFolic acid 5mg tablets

Dose: Women at high risk of neural tube defects (see prescribing notes), including those with diabetes or a BMI of 30 and above, 5mg daily until week 12 of pregnancy

Vitamin D

Vitamin D

Encourage ALL pregnant women to take 10micrograms of Vitamin D throughout pregnancy and whilst breastfeeding.

Advise to purchase OTC

See section 9.6.4

Prescribing notes

Folic acid supplements taken before and during pregnancy can reduce the occurrence of neural tube defects. The risk of a neural tube defect occurring in a child should be assessed and folic acid given as follows:

  • Women at a low risk of conceiving a child with a neural tube defect(NTD) should be advised to take folic acid as a medicinal or food supplement at a dose of 400 micrograms daily before conception and until week 12 of pregnancy. Women who have not been taking folic acid and who suspect they are pregnant should start at once and continue until week 12 of pregnancy.
  • Women at high risk* of neural tube defects who wish to become pregnant (or who are at risk of becoming pregnant) should be advised to take folic acid 5mg daily and continue until week 12 of pregnancy. Women with sickle-cell disease, thalassaemia or thalassaemia trait should take folic acid 5mg throughout pregnancy.

*High risk may include if:

    • Either partner has an NTD, they have had a previous pregnancy affected by an NTD, or they have a family history of an NTD.
    • The woman is taking anti–epileptic medication or certain anti-retroviral medication for HIV
    • The woman has diabetes mellitus, sickle cell anaemia, or thalassaemia.
    • The woman is obese (BMI of 30 and above)