Acyclovir
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Acyclovir: From Herpes Simplex Infection to Common Wart
One-Sentence Summary
Acyclovir is an antiviral drug originally used to treat herpes simplex, herpes zoster (shingles), chickenpox, herpes labialis, herpes simplex encephalitis and genital herpes. The TxGNN model predicts it may be effective for common wart (intralesional use), with 4 registered clinical trials and 19 publications currently supporting this direction. The evidence is small-scale and mostly from single centres, so it is best viewed as a research question rather than a ready-to-adopt therapy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Herpes simplex infection, herpes zoster, chickenpox, herpes labialis, herpes simplex encephalitis, genital herpes (the authorisation records compiled for this report contain no indication text) |
| Predicted New Indication | Common wart |
| TxGNN Prediction Score | 99.46% |
| Evidence Level | L2 |
| UK Market Status | Marketed |
| Number of Marketing Authorisations | 5 |
| Recommended Decision | Proceed with Guardrails (research use only) |
Note on the choice of indication: The top-ranked TxGNN prediction (punctate epithelial keratoconjunctivitis, 99.67%) has only L5 evidence and no supportive clinical data. This report therefore focuses on the highest-ranked prediction with meaningful clinical evidence, common wart (rank 2). Other predictions are summarised briefly below.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Acyclovir is a well-known guanosine analogue. In herpesvirus-infected cells it is activated by viral thymidine kinase and interferes with viral DNA synthesis. Its efficacy in herpes infections is well established.
Warts are caused by human papillomavirus (HPV), not a herpesvirus, and acyclovir is not a classical HPV antiviral. Proposed explanations for the observed benefit include interference with viral DNA synthesis and an immunomodulatory effect from intralesional injection (a possible local inflammatory response). These mechanisms remain hypotheses.
Several small randomised or comparative studies of intralesional acyclovir exist. They compare it with cryotherapy, 5-fluorouracil, Candida antigen, vitamin D3, HPV vaccine, PPD and hepatitis B vaccine. Sample sizes are small and heterogeneity is high, so this is repurposing-grade evidence that needs confirmation in larger trials.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT06261684 | Phase 2/3 | Unknown | 92 | Randomised trial of intralesional acyclovir vs cryotherapy in plantar warts; safety and efficacy. A corresponding RCT publication exists (PMID 40889709) |
| NCT05429151 | Phase 4 | Unknown | 40 | Intralesional acyclovir vs Candida antigen in plantar warts, with dermoscopic assessment |
| NCT07448844 | Phase 4 | Recruiting | 40 | Intralesional vitamin D3 vs acyclovir in common, plantar, flat and periungual warts; primary outcome is complete clearance by week 8. No results yet |
| NCT05324904 | Not specified | Unknown | 44 | Intralesional vitamin D3 vs acyclovir in plantar warts; efficacy and safety |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40889709 | 2026 | RCT | J Am Acad Dermatol | Intralesional acyclovir vs cryotherapy in plantar warts, which are known to be recalcitrant |
| 38822848 | 2024 | RCT | Arch Dermatol Res | Intralesional acyclovir vs intralesional hepatitis B vaccine in resistant plantar warts (48 patients completed) |
| 41686619 | 2026 | Systematic review / network meta-analysis | Medicine | Compares treatment modalities for cutaneous warts; intralesional acyclovir is described as a novel option |
| 40488756 | 2025 | Comparative study | Arch Dermatol Res | Intralesional acyclovir vs 5-fluorouracil in recalcitrant warts; complete response reported in most patients |
| 40056255 | 2025 | Clinical trial | Arch Dermatol Res | Intralesional acyclovir vs quadrivalent HPV vaccine in 60 patients with recalcitrant warts |
| 37303436 | 2023 | Comparative study | Cureus | Intralesional acyclovir vs PPD immunotherapy in viral warts |
| 34412535 | 2022 | Clinical study | J Cutan Med Surg | Intralesional acyclovir proposed as a potential option for cutaneous warts |
| 38793636 | 2024 | Case series and review | Viruses | Remission of HPV-related disease (including penile condyloma) with acyclovir or valaciclovir |
| 26885794 | 2016 | Case report | J Drugs Dermatol | Persistent plantar warts resolved after a 10-day course of oral acyclovir given for herpes zoster |
| 6467981 | 1984 | Report | Cutis | Early report on acyclovir ointment in common warts (no abstract available) |
UK Market Information
| Marketing Authorisation Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 0503021C0AAAAAA | Aciclovir Oral Suspension 200mg/5ml (sugar-free) | Oral suspension | Not recorded in the data compiled |
| 1310030C0BDAAAA | Soothelip Cold Sore Cream 5% | Cream | Not recorded in the data compiled |
| 1310030C0BBABAA | Zovirax Cold Sore Cream 5% | Cream | Not recorded in the data compiled |
| 1310030C0BFAAAA | Virasorb Cold Sore Cream 5% | Cream | Not recorded in the data compiled |
| 1310030C0BNAAAA | Cymex Ultra Cream 5% | Cream | Not recorded in the data compiled |
All five authorisations are valid single-ingredient products. The identifiers shown are those in the compiled records and are not in the usual PL format. Please verify them against the MHRA register. No UK licensed product carries a wart indication, and intralesional injection is not a licensed route for any of these products. The trials above used injectable acyclovir diluted for intralesional use (for example 250 mg vial diluted to about 70 mg/ml). Use for warts would be off-label.
