Hydroxocobalamin

• Primary Indications
• Vitamin B12 deficiency: Treatment of pernicious anemia, dietary deficiency, and malabsorption-related B12 deficiency
• Cyanide poisoning: Emergency treatment due to its ability to bind cyanide and form cyanocobalamin for renal excretion
• Off-label / Clinically Accepted Uses
• Megaloblastic anemia due to folate deficiency (when co-existing B12 deficiency suspected)
• Adjunct therapy in certain neuropathies and myelopathies associated with B12 deficiency
• Chronic B12 deficiency prophylaxis in patients with gastrointestinal malabsorption

• Adults
• Vitamin B12 deficiency: 1 mg (1000 mcg) intramuscular (IM) or intravenous (IV) injection daily for 1 week, then weekly for 4–8 weeks, followed by monthly maintenance
• Cyanide poisoning: 5 g IV infusion over 15 minutes; repeat as needed based on cyanide exposure severity
• Pediatrics
• B12 deficiency: 25–50 mcg/kg/day IM or IV for 5–10 days, then maintenance 10–25 mcg/kg monthly
• Cyanide poisoning: 70 mg/kg IV infusion over 15 minutes; repeat cautiously if needed
• Elderly
• Standard adult dosing; monitor for renal function and comorbidities
• Special Populations
• Renal impairment: Monitor B12 levels; dosing adjustments usually unnecessary but caution advised in cyanide detoxification
• Hepatic impairment: Standard dosing; monitor liver function

Hydroxocobalamin is a form of Vitamin B12, acting as a cofactor in enzymatic reactions such as methionine synthase and methylmalonyl-CoA mutase. It facilitates DNA synthesis, red blood cell formation, and neuronal function. In cyanide poisoning, hydroxocobalamin binds cyanide ions to form cyanocobalamin, which is non-toxic and excreted via urine, thereby neutralizing cyanide’s inhibition of cellular respiration and preventing hypoxic tissue damage.

• Absorption: Administered IV or IM; fully bioavailable
• Distribution: Rapidly distributed in plasma and tissues; binds plasma proteins
• Metabolism: Converted to active coenzyme forms (methylcobalamin and adenosylcobalamin) intracellularly
• Elimination: Primarily renal; excreted as cyanocobalamin or hydroxocobalamin metabolites
• Half-life: Approximately 26–31 hours for IM; prolonged tissue retention allows monthly maintenance dosing
• Onset: Hematologic response typically within 1–2 weeks; neurologic recovery may take months

• Pregnancy: Category C (FDA) – limited human data; however, B12 supplementation is generally safe and essential for fetal development
• Breastfeeding: Excreted in breast milk; considered safe and beneficial for infant development
• Caution: High doses for cyanide poisoning only under medical supervision

• Primary Class: Vitamin / Nutritional supplement
• Subclass: Water-soluble vitamin, cyanide antidote

• Known hypersensitivity to hydroxocobalamin or any excipients
• History of allergy to cobalt-containing compounds
• Severe Leber’s optic atrophy (risk of optic nerve damage)

• Monitor patients with renal impairment during high-dose therapy
• High-dose IV administration may cause transient hypertension or allergic reactions
• Cyanide poisoning: Must be administered under emergency medical supervision with supportive care
• Monitor for injection site reactions, rash, or urticaria

• Common: Red discoloration of urine (benign), injection site pain, transient hypertension, headache
• Dermatologic: Rash, pruritus
• Rare / Serious: Anaphylactic reactions, angioedema, thrombocytopenia, pulmonary edema at extremely high doses
• Timing: Typically occurs immediately or within hours of IV/IM administration; usually mild and self-limiting

• Folic acid: May mask B12 deficiency if administered alone
• Chloramphenicol: May interfere with hematologic response to B12 therapy
• Chemotherapy agents: May reduce efficacy in cancer patients; monitor closely
• No major CYP450 involvement; minimal systemic drug interactions

• Guidelines recommend hydroxocobalamin as first-line treatment for cyanide poisoning due to safety and efficacy
• Maintenance therapy for B12 deficiency may continue monthly IM or IV injections for life in pernicious anemia
• Emphasis on early recognition and treatment of neurological complications to prevent permanent damage
• FDA approved high-dose IV hydroxocobalamin for emergency cyanide exposure

• Store at 20°C to 25°C (room temperature)
• Protect from light and freezing
• Keep vials tightly closed
• Avoid shaking vigorously; inspect for particulate matter before administration
• Reconstituted solution: use immediately or follow manufacturer-specific stability guidelines