ADVERSE REACTIONS SECTION.


6 ADVERSE REACTIONS. The most common adverse reaction reported in 82% of patients was sneezing. Events that were reported in 5-16% of patients were cough, throat irritation, and instillation-site (nose) irritation. (6)To report SUSPECTED ADVERSE REACTIONS, contact Oyster Point Pharma at 1-877-EYE-0123 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.In three clinical studies of dry eye disease conducted with varenicline solution nasal spray, 349 patients received at least dose of TYRVAYA. The majority of patients had 31 days of treatment exposure, with maximum exposure of 105 days. The most common adverse reactions reported in 82% of TYRVAYA treated patients was sneezing. Other common adverse reactions that were reported in >5% of patients include cough (16%), throat irritation (13%), and instillation-site (nose) irritation (8%).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisLifetime carcinogenicity studies were performed in CD-1 mice and Sprague-Dawley rats. There was no evidence of carcinogenic effect in mice administered varenicline by oral gavage for years at doses up to 20 mg/kg/day (810 times the maximum recommended human dose [MRHD], on mg/m2 basis). Rats were administered varenicline (1, 5, and 15 mg/kg/day) by oral gavage for years. In male rats (n 65 per sex per dose group), incidences of hibernoma (tumor of the brown fat) were increased at the mid dose (1 tumor, mg/kg/day, 405 times the MRHD on mg/m2 basis) and maximum dose (2 tumors, 15 mg/kg/day, 1216 times the MRHD on mg/m2 basis). The clinical relevance of this finding to humans has not been established. There was no evidence of carcinogenicity in female rats. MutagenesisVarenicline was not genotoxic, with or without metabolic activation, in the following assays: Ames bacterial mutation assay; mammalian CHO/HGPRT assay; and tests for cytogenetic aberrations in vivo in rat bone marrow and in vitro in human lymphocytes.Impairment of FertilityThere was no evidence of impairment of fertility in either male or female Sprague-Dawley rats administered varenicline succinate up to 15 mg/kg/day (1216 times the MRHD on mg/m2 basis). Maternal toxicity, characterized by decrease in body weight gain, was observed at 15 mg/kg/day. decrease in fertility was noted in the offspring of pregnant rats administered varenicline succinate at an oral dose of 15 mg/kg/day. The decrease in fertility in the offspring of treated female rats was not evident at an oral dose of mg/kg/day (243 times the MRHD, on mg/m2 basis).

CLINICAL PHARMACOLOGY SECTION.


12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. The efficacy of TYRVAYA in dry eye disease is believed to be the result of vareniclines activity at heteromeric sub-type(s) of the nicotinic acetylcholine (nACh) receptor where its binding produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film as treatment for dry eye disease. Varenicline binds with high affinity and selectivity at human 42, 462, 34, 354 and neuronal nicotinic acetylcholine receptors. The exact mechanism of action is unknown at this time.. 12.3 Pharmacokinetics. Absorption/Distribution Following administration of 0.12 mg (0.06 mg per 50-uL spray in each nostril), strength of varenicline that is higher than the labeled concentration, varenicline can be detected in plasma by minutes, generally achieves peak concentration within hours, with mean Cmax of 0.34 ng/mL, and has an AUC0-inf of 7.46 hng/mL. The systemic exposure (AUC0-inf) following this intranasal dose was approximately 7.5% of the exposure observed following 1 mg oral dose of varenicline. Metabolism/EliminationThe mean +- SD elimination half-life of varenicline after intranasal administration is approximately 19 +- 10 hours. Varenicline undergoes minimal metabolism with 92% excreted as unchanged drug in the urine.

CLINICAL STUDIES SECTION.


6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.In three clinical studies of dry eye disease conducted with varenicline solution nasal spray, 349 patients received at least dose of TYRVAYA. The majority of patients had 31 days of treatment exposure, with maximum exposure of 105 days. The most common adverse reactions reported in 82% of TYRVAYA treated patients was sneezing. Other common adverse reactions that were reported in >5% of patients include cough (16%), throat irritation (13%), and instillation-site (nose) irritation (8%).