Safety Considerations
Contraindications flagged in the knowledge graph (derived from drug-disease network links, not from label text, so interpret with caution): hypertension, kidney disease and impaired renal function, hyperglycaemia and diabetes mellitus, diabetic ketoacidosis, adrenocortical insufficiency (Addison disease), obesity, stroke and cerebrovascular disorders, myocardial infarction, haemolytic-uraemic syndrome, thrombocytopenic purpura, peripheral vascular disease, skin atrophy and telangiectasia. Several of these look more characteristic of corticosteroids than of acyclovir and may be spurious.
Drug Interactions: 454 potential interactions were identified. The ones graded Moderate are:
- Balsalazide
- Mesalazine
- Olsalazine
- Sulfasalazine
- Trospium
Other listed interactions (for example amphotericin B, metformin, morphine and omeprazole) have no severity grade.
Please refer to the SmPC and BNF for full warnings and contraindications; these were not available in the data compiled. Report suspected adverse reactions via the Yellow Card Scheme.
Other Predictions in the Data (Brief)
| Predicted Indication | TxGNN Score | Evidence Level | Assessment |
|---|---|---|---|
| Punctate epithelial keratoconjunctivitis | 99.67% | L5 | Retrieved papers concern microsporidial and drug-induced corneal disease, not acyclovir benefit. Hold |
| Post-infectious neuralgia | 99.25% | L5 | No trials or literature. Acyclovir treats acute zoster but is not an established treatment for established neuralgia. Hold |
| Hepatitis C-induced cirrhosis | 99.23% | L5 | No known anti-HCV activity; likely a spurious association. Hold |
| Eosinophilic pustular folliculitis | 99.22% | L5 | No viral rationale and no evidence. Hold |
| Sequela of COVID-19 | 99.16% | L4 | Evidence concerns herpesvirus reactivation after COVID-19, not the sequelae themselves. Hold |
| Vulvovaginal candidiasis | 99.11% | L5 | Acyclovir has no antifungal activity. Hold |
| Papular urticaria | 99.09% | L5 | No viral mechanism and no evidence. Hold |
| Disease of orbital region | 99.08% | L3 | Relevant subset is herpetic eye disease, where acyclovir is already standard, so this is closer to an existing use than a new one. Research question |
| Epidemic keratoconjunctivitis | 99.07% | L4 | Adenoviral cause; acyclovir is not expected to be active. Hold |
Conclusion and Next Steps
Decision: Proceed with Guardrails (for common wart, as a research question only)
Rationale: Four registered trials (including one Phase 2/3 RCT with a published report) and several small comparative studies suggest intralesional acyclovir may help recalcitrant warts. However, trials are small, mostly single-centre, and the mechanism is unclear. Most of the other high-scoring predictions have no supportive clinical data and should be held.
To proceed, the following is needed:
- Larger, multicentre, adequately powered RCTs against standard care (such as salicylic acid and cryotherapy), with long-term recurrence follow-up
- Clarification of the mechanism of action in HPV-related lesions
- Safety data and a dosing standard for intralesional administration, since this is an unlicensed route
- Complete SmPC and BNF warnings and contraindications, which were missing from the data compiled
- Review of the knowledge-graph contraindication signals against the label
- Confirmation of UK licence numbers and indication text, which were absent from the authorisation records
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.