Cyanocobalamin
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Cyanocobalamin: From Vitamin B12 Deficiency to Biotin Metabolic Disease
One-Sentence Summary
Cyanocobalamin (vitamin B12, DB00115) is a cobalamin-class vitamin whose established use is treating vitamin B12 deficiency; detailed Taiwan-approved indication text and mechanism-of-action data are not currently available. The TxGNN model predicts a possible link to Biotin Metabolic Disease with a 99.60% prediction score, but the identified evidence base (15 clinical trials, 20 publications) is largely generic B-vitamin/nutrition research rather than trials or literature specific to cyanocobalamin in biotin metabolic disease.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Vitamin B12 deficiency (general pharmacology; Taiwan-specific approved indication text unavailable — drug not currently marketed in Taiwan) |
| Predicted New Indication | Biotin metabolic disease |
| TxGNN Prediction Score | 99.60% (rank 7182) |
| Evidence Level | L4 |
| Taiwan (TFDA) Market Status | Not marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism-of-action data for cyanocobalamin is not available (DrugBank query returned no structured MOA). Based on known pharmacology, cyanocobalamin is a synthetic form of vitamin B12 (cobalamin), acting as a cofactor for methionine synthase and methylmalonyl-CoA mutase; its established clinical role is correcting vitamin B12 deficiency and related megaloblastic anemia/neurological disease.
“Biotin metabolic disease” refers to disorders of vitamin B7 (biotin) metabolism, such as biotinidase deficiency and multiple carboxylase deficiency — a distinct cofactor system from cobalamin, with no established shared biochemical pathway. The TxGNN score of 99.60% is therefore more likely explained by ontology adjacency than by a direct mechanistic link: cobalamin-, folate-, biotin-, and thiamine-responsive inborn errors of metabolism are frequently grouped together in the literature and knowledge-graph structure as a single “vitamin-responsive/cofactor-responsive IEM” cluster, which can inflate similarity scores between individually unrelated cofactor systems.
Given this, the prediction should be treated as a hypothesis requiring manual verification of the TxGNN disease-node definition, not as evidence of a genuine pharmacological relationship. This assessment is reinforced by the absence of any clinical trial or publication directly testing cyanocobalamin in biotin metabolic disease patients.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05687474 | N/A | Completed | 6,824 | Universal newborn genomic screening panel (126 treatable genetic diseases); may include biotinidase deficiency but is a screening, not treatment, study — not specific to cyanocobalamin (Grade C). |
| NCT01474486 | N/A | Completed | 40 | Multi-micronutrient palliative intervention in CHF patients; not specific to biotin metabolic disease or cyanocobalamin alone (Grade C). |
| NCT04312152 | N/A | Unknown | 200 | Cross-over RCT of Q10 ubiquinol + multivitamin B/E in autism (incl. Phelan-McDermid syndrome); no clear link to biotin metabolic disease (Grade C). |
| NCT03444155 | N/A | Completed | 30 | Pilot comparison of natural vs. synthetic vitamin B-complex bioavailability; not disease-specific (Grade C). |
| NCT01173315 | Phase 2 | Completed | 75 | Vitamin/mineral supplementation for neuropathy/nephropathy in type 2 diabetes; unrelated to biotin metabolic disease (Grade C). |
| NCT04586348 | Phase 4 | Active, not recruiting | 794 | Prenatal iodine supplementation and neurodevelopment; no direct relevance to cyanocobalamin or biotin metabolic disease (Grade C). |
| NCT03360435 | N/A | Completed | 99 | Transdermal vitamin absorption in post-bariatric-surgery patients; general micronutrient study, not disease-specific (Grade C). |
| NCT02426775 | Phase 3 | Completed | 33 | Long-term effectiveness of carglumic acid in propionic/methylmalonic acidemia; related organic acidemias but no direct cyanocobalamin-biotin link (Grade C). |
| NCT00572741 | N/A | Completed | 39 | Targeted nutritional intervention for oxidative stress/methylation defects in autism; not biotin-metabolic-disease specific (Grade C). |
| NCT01558193 | N/A | Completed | 202 | Multivitamin/mineral ± fatty acid supplementation and behavior; unrelated to target indication (Grade C). |
(An additional 5 trials returned by the search were not yet relevance-graded — NCT02302729, NCT03655223, NCT05832190, NCT04067921, NCT01643187.)
