Cyanocobalamin
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Cyanocobalamin: From Vitamin B12 Therapy to Biotin Metabolic Disease
One-Sentence Summary
Cyanocobalamin is the injectable form of vitamin B12 and is marketed in the US as several generic products. The TxGNN model predicts it may be effective for biotin metabolic disease. The 15 registered trials and 20 publications retrieved are only indirectly related, and none shows cyanocobalamin treating a primary biotin defect.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Biotin metabolic disease |
| TxGNN Prediction Score | 99.60% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Cyanocobalamin is a form of vitamin B12 (cobalamin). The US labels retrieved contain no approved-indication text, so the original indication cannot be quoted from the data.
The link to biotin metabolic disease is indirect and sits at the pathway level. Biotin-dependent carboxylases, such as propionyl-CoA carboxylase, feed into the cobalamin-dependent methylmalonyl-CoA mutase step. Both vitamins therefore lie on the same propionate and branched-chain amino acid breakdown route. Reviews also group cobalamin and biotin together as “vitamin-responsive disorders.”
The standard treatment for biotin-related disease (biotinidase deficiency, holocarboxylase synthetase deficiency) is biotin itself. No source retrieved shows cyanocobalamin correcting a primary biotin metabolic defect. The very high TxGNN score most likely reflects the two vitamins sitting close together in the knowledge graph, not a demonstrated therapeutic effect.
Clinical Trial Evidence
None of the 15 retrieved trials is specific to cyanocobalamin and biotin metabolic disease. All graded trials were rated “C” (indirect at best). The 10 most relevant are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01643187 | Phase 2 | Unknown | 1000 | Fortified food vs milk on micronutrient status (including serum B12) in malnourished children |
| NCT01173315 | Phase 2 | Completed | 75 | Vitamin and mineral supplementation for neuropathy and nephropathy in type 2 diabetes |
| NCT03360435 | N/A | Completed | 99 | Transdermal vitamin absorption after bariatric surgery |
| NCT02426775 | Phase 3 | Completed | 33 | Carglumic acid in propionic or methylmalonic acidemia (related pathway, different drug; not yet graded) |
| NCT05832190 | N/A | Terminated | 5 | Fiber plus biotin to improve gut microbiota before bariatric surgery; too small to be informative |
| NCT04312152 | N/A | Unknown | 200 | Ubiquinol with vitamin B and E complex in autism and Phelan-McDermid syndrome |
| NCT00572741 | N/A | Completed | 39 | Nutritional intervention for oxidative stress and methylation in autism |
| NCT05687474 | N/A | Completed | 6824 | Genomic newborn screening for treatable genetic diseases; no therapeutic evidence |
| NCT03444155 | N/A | Completed | 30 | Natural vs synthetic vitamin B complex bioavailability (not yet graded) |
| NCT01474486 | N/A | Completed | 40 | Multi-micronutrient intervention in congestive heart failure |
Literature Evidence
No RCTs were found. The retrieved literature consists mainly of reviews and background papers.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23622402 | 2013 | Review | Handb Clin Neurol | Vitamin-responsive disorders involving cobalamin, folate, biotin, B1 and E; vitamins act as enzyme cofactors |
| 38203763 | 2024 | Review | Int J Mol Sci | B12 deficiency and the nervous system; B12 is a cofactor in the succinyl-CoA and methionine pathways |
| 7027768 | 1981 | Review | Acta Vitaminol Enzymol | Vitamins in metabolic diseases: malabsorption, errors of vitamin metabolism, vitamin-dependent syndromes |
| 11031989 | 2000 | Review | Ryoikibetsu Shokogun Shirizu | Overview of vitamin dependency syndromes (no abstract available) |
| 958746 | 1976 | Review | Pediatr Clin North Am | Megavitamin-responsive aminoacidopathies; a therapeutic trial of the specific cofactor is advised |
| 6152513 | 1983 | Review | Adv Clin Chem | Vitamin-responsive inborn errors of metabolism (no abstract available) |
| 5011556 | 1972 | Review | Med J Aust | Vitamin dependency syndromes (no abstract available) |
| 1909779 | 1991 | Clinical study | Pediatr Res | 13C-propionate metabolism in propionic and methylmalonic acidemia, including B12-responsive patients; no biotin metabolic disease treated with B12 |
| 25388747 | 2015 | Review | Endocr Metab Immune Disord Drug Targets | Vitamins and type 2 diabetes; biotin and other B vitamins discussed |
| 36476407 | 2023 | Animal study | J Endocrinol | B12 deficiency causes glucose intolerance in female rats; not related to biotin disease |
US Market Information
The retrieved licenses contain no approved-indication text. The table below lists the manufacturer instead. Twenty licenses are on record; five are shown. Other dosage forms on the market include spray.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA214655 | cyanocobalamin | Injection, solution | Zydus Lifesciences Limited |
| ANDA206503 | cyanocobalamin | Injection | Asclemed USA, Inc. |
| ANDA080737 | Cyanocobalamin | Injection, solution | American Regent, Inc. |
| ANDA217839 | Cyanocobalamin | Injection, solution | Lifestar Pharma LLC |
| ANDA214655 | cyanocobalamin | Injection, solution | Zydus Pharmaceuticals USA Inc. |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score is not backed by direct evidence. Biotin-related disease is treated with biotin, and no trial or publication shows cyanocobalamin correcting a biotin metabolic defect. The evidence is limited to pathway-level links and general vitamin reviews (L4).
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Expert review of whether B12 has any role in biotinidase or holocarboxylase synthetase deficiency beyond standard biotin therapy
- Any direct preclinical or clinical study of cyanocobalamin in biotin metabolic disease
- Confirmation of the original approved indications from the US labels
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.