By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a nasal spray to treat dry eyes using the nasolacrimal reflex pathway. The active ingredient, varenicline (a selective partial agonist of the alpha-4 beta-2 nicotine acetylcholine receptor) has been used as pharmacotherapy for smoking cessation since 2006. The nasal spray is marketed as Tyrvaya.
INDICATIONS
Varenicline nasal spray (NS) is indicated to treat the signs and symptoms of dry eye disease.1
DOSAGE
The recommended dose is one spray in each nostril twice daily, approximately 12 hours apart.1 Varenicline NS is available in a device that delivers 0.03 mg with each actuation. Each bottle is expected to last 15 days based on the recommended dose.
POTENTIAL ADVANTAGES
Varenicline NS provides a drug with a different mode of action to treat dry eye disease and is an option for patients who struggle with eye drops.
POTENTIAL DISADVANTAGES
Frequently reported adverse reactions were sneezing (82%), cough (16%), throat irritation (13%), and nose irritation (8%).1 Some patients may find these adverse reactions bothersome. Long-term safety, tolerability, and effectiveness have not been established. In clinical trials, the maximum exposure was 105 days.1
COMMENTS
Varenicline increases production of basal tear film and is believed to cause chemical activation of the trigeminal parasympathetic nasolacrimal reflex pathway.1,2 Afferent (sensory) pathways, including ophthalmic and maxillary branches, are found in nasal mucosa. Its efficacy was supported by two randomized, double-masked, vehicle-controlled studies (ONSET-1 [n = 91] and ONSET-2 [n = 512]).1 Subjects had a baseline anesthetized Schirmer score of about 5 mm. This test involves applying a sterile paper strip into the inferior-temporal aspect of the conjunctival sac of each eye. The wetted length (in millimeters) is used to quantify basal tear secretion.3 At the recommended dose, 52% of subjects achieved 10 mm or better improvement from baseline at day 28 vs. 14% with the vehicle in ONSET-1, and 47% and 28%, respectively, for ONSET-2. The mean change was 11.7 mm and 11.3 mm vs. 3.2 mm and 6.3 mm, respectively. A Schirmer score > 15 mm is normal basal tear secretion, and mildly dry is between 10 mm and 15 mm. The systemic exposure following one spray in each nostril at twice the recommended dose (0.06 mg) is approximately 7.5% of a 1 mg oral dose of varenicline (half the dose for smoking cessation).1
CLINICAL IMPLICATIONS
Dry eye disease is a multifactorial condition (e.g., tear film instability and ocular surface inflammation) and is estimated to occur in 9.3% of adults.3,4 Risk factors include age, female gender, use of contact lens, low humidity environment, and autoimmune disease. Currently, there are two FDA-approved pharmacotherapies with anti-inflammatory properties: topical cyclosporine and topical lifitegrast. A Cochrane Review showed the evidence of effect for cyclosporine to be inconsistent and may not be different from vehicle or artificial tears.5 In addition, it may take three months to show clinical efficacy.3 Lifitegrast significantly improved symptoms as assessed by eye dryness score as early as day 14.6 A neurostimulator (iTEAR100) received FDA approval in May 2020.7 This device stimulates the trigeminal nerve through application to the skin of the external nasal region for up to 30 seconds. An earlier intranasal neurostimulator (TrueTear) was discontinued because of prohibitive cost.8 There are no direct comparisons between varenicline NS and topical cyclosporine, lifitegrast, or the neurostimulators. Varenicline offers another option with a different mode of action. The cost for a 30-day supply (two bottles) is $492.29.
REFERENCES
- Oyster Point Pharma. Tyrvaya prescribing information. October 2021.
- O’Neil EC, Henderson M, Massaro-Giordano M, Bunya VY. Advances in dry eye disease. Curr Opin Ophthalmol 2019;30:166-178.
- Science Direct. Schirmer test.
- Baiula M, Spampinato S. Experimental pharmacotherapy for dry eye disease: A review. J Exp Pharmacol 2021;13:345-358.
- de Paiva CS, Pflugfelder SC, Ng SM, Akpek EK. Topical cyclosporine: A therapy for dry eye syndrome. Cochrane Database Syst Rev 2019;9:CD010051.
- Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: Results of a Phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Opthalmology 2017;124:53-60.
- Olympic Ophthalmics. Olympic Ophthalmics receives FDA clearance for iTEAR100 neurostimulator. May 14, 2020.
- Yu MD, Park JK, Kossler AL. Stimulating tear production: Spotlight on neurostimulation. Clin Ophthalmol 2021;15:4219-4226.
Varenicline nasal spray is indicated to treat the signs and symptoms of dry eye disease.
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