CONTRAINDICATIONS SECTION.


4 CONTRAINDICATIONS. None. None.

DESCRIPTION SECTION.


11 DESCRIPTION. TYRVAYA nasal spray contains varenicline which is partial nicotinic acetylcholine receptor agonist of 42, 462, 34, and 354 receptors and full receptor agonist.Varenicline, as the tartrate salt, is powder which is white to off-white to slightly yellow solid whose chemical name is 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine, (2R,3R)-2,3-dihydroxybutanedioate (1:1). It is highly soluble in water. Varenicline tartrate has molecular weight of 361.35 Daltons and molecular formula of C13H13N3 C4H6O6. The chemical structure is:TYRVAYA (varenicline solution) nasal spray is formulated for intranasal use as clear 0.6 mg/mL strength solution, at pH 6.4. After priming see Dosage and Administration (2.2) ], each actuation delivers 0.05 mL spray containing 0.03 mg varenicline free base, equivalent to 0.05 mg of varenicline tartrate. The formulation also contains the following inactive ingredients: sodium phosphate dibasic heptahydrate, monobasic sodium phosphate anhydrous, sodium chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH) and water for injection.. The chemical structure.

DOSAGE & ADMINISTRATION SECTION.


2 DOSAGE AND ADMINISTRATION. One spray in each nostril twice daily (approximately 12 hours apart). (2.1) Prime with seven (7) actuations before initial use. Re-prime with actuation if not used for more than five (5) days. (2.2). One spray in each nostril twice daily (approximately 12 hours apart). (2.1) Prime with seven (7) actuations before initial use. Re-prime with actuation if not used for more than five (5) days. (2.2). 2.1 Dosing Information. Spray TYRVAYA once in each nostril twice daily (approximately 12 hours apart). If dose is missed, resume regular dosing at the next scheduled dose time.. 2.2 Priming Instructions. Priming: Prime TYRVAYA before initial use by pumping seven (7) actuations into the air away from the face. When TYRVAYA has not been used for more than days, re-prime with spray into the air. Do not shake.

DOSAGE FORMS & STRENGTHS SECTION.


3 DOSAGE FORMS AND STRENGTHS. Nasal spray delivering 0.03 mg of varenicline in each spray (0.05 mL).. Nasal spray delivering 0.03 mg of varenicline in each spray (0.05 mL). (3).

GERIATRIC USE SECTION.


8.5 Geriatric Use. No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

HOW SUPPLIED SECTION.


16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. TYRVAYA (varenicline solution) nasal spray is available in carton containing two (2) nasal spray amber glass Type bottles. Each bottle consists of white nasal pump and blue dust cover, delivering 0.03 mg varenicline per spray (0.05 mL). Each bottle delivers one spray in each nostril twice daily for 15 days. Two nasal spray bottles in each carton, containing 60 sprays per bottle, equivalent to 30-days supply with one spray in each nostril twice daily (NDC 73521-030-02).. 16.2 Storage and Handling. Store TYRVAYA nasal spray at 20C to 25C (68F to 77F). Do not freeze. Discard TYRVAYA nasal spray bottle 30 days after opening bottle.. Store TYRVAYA nasal spray at 20C to 25C (68F to 77F). Do not freeze. Discard TYRVAYA nasal spray bottle 30 days after opening bottle.

INDICATIONS & USAGE SECTION.


1 INDICATIONS AND USAGE. TYRVAYA (varenicline solution) nasal spray is indicated for the treatment of the signs and symptoms of dry eye disease.. TYRVAYA (varenicline solution) nasal spray is cholinergic agonist indicated for the treatment of the signs and symptoms of dry eye disease. (1).

INFORMATION FOR PATIENTS SECTION.


