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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYRVAYA (TYRVAYA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Systemic exposure after ophthalmic administration is negligible. M/P ratio: not determined. Due to low systemic absorption, risk is likely low but caution advised. |
| 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. |
■ 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."] |
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| 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. |