Cyanocobalamin is a synthetic solution of vitamin B12 used mainly to treat deficiencies of the vitamin.[1] Chemically it belongs to "corrinoids," and it is a crystallizable cobalt-complex. The name cyanocobalamin is owing to the fact it has a cyanide group attached to the molecule.[2] It has a role in several methylation reactions in the body.[3] In the body, in the form of methylcobalamin, it acts as a cofactor in the conversion of homocysteine to methionine and the form of adenosylcobalamin for the conversion of methylmalonyl-CoA to succinyl-CoA. Both these reactions are vital for cell division and growth.
FDA approved indications:
Non-FDA approved indications:
Oral cyanocobalamin absorption occurs through the small intestine after binding to intrinsic factor and other cobalamin binding proteins.[9] When given by the parenteral route, it reaches the blood quite immediately.[10]
In the blood, it attaches itself to plasma proteins. Tissues absorb vitamin B12 by specific B12 binding proteins, transcobalamin I and II, to enter the cells. Most of the vitamin is stored in the liver. Vitamin B12 is essential for DNA synthesis and energy production, particularly in erythroid progenitor cells.
Vitamin B12 serves as a cofactor for two vital enzymes in the body: methylmalonyl-CoA mutase and methionine synthase. These methylation reactions are responsible for annealing Okazaki fragments during DNA synthesis.[2]
The replenishment causes total improvement of megaloblastic anemia and the gastrointestinal manifestations of vitamin B12 deficiency. The neurological symptoms in vitamin B12 deficiency improve upon cyanocobalamin administration, but the level of improvement depends on the duration and severity of deficiency.[11]
The reported but unconfirmed mechanism of action of hydroxocobalamin in vasoplegic shock is direct inhibition of nitric oxide and inhibition of guanylate cyclase.
Cyanocobalamin administration is by the oral, sublingual, intramuscular, subcutaneous, and intranasal routes. The choice of oral and other parenteral routes depends on the cause as well as the presentation of the patient.[12] A severe deficiency requires treatment with parenteral therapy (IM/SC). A patient with malabsorption cannot benefit from treatment with the oral formulation due to impaired absorption.[13]
The initial replacement of overt deficiency is usually through parenteral therapy. Typically, 100 mcg cyanocobalamin is given daily for one week, weekly for a month, and then monthly for life. Oral/sublingual treatment is given after the initial correction of vitamin deficiency.
An intradermal test dose is an option for patients suspected of cyanocobalamin sensitivity before any parenteral treatment. Due to the possibility of anaphylaxis, cyanocobalamin should never be given intravenously (I.V.).[14]
As the vitamin is light-sensitive, the vials should be protected from light and stored at room temperature.
There are several case reports of hydroxycobalamin therapy for vasoplegic shock. The dose used in these case reports was 5 g over 15 min intravenously, with some instances of it being repeated in six hours.[15]
Cyanocobalamin, though only a vitamin, can cause several adverse effects. The patients with sensitivity can even experience life-threatening anaphylactic reactions. Apart from that, allergic reactions like itching, erythema, wheals may appear.
Other common adverse effects include:
Sensitivity to cobalt and/or vitamin B12 due to the risk of anaphylaxis.[16]
Patients with early Leber disease suffered severe and rapid optic atrophy when they received treatment with cyanocobalamin.[17]
Aluminum is present in the preparation of cyanocobalamin. CNS and bone toxicity secondary to aluminum accumulation is possible in patients with renal impairment. Thus, it is a relative contraindication to cyanocobalamin.
The clinician should obtain vitamin B12, folate, and iron levels along with hematocrit and reticulocyte count before treatment.
When giving cyanocobalamin to treat vitamin B12 deficiency, there is an increase in erythrocyte metabolism, which leads to hypokalemia. As the anemia is corrected, thrombocytosis could also occur. Therefore, serum potassium levels and the platelet count should be monitored carefully during therapy. Recommendations are to monitor vitamin B12 blood levels and peripheral blood counts in one month.
The clinicians should always ask about a history of allergies as there is a risk of anaphylaxis if a patient is allergic to cobalt or other components of the medication. Decreased therapeutic response to vitamin B12 may be due to uremia, infection, marrow suppressants like chloramphenicol, and concomitant iron or folic acid deficiency.
Folic acid supplementation is also necessary if folate levels are low. Folic acid may improve vitamin B12-deficient megaloblastic anemia, but it is not a substitute. If the clinician only uses only folic acid to treat vitamin B12 deficient megaloblastic anemia, progressive and irreversible neurologic damage could result; this is because it can aggravate vitamin B12 deficiency by increasing demand for the vitamin.
Cyanocobalamin secretion is usually in bile. With higher doses of cyanocobalamin, it undergoes rapid elimination in the urine. No overdosage occurs with cyanocobalamin. There is no antidote to vitamin B12.
Cyanocobalamin treats a variety of different conditions related to vitamin B12 deficiency. Healthcare professionals, including physicians, nurse practitioners, pharmacists, and nutritionists, have to work together to manage the condition. Early detection will prevent severe and permanent complications as prolonged Vitamin B12 deficiency may lead to permanent degenerative lesions of the spinal cord.[18] Due to the risk of hypokalemia early in treatment, electrolytes should be tested in the followup visit, which requires rigorous lab review after the office visit. This surveillance can be done by any clinician so as not to miss any abnormality.
As there are several completely unrelated causes of this deficiency, a physician is responsible for not only the identification of the probable cause but also tailor therapy and further management for different individuals depending on case to case basis.[19]
The involvement of specialists may prove necessary in several instances. For example,
Due to the possibility of hypersensitivity to the drug, it is essential that the provider administers it with necessary precautions and carry out an intradermal test if an allergy is suspected. Education about the allergic reactions and other side effects is essential for optimal outcome and prevention of anaphylactic shock. [Level 5]
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