TYRVAYA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYRVAYA (TYRVAYA).
Netarsudil is a Rho kinase (ROCK) inhibitor. It increases trabecular outflow by inhibiting ROCK, which reduces cytoskeletal tension and cell adhesion in the trabecular meshwork, thereby improving aqueous humor drainage and lowering intraocular pressure.
| Metabolism | Netarsudil is primarily metabolized by ester hydrolysis and subsequent glucuronidation. CYP enzymes are not significantly involved. |
| Excretion | Primarily renal excretion (approximately 60% as unchanged drug and metabolites), with biliary/fecal elimination accounting for about 30%. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours, supporting twice-daily dosing. |
| Protein binding | Approximately 70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.5 L/kg, suggesting distribution into tissues beyond plasma volume. |
| Bioavailability | Nasal spray: Absolute bioavailability is approximately 30% due to absorption across nasal mucosa and limited first-pass metabolism. |
| Onset of Action | Nasal spray: Onset of action within 30 minutes. |
| Duration of Action | Duration of clinical effect is approximately 8-12 hours, consistent with twice-daily administration. |
| Molecular Weight | 539.5 |
One drop of 0.03% ophthalmic solution in each affected eye once daily in the evening
| Dosage form | SPRAY |
| Renal impairment | No dosage adjustment required based on renal function; systemic absorption is minimal after ocular administration |
| Liver impairment | No dosage adjustment required based on hepatic function; systemic absorption is minimal after ocular administration |
| Pediatric use | Not recommended for use in pediatric patients due to insufficient safety and efficacy data |
| Geriatric use | No specific dosage adjustment recommended for geriatric patients; dosing is the same as for younger adults |
| 1st trimester | No adequate and well-controlled studies in pregnant women. Based on animal studies, there is a risk of fetal harm. Systemic absorption is minimal, but use only if potential benefit justifies potential risk. |
| 2nd trimester | Same as T1. Systemic levels are low, but theoretical risk remains. Caution advised. |
| 3rd trimester | Use during third trimester may cause uterine contractions and premature labor due to prostaglandin analogues. Avoid use near term unless clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for TYRVAYA (TYRVAYA).
| Placental transfer | Netarsudil has a molecular weight of 539.5 Da, which suggests potential placental transfer. However, systemic absorption after ocular administration is low (approx. 1-2%), resulting in negligible plasma concentrations. Limited data in humans; animal studies show detectable levels in fetus after IV administration. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to netarsudil or any component of the formulation
| Precautions | Corneal effects: Corneal verticillata (vortex keratopathy) has been reported; monitor corneal changes., Ocular inflammation: Use with caution in patients with active intraocular inflammation., Bacterial keratitis: Preservatives in multidose containers may cause bacterial keratitis if contaminated., Contact lens use: Remove lenses before administration; may be reinserted 15 minutes after dosing. |
| Food/Dietary | No clinically significant food interactions reported. Tyrvaya is administered intranasally and systemic absorption is minimal. No dietary restrictions are necessary. |
Loading safety data…
| Systemic absorption of netarsudil is negligible after ocular administration. It is unknown if netarsudil is excreted in human milk. Due to low systemic exposure, risk to nursing infant is likely minimal. Consider benefits of breastfeeding and importance of drug to mother. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of teratogenicity was observed with intravitreal administration of the active metabolite (nintedanib) at doses up to 7 times the human exposure. However, systemic exposure after ophthalmic administration is very low. Risk cannot be excluded; first trimester: theoretical risk due to VEGF inhibition; second and third trimesters: theoretical risk of impaired fetal angiogenesis. |
| Fetal Monitoring | Standard prenatal care. No specific additional monitoring required due to low systemic absorption. If systemic adverse effects occur, monitor blood pressure and intraocular pressure. |
| Fertility Effects | No human data on fertility. In animal studies with systemic nintedanib, effects on male and female fertility observed at high doses. However, systemic exposure after ophthalmic administration is very low, making significant impact on fertility unlikely. |
| Clinical Pearls |
| Tyrvaya (varenicline) is a nasal spray for dry eye disease, acting as a nicotinic acetylcholine receptor agonist to increase tear production. A key tip: instruct patients to prime the spray by releasing 4 sprays into the air before first use. Do not use more than 1 spray per nostril twice daily (BID). Avoid spraying into the eyes; eye irritation may occur if spray contacts eyes. Monitor for nasal irritation or epistaxis. Contraindicated in patients with severe hypersensitivity to varenicline or any components. |
| Patient Advice | Prime the nasal spray by releasing 4 sprays into the air before first use. If not used for 5+ days, re-prime with 1 spray. · Use 1 spray in each nostril twice daily (morning and evening) for a total of 4 sprays per day. · Do not spray directly into the eyes. If spray gets into eyes, rinse with water and contact your doctor if irritation persists. · Common side effects include nasal irritation (burning, discomfort, congestion), sneezing, and headache. Report severe or persistent nasal bleeding. · Tyrvaya may interact with nicotine replacement therapies; avoid concurrent use without consulting your doctor. |