Introduction
Restasis (cyclosporine ophthalmic emulsion) 0.05% is an immunomodulatory agent approved for the treatment of chronic dry eye disease. It represents a unique therapeutic approach to managing ocular surface inflammation, which is increasingly recognized as a key component of dry eye pathophysiology. Unlike artificial tears that provide temporary symptomatic relief, Restasis addresses the underlying inflammatory process.
Mechanism of Action
Restasis contains cyclosporine, a calcineurin inhibitor that acts as a selective immunomodulator. Its primary mechanism involves inhibiting T-cell activation and subsequent cytokine production. In dry eye disease, inflammation mediated by T-cells leads to reduced tear production and ocular surface damage. By suppressing this localized immune response, Restasis helps restore the ocular surface environment, potentially increasing natural tear production and improving goblet cell density over time.
Indications
- FDA-approved for increasing tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca (chronic dry eye disease)
- Typically indicated in patients who have not responded adequately to artificial tears
Dosage and Administration
- Standard dosing: One drop in each eye twice daily, approximately 12 hours apart
- Administration: Shake vial well before use. Instill drops into the conjunctival sac of each eye
- Special populations: No dosage adjustment required for renal or hepatic impairment
- Geriatric patients: No specific dosage recommendations
- Pediatric patients: Safety and effectiveness in pediatric patients have not been established
Pharmacokinetics
- Absorption: Minimal systemic absorption following ocular administration. Blood concentrations are generally undetectable (< 0.1 ng/mL) in most patients
- Distribution: Primarily local ocular distribution with minimal systemic exposure
- Metabolism: Primarily hepatic via cytochrome P450 3A4 when systemically absorbed
- Elimination: Primarily biliary excretion when systemically absorbed
- Half-life: Not fully characterized for ophthalmic administration due to minimal systemic exposure
Contraindications
- Hypersensitivity to cyclosporine or any component of the formulation
- Active ocular infections
- Patients with known hypersensitivity to the emulsion vehicle components
Warnings and Precautions
- Ocular effects: May cause ocular burning, conjunctival hyperemia, eye pain, foreign body sensation, itching, stinging, and visual disturbances
- Contact lens use: Patients should not wear contact lenses during treatment with Restasis
- Infection risk: Not recommended in patients with active ocular infections
- Corticosteroid effects: Although minimal systemic absorption occurs, potential systemic effects should be considered in patients with specific comorbidities
- Driving and operating machinery: May cause temporary blurred vision after instillation
Drug Interactions
- Systemic interactions: Minimal expected due to low systemic absorption
- Theoretical interactions: Potential interaction with systemic cyclosporine if used concurrently, though unlikely due to minimal ocular absorption
- Other ophthalmic medications: Should be administered at least 15 minutes apart from other ophthalmic preparations
Adverse Effects
Most common adverse reactions (≥1%-4%):- Ocular burning (17%)
- Conjunctival hyperemia (6%)
- Eye discharge (4%)
- Eye pain (4%)
- Foreign body sensation (4%)
- Pruritus (4%)
- Stinging (4%)
- Blurred vision (3%)
- Dry eye, itching, redness, tearing, visual disturbance
Monitoring Parameters
- Ocular symptoms: Regular assessment of dry eye symptoms and signs
- Visual acuity: Periodic evaluation
- Corneal integrity: Slit-lamp examination as clinically indicated
- Tear production: Schirmer's test may be used to monitor response
- Tolerance: Assessment of local adverse effects
- Therapeutic response: Subjective improvement in dry eye symptoms typically observed after 3-6 months of treatment
Patient Education
- Administration technique: Shake vial well before use. Wash hands before instillation. Avoid touching dropper tip to any surface
- Timing: Use twice daily, approximately 12 hours apart
- Contact lenses: Do not wear contact lenses during treatment
- Multiple medications: Wait at least 15 minutes between instilling different eye medications
- Temporary blurring: May experience temporary blurred vision after instillation; avoid driving or operating machinery until vision clears
- Consistency: Therapeutic effect may take several weeks to months; continue use as prescribed
- Storage: Store at room temperature (15-30°C/59-86°F). Do not freeze. Discard vial immediately after use
References
1. FDA Prescribing Information: Restasis (cyclosporine ophthalmic emulsion) 0.05%. Allergan, Inc. 2. Sall K, Stevenson OD, Mundorf TK, et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. Ophthalmology. 2000;107(4):631-639. 3. Perry HD, Solomon R, Donnenfeld ED, et al. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthalmol. 2008;126(8):1046-1050. 4. Stevenson D, Tauber J, Reis BL. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. Ophthalmology. 2000;107(5):967-974. 5. American Academy of Ophthalmology Cornea/External Disease Panel. Dry Eye Syndrome Preferred Practice Pattern. 2018. 6. Pflugfelder SC, Maskin SL, Anderson B, et al. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138(3):444-457.