Cyanocobalamin

Cyanocobalamin is the synthetic, stable form of vitamin B12, used orally or by intramuscular injection to treat and prevent cobalamin deficiency.

Classification. Haematinic; water-soluble vitamin.

Mechanism. Converted to methylcobalamin and adenosylcobalamin, cofactors for methionine synthase (DNA synthesis and homocysteine metabolism) and methylmalonyl-CoA mutase (myelin and fatty acid metabolism).

Pharmacokinetics. Physiological absorption is in the terminal ileum via intrinsic factor and saturates at about 1.5 µg each dose; high oral doses (1000 µg or more) are absorbed by passive diffusion at about 1%. Intramuscular dosing reaches peak levels in 1 hour. Cyanocobalamin is cleared in urine faster than hydroxocobalamin and is retained less well.

Cobalamin deficiency without neurological involvement (adults).

• Loading dose: 1000 µg intramuscularly on alternate days for 2 weeks (or daily for 1 week).
• Maintenance: 1000 µg intramuscularly every month for pernicious anaemia or irreversible causes, for life. Doses beyond 1000 µg offer no added benefit. Maximum: 1000 µg each dose.

Deficiency with neurological involvement. 1000 µg intramuscularly on alternate days until no further improvement (up to 3 weeks or more), then 1000 µg every 1 to 2 months.

Dietary deficiency, mild or malabsorption of food cobalamin. 1000 to 2000 µg orally daily; maintenance 50 to 150 µg daily where the cause persists.

Children. 1 month to 11 years: 250 to 1000 µg intramuscularly on alternate days for 2 weeks, then 250 µg weekly until blood counts are normal, then 1000 µg every 3 months. 12 to 17 years: adult dosing.

Adjustments. Kidney: use hydroxocobalamin where possible in chronic kidney disease because of cyanide accumulation. Liver: none. Pregnancy: dose unchanged.

Contraindications. Hypersensitivity to cobalamin or cobalt; Leber hereditary optic neuropathy (can worsen optic atrophy).

Warnings. Severe megaloblastic anaemia treated with cobalamin can cause sudden hypokalaemia and thrombocytosis in the first days. Treat folate deficiency alongside cobalamin when both are present.

Adverse effects. Injection-site pain, itching, headache, nausea, acne; rare anaphylaxis.

Interactions. Chloramphenicol may blunt the haematological response. Metformin and long-term proton pump inhibitors reduce absorption of dietary cobalamin and cause deficiency.

Pregnancy and breastfeeding. Safe; requirements rise in both.

Common errors. Giving folic acid alone in cobalamin deficiency; stopping injections in pernicious anaemia; failing to check potassium in severe anaemia.

Administration. Deep intramuscular injection; oral for dietary deficiency and mild malabsorption, with intramuscular dosing if neurological features exist.

Baseline. Full blood count, blood film, serum cobalamin (under 148 pmol/L, about 200 ng/L, is deficient; borderline up to 250 pmol/L needs methylmalonic acid or homocysteine), folate, ferritin, and anti-intrinsic-factor antibodies.

Monitoring. Reticulocytosis appears in 3 to 8 days; haemoglobin rises steadily over 8 weeks. Check potassium in the first 48 hours in severe anaemia. Neurological recovery can take 6 to 12 months and may be incomplete.

Referral and escalation. Refer to haematology for pancytopenia, haemolysis or neurological deficit; urgent treatment with same-day injection for neurological signs.