17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Instruct patients that TYRVAYA works to increase tear production in the eye after being sprayed in the nose. Instruct patients to prime the bottle before using it for the first time by pumping seven (7) sprays into the air away from the face and to re-prime it by pumping spray into the air away from the face if the bottle has not been used in more than five (5) days. Instruct patients to wipe the nasal applicator with clean tissue after each use. Instruct patients to not shake or freeze the bottle.Manufactured for: Oyster Point Pharma, Inc, 202 Carnegie Center, Suite 109, Princeton, NJ 08540 Copyrights and Trademarks are property of their respective owners. TYRVAYA(TM) is trademark of Oyster Point Pharma, Inc.TYRVAYA(TM) and/or the use of TYRVAYA(TM) in method may be covered by one or more patents or patent applications, available at www.oysterpointrx.com/patent-notices.(C)2021 Oyster Point Pharma, Inc. All Rights Reserved.Issued: Oct/2021. Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Instruct patients that TYRVAYA works to increase tear production in the eye after being sprayed in the nose. Instruct patients to prime the bottle before using it for the first time by pumping seven (7) sprays into the air away from the face and to re-prime it by pumping spray into the air away from the face if the bottle has not been used in more than five (5) days. Instruct patients to wipe the nasal applicator with clean tissue after each use. Instruct patients to not shake or freeze the bottle.

INSTRUCTIONS FOR USE SECTION.


Instructions for Use Tyrvaya(TM) (Teer-vye-ah)(varenicline solution)nasal spray, for intranasal useRead this Instructions for Use before you start using TYRVAYA and each time you get refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.Important information you need to know before using TYRVAYA:Parts of your TYRVAYA nasal spray: TYRVAYA is for use in the nose.Do not shake the bottles.The TYRVAYA carton contains enough medicine for 30 days. Each carton has glass nasal spray bottles. Each nasal spray bottle has enough medicine for 15 days of treatment. Do not open the second nasal spray bottle until you have used the entire first bottle. Steps for priming TYRVAYA before first UseStep 1. Remove the cap and the clip. Do ot throw away the cap or the clip. The cap and the clip will be placed back on to the nasal applicator after each use.Step 2. Hold the nasal spray bottle upright and away from your face. Place finger on each side of the base of the nasal applicator and place your thumb underneath the bottle. Step 3. Prime the nasal spray bottle by pressing and releasing the nasal applicator times with your thumb and fingers. You may not see spray released each time you press and release the nasal applicator. Spray away from yourself and others. TYRVAYA is now primed for use.Reprime: If you do not use TYRVAYA for more than days, you will need to reprime the nasal spray bottle with spray before you start using it. To reprime, hold the nasal spray bottle upright and away from your face and press and release the nasal spray applicator time. Avoid priming the nasal spray bottle more than needed: Priming the nasal spray bottle more than needed will reduce the amount of medicine in the nasal spray bottle. Steps for using TYRVAYA nasal spray after primingStep 1. Blow your nose to clear your nostrils, if needed. Step 2. Remove the cap and clip. Do ot throw away the cap or the clip. The cap and the