Introduction
Tyrvaya (varenicline solution) nasal spray is a novel pharmaceutical agent approved by the US Food and Drug Administration (FDA) for the treatment of dry eye disease. It represents the first and only nasal spray approved for this indication, offering a unique approach to managing ocular surface disease through neurostimulation rather than direct ocular application.
Mechanism of Action
Tyrvaya contains varenicline, a cholinergic agonist that binds to nicotinic acetylcholine receptors in the nasal mucosa. This binding activates the trigeminal parasympathetic pathway, which stimulates the lacrimal functional unit to produce natural tears. Unlike traditional dry eye treatments that act locally on the eye, Tyrvaya works through a neurostimulatory mechanism that enhances basal tear production, improves tear film stability, and promotes goblet cell mucin secretion.
Indications
Tyrvaya is indicated for the treatment of the signs and symptoms of dry eye disease. It is approved for use in adults regardless of whether the dry eye is primarily due to reduced tear production or increased tear evaporation.
Dosage and Administration
- Recommended dosage: One spray in each nostril twice daily (morning and evening)
- Administration: Prime the device before first use by spraying until a fine mist appears (approximately 5 sprays)
- Special populations: No dosage adjustment required for geriatric patients or those with renal or hepatic impairment
- Instructions: Insert nozzle into nostril, point slightly outward, and spray while breathing gently through the nose
Pharmacokinetics
- Absorption: Minimal systemic absorption following intranasal administration
- Distribution: Primarily local action with limited systemic distribution
- Metabolism: Minimal hepatic metabolism
- Elimination: Primarily renal excretion with elimination half-life of approximately 24 hours
- Bioavailability: Less than 5% systemic bioavailability due to primarily local action
Contraindications
Tyrvaya is contraindicated in patients with:
- Known hypersensitivity to varenicline or any component of the formulation
- History of severe nasal disorders or recent nasal surgery
- Active nasal infections or significant nasal trauma
Warnings and Precautions
- Nasal irritation: May cause sneezing, cough, or throat irritation
- Ocular effects: Temporary blurred vision may occur immediately after use
- Systemic effects: Although minimal systemic absorption occurs, monitor for potential cholinergic effects
- Nasal examination: Regular nasal examinations recommended during prolonged use
- Pregnancy: Use during pregnancy only if potential benefit justifies potential risk
- Pediatric use: Safety and effectiveness not established in pediatric patients
Drug Interactions
- Cholinergic agents: Potential additive effects with other cholinergic medications
- Anticholinergic drugs: May reduce the efficacy of Tyrvaya
- Nasal decongestants: Concurrent use may affect nasal absorption
- Nicotine replacement therapy: Theoretical interaction due to similar receptor binding
Adverse Effects
Most common adverse reactions (≥5%):- Sneezing (82%)
- Cough (40%)
- Throat irritation (20%)
- Nasal discomfort (15%)
- Rhinorrhea (4%)
- Nasal congestion (3%)
- Transient blurred vision (2%)
- Headache (2%)
- Severe nasal reactions (<1%)
- Hypersensitivity reactions (rare)
Monitoring Parameters
- Ocular assessment: Regular evaluation of dry eye symptoms and signs
- Nasal examination: Periodic assessment of nasal mucosa
- Visual acuity: Monitor for transient blurred vision
- Patient compliance: Assess proper administration technique
- Therapeutic response: Evaluate improvement in dry eye symptoms and signs
Patient Education
- Administer one spray in each nostril twice daily
- Prime the device before first use
- Blow nose gently before administration if congested
- Avoid blowing nose for 30 minutes after administration
- Temporary sneezing or cough is common and expected
- May cause temporary blurred vision - avoid activities requiring clear vision immediately after use
- Store at room temperature (15-30°C)
- Discard 30 days after first use
- Report persistent nasal irritation or breathing difficulties
- Continue other prescribed dry eye treatments unless instructed otherwise
References
1. FDA Approval Package: Tyrvaya (varenicline solution) nasal spray. 2021 2. Wirta D, et al. Ocul Surf. 2022;23:117-125 3. Torkildsen G, et al. Clin Ophthalmol. 2022;16:1551-1566 4. Tyrvaya [package insert]. Lake Forest, CA: Oyster Point Pharma, Inc.; 2021 5. Mah F, et al. Cornea. 2022;41(5):582-588 6. ClinicalTrials.gov: NCT04036292 and NCT04583742 7. American Academy of Ophthalmology Dry Eye Syndrome PPP 2018 8. Jones L, et al. Cont Lens Anterior Eye. 2021;44(3):101337