Bexipred

A. Approved Ophthalmic Indications

• Anterior Uveitis
• Iritis and Iridocyclitis
• Keratitis and Keratoconjunctivitis (non-infectious origin)
• Allergic Conjunctivitis with significant inflammatory response
• Post-operative Ocular Inflammation, including:
• After cataract extraction
• After corneal transplantation
• Corneal injury due to chemical, thermal, or radiation burns

B. Clinically Accepted (Off-label) Indications

• Episcleritis and Scleritis (adjunctive short-term use)
• Inflammatory Ocular Surface Disorders (e.g., severe dry eye with inflammation)
• Prophylaxis of Corneal Graft Rejection (short-term under specialist care)
• Inflammatory Pseudotumor of the Orbit (when systemic steroids are not suitable)

General Instructions

• Route: Ophthalmic (topical)
• Form: Ophthalmic suspension (commonly 1% w/v)
• Shake well before use.

Adults:

• Mild to Moderate Inflammation:
  1–2 drops in the affected eye(s) 2 to 4 times daily
• Severe Inflammation:
  1–2 drops every 1 to 2 hours, then reduce frequency as symptoms improve
• Post-operative Use:
  1–2 drops 4 times daily beginning 24 hours after surgery, typically for 1–2 weeks

Pediatrics:

• Children ≥2 years:
  Same dosage as adults under ophthalmologist supervision
• Children <2 years:
  Use only if essential, with close monitoring

Elderly:

• No dose adjustment required, but monitor intraocular pressure (IOP) closely

Renal/Hepatic Impairment:

• Not systemically significant; no dosage adjustment needed

Important Notes:

• Do not discontinue abruptly after prolonged use—taper slowly
• Avoid contact lenses during active treatment

Prednisolone acetate is a synthetic glucocorticoid that penetrates the corneal epithelium and binds to intracellular glucocorticoid receptors in ocular cells. This receptor-ligand complex enters the nucleus and modifies the transcription of inflammatory genes by suppressing pro-inflammatory cytokines (e.g., interleukins, prostaglandins, TNF-alpha) and increasing anti-inflammatory proteins like lipocortin-1. The result is a reduction in leukocyte infiltration, edema, capillary dilation, fibrin deposition, and fibroblast proliferation, effectively suppressing ocular inflammation, redness, and discomfort.

Following ophthalmic administration:

• Absorption:
  Rapidly penetrates the cornea and is absorbed into the anterior segment. Systemic absorption is minimal with intact epithelium.
• Bioavailability:
  High local ocular bioavailability; low systemic bioavailability (<5%)
• Distribution:
  Concentrated in corneal and anterior ocular tissues; negligible systemic distribution
• Metabolism:
  Hydrolyzed locally in ocular tissues to active prednisolone. Systemically absorbed amounts are metabolized by the liver (mainly via CYP3A4).
• Half-life:
  Ocular half-life: ~4–6 hours
  Systemic half-life (if absorbed): ~2–4 hours
• Elimination:
  Inactive metabolites are excreted by the kidneys

• Pregnancy:
  FDA Category C
  Animal studies show risk of fetal harm with corticosteroids. No adequate human studies. Use only if benefits outweigh potential risks. Avoid prolonged or repeated use during pregnancy.
• Lactation:
  Unlikely to be excreted in breast milk in significant amounts after topical ophthalmic use. Minimal risk to infants. Caution is advised during prolonged treatment; monitor infant for signs of corticosteroid exposure (e.g., poor weight gain, adrenal suppression).

• Primary Class: Ophthalmic Anti-inflammatory
• Subclass: Synthetic Glucocorticoid (Topical Corticosteroid)

• Hypersensitivity to prednisolone acetate or any component of the formulation
• Viral infections of the eye, including:
• Active herpes simplex keratitis (dendritic or geographic ulcers)
• Vaccinia
• Varicella (chickenpox)
• Mycobacterial infections of the eye, such as tuberculosis
• Fungal diseases of ocular structures
• Untreated purulent ocular infections
• Corneal epithelial damage or thinning

• Glaucoma Risk:
  Prolonged use may increase intraocular pressure (IOP) → optic nerve damage, visual field loss
• Cataract Formation:
  Risk of posterior subcapsular cataracts with chronic use
• Secondary Infections:
  May suppress immune response and mask bacterial, fungal, or viral eye infections
• Corneal Thinning or Perforation:
  Especially in those with preexisting thinning or ulcers
• Delayed Wound Healing:
  Can delay healing of corneal wounds, especially post-surgery
• Monitoring:
  Monitor IOP if used longer than 10 days
  Use fluorescein staining before initiation to rule out corneal epithelial defects
• Herpes Simplex:
  Use only under strict ophthalmologic supervision due to risk of reactivation

Common (Mild, Transient):

• Burning or stinging sensation after instillation
• Blurred vision
• Eye redness
• Foreign body sensation
• Tearing or dryness

Less Common / Serious:

• Elevated intraocular pressure
• Posterior subcapsular cataract formation
• Superinfection (fungal or bacterial)
• Corneal thinning, ulceration, or perforation
• Reactivation of herpes simplex keratitis
• Hypersensitivity reactions (itching, swelling)

Adverse effects are dose- and duration-dependent.

• Live Vaccines:
  Systemic immunosuppression from absorbed corticosteroids may interfere with vaccine efficacy
• Ocular NSAIDs:
  May impair corneal healing when used concurrently
• Multiple Ophthalmic Products:
  Separate instillation by at least 5 minutes to avoid washout
• Systemic CYP3A4 Inhibitors:
  May reduce clearance of systemically absorbed prednisolone, but unlikely to be clinically significant at ophthalmic doses

• AAO Guidelines:
  Reinforce short-term corticosteroid use and emphasize intraocular pressure monitoring in all patients treated beyond 10 days
• Label Updates:
  Include stronger precautions regarding secondary infections and corneal thinning
• Post-Surgical Use Recommendations:
  Typically limited to 2 weeks or less unless otherwise indicated by the surgeon

• Temperature Range: 15°C to 25°C (59°F to 77°F)
• Protection: Store away from direct light and moisture
• Handling: Shake well before use (suspension)
• Do Not Freeze
• After Opening: Discard 28 days after first use unless otherwise specified
• Packaging: Keep bottle tightly closed and out of reach of children