clip will be placed back on to the nasal applicator after each use. Step 3. Hold the nasal spray bottle upright. Place finger on each side of the base of the nasal applicator and your thumb underneath the bottle.Step 4. Tilt your head back slightly without lying down.Step 5. Insert the nasal applicator into the left or right nostril. Tilt the nasal applicator and point the tip of the nasal applicator towards the top of the ear on the same side as your nostril. Do ot press the tip of the nasal applicator against the wall of the inside of your nose. Leave space between the tip of the nasal applicator and the wall of the inside of your nose.Step 6. Place your tongue to the roof of your mouth and breathe gently while pressing and releasing the nasal applicator - time to release spray into your nostril. Repeat Steps and to deliver second spray in the other nostril. Step 7. Wipe the nasal applicator with clean tissue. Step 8. Replace the clip and the cap. Repeat Steps to each time you use TYRVAYA This Instructions for Use has been approved by the U.S. Food and Drug Administration.TYRVAYA(TM) is trademark of Oyster Point Pharma, Inc.TYRVAYA(TM) and/or the use of TYRVAYA(TM) in method may be covered by one or more patents or patent applications, available at www.oysterpointrx.com/patent-notices.Manufactured for: Oyster Point Pharma, Inc., 202 Carnegie Center, Suite 109, Princeton, NJ 08540(C)2021 Oyster Point Pharma, Inc. Issued: 10/2021. TYRVAYA is for use in the nose.. Do not shake the bottles.. The TYRVAYA carton contains enough medicine for 30 days. Each carton has glass nasal spray bottles. Each nasal spray bottle has enough medicine for 15 days of treatment. Do not open the second nasal spray bottle until you have used the entire first bottle. Each carton has glass nasal spray bottles. Each nasal spray bottle has enough medicine for 15 days of treatment. Do not open the second nasal spray bottle until you have used the entire first bottle. Reprime: If you do not use TYRVAYA for more than days, you will need to reprime the nasal spray bottle with spray before you start using it. To reprime, hold the nasal spray bottle upright and away from your face and press and release the nasal spray applicator time. Avoid priming the nasal spray bottle more than needed: Priming the nasal spray bottle more than needed will reduce the amount of medicine in the nasal spray bottle. Tyrvaya Nasal Spray. Remove clip/cap. Step 2. Hold the nasal spray upright and away from your face. Place one finger on each side of the base of the nasal applicator, and place your thumb underneath the bottle.. Press times. Step 1. Blow nose to clear nostrils if needed. Remove cap/clip. Step 3. Hold the nasal spray upright. Place one finger on each side of the base of the nasal applicator and your thumb underneath the bottle.. Step 4. Tilt your head back slightly.. Step 5. Insert the nasal applicator into the left or right nostril. Tilt the nasal applicator and aim the tip towards the top of the ear on the same side. DO NOT press the tip of nasal applicator against the wall of the inside of your nose. Allow for space between the tip of nasal applicator and the wall of the inside of your nose for proper dose administration.. Step 6. Place tongue to the roof of the mouth and breathe gently while spraying (one) time. Repeat administration in the other nostril. Wait (two) or (three) minutes before blowing nose if needed.. Step 7. Wipe the nasal applicator with clean tissue.. Step 8. Replace clip and cap.

