Zypred

Approved Indications:

• Postoperative Ocular Inflammation with Risk of Bacterial Infection:
  Indicated for the treatment of inflammation and prevention of infection following ocular surgeries such as cataract extraction.
• Steroid-Responsive Ocular Inflammatory Conditions with Suspected Bacterial Infection:
  Used in conjunctivitis, blepharitis, and keratitis when both inflammation and risk of bacterial infection are present.
• Bacterial Conjunctivitis with Associated Inflammation:
  For treating bacterial eye infections accompanied by ocular inflammation.

Clinically Accepted Off-Label Uses:

• Prophylaxis in high-risk ocular procedures (e.g., LASIK, intravitreal injections)
• Chronic blepharoconjunctivitis with bacterial superinfection
• Contact lens-induced corneal irritation with secondary infection

Route: Ophthalmic (eye drops)

Adults:

• Instill 1 drop into the affected eye(s) every 4 to 6 hours.
• In severe cases, dosage may be increased to 1 drop every 1 to 2 hours initially, then tapered as inflammation improves.

Pediatrics (≥2 years):

• Same as adult dosage. Use under specialist supervision.

Elderly:

• No dose adjustment necessary. Monitor intraocular pressure during prolonged use.

Renal/Hepatic Impairment:

• No dose adjustment required due to minimal systemic absorption.

Duration:

• Short-term use is recommended, typically 7–14 days. Taper gradually to prevent rebound inflammation.

This fixed-dose combination provides dual pharmacologic effects:

• Loteprednol Etabonate is a corticosteroid that binds to glucocorticoid receptors in ocular tissues, inhibiting inflammatory mediators such as prostaglandins and leukotrienes. It reduces vascular permeability, cellular infiltration, and edema. It is retrometabolically designed to rapidly convert to inactive metabolites, reducing the risk of steroid-induced intraocular pressure elevation.
• Gatifloxacin is a fourth-generation fluoroquinolone that inhibits bacterial enzymes DNA gyrase and topoisomerase IV, blocking bacterial DNA replication and transcription, resulting in bacterial cell death. It is effective against a broad spectrum of Gram-positive and Gram-negative ocular pathogens.

Loteprednol Etabonate:

• Absorption: Minimal systemic absorption
• Distribution: Localized ocular penetration
• Metabolism: Rapidly hydrolyzed by esterases into inactive metabolites
• Excretion: Inactive metabolites excreted renally
• Half-life: Short ocular half-life

Gatifloxacin:

• Absorption: Low systemic absorption
• Distribution: Well distributed in conjunctival and corneal tissues
• Metabolism: Not significantly metabolized
• Excretion: Mainly excreted unchanged via urine
• Half-life: ~7–8 hours (systemic, not clinically significant in topical use)

Pregnancy:

• No assigned FDA pregnancy category.
• Animal data show no fetal harm. Use only if clearly needed and prescribed by a physician.

Lactation:

• It is unknown whether the components are excreted in human milk after topical use.
• Due to low systemic absorption, the risk to nursing infants is minimal. Use with caution.

• Primary Class: Ophthalmic anti-inflammatory and anti-infective combination
• Subclasses:
• Loteprednol Etabonate: Corticosteroid (retrometabolic "soft" steroid)
• Gatifloxacin: Fourth-generation fluoroquinolone antibiotic

• Hypersensitivity to loteprednol, gatifloxacin, or any excipients
• Active viral infections of the eye (e.g., herpes simplex keratitis, varicella)
• Fungal or mycobacterial ocular infections
• Untreated purulent ocular infections
• Children under 2 years (safety not established)

• Increased Intraocular Pressure (IOP):
  Monitor IOP during prolonged use, especially in patients with glaucoma.
• Cataract Formation:
  Risk of posterior subcapsular cataract with extended corticosteroid use.
• Delayed Healing:
  Corticosteroids may impair wound healing. Use cautiously in corneal thinning or after ocular surgery.
• Secondary Infections:
  Steroids may mask infection symptoms or promote secondary infections (bacterial, viral, fungal).
• Contact Lens Wearers:
  Remove contact lenses prior to use and wait at least 15 minutes before reinserting.

Common (≥1%):

• Eye irritation or stinging
• Conjunctival hyperemia
• Blurred vision
• Increased tearing
• Foreign body sensation

Less Common/Serious:

• Elevated intraocular pressure
• Posterior subcapsular cataracts (with prolonged use)
• Secondary infections (e.g., herpes keratitis)
• Corneal thinning or perforation
• Hypersensitivity reactions

Severity and Timing:

• Most side effects are mild and occur early in treatment.
• Serious adverse effects generally arise with prolonged or inappropriate use.

• Other Ophthalmic Corticosteroids or NSAIDs:
  May increase risk of delayed healing and ocular toxicity.
• Contact Lens Preservatives (e.g., benzalkonium chloride):
  Can adhere to soft lenses and cause irritation.
• Systemic Drug Interactions:
  None known due to negligible systemic absorption.
• CYP450 Enzyme Involvement:
  Not clinically relevant; the drug does not significantly inhibit or induce CYP isoenzymes.

• AAO and ESCRS Recommendations (2023):
  Combination therapy of corticosteroid and antibiotic is recommended for short-term postoperative inflammation with infection risk.
• FDA Advisory (2022–2023):
  Emphasized tapering of corticosteroids and regular monitoring of intraocular pressure in long-term use.
• Clinical Preference:
  Increasingly preferred over older combinations (e.g., dexamethasone + tobramycin) due to a better safety profile for IOP elevation and bacterial coverage.

• Temperature: Store at 15°C to 25°C (59°F to 77°F)
• Humidity: Protect from moisture
• Light: Store in original container away from light
• Handling Instructions:
• Shake well before each use (for suspension)
• Do not touch the dropper tip to any surface
• Do not freeze
• Discard after 30 days of opening or as indicated on the packaging