Refemoline

Approved Indications:

• Allergic Conjunctivitis: For the treatment of ocular redness, itching, and inflammation associated with allergic conjunctivitis.
• Non-infectious Ocular Inflammation: Used to relieve inflammation caused by non-infectious conditions such as episcleritis, post-surgical inflammation, or mild iritis.
• Ocular Irritation with Redness: Provides temporary relief from redness and discomfort due to minor eye irritants (e.g., smoke, dust, wind, or swimming).

Clinically Accepted Off-label Uses:

• Dry Eye Flare-ups with Redness: Occasionally used in short-term management of dry eye exacerbations with inflammation and redness.
• Postoperative Redness and Inflammation: Sometimes used in the post-surgical period to reduce conjunctival hyperemia and local inflammation.

Adults:

• Typical Dose: Instill 1 drop into the affected eye(s) every 4 to 6 hours.
• In severe cases, dosing may be increased to 1 drop every 2 hours during the first 24–48 hours, then tapered.

Pediatrics (≥6 years):

• Dose: 1 drop every 6 hours, under medical supervision.
• Safety in children under 6 years has not been fully established; use only when clearly indicated.

Elderly:

• Same dosage as adults.
• Monitor for elevated intraocular pressure more frequently due to age-related sensitivity to corticosteroids.

Renal/Hepatic Impairment:

• No specific dose adjustment is required.
• Caution advised due to potential for systemic absorption.

Route of Administration:

• Ophthalmic (topical) only.
• Not for intraocular or systemic use.

Duration of Use:

• Should not exceed 7 consecutive days without re-evaluation.
• Taper gradually to prevent rebound redness or steroid withdrawal.

Special Instructions:

• Shake the bottle well before each use.
• Contact lenses should be removed before administration and reinserted after at least 15 minutes.

Fluorometholone is a synthetic corticosteroid that inhibits inflammation at the cellular level. It binds to glucocorticoid receptors in the cytoplasm, altering gene transcription and reducing the synthesis of inflammatory mediators like prostaglandins and leukotrienes. This leads to reduced capillary permeability, leukocyte infiltration, and fibroblast activity in ocular tissues.

Tetrahydrozoline is a selective α-adrenergic agonist. It acts on α1-adrenergic receptors in the conjunctival blood vessels, causing vasoconstriction. This reduces redness and swelling associated with ocular irritation. Its local vasoconstrictive effect leads to symptomatic relief without significant systemic effects when used correctly.

Together, the combination provides anti-inflammatory action from fluorometholone and rapid relief of redness from tetrahydrozoline.

Fluorometholone:

• Absorption: Minimally absorbed systemically when applied topically to the eye.
• Distribution: Primarily localized to ocular tissues such as the cornea and conjunctiva.
• Metabolism: Metabolized within ocular tissues; minimal hepatic metabolism after systemic absorption.
• Half-life: Not clearly defined due to local application.
• Elimination: Mainly eliminated via biliary route after systemic absorption.

Tetrahydrozoline:

• Absorption: Low systemic absorption through conjunctival membranes.
• Onset of Action: Within 1–5 minutes of instillation.
• Duration of Effect: Approximately 4–8 hours.
• Metabolism: Hepatic metabolism.
• Elimination: Renally excreted.

Pregnancy:

• FDA Category (former): Category C (Use only if clearly needed).
• Risk Summary: No adequate human studies. Animal data suggest potential fetal risk with corticosteroids at high doses. Tetrahydrozoline, if systemically absorbed, may cause vasoconstrictive effects.

Lactation:

• Unknown if either drug is excreted in human milk after ophthalmic use.
• Recommendation: Use with caution. To reduce systemic exposure, apply nasolacrimal occlusion (press the inner corner of the eye for 1–2 minutes after drop administration).

• Primary Class: Ophthalmic Combination – Anti-inflammatory and Vasoconstrictor
• Components:
• Fluorometholone: Corticosteroid (low-potency, ophthalmic)
• Tetrahydrozoline: Ocular vasoconstrictor (alpha-adrenergic agonist)

• Known hypersensitivity to fluorometholone, tetrahydrozoline, or any excipients in the formulation.
• Active ocular infections (bacterial, viral, or fungal) without appropriate antimicrobial coverage.
• Herpetic keratitis (especially dendritic lesions).
• Angle-closure glaucoma or narrow anterior chamber angles.
• Use in children under 6 years (unless directed by a physician).

• Steroid-induced Glaucoma: Long-term use may increase intraocular pressure, leading to optic nerve damage or glaucoma.
• Cataract Formation: Risk of posterior subcapsular cataract with prolonged use.
• Ocular Infections: Corticosteroids may mask signs of infection or worsen existing conditions.
• Rebound Hyperemia: Prolonged use of tetrahydrozoline may lead to rebound redness.
• Systemic Effects: Excessive use can lead to systemic absorption and cause cardiovascular or CNS effects, particularly in children and elderly.
• Monitoring: Regular intraocular pressure checks are recommended if used longer than 7–10 days.

Common:

• Mild eye irritation or burning on instillation
• Temporary blurred vision
• Dry eyes
• Mild stinging or itching

Less Common:

• Eye redness (paradoxical)
• Foreign body sensation
• Eyelid swelling
• Headache

Serious (Rare):

• Elevated intraocular pressure
• Optic nerve damage
• Posterior subcapsular cataract
• Secondary ocular infections (e.g., fungal keratitis)
• Rebound conjunctival hyperemia

Onset:

• Local irritation usually occurs immediately after instillation and is transient.
• Serious side effects usually occur with prolonged use (>2 weeks) or in steroid responders.

• Monoamine Oxidase Inhibitors (MAOIs): Co-use with tetrahydrozoline may cause hypertensive crisis.
• Tricyclic Antidepressants: May enhance vasoconstrictive effects of tetrahydrozoline.
• Ophthalmic NSAIDs: May delay corneal healing when used with corticosteroids.
• Antiglaucoma Medications: May have reduced efficacy due to IOP elevation from corticosteroids.
• CYP450 System: Not significantly involved due to minimal systemic absorption.

• Labeling Updates: Several manufacturers have updated labeling to include warnings regarding rebound hyperemia and intraocular pressure monitoring.
• Pediatric Use: Regulatory agencies recommend avoiding use in children under 6 without physician supervision due to increased risk of CNS effects from tetrahydrozoline.
• Monitoring Protocols: Updated recommendations now suggest measuring IOP if therapy exceeds 7–10 days.

• Storage Temperature: Store at 15°C to 25°C (59°F to 77°F).
• Light Sensitivity: Protect from direct light.
• Do Not Freeze.
• Handling: Keep bottle tightly closed. Avoid touching the dropper tip to any surface to prevent contamination.
• After Opening: Discard the bottle 28 days after first opening, even if solution remains.