Natamycin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Natamycin: From Mycotic Corneal Ulcer to Vulvovaginal Candidiasis
One-Sentence Summary
Natamycin is a polyene antifungal, originally used for mycotic corneal ulcer (fungal keratitis). The TxGNN model predicts it may be effective for Vulvovaginal Candidiasis, with 1 completed Phase 3 clinical trial and 14 publications currently supporting this direction. The Phase 3 trial tested a natamycin–lactulose combination, so natamycin's own contribution cannot be isolated.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Mycotic corneal ulcer |
| Predicted New Indication | Vulvovaginal candidiasis |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L1 (see note below) |
| New Zealand Market Status | Cancelled only |
| Number of Authorizations | 1 |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: Strictly, L1 requires two or more completed Phase 3 RCTs. Only one completed Phase 3 trial is available, and it tested a combination product. The evidence is therefore best viewed as sitting between L1 and L2.
Why is This Prediction Reasonable?
Natamycin is a polyene antifungal. It binds ergosterol in the fungal cell membrane and impairs membrane integrity. Detailed mechanism of action data are not available in the data compiled for this report, but this is the well-known class mechanism for polyenes.
Candida species, the cause of vulvovaginal candidiasis, contain ergosterol and are susceptible. The mechanism is the same as in the original corneal fungal infection and is applied to a different mucosal site, in this case as a vaginal formulation.
The prediction is also supported by clinical history. Older studies, including a New Zealand report from 1980 (50 women, 76% cure rate at two weeks, maintained at four weeks), a Danish trial (cure rates of 88–94%), and comparative work against amphotericin B pessaries, describe natamycin vaginal products for vaginal candidiasis. A recent Phase 3 trial adds modern evidence, with the caveat that it used a fixed-dose combination with lactulose.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06411314 | Phase 3 | Completed | 218 | Natamycin 100 mg + lactulose 300 mg vaginal suppositories vs Pimafucin (natamycin 100 mg) or lactulose alone in non-pregnant adult women with vulvovaginal candidiasis; tests superiority and safety |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39979898 | 2025 | RCT | BMC Women's Health | Published report of the Phase 3 natamycin + lactulose suppository trial in vulvovaginal candidiasis |
| 4561566 | 1972 | Comparative trial | Med J Aust | Amphotericin B (Fungilin) vs natamycin (Pimafucin) pessaries in vaginal candidiasis |
| 6760652 | 1982 | Clinical trial | Acta Obstet Gynecol Scand | 33 patients on natamycin vaginal tablets for 10 days; cure rate 94% with partner treated vs 88% with placebo, not significantly different |
| 6966774 | 1980 | Clinical study | N Z Med J | 50 women, Pimafucin vaginal tablets for 10 days; 76% cure rate at 2 weeks, maintained at 4 weeks |
| 159686 | 1979 | Controlled trial | Aust N Z J Obstet Gynaecol | 120 patients with monilial vulvovaginitis; adding Elase to natamycin improved symptom relief and eradication vs natamycin alone |
| 12849848 | 2003 | Case-control (safety) | Reprod Toxicol | Teratology study of vaginal natamycin in pregnancy |
| 11048415 | 1999 | Review | Ceska Gynekol | Diagnosis and treatment of chronic vaginal candidiasis; natamycin compared with clotrimazole |
| 1082689 | 1975 | Clinical report | Zentralbl Gynakol | Oral metronidazole plus vaginal natamycin; Candida infections of the vagina cured clinically in 89% after first course |
| 4584444 | 1973 | Clinical study | Practitioner | Natamycin for vaginal candidiasis in pregnancy |
| 41412769 | 2025 | Survey | Ceska Slov Farm | Survey of 408 women in Lviv; lifetime VVC prevalence 72.6% (epidemiology, not efficacy) |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 260282 | Pimafucort | Ointment, natamycin 1% with neomycin sulphate 0.5% | Not recorded; licence status cancelled |
The only New Zealand licence, a combination ointment with neomycin, is cancelled. There is currently no valid licence for natamycin in New Zealand.
Safety Considerations
- Pregnancy: A case-control teratology study of vaginal natamycin use during pregnancy is available (PMID 12849848). It is relevant for any population-specific safety plan.
- Drug interactions: No interactions were found in the queried data.
Please refer to the package insert for further safety information, including warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 RCT (n=218) and several older clinical studies support natamycin in vulvovaginal candidiasis, with a plausible antifungal mechanism. Because the Phase 3 trial used a combination product and natamycin currently has no valid New Zealand licence, the decision should be conditional.
To proceed, the following is needed:
- Trial results, to separate natamycin's effect from lactulose's
- Medsafe package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- Route and formulation compatibility assessment (vaginal products vs the cancelled ointment), plus a regulatory pathway given the cancelled licence
- A safety plan for pregnant women
Other predicted indications (for reference):
- Candidiasis, vulvitis, vulvovaginitis, vaginitis: Supported only by the same vulvovaginal candidiasis evidence, applicable to the candidal subtype only. Proceed with Guardrails.
- Tinea nigra: Mechanistically plausible but no clinical evidence. Research question only.
- Trichomonal vulvovaginitis: Natamycin is not active against protozoa, and the apparent benefit is likely due to metronidazole. Hold.
- Postmenopausal atrophic vaginitis, vulvar ulceration, vulvar neoplasm: No plausible mechanism or evidence. Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.