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Netarsudil Mesylate

Class: Rho Kinase Inhibitors
Chemical Name: [4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate;methanesulfonic acid
Molecular Formula: C30H35N3O9S2
CAS Number: 1422144-42-0
Brands: Rhopressa

Medically reviewed by Drugs.com on Nov 16, 2020. Written by ASHP.

Introduction

Ocular hypotensive agent; rho kinase (ROCK) inhibitor and norepinephrine transporter (NET) inhibitor.

Uses for Netarsudil Mesylate

Ocular Hypertension and Glaucoma

Netarsudil 0.02%: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. Once-daily administration of netarsudil 0.02% appears to be noninferior to twice-daily administration of timolol 0.5% in reducing IOP.

Fixed-combination netarsudil 0.02% and latanoprost 0.005%: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. When administered once daily, mean IOP reduction was approximately 1–3 mm Hg greater than that achieved with once-daily administration of either drug alone.

When selecting an initial ocular hypotensive agent, consider extent of the required IOP reduction, coexisting medical conditions, and drug characteristics (e.g., dosing frequency, adverse effects, cost). With single-agent regimens, the reduction in IOP is approximately 25–33% with topical prostaglandin analogs; 20–25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20–30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15–20% with topical carbonic anhydrase inhibitors.

A prostaglandin analog frequently is considered for initial therapy in the absence of other considerations (e.g., contraindications, cost considerations, intolerance, adverse effects, patient refusal) because of relatively greater activity, once-daily administration, and low frequency of systemic adverse effects; however, ocular adverse effects can occur.

Goal is to maintain an IOP at which visual field loss is unlikely to substantially reduce quality of life during the patient's lifetime.

Reduction of pretreatment IOP by ≥25% shown to slow progression of primary open-angle glaucoma. Set an initial target IOP (based on extent of optic nerve damage and/or visual field loss, baseline IOP at which damage occurred, rate of progression, life expectancy, and other considerations) and reduce IOP toward this goal. Adjust target IOP up or down as needed over course of disease.

Combination therapy with drugs from different therapeutic classes often required to control IOP.

Netarsudil Mesylate Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the eye(s) as an ophthalmic solution containing netarsudil alone or in fixed combination with latanoprost.

Avoid contaminating the solution container. (See Bacterial Keratitis under Cautions.)

Remove soft contact lenses prior to administration of each dose; may reinsert contact lenses 15 minutes after the dose. (See Use with Contact Lenses under Cautions.)

If more than one topical ophthalmic preparation is used, administer the preparations at least 5 minutes apart.

If a dose is missed, skip the dose and resume treatment with the next scheduled dose.

Dosage

Available as netarsudil mesylate; dosage and concentration expressed in terms of netarsudil.

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

Netarsudil 0.02% ophthalmic solution: One drop in the affected eye(s) once daily in the evening. Twice-daily dosing not well tolerated and not recommended.

Netarsudil 0.02% and latanoprost 0.005% ophthalmic solution: One drop in the affected eye(s) once daily in the evening. Do not administer more frequently than once daily.

If target IOP not achieved, may initiate additional or alternative ocular hypotensive agents. (See Ocular Hypertension and Glaucoma under Uses.)

Special Populations

No special population dosage recommendations.

Cautions for Netarsudil Mesylate

Contraindications

  • Manufacturer states none known.

Warnings/Precautions

Bacterial Keratitis

Bacterial keratitis reported with use of multiple-dose containers of topical ophthalmic preparations. These containers were inadvertently contaminated by patients who, in most cases, had concurrent corneal disease or disruption of the ocular epithelial surface.

Improper handling of ocular solutions can result in contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions. (See Advice to Patients.)

Use with Contact Lenses

Netarsudil and fixed-combination netarsudil and latanoprost ophthalmic solutions contain benzalkonium chloride preservative, which may be absorbed by soft contact lenses.

Remove contact lenses prior to administration of each dose; may reinsert lenses 15 minutes after the dose.

Specific Populations

Pregnancy

No data available regarding use in pregnant women. Systemic exposure following topical application to the eye is low.

No evidence of embryofetal effects following IV administration in pregnant rats and rabbits during organogenesis at clinically relevant systemic exposures.