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23622402 | 2013 | Review (Tier 1) | Handbook of Clinical Neurology | Reviews vitamin-responsive disorders including cobalamin, folate, biotin, B1, and E — the most directly relevant source, discussing cobalamin and biotin as parallel but distinct cofactor-dependent disease categories. |
| 958746 | 1976 | Review/Case Series (Tier 2) | Pediatric Clinics of North America | Discusses megavitamin-responsive aminoacidopathies where B-vitamin cofactors (including B12 and biotin) activate deficient apoenzymes. |
| 7027768 | 1981 | Review (Tier 2) | Acta Vitaminologica et Enzymologica | Reviews vitamins implicated in inborn metabolic errors via malabsorption, metabolic errors, or vitamin-dependent syndromes. |
| 11031989 | 2000 | Review (Tier 2) | Ryoikibetsu Shokogun Shirizu | Japanese-language review of vitamin dependency syndromes; abstract not available. |
| 38203763 | 2024 | Review (Tier 2) | International Journal of Molecular Sciences | Reviews vitamin B12’s cofactor role (methylmalonyl-CoA/biotin-adjacent pathway, methionine synthesis) and neurological effects of deficiency. |
| 25388747 | 2015 | Review (Tier 3) | Endocrine, Metabolic & Immune Disorders Drug Targets | Reviews vitamins (including B-group and biotin) in type 2 diabetes; general, not disease-specific. |
| 29173522 | 2017 | Review (Tier 3) | Gastroenterology Clinics of North America | Reviews vitamin/mineral deficiencies in IBD; general micronutrient context. |
| 7015958 | 1980 | Review (Tier 3) | Annals of the New York Academy of Sciences | Reviews interactions among B-complex vitamins including thiamin and riboflavin. |
| 36476407 | 2023 | Preclinical (Tier 3) | The Journal of Endocrinology | Rat study: B12 deficiency induces glucose intolerance and a prediabetic-like phenotype. |
| 1368195 | 1992 | Review — industrial process (Tier 3) | Journal of Chemical Technology and Biotechnology | Reviews biotechnological production of vitamins/coenzymes; not clinically relevant. |
(10 additional publications were returned but remain unclassified/pending review.)
Taiwan Market Information
No marketed cyanocobalamin products are currently registered with TFDA under this evidence pack (0 licenses, market status: Not marketed / Not marketed).
Safety Considerations
Drug Interactions: 313 total documented interactions on file. Representative interactions include:
- Minor — reduced absorption with acid-reducing agents: Famotidine, Ranitidine, Ranitidine (bismuth citrate), Cimetidine, Nizatidine (H2 blockers); Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Dexlansoprazole (PPIs); and Potassium chloride.
- Unknown clinical significance — Metformin, Glimepiride, Rosiglitazone, Acarbose, Doxycycline, Morphine, Mesalazine, Sucralfate.
Taiwan-specific label warnings and contraindications are not currently available in this evidence pack; please refer to the package insert once TFDA labeling data is obtained.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high, but the review indicates it is likely driven by ontology adjacency (cofactor-responsive IEMs being clustered together) rather than a genuine biochemical link between cobalamin and biotin pathways. No clinical trial or publication was found that directly tests cyanocobalamin in biotin metabolic disease — all trials are Grade C (tangential) or unassessed, and the strongest literature source (PMID 23622402) discusses cobalamin and biotin as parallel, not overlapping, disorders.
To proceed, the following is needed:
- Cyanocobalamin MOA data from DrugBank (DG002, High severity)
- TFDA label warnings/contraindications (DG001, Blocking — required before any S1 safety screening)
- Manual review of the TxGNN “biotin metabolic disease” node definition to rule out an ontology-clustering artifact
- Targeted search for any case reports or trials specifically evaluating cobalamin/B12 supplementation in biotinidase deficiency or multiple carboxylase deficiency patients
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.