Acyclovir
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Acyclovir: From Herpes Simplex Infection to Punctate Epithelial Keratoconjunctivitis
One-Sentence Summary
Acyclovir is an antiviral drug originally used to treat herpes simplex infections, herpes zoster, chickenpox, herpes labialis, herpes simplex encephalitis and genital herpes. The TxGNN model predicts it may be effective for punctate epithelial keratoconjunctivitis, but no clinical trials and only 2 publications (case series on unrelated eye conditions) currently support this specific prediction. Among the other predictions for this drug, common wart (intralesional use) has the strongest evidence, with 4 clinical trials and 20 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Herpes simplex infection, herpes zoster, chickenpox, herpes labialis, herpes simplex encephalitis, genital herpes (the registration records compiled for this report contain no approved indication text) |
| Predicted New Indication | Punctate epithelial keratoconjunctivitis |
| TxGNN Prediction Score | 99.67% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold |
Note: The top-ranked prediction has no supporting evidence. The second-ranked prediction, common wart, has the strongest evidence (L2) and is discussed below as the most promising repurposing direction.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From general pharmacology, acyclovir is a nucleoside analogue that is phosphorylated by viral thymidine kinase and then inhibits herpesvirus DNA polymerase. Its efficacy in herpes infections is well established.
Punctate epithelial keratoconjunctivitis (top prediction): Punctate epithelial keratitis can have a herpetic cause, so the link is plausible but indirect. The two retrieved papers concern microsporidial keratoconjunctivitis and corneal lipidosis in AIDS. Neither is an acyclovir-responsive condition, so the prediction rests on the model score alone.
Common wart (best-supported prediction): Warts are caused by HPV, which has no thymidine kinase of its own, so the classical acyclovir mechanism does not directly apply. Proposed explanations for intralesional acyclovir include inhibition of viral DNA synthesis in lesional cells and a local immune-modulating effect. Several comparative trials, including a Phase 2/3 randomised trial against cryotherapy, show clinical activity.
Other predictions are weakly supported:
- Post-infectious neuralgia, COVID-19 sequelae and epidemic keratoconjunctivitis have only indirect links.
- Hepatitis C cirrhosis, vulvovaginal candidiasis, eosinophilic pustular folliculitis and papular urticaria have no antiviral rationale and are likely model artefacts.
- Disease of the orbital region mostly captures herpetic eye disease, which is already an on-label use, so it is not a novel signal.
Clinical Trial Evidence
No clinical trials are registered for punctate epithelial keratoconjunctivitis. The trials below relate to the best-supported prediction, common wart:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06261684 | Phase 2/3 | Unknown | 92 | Randomised trial of intralesional acyclovir vs cryotherapy in plantar warts; results published in 2026 (PMID 40889709) |
| NCT05429151 | Phase 4 | Unknown | 40 | Intralesional acyclovir vs Candida antigen in plantar warts |
| NCT07448844 | Phase 4 | Recruiting | 40 | Intralesional vitamin D3 vs acyclovir in cutaneous viral warts; results not yet available |
| NCT05324904 | Not applicable | Unknown | 44 | Intralesional vitamin D3 vs acyclovir in plantar warts |
Trials for the broader "disease of the orbital region" category (herpetic eye disease) include NCT06757907 (topical ganciclovir vs systemic acyclovir in herpetic keratitis, completed, n=20) and NCT03389191 (oral acyclovir in viral uveitis, unknown status, n=30). These are small and mostly non-randomised, and they largely fall within acyclovir's existing indications.
