Netarsudil

RHOPRESSA is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. RHOPRESSA ® is a Rho kinase inhibitor indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. ( 1 )

Ophthalmic solution containing netarsudil 0.02% (0.2 mg/mL). Ophthalmic solution containing netarsudil 0.02%. ( 3 )

None. None. ( 4 )

5.1 Epithelial Corneal Edema Epithelial corneal edema, described as honeycomb or bullous, has been reported in some patients with pre-existing corneal stromal edema or following ocular procedures that could affect corneal endothelial function. Epithelial corneal edema typically resolves upon discontinuation of RHOPRESSA. Advise patients to notify their physician if they experience eye pain or decreased vision while using RHOPRESSA [see Adverse Reactions ( 6.2 ) and Patient Counselling Information ( 17 )] .

5.2 Bacterial Keratitis There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information ( 17 )].

5.3 Use with Contact Lenses Contact lenses should be removed prior to instillation of RHOPRESSA and may be reinserted 15 minutes following its administration.

The most common adverse reaction is conjunctival hyperemia (53%). Other common adverse reactions, approximately 20% include: corneal verticillata, instillation site pain, and conjunctival hemorrhage. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1‑800-757-9195, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most common ocular adverse reaction observed in controlled clinical studies with RHOPRESSA dosed once daily was conjunctival hyperemia which was reported in 53% of patients. Six percent of patients discontinued therapy due to conjunctival hyperemia. Other common (approximately 20%) ocular adverse reactions reported were: corneal verticillata, instillation site pain, and conjunctival hemorrhage. Instillation site erythema, corneal staining, blurred vision, increased lacrimation, erythema of eyelid, and reduced visual acuity were reported in 5-10% of patients. Corneal Verticillata Corneal verticillata occurred in approximately 20% of the patients in controlled clinical studies. The corneal verticillata seen in RHOPRESSA-treated patients were first noted at 4 weeks of daily dosing. This reaction did not result in any apparent visual functional changes in patients. Most corneal verticillata resolved upon discontinuation of treatment.

6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of RHOPRESSA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : Epithelial corneal edema has been reported in some patients with pre-existing corneal stromal edema or following ocular procedures (that could affect corneal endothelial function) [see Warnings and Precautions ( 5.1 )] .

8.1 Pregnancy Risk Summary There are no available data on RHOPRESSA use in pregnant women to inform any drug associated risk; however, systemic exposure to netarsudil from ocular administration is low [see Clinical Pharmacology ( 12.3 ) ] . Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal effects at clinically relevant systemic exposures [see Data] . Data Animal Data Netarsudil administered daily by intravenous injection to rats during organogenesis caused abortions and embryofetal lethality at doses ≥0.3 mg/kg/day (126-fold the plasma exposure at the recommended human ophthalmic dose [RHOD], based on C max ). The no-observed-adverse-effect-level (NOAEL) for embryofetal development toxicity was 0.1 mg/kg/day (40-fold the plasma exposure at the RHOD, based on C max ). Netarsudil administered daily by intravenous injection to rabbits during organogenesis caused embryofetal lethality and decreased fetal weight at 5 mg/kg/day (1480-fold the plasma exposure at the RHOD, based on C max ). Malformations were observed at ≥3 mg/kg/day (1330-fold the plasma exposure at the RHOD, based on C max ), including thoracogastroschisis, umbilical hernia and absent intermediate lung lobe. The NOAEL for embryofetal development toxicity was 0.5 mg/kg/day (214-fold the plasma exposure at the RHOD, based on C max ).

8.2 Lactation Risk Summary There are no data on the presence of RHOPRESSA in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to netarsudil following topical ocular administration is low [see Clinical Pharmacology ( 12.3 )] , and it is not known whether measurable levels of netarsudil would be present in maternal milk following topical ocular administration. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RHOPRESSA and any potential adverse effects on the breast-fed child from RHOPRESSA.

8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

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

Netarsudil is a rho kinase inhibitor, which is believed to reduce IOP by increasing the outflow of aqueous humor through the trabecular meshwork. The exact mechanism is unknown.