Cyanocobalamin
Cyanocobalamin
Generic Name
Cyanocobalamin
Mechanism
- Reduces methylmalonic acid (MMA) and homocysteine by functioning as a cofactor for *methylmalonyl‑CoA mutase* and *methionine synthase*, respectively.
- Prevents myelin sheath degradation and supports DNA synthesis in rapidly dividing cells.
- Acts as a neurotrophic factor promoting neuronal repair and neurotransmitter synthesis (e.g., dopamine, serotonin).
Pharmacokinetics
- Absorption: Intestinal absorption requires intrinsic factor (IF) for oral therapy; intramuscular (IM) bypasses IF dependence.
- Distribution: Widely distributed in the plasma, bound minimally to plasma proteins (~4 %); lipids and tissues incorporate B12 into the cobalamin pool.
- Metabolism: Converted intracellularly to active cofactors *hydroxocobalamin* and *methylcobalamin*.
- Elimination: Renal excretion; half‑life ~10 days for tissue stores, ~30 min for serum.
Indications
- Vitamin B12 deficiency (pernicious anemia, diet‑based deficiency, malabsorption).
- Macrocytic anemia from folate deficiency or marrow suppression.
- Neurologic disorders: subacute combined degeneration, demyelinating neuropathies, peripheral neuropathies associated with diabetes.
- Chronic myopathy (e.g., metabolic muscle disease).
- Adjunct in chemotherapy‑induced neuropathy and hematologic cytopenias.
Contraindications
- Hypersensitivity to cyanocobalamin or any excipients.
- Allergy to cyanide: rare, but cyanocobalamin contains a low cyanide content; caution in patients with severe cyanide exposure.
- Uncontrolled thrombocytopenia: high doses may transiently raise platelet counts.
- Pediatric use: limited data in infants <12 months on safety of high‑dose therapy.
Dosing
| Route | Typical Regimen | Notes |
| Intramuscular (IM) | 1 mg daily → 1 mg weekly → 1 mg monthly | Standard for deficiency; can be given intramuscularly in deltoid or gluteal muscle. |
| Oral | 500 µg‑1 mg daily | Effective in mild to moderate deficiency; requires intact IF. |
| Subcutaneous | 1 mg weekly → monthly | Alternative when IM contraindicated; similar efficacy. |
| Sublingual | 500 µg‑1 mg daily | Rapid absorption; good for patients with malabsorption. |
• Loading dose: For severe deficiency (e.g., MMA >400 nmol/L), a loading dose of 1 mg IM daily for 5 days may be employed.
• Maintenance: Monthly IM or weekly oral/subcutaneous for lifelong deficiency correction.
Monitoring
- CBC with differential (baseline, 4–6 weeks, then every 3 months).
- Serum MMA and homocysteine (baseline, 4–8 weeks, then annually).
- Neurologic assessment (strength, reflexes, sensation).
- Platelet count after high‑dose or long‑term therapy.
Clinical Pearls
- IM is the gold standard for pernicious anemia; oral therapy is reserved for partial deficiency or patients who cannot receive injections.
- Cyanocobalamin’s cyanide moiety is minimal (~5 µg per 1 mg dose) and is rapidly converted to innocuous hydroxocobalamin.
- High‑dose IM (e.g., 1 mg daily for 5 days) corrects severe functional deficiencies quickly, evident by MMA drop within 1–2 weeks.
- Orally administered formulations with 500–1000 µg are effective even in patients with impaired IF, likely due to passive, non‑IF–dependent absorption.
- Adjunctive therapy: Combining cyanocobalamin with folic acid or vitamin B6 enhances methylation pathways, benefiting patients with homocysteine‑related vascular risk.
- Cost‑effective: Cyanocobalamin is inexpensive; oral preparations are most affordable for long‑term management.
This drug card offers a clear, evidence‑based summary tailored for medical students and clinicians seeking quick reference on cyanocobalamin pharmacology.