Megaloblastic anemia treatment pearls

Vitamin B12 supplementation

The schedules and dosages of vitamin B12 treatment are widely variable and there is no consensus on it. The cause of megaloblastic anemia and the response to therapy should decide the dose and duration of therapy.

  • There is no weight-based dosing in children. Effective, age-appropriate doses in young children with malabsorption have not been systematically defined. 
  • Doses vary from 100 mcg to 1000 mcg per dose. The dose amount does not determine the rapidity and extent of response but may affect its total duration. 
  • Any preparation- hydroxo or cyanocobalamin or methylcobalamin can be used.

The route of administration

Parenteral and oral are generally considered to be equally efficacious (except faster recovery with parenteral in neurological manifestations). Intramuscular route should be avoided when platelet count < 50,000. Oral should be avoided if features of malabsorption or intrinsic factor deficiency are present.

However, a recently published randomized trial from Gujarat showed parenteral route to be better than oral. (Reference: Tandon R etal. Indian Pediatrics; May 31 2022-CLICK FOR PDF).

IAP 2022 guidelines for B12

  • 500–1,000 μg/day orally daily for 4–6 weeks, then once a week (or)
  • 1,000 μg/day intramuscular/intravenous for 2 weeks or thrice weekly for 2 weeks followed by weekly for another six doses till hematocrit returns to normal. 


  • Parenteral administration of 250-1,000 μg vitamin B 12, daily or alternate days in first week, followed by weekly for the first 1-2 mo and then monthly thereafter. Children having only hematologic presentation recover within 2-3 mo, whereas those with neurologic disease need at least 6 mo of therapy

Nathan and Oski

  • 1000 μg of CNCbl or OHCbl by injection daily for 1 week, followed by 100 μg of CNCbl weekly for 1 month and then monthly thereafter

Author’s Approach for B12: 

In severe symptomatic deficiency- use any easily available injectable (iv/im) formulation to start with for 1 to 2 weeks (daily or alternate day) followed by weekly for 3 to 4 weeks and then switch to monthly.  In mild deficiency, give 500 to 1500 mcg daily oral for 2 -3 months. CBC, retic count, LDH after 1 week and then CBC monthly to see the response. 

Folic acid supplementation
  • Similar to Vitamin B12, no consensus on one regimen. Recommended doses generally vary from 0.1 mg to 2 mg oral /day for 2 to 4 weeks. 

IAP guidelines 2022 for Folic Acid: 

<6 months of age—50 μg/day
7 months to 13 years—1 mg/day for 2–3 weeks, then 0.1–0.5 mg/day ; >13 years—1 mg/day for 2–3 weeks, then 0.5 mg/day 

Author’s  approach for Folic Acid:  

2.5 mg to 5 mg/day for 1 month (because of ease of availability of 5 mg tablets).

Megaloblastic AnemiaMonitoring of response:

  • Symptomatic response is usually seen within 48–72 hours. 
  • Brisk reticulocytosis within 2–3 days, peaking at 5–8 days—degree of response is inversely proportional to degree of anemia. 
  • Serum LDH, homocysteine, and methylmalonic acid (MMA) normalize within a week. 
  • Bone marrow ineffective erythropoiesis is reversed within 72 hours. 
  • Hemoglobin levels normalize within 4–8 weeks

Practice Points

  • Don’t miss aplastic anemia or acute leukemia because the clinical presentation can be similar to severe megaloblastic anemia with fever/bleeding/pancytopenia.
  • Upfront folate supplementation may worsen neurological symptoms. So it should start after Vitamin B12 has been supplemented for some time. 
  • Hypokalemia and iron deficiency can happen during treatment of megaloblastic anemia.
  • Anaphylactic reaction after im/iv injection is an uncommon and potentially serious side effect. However, routine pre-medication is not done. Anaphylaxis happens due to benzyl alcohol as preservative, or due to antigens/impurities during manufacturing, or due to cobalamin itself acting as an antigen (? Due to cobalt in it).

Effect of long-term use

Cobalamin is considered nontoxic, but the long-term effects of daily oral doses of 1000 μg are unknown, especially in children. Increased risk for some cancers, for example, has been reported in elderly persons chronically receiving high cobalamin and folic acid doses 

**Commonly used preparations of Vitamin B12

  • Inj Optineuron: 1000 mcg Cyanocobalamin
  • Inj Neurobion Forte: 1000 mcg Mecobalamin
  • Tab Meganeuron: 750 mcg Mecobalamin + 1.5 mg Folic acid
  • Tab Meganeurom OD plus: 1500 mcg Mecobalamin + 5 mg Folic acid
  • Tab Neurobion plus: 750 mcg Mecobalamin

**Disclaimer “All product and company names are trademarks™ or registered® trademarks of their respective holders. Use of them does not imply any affiliation with or endorsement by them” 

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