Literature Evidence
For punctate epithelial keratoconjunctivitis, only two papers were retrieved, and neither supports acyclovir efficacy:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21934222 | 2011 | Case series | Indian J Pathol Microbiol | Microsporidial keratoconjunctivitis, not an acyclovir-responsive condition |
| 7825685 | 1995 | Case series | Am J Ophthalmol | Drug-induced corneal lipidosis in AIDS patients, not related to efficacy |
For the best-supported prediction, common wart, the main publications are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40889709 | 2026 | RCT | J Am Acad Dermatol | Intralesional acyclovir vs cryotherapy in plantar warts |
| 38822848 | 2024 | RCT | Arch Dermatol Res | Intralesional acyclovir vs hepatitis B vaccine in resistant plantar warts (48 patients) |
| 41686619 | 2026 | Systematic review / network meta-analysis | Medicine | Compares treatments for cutaneous warts, including intralesional acyclovir |
| 40488756 | 2025 | Comparative study | Arch Dermatol Res | Intralesional acyclovir vs intralesional 5-fluorouracil in recalcitrant warts |
| 40056255 | 2025 | Clinical trial | Arch Dermatol Res | Intralesional acyclovir vs quadrivalent HPV vaccine in recalcitrant warts (60 patients) |
| 37303436 | 2023 | Comparative study | Cureus | Intralesional acyclovir vs PPD immunotherapy in viral warts |
| 34412535 | 2022 | Clinical study | J Cutan Med Surg | Intralesional acyclovir as a potential option for cutaneous warts |
| 38793636 | 2024 | Case reports and review | Viruses | Remission of HPV-related disease with acyclovir or valaciclovir |
| 26885794 | 2016 | Case report | J Drugs Dermatol | Persistent plantar warts resolved after oral acyclovir given for herpes zoster |
Singapore Market Information
Twenty valid single-ingredient registrations are on record. The records compiled for this report contain no approved indication text. The main ones are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN01192P | ZOVIRAX SUSPENSION 200 mg/5 ml | Suspension | Not available |
| SIN01191P | ZOVIRAX CREAM 5% w/w | Cream | Not available |
| SIN14645P | SALACLOVIR POWDER FOR SOLUTION FOR INFUSION 250MG/VIAL | Injection, powder, for solution | Not available |
| SIN10307P | APO-ACYCLOVIR TABLET 400 mg | Tablet | Not available |
| SIN08761P | MEDOVIR 200 TABLET 200 mg | Tablet, film coated | Not available |
Available dosage forms cover oral (tablet, film-coated tablet), topical (cream), suspension and injectable (powder for infusion) routes.
Safety Considerations
- Disease-related cautions (from the knowledge graph, not label text): Contraindication links include kidney disease and impaired renal function, hemolytic-uremic syndrome, thrombocytopenic purpura, hypertension, diabetes and hyperglycaemia, diabetic ketoacidosis, adrenocortical insufficiency, stroke and cerebrovascular disorders, myocardial infarction, peripheral vascular disease and skin atrophy. These come from graph relationships and should be confirmed against the package insert.
- Drug Interactions: The interaction check was completed, and 100 interactions were recorded. Moderate-level interactions include balsalazide, mesalazine, olsalazine, sulfasalazine and trospium. Others listed with unknown severity include amphotericin B, metformin, morphine, omeprazole and pantoprazole.
Please refer to the package insert for key warnings and formal contraindications.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, punctate epithelial keratoconjunctivitis)
Rationale: The prediction has only a model score behind it (L5). The two retrieved papers are unrelated to acyclovir efficacy, and no trials exist. The mechanistic link is plausible only where the keratitis is herpetic, which is already an existing use.
Alternative direction: Common wart (intralesional acyclovir) reaches evidence level L2, with a Phase 2/3 RCT and several comparative trials. It could be considered a research question. The trials are small, mostly from a single region, with unknown status and varied comparators.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently missing and block safety screening
- Detailed mechanism of action data
- For common wart, results of the Phase 2/3 RCT and larger multi-centre, blinded trials
- For common wart, a decision on formulation and route, since intralesional use of the injectable powder would be outside the registered labelling
- For punctate epithelial keratoconjunctivitis, evidence that the condition is herpetic, or abandon this prediction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.