Natacyn®

Natamycin 5% · ophthalmic suspension

Antifungal

Approved uses

Fungal keratitis, including Fusarium solani

1 drop into the conjunctival sac hourly or every 2 hours, reduced to 6 to 8 times daily after the first 3 to 4 days, continued 14 to 21 days or until active keratitis resolves

Gains 1.8 lines of acuity over voriconazole by 3 months, 4.1 lines in Fusarium ulcers.

Fungal blepharitis and conjunctivitis

4 to 6 applications daily

OFF-LABELNot in the FDA label for this product

Recalcitrant deep fungal keratitis, intrastromal injection

10 mcg/0.1 mL intrastromal, repeated as needed, with topical 5% every 4 hours until the ulcer heals

Single-center trial · n=60

Single-center trial in 60 eyes with microbiologically proven ulcers larger than 2 mm, deeper than half the stroma, and unresponsive to 2 weeks of topical therapy, allocated 20 per arm to intrastromal natamycin 10 mcg/0.1 mL, voriconazole 50 mcg/0.1 mL, or amphotericin B 5 mcg/0.1 mL. Mean time to healing was 34 days (SD 5.2) with natamycin versus 36.1 days (SD 4.8) and 39.2 days (SD 7.2), P = 0.02, with successful healing in 95%, 95%, and 90% and deep vascularization after healing more common in the amphotericin B arm (55% versus 26% and 31%, P = 0.02). Every arm received an intrastromal injection on top of topical therapy, so the trial cannot show whether adding an injection beats topical therapy alone. The authors call it a randomized controlled trial; PubMed indexes it as a journal article only.

Saluja G, Sharma N, Agarwal R, et al. Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial. Clin Ophthalmol. 2021;15:2437-2446 (n = 60 eyes).

Contraindications

History of hypersensitivity to any component of the formulation.

Available Forms

5% (50 mg/mL) suspension, 15 mL fill in an amber glass bottle, dropper packaged separately

Mechanism of Action

Tetraene polyene antifungal derived from Streptomyces natalensis; binds the sterol moiety of the fungal cell membrane, and the polyene-sterol complex alters membrane permeability enough to deplete essential cellular constituents, giving predominantly fungicidal activity against Candida, Aspergillus, Cephalosporium, Fusarium, and Penicillium. Topical dosing reaches effective concentrations within the corneal stroma but not intraocular fluid, and there is no in vitro activity against gram-positive or gram-negative bacteria.

Warnings & Precautions

Diagnostic confirmation: Initial and sustained therapy should follow the clinical diagnosis, smear and culture of corneal scrapings, and drug response, with in vitro activity against the responsible fungus determined whenever possible.
Endophthalmitis: Effectiveness as a single agent in fungal endophthalmitis is not established.
Limited intraocular penetration: Topical dosing produces effective concentrations within the corneal stroma but not in intraocular fluid, and rabbit studies found no measurable compound in aqueous humor or sera at a stated assay sensitivity no greater than 2 mg/mL.
No antibacterial activity: Inactive in vitro against gram-positive and gram-negative bacteria.
Dropper contamination: Touching the dropper tip to any surface can contaminate the suspension.
Contact lens wear: Lenses are not to be worn while signs and symptoms of fungal blepharitis, conjunctivitis, or keratitis are present.

Common Side Effects

Ocular, post-marketing, frequency not estimable: Eye discomfort, eye irritation, eye pain, eye hyperemia, eye edema, foreign body sensation, tearing, change in vision, corneal opacity.
Systemic, post-marketing, frequency not estimable: Allergic reaction, chest pain, dyspnea, paresthesia.

Pregnancy & Lactation

Pregnancy: No animal reproduction studies have been conducted; whether the drug can cause fetal harm or affect reproductive capacity is unknown, so give only if clearly needed.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.