CYANOCOBALAMIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYANOCOBALAMIN (CYANOCOBALAMIN).
Cyanocobalamin is a synthetic form of vitamin B12 that is converted to active coenzymes methylcobalamin and adenosylcobalamin. These coenzymes are essential for DNA synthesis, myelin formation, and hematopoiesis. Methylcobalamin acts as a cofactor for methionine synthase, converting homocysteine to methionine, while adenosylcobalamin is a cofactor for methylmalonyl-CoA mutase, converting methylmalonyl-CoA to succinyl-CoA.
| Metabolism | Cyanocobalamin is metabolized in the liver and other tissues to active coenzymes methylcobalamin and adenosylcobalamin. The cyanide moiety is converted to thiocyanate and excreted in urine. |
| Excretion | Primarily renal (50-90% as unchanged drug); biliary/fecal (minor, <10%) |
| Half-life | Approximately 6 days (400 h) in plasma; tissue stores extend terminal half-life to 40-90 days |
| Protein binding | Highly bound to haptocorrin (~90%) and transcobalamin II (~10%) |
| Volume of Distribution | 0.6-1.2 L/kg; large Vd due to extensive tissue distribution and binding |
| Bioavailability | IM/SC: 100%; Oral: approximately 1% (with intrinsic factor), <1% without; Intranasal: comparable to IM at high doses |
| Onset of Action | IM/SC: hematologic response within 48-72 hours; neurologic improvement within weeks to months |
| Duration of Action | Single dose maintains adequate levels for 3-6 months due to hepatic storage |
1000 mcg IM once daily for 7 days, then 1000 mcg IM once weekly for 4 weeks, then 1000 mcg IM once monthly. Oral: 1000-2000 mcg PO once daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Hemodialysis: No supplemental dose needed. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Vitamin B12 deficiency: 1000 mcg IM once daily for at least 2 weeks, then 100-1000 mcg IM once monthly. Maintenance: 100 mcg IM once monthly. |
| Geriatric use | Use same dosing as adults. Monitor for hypokalemia during initial therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYANOCOBALAMIN (CYANOCOBALAMIN).
| Breastfeeding | Cyanocobalamin is excreted into breast milk. The estimated average concentration in mature milk is 0.97 mcg/L. The M/P ratio is not well defined but is estimated to be low. At recommended doses, it is considered compatible with breastfeeding. High doses should be used with caution. |
| Teratogenic Risk | Cyanocobalamin is a water-soluble vitamin essential for DNA synthesis and neurological function. At physiological or standard therapeutic doses, no teratogenic effects have been reported in any trimester. No increased risk of congenital anomalies has been observed. Supplementation is recommended in deficiency states to prevent maternal and fetal complications. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to cyanocobalamin, cobalt, or any component of the formulation","Leber's disease (hereditary optic nerve atrophy) – relative contraindication"]
| Precautions | ["Pernicious anemia: Parenteral administration required; oral absorption is unreliable.","Hypokalemia and thrombocytosis may occur during initial therapy for megaloblastic anemia; monitor potassium and platelets.","Folic acid deficiency: Cyanocobalamin may mask folic acid deficiency if folic acid is not co-administered.","Leber's disease (hereditary optic nerve atrophy): Use with caution; rapid optic atrophy may occur.","Allergic reactions: Anaphylaxis has been reported with parenteral administration."] |
| Food/Dietary | Alcohol consumption can reduce vitamin B12 absorption. High intake of folic acid may mask B12 deficiency. There are no significant food-drug interactions; however, foods rich in folic acid (e.g., leafy greens) can complicate diagnosis. No specific dietary restrictions; absorption of oral cyanocobalamin is not affected by food, but it is recommended to take with food if gastrointestinal upset occurs. |
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| Fetal Monitoring | Monitor maternal hemoglobin, hematocrit, and red blood cell indices (MCV, MCH). For pernicious anemia or prolonged deficiency, assess serum vitamin B12 levels, homocysteine, and methylmalonic acid. In pregnancy, periodic monitoring of B12 levels is recommended to maintain adequacy for both mother and fetus. |
| Fertility Effects | Vitamin B12 deficiency may impair fertility due to effects on oocyte quality and implantation. Correction of deficiency with cyanocobalamin can restore normal reproductive function. No adverse effects on fertility have been reported at standard doses. |
| Clinical Pearls | For intramuscular injection in pernicious anemia, use deep IM in the upper outer quadrant of the gluteus maximus; avoid IV administration. Monitor serum potassium during initiation of therapy for megaloblastic anemia due to risk of hypokalemia. Sublingual and oral formulations are not interchangeable with parenteral for severe B12 deficiency or malabsorption. Patients with Leber's disease may experience optic atrophy with cyanocobalamin use. Evaluate vitamin B12 levels before supplementation and consider checking methylmalonic acid (MMA) and homocysteine for accurate diagnosis. |
| Patient Advice | Take cyanocobalamin exactly as prescribed; do not stop without consulting your doctor. · If you have pernicious anemia or other conditions causing B12 malabsorption, you will likely need lifelong injections. · Report any signs of swelling, pain, or redness at the injection site to your healthcare provider. · Seek immediate medical attention if you experience difficulty breathing, rash, or swelling of the face, tongue, or throat (possible allergic reaction). · Do not substitute oral or sublingual forms for injections unless directed by your physician. · Maintain a balanced diet but do not rely on food to correct a severe B12 deficiency. |