Adenosylcobalamin

Usage

Adenosylcobalamin, a naturally occurring and active form of Vitamin B12, is prescribed for the treatment and prevention of Vitamin B12 deficiency. This deficiency can arise from dietary inadequacy (especially in vegans and vegetarians), malabsorption syndromes (like pernicious anemia), or other medical conditions. It is crucial for numerous bodily functions, including:

• Red blood cell formation: B12 is essential for proper red blood cell development, preventing megaloblastic anemia.
• Neurological function: It maintains the health of nerve cells and myelin sheaths, impacting nerve conduction and preventing peripheral neuropathy.
• DNA synthesis: B12 plays a critical role in DNA replication and cell division.

Pharmacological Classification: Vitamin, Hematopoietic agent, Neurotrophic agent

Mechanism of Action: Adenosylcobalamin acts as a coenzyme for two important enzymes: methylmalonyl-CoA mutase and methionine synthase. These enzymes participate in crucial metabolic pathways, including the conversion of methylmalonyl-CoA to succinyl-CoA and the synthesis of methionine from homocysteine. These processes are essential for DNA synthesis, red blood cell production, and nerve function.

Alternate Names

• Cobamamide
• Dibencozide
• (Sometimes referred to simply as Vitamin B12, although this can encompass other forms as well)

How It Works

Pharmacodynamics: Adenosylcobalamin’s primary effects are observed in the hematopoietic (blood cell formation) and nervous systems. It corrects megaloblastic anemia by enabling normal DNA synthesis and cell division in red blood cell precursors. It supports neuronal function by maintaining myelin integrity and promoting nerve regeneration.

Pharmacokinetics: Adenosylcobalamin is absorbed through the gastrointestinal tract, primarily via active transport in the ileum (requiring intrinsic factor). Once absorbed, it’s transported to the liver and other tissues, where it is stored. A small amount is excreted in bile and urine.

Mode of Action: Adenosylcobalamin functions as a coenzyme for:

• Methylmalonyl-CoA mutase: Converts methylmalonyl-CoA to succinyl-CoA, which is essential for myelin synthesis and energy production.
• Methionine synthase: Catalyzes the conversion of homocysteine to methionine, necessary for DNA and protein synthesis.

Elimination Pathways: Excreted through both renal (urine) and hepatic (bile) pathways.

Dosage

Dosage depends on the specific condition, its severity, and individual patient factors. Always adhere to physician recommendations.

Standard Dosage

Adults:

• For B12 Deficiency: Oral doses typically range from 1000 mcg daily to 2000 mcg weekly. Intramuscular injections are more efficient in cases of malabsorption and typically range from 1000 mcg daily for two weeks, then weekly for one month, finally, once monthly for maintenance.

Children:

• Pediatric dosing needs to be determined by a physician based on the child’s age, weight, and specific condition.

Special Cases:

• Elderly Patients: May require higher doses or more frequent administration due to age-related changes in absorption and metabolism.
• Patients with Renal Impairment: Dose adjustment may be necessary based on creatinine clearance.
• Patients with Hepatic Dysfunction: Careful monitoring is advised, although dosage adjustments may not always be needed.
• Patients with Comorbid Conditions: Dose modification should be considered in the presence of other medical conditions that may impact absorption or metabolism.

Clinical Use Cases:

Adenosylcobalamin is not generally recommended for clinical use cases requiring short-term dosage adjustments like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations.

Dosage Adjustments:

Specific adjustments should be guided by laboratory values (serum B12 levels, homocysteine, methylmalonic acid) and clinical response.

Side Effects

Common Side Effects:

• Diarrhea
• Nausea
• Vomiting
• Mild transient diarrhea
• Headache
• Dizziness

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling, anaphylaxis)
• Hypokalemia (low potassium levels)
• Pulmonary edema (fluid in the lungs)
• Heart failure
• Polycythemia vera (excess red blood cells)

Long-Term Effects:

Generally well-tolerated in long-term use, but monitoring for potential adverse effects is advisable.

Adverse Drug Reactions (ADR):

Severe allergic reactions require immediate medical attention. Other ADRs, such as heart failure or pulmonary edema, warrant urgent evaluation and intervention.

