Levocarnitine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Levocarnitine
- Pharmacist Assessment Report
- Levocarnitine: From Carnitine Deficiency Support to autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Levocarnitine: From Carnitine Deficiency Support to autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
One-Sentence Summary
Levocarnitine is a form of carnitine that carries long-chain fatty acids into mitochondria for energy production. It is marketed in Canada under several DINs, but the data compiled for this report do not include approved indication text. The TxGNN model’s top-ranked prediction is a rare vascular disorder with no supporting evidence. The best-supported prediction is Congestive Heart Failure, with 3 clinical trials (including 1 completed Phase 2/3 trial) and 11 publications currently supporting this direction. This report therefore focuses on heart failure, the new indication with the strongest evidence among the top 10 predictions.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no approved indication text in the Canadian licence data) |
| Predicted New Indication | Congestive heart failure (the rank 1 prediction, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, has no evidence and is not the focus of this report) |
| TxGNN Prediction Score | 0.9947 (heart failure); 0.9994 for the rank 1 prediction |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 4 of 4) |
| Number of DINs | 4 (marketed: 4) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, levocarnitine is the biologically active form of carnitine and is essential for fatty acid metabolism. It carries long-chain fatty acids into mitochondria for beta-oxidation.
The heart relies heavily on fatty acid oxidation for energy. Myocardial carnitine depletion has been described in failing hearts, so supplementation may improve myocardial energy metabolism. A review in the literature (PMID 15591005) also notes that levocarnitine reduces the toxic effects of free fatty acids during ischaemia and improves carbohydrate metabolism.
This fits heart failure better than the model’s highest-scoring predictions. The rank 1 and 2 predictions are rare collagen IV-related vascular disorders. Those scores likely reflect network proximity rather than a plausible carnitine mechanism, and no trials or publications support them.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01580553 | Phase 2/3 | Completed | 268 | Multicentre, randomised, double-blind, placebo-controlled study of L-carnitine injection in Chinese patients with heart failure (7-day treatment, 1-month follow-up). Results were not provided. |
| NCT07201714 | Early Phase 1 | Recruiting | 20 | Oral L-carnitine in cardiorenal heart failure, assessing symptoms, heart function and quality of life. No results yet. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29468383 | 2018 | RCT | Paediatric Drugs | Randomised trial in 29 children with dilated cardiomyopathy, testing levocarnitine added to conventional therapy. |
| 40172612 | 2025 | Systematic review / meta-analysis | Int Urol Nephrol | Safety and efficacy of L-carnitine for cardiac function in haemodialysis patients. |
| 15591005 | 2004 | Review | Ann N Y Acad Sci | Levocarnitine and propionyl-L-carnitine in cardiovascular disease. Reduces myocardial injury after ischaemia and reperfusion. |
| 30195728 | 2020 | Clinical study | Hellenic J Cardiol | Effects of levocarnitine on cardiac function and biomarkers (BNP, troponin, hs-CRP) in coronary heart disease with heart failure. |
| 30041211 | 2018 | Clinical study / review | Contrib Nephrol | Levocarnitine effects on cardiac function and renal anaemia in haemodialysis patients. |
| 24125620 | 2013 | Clinical study | Zhonghua Liu Xing Bing Xue Za Zhi | Effects of levocarnitine on heart function and endocrine markers in elderly patients with chronic heart failure. |
| 30646314 | 2018 | RCT | JAMA Netw Open | RACE trial of levocarnitine in septic shock (not heart failure). Provides general safety and metabolic context only. |
| 37979716 | 2023 | Case series / review | Eur J Med Genet | Cardiovascular involvement in later-onset malonyl-CoA decarboxylase deficiency. |
| 35712814 | 2022 | Case report | Mol Genet Genomic Med | Early cardiomyopathy in cblB-type methylmalonic acidaemia. |
| 40713745 | 2025 | Preclinical | Stem Cell Res Ther | NEXN deficiency causes dilated cardiomyopathy in stem cell-derived cardiomyocytes. Indirectly relevant. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02144344 | CARNITOR | Not listed | Not listed |
| 02144336 | CARNITOR | Not listed | Not listed |
| 02144328 | CARNITOR | Not listed | Not listed |
| 02492105 | ODAN LEVOCARNITINE | Not listed | Not listed |
Safety Considerations
- Disease associations in the knowledge graph (not label text): The TxGNN knowledge graph links levocarnitine to contraindication edges for epilepsy, kidney disease, pyoureter, liver disease, gallbladder disease, hypotensive disorder, blood coagulation disease, cholestasis, benign recurrent intrahepatic cholestasis and familial intrahepatic cholestasis. These come from the graph, not the package insert, and should be verified against the label.
- Drug Interactions: 68 potential interactions were identified. Two are rated Moderate: warfarin and dicoumarol. Anticoagulant patients need INR monitoring. Others are of unknown severity, including calcitriol, folic acid, ramipril, nicotine, lorazepam, fluconazole, pantoprazole, citalopram, metoprolol, topiramate, valproic acid, acetaminophen, omeprazole, diltiazem, sucralfate, mirtazapine, amlodipine and digoxin.
- Other considerations noted in the evidence: Known carnitine adverse effects include gastrointestinal effects, and there is a TMAO-related cardiovascular concern with long-term oral use.
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails (for congestive heart failure only)
Rationale: A completed Phase 2/3 randomised, placebo-controlled trial (n=268) and several clinical publications support a possible benefit of levocarnitine on cardiac function, on top of a sound metabolic rationale. However, trial results were not available, and much of the literature comes from haemodialysis or cardiorenal populations with mixed quality, so the evidence does not reach L1.
Other predictions are weaker:
- Rheumatoid arthritis: Hold. Evidence level L3, with only one small pilot (n=15). The trial NCT03953703 is titled as a Sjögren’s syndrome dry eye study, which does not match the predicted indication, so the link needs checking.
- Diabetic nephropathy: Research question. Evidence level L4, with one 2026 publication on a levocarnitine-alprostadil combination.
- All other predictions, including the rank 1 and 2 collagen IV-related disorders: Hold. Evidence level L5, prediction only.
To proceed, the following is needed:
- Outcome data from NCT01580553, with verification in non-dialysis heart failure populations
- Package insert warnings, contraindications and approved indications from Health Canada, which are currently missing and block formal safety screening
- Mechanism of action data from DrugBank
- A review of safety in patients taking anticoagulants (warfarin, dicoumarol) and in those with kidney or liver disease
- Long-term safety assessment of oral use, including the TMAO-related concern
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.