Evidence of abortions and embryofetal lethality in rats and malformations, embryofetal lethality, and decreased fetal weight in rabbits receiving IV netarsudil at dosages associated with higher plasma exposures than those resulting from recommended human daily ophthalmic dosage.

Lactation

Not known if distributed into milk; data not available on effects of the drug on the breast-fed child or on milk production.

Systemic exposure following topical application to the eye is low; not known whether measurable concentrations are present in human milk following topical ophthalmic administration.

Consider benefits of breast-feeding along with the importance of the drug to the woman and any potential adverse effects from the drug on the breast-fed child.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.

Common Adverse Effects

Netarsudil ophthalmic solution: Conjunctival hyperemia, corneal verticillata, instillation site pain, conjunctival hemorrhage, instillation site erythema, corneal staining, blurred vision, increased lacrimation, eyelid erythema, reduced visual acuity.

Netarsudil and latanoprost ophthalmic solution: Conjunctival hyperemia, instillation site pain, corneal verticillata, conjunctival hemorrhage, ocular itching, decreased visual acuity, increased lacrimation, instillation site discomfort, blurred vision.

Interactions for Netarsudil Mesylate

No formal drug interaction studies to date. Interactions not expected because of limited systemic exposure following topical application to the eye.

Netarsudil Mesylate Pharmacokinetics

Absorption

Bioavailability

Prodrug; absorbed through the cornea and into the aqueous humor following ocular instillation and metabolized by esterases in the cornea to active form (netarsudil-M1; AR-13503).

Topical administration to the eye does not result in clinically important systemic exposure to the drug or its active metabolite.

Following topical administration of 1 drop of netarsudil 0.02% ophthalmic solution to the eyes of healthy adults once daily for 8 days, plasma concentrations of netarsudil were undetectable (lower limit of quantitation 0.1 ng/mL) on days 1 and 8. The active metabolite was detected in only one of these adults and only at one time point (0.11 ng/mL at 8 hours post-dose on day 8).

Duration

Rabbit study indicates effects on IOP generally persist for ≥24 hours.

Distribution

Extent

Not known whether the drug or its metabolite distribute into milk following topical administration to the eyes in humans.

Elimination

Metabolism

Metabolized by esterases in the eye to active form (netarsudil-M1; AR-13503).

Half-life

Elimination half-life from aqueous humor is 16–17 hours in rabbits.

Stability

Storage

Ophthalmic

Solution

Netarsudil: Store unopened bottles at 2–8°C. During shipment, may be maintained at up to 40°C for ≤14 days. Store opened bottles at 2–25°C for up to 6 weeks; if opened bottle maintained at 2–8°C, may be used until the manufacturer's labeled expiration date.

Netarsudil and latanoprost: Store at 2–8°C and protect from light; may use opened bottle until the manufacturer's labeled expiration date. During shipping, may be maintained at up to 40°C for ≤14 days.

Actions

  • ROCK inhibitor and NET inhibitor.

  • Exact mechanism of action in reduction of IOP unknown; multiple mechanisms involved.

  • Appears to reduce IOP by increasing outflow of aqueous humor through the trabecular meshwork and decreasing episcleral venous pressure via its inhibitory effect on rho kinases.

  • Appears to decrease production of aqueous humor via its inhibitory effect on NET.

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contaminating the ophthalmic solution; instruct patients to avoid allowing the tip of the container to contact eyes or surrounding structures, fingers, or any other surface. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic preparations.

  • Importance of patients immediately informing a clinician before continuing therapy if they develop a new ocular condition (e.g., trauma, infection) or an ocular reaction (particularly conjunctivitis, eyelid reactions) or have ocular surgery.

  • Importance of removing contact lenses prior to administration of each dose since the ophthalmic solutions contain benzalkonium chloride preservative, which may be absorbed by soft lenses; may reinsert contact lenses 15 minutes after the dose.

  • If using more than one ophthalmic preparation, importance of administering the preparations at least 5 minutes apart.

  • Importance of advising patients that if a dose is missed, skip the dose and continue treatment with the next evening dose.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Netarsudil Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.02% (of netarsudil)

Rhopressa

Aerie

Netarsudil Mesylate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.02% (of netarsudil) with Latanoprost 0.005%

Rocklatan

Aerie

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 16, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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