Rhopressa (netarsudil): Uses, Dosage, Side Effects & Warnings

Uses

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. ( 1 )

Dosage and administration

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 [see Patient Counseling Information ( 17 )]. One drop into the affected eye(s) once daily in the evening. ( 2 )

Dosage forms and strengths

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

Contraindications

None. None. ( 4 )

Warnings and precautions

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.

Side effects

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 )] .

Use in specific populations

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.

Pregnancy

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 ).

Pediatric use

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

Geriatric use

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

Description

Netarsudil is a Rho kinase inhibitor. Its chemical name is (S)-4-(3-amino-1-(isoquinolin-6-yl-amino)-1-oxopropan-2-yl) benzyl 2,4-dimethylbenzoate dimesylate. The molecular formula of the free base is C 28 H 27 N 3 O 3 and the molecular formula of the dimesylate is C 30 H 35 N 3 O 9 S 2 . The molecular weight of the free base is 453.54 and the molecular weight of the dimesylate is 645.74. The chemical structure is: Netarsudil dimesylate is a light yellow-to-white powder that is freely soluble in water, soluble in methanol, sparingly soluble in dimethyl formamide, and practically insoluble in dichloromethane and heptane. RHOPRESSA (netarsudil ophthalmic solution) 0.02% is supplied as a sterile, isotonic, buffered aqueous solution of netarsudil dimesylate with a pH of approximately 5 and an osmolality of approximately 295 mOsmol/kg. It is intended for topical application in the eye. Each mL of RHOPRESSA contains 0.2 mg of netarsudil (equivalent to 0.28 mg of netarsudil dimesylate). Benzalkonium chloride, 0.015%, is added as a preservative. The inactive ingredients are: boric acid, mannitol, sodium hydroxide to adjust pH, and water for injection. Netarsudil structural formula

Mechanism of action

12.1 Mechanism of Action 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.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING RHOPRESSA ® (netarsudil ophthalmic solution) 0.02% (0.2 mg per mL) is supplied sterile in opaque white low density polyethylene bottles and tips with white polypropylene caps. 2.5 mL fill in a 4 mL container NDC # 70727-497-25 Storage: Store at 2°C to 8°C (36°F to 46°F) until opened. After opening, the product may be kept at 2°C to 25°C (36°F to 77°F) for up to 6 weeks. If after opening the product is kept refrigerated at 2°C to 8°C (36°F to 46°F), then the product can be used until the expiration date stamped on the bottle. During shipment, the bottle may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 14 days.

Patient information

Handling the Container Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to minimize contamination of the solution. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions ( 5.2 )]. When to Seek Physician Advice Advise patients that if they develop an intercurrent ocular condition (e.g., trauma, infection, or decreased vision with or without eye pain), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of RHOPRESSA. Use with Contact Lenses Advise patients that RHOPRESSA contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of RHOPRESSA and may be reinserted 15 minutes following its administration. Use with Other Ophthalmic Drugs Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications. Missed Dose Advise patients that if one dose is missed, treatment should continue with the next dose in the evening. © 2024 Alcon Inc. U.S. Pat.: www.alconpatents.com ALCON LABORATORIES, INC. 6201 South Freeway Fort Worth, Texas 76134 USA 1-800-757-9195 Alcon.medinfo@alcon.com

Active ingredients

Netarsudil Mesylate in 1 product

Rhopressa NDC products (1)

NDC	Strength & form	Labeler	Type
70727-497	Netarsudil Mesylate .2 mg/mL Solution/ Drops	Alcon Laboratories, Inc.	NDA

Frequently asked questions

What is Rhopressa used for?

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. ( 1 )

What are the side effects of Rhopressa?

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… See the full label for the complete list.

Who makes Rhopressa?

Rhopressa is listed by 1 labeler in the FDA NDC directory, including Alcon Laboratories, Inc..