Rhopressa

1 INDICATIONS AND USAGE 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.

The recommended dosage is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose in the evening. Twice a day dosing is not well tolerated and is not recommended. If RHOPRESSA is to be used concomitantly with other topical ophthalmic drug products to lower IOP, administer each drug product at least 5 minutes apart . One drop into the affected eye(s) once daily in the evening.

5 WARNINGS AND PRECAUTIONS

5.1Epithelial 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 .

5.2Bacterial 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 .

5.3Use with Contact Lenses Contact

lenses should be removed prior to instillation of RHOPRESSA and may be reinserted 15 minutes following its administration.

None. None.

8.1Pregnancy 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 . Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal effects at clinically relevant systemic exposures . 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 ).

The most common adverse reaction is conjunctival hyperemia (53%). Other common adverse reactions, approximately 20% include: corneal verticillata, instillation site pain, and conjunctival hemorrhage. 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 .

6.1Clinical 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.

6.2Postmarketing 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) .