Usage
Hydroxocobalamin is prescribed for the treatment of vitamin B12 deficiency, including pernicious anemia (due to intrinsic factor deficiency), other macrocytic anemias without neurological involvement, and anemias with neurological involvement. It is also used in the treatment of tobacco amblyopia, Leber’s optic atrophy, and cyanide poisoning. Its pharmacological classifications include vitamin (water-soluble) and antidote. Hydroxocobalamin is a precursor to cyanocobalamin (vitamin B12) and acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism, protein synthesis, cell replication, and hematopoiesis. In cyanide poisoning, it binds cyanide ions, forming cyanocobalamin, which is then excreted in the urine.
Alternate Names
Hydroxocobalamin is also known as Vitamin B12a. Brand names include Cyanokit, Cobalin-H, and Neo-Cytamen.
How It Works
Pharmacodynamics: Hydroxocobalamin is converted to the active coenzymes methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin is essential for the synthesis of methionine from homocysteine and for the metabolism of folate. 5-deoxyadenosylcobalamin is a coenzyme for methylmalonyl-CoA mutase, which is involved in the metabolism of fatty acids and carbohydrates.
Pharmacokinetics:
- Absorption: Administered intramuscularly (IM) or intravenously (IV). IM administration provides slow, sustained absorption.
- Metabolism: Converted to the active coenzymes methylcobalamin and 5-deoxyadenosylcobalamin. Does not undergo metabolism in the traditional sense.
- Elimination: Primarily excreted in the urine as unchanged hydroxocobalamin and cyanocobalamin. Approximately 50% to 60% of a dose is excreted within the first 72 hours. Elimination half-life is 26 to 31 hours. Exhibits significant protein binding, forming various cobalamin-(III) complexes.
Mode of Action: Hydroxocobalamin binds to transcobalamin II, a transport protein, to be delivered to cells. Inside the cells, it is converted to the active coenzyme forms, methylcobalamin and 5-deoxyadenosylcobalamin, which are required for crucial enzymatic reactions in various metabolic pathways.
Receptor Binding, Enzyme Interactions: Methylcobalamin acts as a coenzyme for methionine synthase, while 5-deoxyadenosylcobalamin acts as a coenzyme for methylmalonyl-CoA mutase. In cyanide poisoning, hydroxocobalamin directly binds cyanide ions, forming cyanocobalamin.
Elimination Pathways: Primarily renal excretion (as unchanged drug and cyanocobalamin).
Dosage
Standard Dosage
Adults:
- Vitamin B12 Deficiency (without neurological involvement): Initially 250 to 1000 mcg IM on alternate days for 1-2 weeks, then 250 mcg weekly until blood count normalizes. Maintenance: 1000 mcg IM every 2-3 months.
- Vitamin B12 Deficiency (with neurological involvement): Initially 1000 mcg IM on alternate days for 1-2 weeks. Maintenance: 1000 mcg IM every 2 months.
- Prophylaxis of Vitamin B12 Deficiency (post-gastrectomy, malabsorption, nutritional deficiencies): 1000 mcg IM every 2-3 months.
- Tobacco Amblyopia and Leber’s Optic Atrophy: Initially 1000 mcg IM daily for 2 weeks, then twice weekly for 4 weeks. Maintenance: 1000 mcg IM monthly.
- Cyanide Poisoning: 5 g IV infusion over 15 minutes. A second dose of 5 g may be administered if needed.
Children: Dosing is similar to adults for vitamin B12 deficiency. For cyanide poisoning, a dose of 70 mg/kg has been used. Pediatric safety considerations include monitoring for potential hypokalemia during treatment for severe anemia.
Special Cases:
- Elderly Patients: No specific dose adjustment is required.
- Patients with Renal Impairment: Hydroxocobalamin and cyanocobalamin are eliminated renally. Monitoring of renal function is recommended.
- Patients with Hepatic Dysfunction: No specific dose adjustment is suggested.
- Patients with Comorbid Conditions: Monitor potassium levels closely in patients with megaloblastic anemia.
Clinical Use Cases
Dosage recommendations for clinical use cases such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations (other than cyanide poisoning) are not specifically defined. Dosing should be based on the underlying indication for hydroxocobalamin (e.g., vitamin B12 deficiency). For cyanide poisoning, refer to the recommended dosage.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient response and clinical presentation. Monitor hematological parameters and serum potassium levels, particularly in patients with severe anemia. For renal impairment, close monitoring of renal function and serum hydroxocobalamin levels may be beneficial.
Side Effects
Common Side Effects
Injection site reactions (pain, swelling, itching, redness), nausea, headache, diarrhea, dizziness, hot flushes, rash, reddish urine (transient).
