Zidovudine
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
- Zidovudine
- Pharmacist Assessment Report
- Zidovudine: From HIV Infection to Feline Acquired Immunodeficiency Syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Zidovudine: From HIV Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Zidovudine is a nucleoside reverse transcriptase inhibitor, with HIV infectious disease and AIDS recorded as its original indications in the knowledge graph. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome. The supporting evidence is 0 clinical trials and 19 publications, nearly all of them veterinary or animal studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (relations recorded in the knowledge graph; the Indian licence records contain no indication text) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 0.9996 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (19 of 19) – CDSCO approval status is not included in this data |
| Number of Listed Products | 19 (valid: 19) |
| Number of Approvals | 19 licences (all single-ingredient products) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI). Its use against HIV is recorded in the knowledge graph.
Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses that depend on reverse transcriptase, so zidovudine is biologically plausible against them. Studies in cats and in experimentally infected animals report lower plasma virus titers, reduced provirus burden, and higher CD4 counts. Some studies found that treatment did not prevent infection or the spread of the virus, and one FeLV study found no effect on circulating virus without interferon.
This is a veterinary indication, and it is essentially the animal model of the human disease rather than a new human use. Its relevance to human drug repurposing is limited. Zidovudine toxicity in FeLV-infected cats is documented, so haematological safety is a concern.
On the evidence level: the literature does study this disease directly, but only as animal studies. There are no clinical trials, and no systematic review or observational study in humans. Under the evidence rules, the level is L5 rather than the L3 shown in the internal scoring.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Showing the most relevant publications (animal studies, clinical studies in cats, and one review):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22816032 | 2012 | Clinical study in naturally infected cats | Viruses | Compared zidovudine alone and combined with interferon-α, lamivudine or valproic acid in naturally FIV-infected cats over one year |
| 7495172 | 1995 | Clinical study in cats | Zentralblatt fur Veterinarmedizin A | Long-term oral AZT versus conventional symptomatic therapy in FIV-seropositive cats with clinical symptoms |
| 25855689 | 2016 | Follow-up study in cats | J Feline Med Surg | Effects of long-term antiretroviral therapy starting with AZT for 5-6 years in FIV-infected cats |
| 1363008 | 1992 | Clinical study in cats | Vet Immunol Immunopathol | Efficacy and side effects of AZT and PMEA in naturally FIV- and FeLV-infected cats with symptoms |
| 7688949 | 1993 | Animal study | Arch Virol | Zidovudine did not prevent FIV infection, but plasma virus titers were lower than controls at 2 weeks |
| 8381867 | 1993 | Animal study | J Acquir Immune Defic Syndr | Prophylactic ZDV prevented early viremia and lymphocyte decline but not primary infection |
| 7749786 | 1995 | Animal study | J Acquir Immune Defic Syndr Hum Retrovirol | Early suppression of viremia kept CD4 counts higher but did not alter spread of infection |
| 7618256 | 1995 | Animal study | Vet Immunol Immunopathol | Reduced provirus burden and enhanced humoral immune function in AZT-treated SCID-feline mice |
| 2163339 | 1990 | Animal toxicity study | Fundam Appl Toxicol | Zidovudine toxicity evaluated in FeLV-infected cats |
| 8820595 | 1995 | Review | Semin Vet Med Surg (Small Anim) | Management of retrovirus-infected cats, including virus-specific therapy such as zidovudine |
India Market Information
The 19 licences are all single-ingredient products, and none carries approved-indication text in the records. The first five are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 250241 | Zido H 100mg Capsule | Strip of 10 capsules | Not stated in the records |
| 251540 | Zidomax 100mg Capsule | Strip of 10 capsules | Not stated in the records |
| 251471 | Zidohope 100mg Tablet | Bottle of 100 tablets | Not stated in the records |
| 251604 | Zidovex 100mg Capsule | Strip of 10 capsules | Not stated in the records |
| 248526 | Zidine 300mg Tablet | Bottle of 60 tablets | Not stated in the records |
Safety Considerations
- Relations recorded in the knowledge graph (not label text): the knowledge graph records zidovudine contraindication relations with liver failure, liver disease, kidney disease, pancreatitis, neutropenia, agranulocytosis, anaemia (including macrocytic anaemia), lactic acidosis, myopathy, myositis, dermatomyositis, fatty liver disease and hypertriglyceridaemia, among others.
- Drug Interactions: 235 interactions were found. Moderate-level examples include amphotericin B, corticosteroids (dexamethasone, prednisone, hydrocortisone, betamethasone, budesonide, prednisolone, triamcinolone), rosuvastatin, simvastatin, naltrexone and orlistat. Minor-level examples include cimetidine and clarithromycin.
- Animal toxicity: zidovudine toxicity has been documented in FeLV-infected cats, so haematological monitoring is relevant.
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Support for feline acquired immunodeficiency syndrome comes entirely from veterinary and animal studies, with no registered clinical trials. It is essentially the animal model of zidovudine’s existing HIV use. It therefore does not constitute a new human indication, and the evidence level is L5.
To proceed, the following is needed:
- Confirmation of whether a veterinary development path is actually intended, since human repurposing relevance is limited
- Package insert warnings and contraindications from the Indian licence holders
- Mechanism of action data
- Haematological and mitochondrial safety data relevant to the target species
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.