Pharmacology Update: Cyclosporine Ophthalmic Emulsion 0.05% (Restasis — Allergan)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved cyclosporine ophthalmic emulsion for the treatment of dry eyes due to keratoconjuctivitis sicca (KCS) and associated reduced tear production. Cyclosporine is an immunomodulating agent that increases tear production in patients with KCS. It will be marketed by Allergan as Restasis.
Indications
Cyclosporine ophthalmic is indicated for patients with suppressed tear production due to ocular inflammation associated with KCS.1
Dosage
The recommended dose is 1 drop in each eye twice daily (12 hours apart). It may be used concomitantly with artificial tears but should be instilled 15 minutes apart.1 Cyclosporine emulsion is supplied as preservative-free, single-use vials each containing 0.4 mL of emulsion. The drug should not be administered with a contact lens in place. The lens should be removed and reinserted after 15 minutes.
Potential Advantages
Cyclosporine emulsion provides certain objective and subjective improvement in patients with moderate-to-severe dry eye disease.1,2 Improvement in the integrity of the ocular surface and on baseline tearing has also been reported. The patients also reported less blurred vision and decrease in the use of artificial tears.
Potential Disadvantages
The most common side effect is burning eyes (14.7% vs 6.5% for vehicle). No increases in tear production were seen in patients on topical anti-inflammatory drugs or using punctal plugs.1 Cyclosporine appeared to affect baseline tearing but not reflexive tearing.2
Comments
Cyclosporine appears to have modest beneficial effects on moderate-to-severe dry eyes in patients with KCS. The mechanism of action is not well understood but may involve suppression of the inflammatory process. After 6 months of treatment, cyclosporine emulsion was reported to result in an increase of goblet cells in the conjunctiva and reduction in the number of activated T lymphocytes within the ocular surface in patients with non-Sjögren syndrome-associated and Sjögren syndrome-associated KCS.3,4 Efficacy was demonstrated in 4 multicenter, randomized studies in about 1200 patients with moderate-to-severe KCS. Two multicenter, randomized studies (293 treated with cyclosporine 0.05% and 292 treated with vehicle) were published. Statistically significant improvement was seen in 2 objective measures (corneal staining and Schirmer values) and 2 subjective measures (blurred vision and use of lubricating drops).2 The beneficial effects appeared to be relatively modest at 6 months. A mean difference of 0.5 units from baseline in the Schirmer score (5-point scale) was observed. Significant tear production (Schirmer wetting of 10 mm) was seen in 15% of cyclosporine-treated patients compared to 5% for the vehicle.1 A mean difference of about 0.5 units was observed in the blurred vision score (4-point scale). There was mean reduction of a 0.5 unit per day use of artificial tears compared to vehicle. Based on physicians’ subjective assessment of global response, 35.5% of treated patients were considered to have at least a moderate response compared to 31.9% in the vehicle group. The castor oil in the vehicle may contribute to improvement of symptoms by reducing the evaporation of the natural tears.2 Patients with end-stage lachrymal gland disease or destruction of conjunctival goblet cells or scarring were excluded. Cyclosporine ophthalmic emulsion appears to be well tolerated. There are no detectable cyclosporine levels detected in the blood after 12 months of treatment.1
The product is expected to be launched in the second quarter of 2003.
Clinical Implications
The pathophysiology of KCS is believed to be an immune-based inflammatory condition characterized by decreased tear production by lacrimal gland and increase evaporation of tears from the ocular surface.3,5 Symptoms include burning, irritation, blurred vision, contact lens intolerance, and the inability to produce emotional tears. These patients are also at increased risk of infections and ocular surface damage. The incidence increases with age, in postmenopausal women, and patients with diseases such as Sjögren’s syndrome, rheumatoid arthritis, lupus, and diabetes. Current treatment is artificial tears and punctal occlusion procedures. Cyclosporine ophthalmic emulsion is the first therapeutic treatment approved by the FDA. While improvements appeared to be modest, it does, however, offer a new treatment option for patients suffering from moderate-to-severe KCS.
Dr. Elliott is Chair, Formulary
Committee, Northern California Kaiser Permanente and Asst. Clinical Professor
of Medicine, University of California-San Francisco. Dr.
Chan is Pharmacy Quality and Outcomes Manager at Kaiser Permanente in Oakland,
CA.
References
1. Restasis Product Information. Allergan, Inc. 2002.
2. Sall K, et al. Opthalmology. 2000;107:631-639.
3. Kunert KS, et al. Arch Ophthalmol. 2002;120:330-337.
4. Kunert KS, et al. Arch Ophthalmol. 2000;118: 1489-1496.
5. Lemp M. Rheumatolol. 2000;61(Suppl):11-14.
The FDA has approved cyclosporine ophthalmic emulsion for the treatment of dry eyes due to keratoconjuctivitis sicca (KCS) and associated reduced tear production. Cyclosporine is an immunomodulating agent that increases tear production in patients with KCS.
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