ATC Class:S01AA10

VA Class:OP210

AHFS Class:

• Antifungals 52:04.16

Generic Name(s):

• Natamycin

Natamycin, a tetraene polyene, is an antifungal agent.1

Natamycin 5% ophthalmic suspension is used in the topical treatment of blepharitis, conjunctivitis, and keratitis caused by susceptible fungi, including keratitis caused by Fusarium solani .1 The effectiveness of topical natamycin used alone in the treatment of fungal endophthalmitis has not been established.1

The clinical diagnosis, laboratory diagnosis by smear and culture of corneal scrapings, and response to the drug should be used to guide initial and continued therapy of fungal keratitis.1 Whenever possible, in vitro susceptibility testing should be performed to confirm that the causative organism is susceptible to natamycin.1

Administration

Ophthalmic Administration

Natamycin is applied topically to the eye as a 5% ophthalmic suspension.1

Natamycin ophthalmic suspension is for topical ophthalmic use only and should not be injected into the eye.1

To avoid contaminating the ophthalmic suspension, the tip of the dispensing dropper should not be allowed to touch any surface.1

The ophthalmic suspension should be shaken well prior to each use.1

Dosage

Fungal Blepharitis or Conjunctivitis

For the topical treatment of fungal blepharitis and conjunctivitis in adults, 1 drop of natamycin 5% ophthalmic suspension should be instilled into the conjunctival sac of the affected eye(s) 4-6 times daily.1

Fungal Keratitis

For the topical treatment of fungal keratitis in adults, 1 drop of natamycin 5% ophthalmic suspension should be instilled into the conjunctival sac of the affected eye(s) every 1-2 hours.1 After 3-4 days, the frequency of administration can usually be decreased to 1 drop 6-8 times daily;1 in many cases, frequency may be gradually decreased every 4-7 days.1

If there are no signs of improvement after 7-10 days of topical natamycin therapy, the infection may be caused by pathogens not susceptible to the drug and continued therapy should be based on clinical reevaluation and additional laboratory studies.1

If there is evidence of improvement, natamycin ophthalmic 5% suspension should generally be continued for 14-21 days or until there are no signs or symptoms of active fungal keratitis.1

Adverse Effects

The most frequent adverse effects of natamycin 5% ophthalmic suspension include allergic reaction, change in vision, chest pain, corneal opacity, dyspnea, eye discomfort, eye edema, eye hyperemia, eye irritation or pain, foreign body sensation, paresthesia, and tearing.1

Precautions and Contraindications

Natamycin 5% ophthalmic suspension is contraindicated in patients hypersensitive to the drug or any ingredient in the formulation.1

The ophthalmic suspension is for topical ophthalmic use only and should not be injected into the eye.1

Patients should be warned not to wear contact lenses if any signs or symptoms of fungal blepharitis, conjunctivitis, or keratitis are present.1

Pediatric Precautions

Safety and efficacy of natamycin 5% ophthalmic suspension have not been established in pediatric patients.1

Geriatric Precautions

No overall differences in safety and efficacy of natamycin 5% ophthalmic suspension have been observed between geriatric and younger adults.1

Mutagenicity and Carcinogenicity

No long-term animal studies have been performed to evaluate the mutagenic or carcinogenic potential of natamycin.1

Pregnancy, Fertility, and Lactation

Animal reproduction studies have not been performed to evaluate whether natamycin can cause fetal harm or affect reproduction capacity.1

Natamycin 5% ophthalmic suspension should be used during pregnancy only if clearly needed.1

It is not known whether natamycin is distributed into human milk.1 Because many drugs are distributed into human milk, natamycin 5% ophthalmic suspension should be used with caution in nursing women.1

No formal drug interaction studies have been performed using natamycin 5% ophthalmic suspension.1

Mechanism of Action

Natamycin appears to be predominantly fungicidal.1 The drug exerts its antifungal activity by binding to sterols in the fungal cell membrane.1 The polyenesterol complex alters the permeability of the membrane to produce depletion of essential cellular constituents.1 The mechanism of action appears to be similar to that of amphotericin B and nystatin.

Spectrum

Natamycin has in vitro activity against a variety of yeast and filamentous fungi,1 including Aspergillus ,1 Candida ,1 Cephalosporium ,1 Fusarium ,1 and Penicillium .1 The minimum inhibitory concentration (MIC) of natamycin for most susceptible fungi in vitro is 1-10 mcg/mL.

Natamycin is inactive in vitro against gram-positive or gram-negative bacteria.1

Pharmacokinetics

Systemic absorption is not expected following topical application of natamycin to the eye.1

Following topical application of natamycin 5% ophthalmic suspension to the eye, the drug adheres to the cornea in areas of epithelial ulceration and is retained in the conjunctival fornices.1 Topical application to the eye appears to produce effective natamycin concentrations within the corneal stroma, but not in intraocular fluid.1

Chemistry and Stability

Chemistry

Natamycin is an antifungal antibiotic derived from Streptomyces natalensis .1 The drug is a polyene macrolide structurally related to amphotericin B and nystatin. Natamycin occurs as a white crystalline powder and is very slightly soluble in water and in alcohol.

Commercially available natamycin ophthalmic 5% suspension has a pH of 5-7.5.1 Each mL of the ophthalmic suspension contains 50 mg of natamycin and also contains benzalkonium chloride 0.02% as a preservative, purified water, and sodium hydroxide and/or hydrochloric acid to adjust pH.1

Stability

Natamycin 5% ophthalmic suspension should be stored at 2-24°C.1 The ophthalmic suspension should not be exposed to light or excessive heat and should not be frozen.1

Only references cited for selected revisions after 1984 are available electronically.

1. Alcon Laboratories, Inc. Natacyn^® (natamycin) 5% ophthalmic suspension prescribing information. Fort Worth, TX; 2016 May.