LACTATION SECTION.


8.2 Lactation. Risk SummaryThere are no data on the presence of varenicline in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies varenicline was present in milk of lactating rats. However, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. The lack of clinical data during lactation precludes clear determination of the risk of TYRVAYA to an infant during lactation; however, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for TYRVAYA and any potential adverse effects on the breastfed child from TYRVAYA.

MECHANISM OF ACTION SECTION.


12.1 Mechanism of Action. The efficacy of TYRVAYA in dry eye disease is believed to be the result of vareniclines activity at heteromeric sub-type(s) of the nicotinic acetylcholine (nACh) receptor where its binding produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film as treatment for dry eye disease. Varenicline binds with high affinity and selectivity at human 42, 462, 34, 354 and neuronal nicotinic acetylcholine receptors. The exact mechanism of action is unknown at this time.

NONCLINICAL TOXICOLOGY SECTION.


13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisLifetime carcinogenicity studies were performed in CD-1 mice and Sprague-Dawley rats. There was no evidence of carcinogenic effect in mice administered varenicline by oral gavage for years at doses up to 20 mg/kg/day (810 times the maximum recommended human dose [MRHD], on mg/m2 basis). Rats were administered varenicline (1, 5, and 15 mg/kg/day) by oral gavage for years. In male rats (n 65 per sex per dose group), incidences of hibernoma (tumor of the brown fat) were increased at the mid dose (1 tumor, mg/kg/day, 405 times the MRHD on mg/m2 basis) and maximum dose (2 tumors, 15 mg/kg/day, 1216 times the MRHD on mg/m2 basis). The clinical relevance of this finding to humans has not been established. There was no evidence of carcinogenicity in female rats. MutagenesisVarenicline was not genotoxic, with or without metabolic activation, in the following assays: Ames bacterial mutation assay; mammalian CHO/HGPRT assay; and tests for cytogenetic aberrations in vivo in rat bone marrow and in vitro in human lymphocytes.Impairment of FertilityThere was no evidence of impairment of fertility in either male or female Sprague-Dawley rats administered varenicline succinate up to 15 mg/kg/day (1216 times the MRHD on mg/m2 basis). Maternal toxicity, characterized by decrease in body weight gain, was observed at 15 mg/kg/day. decrease in fertility was noted in the offspring of pregnant rats administered varenicline succinate at an oral dose of 15 mg/kg/day. The decrease in fertility in the offspring of treated female rats was not evident at an oral dose of mg/kg/day (243 times the MRHD, on mg/m2 basis).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PRINCIPAL DISPLAY PANELNDC 73521-030-02tyrvaya(varenicline) nasal spray0.03 mg per spray2 nasal spray bottlesfor 30-day supply. DiagramDescription automatically generated.

PEDIATRIC USE SECTION.


8.4 Pediatric Use. Safety and efficacy of TYRVAYA in pediatric patients have not been established.

PHARMACOKINETICS SECTION.


12.3 Pharmacokinetics. Absorption/Distribution Following administration of 0.12 mg (0.06 mg per 50-uL spray in each nostril), strength of varenicline that is higher than the labeled concentration, varenicline can be detected in plasma by minutes, generally achieves peak concentration within hours, with mean Cmax of 0.34 ng/mL, and has an AUC0-inf of 7.46 hng/mL. The systemic exposure (AUC0-inf) following this intranasal dose was approximately 7.5% of the exposure observed following 1 mg oral dose of varenicline. Metabolism/EliminationThe mean +- SD elimination half-life of varenicline after intranasal administration is approximately 19 +- 10 hours. Varenicline undergoes minimal metabolism with 92% excreted as unchanged drug in the urine.

PREGNANCY SECTION.


8.1 Pregnancy. Risk SummaryThere are no available data on TYRVAYA use in pregnant women to inform any drug associated risks. In animal reproduction studies, varenicline did not produce malformations at clinically relevant doses.All pregnancies have risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal DataPregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. While no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (4864 times the MRHD on mg/m2 basis).In pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. Maternal toxicity, characterized by decrease in body weight gain, was observed at 15 mg/kg/day (1216 times the MRHD on mg/m2 basis). Decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day.

SPL PATIENT PACKAGE INSERT SECTION.


