Zidovudine
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
- Zidovudine
- Pharmacist Assessment Report
- Zidovudine: From HIV Infection and AIDS to Feline Acquired Immunodeficiency 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
Zidovudine: From HIV Infection and AIDS to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Zidovudine is a nucleoside reverse transcriptase inhibitor originally used to treat HIV infection and AIDS in humans. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV/FeLV-related disease in cats). This direction currently rests on 0 registered clinical trials and 19 publications, which are almost entirely animal or veterinary studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection; AIDS |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 0.9996 |
| Evidence Level | L5 (preclinical/veterinary studies only) |
| Canada Market Status | Marketed (marketed DINs: 6 of 6) |
| Number of DINs | 6 (marketed: 6) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data was not available in the data compiled for this report. Zidovudine is, however, a known nucleoside reverse transcriptase inhibitor (NRTI). It is phosphorylated in cells and blocks viral DNA synthesis by chain termination.
Feline immunodeficiency virus (FIV) is a lentivirus whose reverse transcriptase is closely related to that of HIV-1. This makes the prediction biologically plausible. FIV-infected cats are also widely used as an animal model of HIV infection.
Preclinical and veterinary reports describe lower plasma virus titres, reduced provirus burden and some immune benefit in treated cats. Results are mixed, though. Zidovudine did not prevent infection in several studies, and benefits were often not sustained after treatment stopped.
This is a veterinary indication, not a new human use. Its value for human medicine is mainly as a model for HIV research.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22816032 | 2012 | Veterinary clinical study | Viruses | Compared zidovudine alone and combined with interferon-α, lamivudine or valproic acid in naturally FIV-infected cats over one year, measuring viral load and CD4+/CD8+ ratios |
| 7618256 | 1995 | Animal model | Vet Immunol Immunopathol | AZT-treated SCID-feline mice inoculated with FIV showed reduced provirus burden and enhanced humoral immune function |
| 7688949 | 1993 | Animal study | Arch Virol | Zidovudine did not prevent FIV infection but lowered plasma virus titres at 2 weeks post-infection |
| 8381867 | 1993 | Animal study | J Acquir Immune Defic Syndr | Prophylactic zidovudine prevented early viremia and lymphocyte decline but not primary infection |
| 7749786 | 1995 | Animal study | J Acquir Immune Defic Syndr Hum Retrovirol | Early viremia suppression did not alter the spread of FIV; CD4 counts were higher in treated cats |
| 1363008 | 1992 | Clinical observation (cats) | Vet Immunol Immunopathol | Evaluated the efficacy and side effects of AZT and PMEA in naturally FIV- or FeLV-infected cats with clinical symptoms |
| 7495172 | 1995 | Clinical observation (cats) | Zentralbl Veterinarmed A | Long-term oral AZT (5 mg/kg three times daily) in symptomatic FIV-seropositive cats compared with conventional symptomatic therapy |
| 25855689 | 2016 | Follow-up study | J Feline Med Surg | Evaluated long-term antiretroviral therapy (5–6 years), starting with AZT, in FIV-infected domestic cats |
| 2163339 | 1990 | Animal toxicity study | Fundam Appl Toxicol | Assessed zidovudine toxicity at 7.5–60 mg/kg/day in FeLV-infected cats |
| 8820595 | 1995 | Review | Semin Vet Med Surg (Small Anim) | Reviews management of retrovirus-infected cats, including zidovudine as a virus-specific therapy |
Canada Market Information
| DIN | Product Name | Type |
|---|---|---|
| 01946323 | APO-ZIDOVUDINE | Single-ingredient |
| 01902652 | RETROVIR (AZT) | Single-ingredient |
| 01902644 | RETROVIR (AZT) | Single-ingredient |
| 02414414 | AURO-LAMIVUDINE/ZIDOVUDINE | Listed as single |
| 02375540 | APO-LAMIVUDINE-ZIDOVUDINE | Listed as single |
A sixth authorization, 02502801 (JAMP LAMIVUDINE / ZIDOVUDINE), is also valid. All six licences are currently valid. Dosage form and approved-indication text were not available for these products. These are human-use products.
Safety Considerations
- Contraindications and risk conditions from the knowledge graph (not label text): These are the disease associations recorded in the TxGNN knowledge graph:
- Haematological: neutropenia, agranulocytosis, anaemia (including macrocytic anaemia)
- Hepatic: liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, gallbladder disease
- Metabolic: lactic acidosis, hypertriglyceridaemia, obesity disorders
- Muscle: myopathy, myositis, dermatomyositis, muscular disease, skeletal muscle disease, familial periodic paralysis
- Other: kidney disease, pancreatitis, pyoureter
- Drug Interactions: The interaction screen returned 100 interactions in total, of which 20 were reviewed here.
- Moderate: amphotericin B (including the cholesteryl sulfate and lipid complex forms), corticosteroids (betamethasone, budesonide, dexamethasone, hydrocortisone, prednisolone, prednisone, triamcinolone), statins (rosuvastatin, simvastatin), naltrexone, orlistat
- Minor: cimetidine, clarithromycin
- Unknown severity: pantoprazole, omeprazole, morphine, metformin
- Veterinary toxicity: A toxicity study in FeLV-infected cats (PMID 2163339) is available and should be reviewed before any dose planning.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high (0.9996), but support is limited to animal and veterinary studies (L4). There are no registered clinical trials. The indication is veterinary and does not extend human use of the drug.
Two other predictions for this drug have much stronger evidence: congenital HIV and AIDS-related complex. Both have Phase 3 trial support and were rated “Proceed with Guardrails”. However, they fall within the drug’s existing HIV/AIDS indication rather than being true repurposing.
To proceed, the following is needed:
- Mechanism-of-action data for the drug
- Package insert warnings and contraindications from Health Canada
- Clarification of whether a veterinary indication is within the programme’s scope
- Controlled veterinary trials with defined endpoints, if the feline indication is pursued
- A review of the toxicity data from cat studies, including haematological effects
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.