Cyanocobalamin

Cyanocobalamin is a synthetic, water-soluble form of vitamin B12. It is FDA approved as Cyanocobalamin Injection, USP for intramuscular or deep subcutaneous use, and as a nasal spray (Nascobal) for maintenance therapy. Oral cyanocobalamin is widely available without a prescription. Compounded injections are made pursuant to patient-specific prescriptions.

FDA-labeled indications of the injection: vitamin B12 deficiency due to malabsorption, as in pernicious anemia, gastrointestinal pathology, dysfunction or surgery (including gluten enteropathy, sprue, small-bowel bacterial overgrowth and total or partial gastrectomy), fish tapeworm infestation, and malignancy of the pancreas or bowel; deficiency where requirements are increased and oral therapy is not feasible; and the Schilling test.

Prescribers also use cyanocobalamin to treat or prevent deficiency associated with metformin, long-term acid suppression, bariatric surgery or vegan diets.

Cyanocobalamin is converted in tissues to the coenzymes methylcobalamin and adenosylcobalamin. Methylcobalamin is the cofactor for methionine synthase, which converts homocysteine to methionine and regenerates tetrahydrofolate needed for DNA synthesis. Adenosylcobalamin is the cofactor for methylmalonyl-CoA mutase, important for myelin integrity. Deficiency causes megaloblastic anemia and neurologic damage.

After intramuscular injection, absorption is rapid, with peak plasma levels within about 1 hour. Cobalamin binds transcobalamin II for tissue delivery and is stored mainly in the liver. The biological half-life is about 6 days, with liver stores persisting far longer (around 400 days). Within 48 hours of a 100 mcg or 1,000 mcg injection, 50% to 98% of the dose appears in the urine, most in the first 8 hours, because doses above binding capacity are excreted unchanged.

• Sensitivity to cobalt or vitamin B12, or any component of the formulation.

• Leber's disease: patients with early hereditary optic nerve atrophy have developed severe and rapid optic atrophy with vitamin B12.
• Hypokalemia and sudden death can occur early in treatment of severe megaloblastic anemia, as new red-cell production consumes potassium; monitor potassium.
• Treatment can unmask polycythemia vera.
• Folic acid can correct the hematologic findings of B12 deficiency while neurologic damage progresses; doses of folic acid above 0.1 mg daily may mask the diagnosis. B12 deficiency left untreated for more than 3 months may cause permanent spinal cord lesions.
• Anaphylaxis has been reported rarely; an intradermal test dose is recommended in patients suspected of sensitivity.
• Aluminum in parenteral products can accumulate to toxic levels with impaired kidney function, particularly in premature neonates.
• Benzyl alcohol, used as a preservative in some products, has been associated with fatal gasping syndrome in premature infants.

• Chloramphenicol may blunt the hematologic response to vitamin B12.
• Oral B12 absorption is reduced by colchicine, para-aminosalicylic acid, metformin, proton pump inhibitors and H2 blockers, and heavy alcohol use; these do not affect injected B12 but can cause the deficiency being treated.
• Most antibiotics, methotrexate and pyrimethamine invalidate microbiological assays of serum B12 and folate.

Injection-site pain, mild transient diarrhea, itching, transient rash and a feeling of swelling of the body. Rare: anaphylaxis, pulmonary edema and congestive heart failure early in treatment, peripheral vascular thrombosis, and polycythemia vera.

Vitamin B12 is an essential nutrient and requirements rise in pregnancy; adequate intake is recommended, and deficiency should be treated. Vitamin B12 passes into breast milk and is compatible with breastfeeding; maternal deficiency can cause deficiency in the nursing infant.

Hematocrit, reticulocyte count, serum B12, folate and iron before treatment; in megaloblastic anemia, potassium and platelets during the first days of treatment and hematologic response over the first weeks; periodic serum B12 and complete blood count during maintenance; and neurologic status. Methylmalonic acid and homocysteine can support the diagnosis.

• Cyanocobalamin Injection, USP Prescribing Information.
• Nascobal (cyanocobalamin) nasal spray Prescribing Information.
• USP General Chapter <797> Pharmaceutical Compounding: Sterile Preparations.