Patient InformationTYRVAYA(TM) (Teer-vye-ah)(varenicline solution)nasal spray, for intranasal useWhat is TYRVAYATYRVAYA is prescription nasal spray used to treat the signs and symptoms of dry eye disease. Before you use TYRVAYA, tell your healthcare provider about all of your medical conditions, including if you:are pregnant or plan to become pregnant. It is not known if TYRVAYA will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if TYRVAYA passes into your breast milk. You and your healthcare provider should decide if you will use TYRVAYA if you plan to breastfeed.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Know the medicines you take. Keep list of them to show your healthcare provider and pharmacist when you get new medicine.How should use TYRVAYASee the Instructions for Use at the end of this Patient Information leaflet for information about the right way to use TYRVAYA. TYRVAYA increases tear production in the eye after being sprayed in the nose. Use TYRVAYA exactly as your healthcare provider tells you to use it. Do not shake the bottles. Spray TYRVAYA time in each nostril, times daily (about 12 hours apart). 1-month supply of TYRVAYA consists of nasal spray bottles. Finish bottle before opening the second. TYRVAYA comes in glass bottles with white nasal pump and blue dust cover. If you miss dose of TYRVAYA, skip that dose and take your next dose at your regular scheduled time. Do not take an extra dose to make up for missed dose. What are the possible side effects of TYRVAYAThe most common side effects of TYRVAYA include sneezing, cough, and throat and nose irritation.These are not the only possible side effects of TYRVAYA. Call your doctor for medical advice about side effects.You may report side effects to FDA at 1-800-FDA-1088.How should store TYRVAYAStore TYRVAYA at room temperature between 68F to 77F (20C to 25C) Do not freeze. Throw away (discard) TYRVAYA nasal spray bottle 30 days after first use. Keep TYRVAYA and all medicines out of the reach of children.General information about the safe and effective use of TYRVAYA.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use TYRVAYA for condition for which it was not prescribed. Do not give TYRVAYA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TYRVAYA that is written for health professionals.What are the ingredients in TYRVAYAActive ingredient: varenicline tartrate Inactive ingredients: sodium phosphate dibasic heptahydrate, monobasic sodium phosphate anhydrous, sodium chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH) and water for injection.TYRVAYA(TM) is trademark of Oyster Point Pharma, Inc. TYRVAYA(TM) and/or the use of TYRVAYA(TM) in method may be covered by one or more patents or patent applications, available at www.oysterpointrx.com/patent-notices. Manufactured for: Oyster Point Pharma, Inc., 202 Carnegie Center, Suite 109, Princeton, NJ 08540This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 10/2021 are pregnant or plan to become pregnant. It is not known if TYRVAYA will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if TYRVAYA passes into your breast milk. You and your healthcare provider should decide if you will use TYRVAYA if you plan to breastfeed.. See the Instructions for Use at the end of this Patient Information leaflet for information about the right way to use TYRVAYA. TYRVAYA increases tear production in the eye after being sprayed in the nose. Use TYRVAYA exactly as your healthcare provider tells you to use it. Do not shake the bottles. Spray TYRVAYA time in each nostril, times daily (about 12 hours apart). A 1-month supply of TYRVAYA consists of nasal spray bottles. Finish bottle before opening the second. TYRVAYA comes in glass bottles with white nasal pump and blue dust cover. If you miss dose of TYRVAYA, skip that dose and take your next dose at your regular scheduled time. Do not take an extra dose to make up for missed dose. Store TYRVAYA at room temperature between 68F to 77F (20C to 25C) Do not freeze. Throw away (discard) TYRVAYA nasal spray bottle 30 days after first use.

SPL UNCLASSIFIED SECTION.


2.1 Dosing Information. Spray TYRVAYA once in each nostril twice daily (approximately 12 hours apart). If dose is missed, resume regular dosing at the next scheduled dose time.

STORAGE AND HANDLING SECTION.


16.2 Storage and Handling. Store TYRVAYA nasal spray at 20C to 25C (68F to 77F). Do not freeze. Discard TYRVAYA nasal spray bottle 30 days after opening bottle.. Store TYRVAYA nasal spray at 20C to 25C (68F to 77F). Do not freeze. Discard TYRVAYA nasal spray bottle 30 days after opening bottle.

USE IN SPECIFIC POPULATIONS SECTION.


8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThere are no available data on TYRVAYA use in pregnant women to inform any drug associated risks. In animal reproduction studies, varenicline did not produce malformations at clinically relevant doses.All pregnancies have risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal DataPregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. While no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (4864 times the MRHD on mg/m2 basis).In pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. Maternal toxicity, characterized by decrease in body weight gain, was observed at 15 mg/kg/day (1216 times the MRHD on mg/m2 basis). Decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day.. 8.2 Lactation. Risk SummaryThere are no data on the presence of varenicline in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies varenicline was present in milk of lactating rats. However, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. The lack of clinical data during lactation precludes clear determination of the risk of TYRVAYA to an infant during lactation; however, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for TYRVAYA and any potential adverse effects on the breastfed child from TYRVAYA. 8.4 Pediatric Use. Safety and efficacy of TYRVAYA in pediatric patients have not been established. 8.5 Geriatric Use. No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.