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:

• Pernicious anemia: this condition is an autoimmune disorder against parietal cells. These cells are responsible for the production of the intrinsic factor. As the parietal cells are destroyed, there is no intrinsic factor to which the dietary B12 can bind; this leads to a deficiency of vitamin B12.
• Malabsorption- Impairment of B12 absorption
• Atrophic gastritis- Impairment of intrinsic factor production, causing impaired vitamin B12 absorption.
• Long term metformin use[4]
• Chronic acid-reducing medication use[5]
• Small bowel bacteria overgrowth- competition for vitamin B12 leads to vitamin deficiency
• Total or partial gastrectomy- eliminates site of intrinsic factor production
• Diphyllobothrium latum infection- parasite utilizes luminal B12
• Helicobacter pylori infection
• Pancreatic insufficiency- causes failure to inactivate cobalamin-binding proteins.
• Malignancy of pancreas or bowel
• Dietary deficiency of vitamin B12- eating strictly vegan foods without animal origin can lead to such deficiency[6]
• Transcobalamin II deficiency- causes impairment in transmembrane transport of B12

Non-FDA approved indications:

• Smoke inhalation
• Cyanide poisoning[7]
• Surgery-associated vasoplegia[8]
• Vasodilatory shock
• Folic acid deficiency

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:

• Shortness of breath (even with mild exertion), swelling, rapid weight gain
• Pulmonary edema, congestive heart failure; peripheral vascular thrombosis
• Hypokalemia--leg cramps, irregular heartbeats, tingling/numbness, muscle weakness or limp feeling
• Numbness or tingling and joint pain
• Fever
• Swollen tongue
• Itching or rash
• Polycythemia (cyanocobalamin can unmask the underlying polycythemia)

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.