Rare but Serious Side Effects
Hypokalemia (muscle cramps, weakness, irregular heartbeat), allergic reactions (including anaphylaxis), polycythemia vera exacerbation (chest pain, weakness on one side, vision changes, slurred speech).
Long-Term Effects
Chronic complications from prolonged use are rare.
Adverse Drug Reactions (ADR)
Anaphylaxis, acute renal failure, acute tubular necrosis, hypokalemia, increased blood pressure.
Contraindications
Hypersensitivity to hydroxocobalamin or cobalt. It should not be used to treat megaloblastic anemia of pregnancy caused by folic acid deficiency.
Drug Interactions
Chloramphenicol may impair the therapeutic response to hydroxocobalamin. Oral contraceptives may lower serum hydroxocobalamin concentrations. High doses of folic acid may reduce vitamin B12 concentrations. Hydroxocobalamin is physically incompatible with diazepam, dobutamine, dopamine, fentanyl, nitroglycerin, pentobarbital, propofol, and thiopental. It is chemically incompatible with ascorbic acid, sodium thiosulfate, and sodium nitrite. Co-administration with blood products through the same IV line is not recommended. Concomitant infection, uremia, or folic acid or iron deficiency may impair the therapeutic response to vitamin B12.
Pregnancy and Breastfeeding
Hydroxocobalamin crosses the placental barrier. While it can be used during pregnancy if the benefits outweigh the risks, it is generally not recommended unless necessary. It is excreted in breast milk and is generally not recommended during breastfeeding unless the maternal benefits outweigh the infant risks. High doses for cyanide poisoning necessitate cessation of breastfeeding.
Drug Profile Summary
- Mechanism of Action: Precursor to cyanocobalamin; coenzyme for metabolic functions; cyanide antidote.
- Side Effects: Injection site reactions, nausea, headache, dizziness, rash, red urine. Rarely, hypokalemia, allergic reactions.
- Contraindications: Hypersensitivity to hydroxocobalamin or cobalt.
- Drug Interactions: Chloramphenicol, oral contraceptives, folic acid, incompatible IV admixtures.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Varies by indication; see detailed dosage section.
- Monitoring Parameters: Serum potassium, hematological parameters, renal function (in renal impairment).
Popular Combinations
Specific popular combinations for hydroxocobalamin are not readily defined. In cases of cyanide poisoning, sodium thiosulfate is sometimes used in conjunction, but not concomitantly through the same IV line.
Precautions
- General Precautions: Screen for allergies and electrolyte imbalances. Monitor potassium levels, especially in patients with severe anemia. Monitor renal function in patients with renal impairment.
- Specific Populations: As outlined in the special cases section.
- Lifestyle Considerations: No specific lifestyle restrictions are generally associated with hydroxocobalamin use, except potentially avoiding alcohol during intensive treatment of vitamin B12 deficiency.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydroxocobalamin?
A: Dosage varies depending on the indication and patient-specific factors. Refer to the detailed dosage section above.
Q2: How is Hydroxocobalamin administered?
A: Intramuscular (IM) or intravenous (IV) injection.
Q3: What are the common side effects of Hydroxocobalamin?
A: Common side effects include injection site reactions, headache, nausea, rash, and temporary reddish discoloration of urine.
Q4: Can Hydroxocobalamin be used during pregnancy?
A: It can be used if the benefits outweigh the risks, but it is generally not recommended unless necessary. It crosses the placental barrier.
Q5: Is it safe to breastfeed while taking Hydroxocobalamin?
A: Hydroxocobalamin is excreted in breast milk. Its use during breastfeeding is generally not recommended unless the maternal benefits outweigh the infant risks. High doses for cyanide poisoning necessitate cessation of breastfeeding.
Q6: What are the contraindications for Hydroxocobalamin?
A: Hypersensitivity to hydroxocobalamin or cobalt is a contraindication.
Q7: How does Hydroxocobalamin work in cyanide poisoning?
A: Hydroxocobalamin directly binds cyanide ions, forming cyanocobalamin, which is then excreted in the urine.
Q8: How should Hydroxocobalamin be administered for cyanide poisoning?
A: Administer 5 g as an IV infusion over 15 minutes. A second dose of 5 g may be given if required.
Q9: What are the key monitoring parameters for patients on Hydroxocobalamin?
A: Monitor serum potassium levels, hematological parameters, and renal function, particularly in patients with renal impairment or severe anemia.
Q10: What is the difference between Hydroxocobalamin and Cyanocobalamin?
A: Hydroxocobalamin is a precursor to cyanocobalamin. Both are forms of vitamin B12, but hydroxocobalamin is preferred for certain conditions, such as cyanide poisoning, due to its superior cyanide-binding properties. It also has a longer half-life and better tissue retention compared to cyanocobalamin.
