Natamycin

Approved Indications:

• Fungal Keratitis: Treatment of fungal infections of the cornea caused by susceptible organisms, including Fusarium, Aspergillus, and Candida species.
• Fungal Conjunctivitis: Management of conjunctival fungal infections caused by susceptible fungi.
• Fungal Blepharitis: Treatment of blepharitis caused by fungal pathogens, particularly in immunocompromised or chronically treated patients.

Clinically Accepted Off-label Uses:

• Fungal Keratoconjunctivitis (Mixed Forms): In cases where both the conjunctiva and cornea are infected simultaneously.
• Prophylaxis in High-Risk Corneal Trauma: Preventive use in corneal injuries involving plant matter or contaminated water where fungal infection is a risk.

Adults:

• Dosage for Fungal Keratitis and Conjunctivitis:
  Instill 1 drop of 5% Natamycin ophthalmic suspension into the affected eye every 1 to 2 hours while awake during the initial treatment phase (first 3 to 4 days).
  Once improvement is observed, reduce frequency to every 3 to 4 hours.
  Continue treatment for 14 to 21 days, or longer if infection persists.

Elderly:

• No dose adjustment required. Administer as in adults.

Pediatric Population:

• Safety and efficacy are established. Use same dosing as adults, particularly in children over 2 years old, under ophthalmologist supervision.

Renal or Hepatic Impairment:

• Not applicable. Systemic absorption is negligible; no dose adjustment required.

Route of Administration: Topical ophthalmic
Frequency: Every 1–2 hours initially, then taper based on clinical response
Duration: Typically 2–3 weeks or as directed by an ophthalmologist

Administration Notes:

• Shake well before use.
• Avoid touching the dropper tip to prevent contamination.
• Remove contact lenses before application and wait at least 15 minutes before reinsertion.

Natamycin is a polyene antifungal that binds specifically to ergosterol, a vital component of fungal cell membranes. This binding disrupts membrane integrity and increases membrane permeability, leading to leakage of intracellular components and subsequent cell death. Unlike some other polyene antifungals, Natamycin does not significantly cause pore formation but rather inhibits essential membrane-bound enzyme functions, particularly in filamentous fungi. Its targeted action against ergosterol makes it effective against a wide spectrum of pathogenic fungi with minimal impact on mammalian cells.

• Absorption: Minimal systemic absorption when applied topically to the eye.
• Distribution: Remains localized at the ocular surface; does not penetrate deeply into the intraocular tissues or systemic circulation.
• Metabolism: Not systemically metabolized due to negligible absorption.
• Elimination: Primarily removed via tear drainage.
• Half-life: Not systemically applicable; ocular residence time depends on tear film and blinking rate.
• Onset of Action: Within 24–48 hours after initiation of therapy for susceptible fungal infections.

Pregnancy:

• FDA Category: Category C (under older classification).
• Animal studies have not shown fetal harm, but adequate studies in pregnant women are lacking. Use only if the potential benefit justifies the potential risk to the fetus.

Lactation:

• Unknown whether Natamycin is excreted in human breast milk.
• Given negligible systemic absorption, it is considered safe during breastfeeding.
• Avoid direct contact with breast tissue and infant's eyes.

Recommendation: Use with caution during pregnancy and lactation. No special precautions needed unless the mother is using the drug in high frequency or in unusual dosing schedules.

• Primary Therapeutic Class: Antifungal (Polyene class)
• Subclass: Topical ophthalmic antifungal agent
• Spectrum: Active primarily against filamentous fungi (e.g., Fusarium, Aspergillus) and some Candida species

• Known hypersensitivity to Natamycin or any of its components
• Ocular trauma or deep stromal involvement without fungal etiology
• Non-fungal eye infections (e.g., bacterial or viral conjunctivitis)

• Delayed Diagnosis: Use only after laboratory or clinical confirmation of fungal etiology; do not initiate empirically in unclear cases.
• No Intraocular Penetration: Not suitable for fungal endophthalmitis or intraocular fungal infections.
• Long-term Use: May lead to secondary bacterial infections or overgrowth of non-susceptible organisms.
• Contact Lenses: Avoid use during active infection unless specifically advised.
• Hypersensitivity Reactions: Discontinue if signs of allergy, irritation, or worsening ocular symptoms occur.

Common Adverse Effects (usually mild and transient):

• Ocular:
• Eye irritation
• Foreign body sensation
• Conjunctival hyperemia
• Increased lacrimation
• Blurred vision (immediate, post-instillation)

Less Common Side Effects:

• Eyelid edema
• Ocular pruritus
• Burning or stinging sensation
• Dry eye or ocular discomfort

Rare but Serious Effects:

• Hypersensitivity reactions (e.g., angioedema, urticaria)
• Superinfection with non-susceptible organisms with prolonged use

Onset: Most side effects occur within minutes of application. They are usually self-limited and resolve without intervention.

• No significant systemic interactions, as Natamycin has negligible systemic absorption.

Topical/Ocular Interaction Considerations:

• Avoid using concurrently with other ophthalmic agents unless advised by an ophthalmologist; spacing doses by 10–15 minutes is advisable to avoid dilution or washout.
• May interfere with diagnostic staining procedures if applied beforehand.

Enzyme Systems:

• Not metabolized via CYP450 enzymes; no involvement in CYP induction or inhibition.

Food and Alcohol Interactions:

• Not applicable.

• AAO (American Academy of Ophthalmology) & WHO Guidance: Continues to recommend Natamycin 5% suspension as the first-line therapy for fungal keratitis, particularly in cases caused by filamentous fungi.
• Recent Trials (2023–2024): Support Natamycin over voriconazole in terms of lower rates of perforation and faster healing in fungal keratitis caused by Fusarium species.
• Global Guidelines (NICE, EMA): No major changes in indications or safety profile in the last 2 years.

• Temperature: Store at 2°C to 8°C (refrigerated); do not freeze.
• Humidity: Keep tightly closed; avoid exposure to moisture.
• Light: Store in original container away from direct light.
• Handling Precautions:
• Shake well before use.
• Do not touch dropper tip to any surface.
• Discard bottle 4 weeks after opening.
• Reconstitution/Refrigeration: Already in suspension form; must remain refrigerated.