Contraindications

• Hypersensitivity to adenosylcobalamin or cobalt.
• Leber’s hereditary optic neuropathy (high doses may worsen the condition).
• Patients with known allergy to adenosylcobalamin or any other inactive ingredients present along with it.

Drug Interactions

• Medications that reduce stomach acid: Proton pump inhibitors (PPIs) like omeprazole and H2 blockers like ranitidine can impair B12 absorption from food but not typically supplements.
• Metformin: May reduce B12 absorption.
• Certain antibiotics: Chloramphenicol, neomycin, gentamicin.
• Colchicine, potassium supplements.
• Antiretroviral medications: Dolutegravir, cabotegravir.
• Chemotherapy medications: Capecitabine, fluorouracil.

Pregnancy and Breastfeeding

Considered likely safe for use during pregnancy and breastfeeding at recommended doses (2.6 mcg/day and 2.8 mcg/day, respectively). Higher doses should be used with caution and under medical supervision. Adequate B12 is essential for fetal neurodevelopment.

Drug Profile Summary

• Mechanism of Action: Coenzyme for methylmalonyl-CoA mutase and methionine synthase, affecting DNA synthesis, nerve function, and red blood cell production.
• Side Effects: Diarrhea, nausea, vomiting, headache, dizziness, rare allergic reactions, hypokalemia, heart failure, pulmonary edema.
• Contraindications: Hypersensitivity to cobalamin or cobalt, Leber’s disease.
• Drug Interactions: PPIs, H2 blockers, metformin, some antibiotics.
• Pregnancy & Breastfeeding: Likely safe at recommended doses.
• Dosage: Varies based on condition and patient; typically 1000 mcg – 2000 mcg/week oral, or IM injections as required.
• Monitoring Parameters: Serum B12 levels, homocysteine, methylmalonic acid, complete blood count.

Popular Combinations:

Frequently combined with other B vitamins (especially folic acid and B6), and sometimes with iron.

Precautions

• Monitor for allergic reactions.
• Assess renal and hepatic function, particularly with higher doses.
• Caution in patients with cardiac or pulmonary conditions.
• Monitor potassium levels.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Adenosylcobalamin?

A: The dosage varies according to the patient’s needs. For adults with B12 deficiency, 1000mcg -2000mcg/ week is common. For maintenance, lower doses might be sufficient. Intramuscular injections are more efficient and given once a month following a loading dose. Pediatric and other special population dosing needs to be determined by a healthcare professional.

Q2: What are the primary uses of adenosylcobalamin?

A: Primarily used to treat and prevent vitamin B12 deficiency.

Q3: How is adenosylcobalamin different from cyanocobalamin?

A: Adenosylcobalamin is a naturally occurring, active form of B12 readily utilized by the body. Cyanocobalamin is a synthetic form that must be converted to active forms (like adenosylcobalamin) before being used.

Q4: Can adenosylcobalamin be used during pregnancy?

A: Yes, considered likely safe at recommended doses during both pregnancy and lactation. Adequate B12 is vital for fetal development.

Q5: What are the signs and symptoms of B12 deficiency?

A: Fatigue, weakness, megaloblastic anemia, neurological symptoms (numbness, tingling, gait disturbances, cognitive impairment), glossitis (sore tongue).

Q6: How is B12 deficiency diagnosed?

A: Serum B12 levels, complete blood count (CBC), homocysteine and methylmalonic acid levels.

Q7: Are there any drug interactions with adenosylcobalamin I should be aware of?

A: Yes, it can interact with certain medications like metformin, some antibiotics, and proton pump inhibitors, which can affect B12 absorption.

Q8: What are the long-term effects of adenosylcobalamin supplementation?

A: Generally considered safe for long-term use. Regular monitoring of B12 levels and relevant clinical parameters is advisable.

Q9: How should I administer adenosylcobalamin – orally or via injection?

A: Both routes are possible. Oral administration is suitable for many patients. However, in cases of malabsorption (e.g., pernicious anemia), intramuscular injections are preferred for better efficacy.

Q10: What is the role of adenosylcobalamin in nerve function?

A: It is essential for myelin synthesis and maintenance, contributing to the proper functioning of the nervous system and preventing neuropathy.