Introduction
Cequa (cyclosporine ophthalmic solution) 0.09% is a novel formulation of cyclosporine specifically developed for ophthalmic use. It represents a significant advancement in the treatment of dry eye disease, utilizing a proprietary nanomicellar technology to enhance drug delivery and bioavailability to ocular tissues. Approved by the FDA in 2018, Cequa offers a higher concentration of cyclosporine than previous ophthalmic formulations while maintaining excellent tolerability.
Mechanism of Action
Cequa exerts its therapeutic effects through immunomodulation and anti-inflammatory actions. Cyclosporine, a calcineurin inhibitor, binds to cyclophilin in T-lymphocytes, inhibiting calcineurin phosphatase activity. This prevents dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NF-AT), ultimately suppressing T-cell activation and subsequent cytokine production. In dry eye disease, this mechanism reduces ocular surface inflammation, increases tear production, and improves goblet cell density, thereby restoring the natural tear film homeostasis.
Indications
Cequa is indicated for the treatment of dry eye disease. Clinical trials have demonstrated its efficacy in:
- Increasing tear production as measured by Schirmer test
- Improving corneal staining scores
- Reducing symptoms of ocular discomfort associated with dry eye
- Enhancing overall ocular surface health
Dosage and Administration
Standard dosing: One drop in each affected eye twice daily, approximately 12 hours apart Administration:- Instill drops directly into the conjunctival sac
- Avoid touching the tip of the dropper to any surface to prevent contamination
- Wait at least 15 minutes before inserting contact lenses
- If using other ophthalmic products, administer Cequa last with at least 5-minute intervals
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution; no specific dosage recommendations
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Limited systemic absorption following ocular administration. The nanomicellar technology enhances corneal penetration while minimizing systemic exposure. Distribution: Primarily localized to ocular tissues with minimal systemic distribution Metabolism: Primarily hepatic via cytochrome P450 3A4 system Elimination: Systemically absorbed drug is eliminated primarily in bile with minimal renal excretion Half-life: Ocular elimination half-life approximately 4-6 hoursContraindications
- Hypersensitivity to cyclosporine or any component of the formulation
- Active ocular infections (bacterial, viral, or fungal)
- Patients with a history of herpes keratitis
Warnings and Precautions
- Ocular effects: May cause ocular burning, irritation, or conjunctival hyperemia
- Infection risk: May increase susceptibility to ocular infections
- Contact lens wear: Should not be administered while contact lenses are in place
- Driving ability: May cause temporary blurred vision; patients should avoid driving until vision clears
- Systemic effects: Although minimal systemic absorption occurs, monitor for potential systemic cyclosporine effects in patients using concomitant systemic immunosuppressants
Drug Interactions
Clinically significant interactions:- Systemic cyclosporine: Potential additive systemic effects, though unlikely due to minimal ocular absorption
- CYP3A4 inhibitors: Ketoconazole, erythromycin, grapefruit juice - may potentially increase cyclosporine levels
- CYP3A4 inducers: Rifampin, phenytoin, St. John's wort - may decrease cyclosporine efficacy
- Other ophthalmic medications: Administer with appropriate time intervals to prevent washout
Adverse Effects
Common (≥1-10%):- Ocular burning (20%)
- Conjunctival hyperemia (15%)
- Eye irritation (8%)
- Visual disturbance (5%)
- Foreign body sensation (5%)
- Eye pain
- Eyelid edema
- Photophobia
- Ocular discharge
- Dry eye symptoms (paradoxical)
- Severe allergic reactions
- Corneal abrasion (if improper administration)
- Increased intraocular pressure
Monitoring Parameters
Clinical monitoring:- Ocular symptoms and signs at each follow-up visit
- Schirmer test results (baseline and periodic)
- Corneal staining scores
- Visual acuity
- Patient-reported symptom improvement
- Signs of ocular infection
- Tolerance assessment
- Compliance with administration technique
- Improvement in dry eye symptoms (using validated questionnaires)
- Reduction in ocular surface inflammation signs
- Increased tear production
Patient Education
Key points for patients:- Use exactly as prescribed - twice daily approximately 12 hours apart
- Wash hands before administration
- Avoid touching dropper tip to prevent contamination
- Wait at least 15 minutes before inserting contact lenses
- Temporary blurred vision may occur after instillation
- Do not discontinue therapy without consulting your ophthalmologist
- Improvement may take several weeks to become noticeable
- Store at room temperature (15-30°C); do not freeze
- Discard bottle 3 months after opening
- Worsening eye symptoms
- Signs of eye infection (redness, pain, discharge)
- Severe or persistent eye irritation
- Vision changes
- Any systemic symptoms possibly related to medication
References
1. FDA prescribing information: Cequa (cyclosporine ophthalmic solution) 0.09% 2. Sheppard JD, et al.. Clin Ophthalmol. 2020;14:3841-3848 3. Tauber J, et al.. 4. Donnenfeld ED, et al. Clin Ophthalmol. 2019;13:887-896 5. Cyclosporine nanomicellar ophthalmic solution 0.09%: phase III safety and efficacy study in dry eye disease. Eur J Ophthalmol. 2021;31(2):189-196 6. American Academy of Ophthalmology Dry Eye Syndrome Preferred Practice Pattern. Ophthalmology. 2018;125(1):P336-P393 7. Jones L, et al. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017;15(3):575-628