Netarsudil

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Netarsudil
Netarsudil.svg
Names
Pronunciationne TAR soo dil
Trade namesRhopressa, Rhokiinsa
Other namesAR-11324
  • [4-[(2S)-3-Amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate
Clinical data
Drug classRho kinase inhibitor[1]
Main usesIncreased intraocular pressure, open-angle glaucoma[2][1]
Side effectsRed eyes, conjunctival bleeding, blurry vision, tearing[1]
Routes of
use
Eye drops, topical
Duration of action≥ 24 hrs
External links
AHFS/Drugs.comMonograph
US NLMNetarsudil
MedlinePlusa618014
Legal
License data
Legal status
Pharmacokinetics
MetabolismEsterases in the cornea
MetabolitesAR-13503 (active metabolite)
Elimination half-life16–17 hrs
Chemical and physical data
FormulaC28H27N3O3
Molar mass453.542 g·mol−1
3D model (JSmol)
  • Cc1ccc(c(c1)C)C(=O)OCc2ccc(cc2)[C@@H](CN)C(=O)Nc3ccc4cnccc4c3
  • InChI=1S/C28H27N3O3/c1-18-3-10-25(19(2)13-18)28(33)34-17-20-4-6-21(7-5-20)26(15-29)27(32)31-24-9-8-23-16-30-12-11-22(23)14-24/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32)/t26-/m1/s1
  • Key:OURRXQUGYQRVML-AREMUKBSSA-N

Netarsudil, sold under the brand name Rhopressa and Rhokiinsa, is a medication used to treat increased intraocular pressure including open-angle glaucoma.[2][1] It is used as an eye drop.[2]

Common side effects include red eyes, conjunctival bleeding, blurry vision, and tearing.[1] Other side effects may include bacterial keratitis.[1] It is a rho kinase inhibitor.[1]

Netarsudil was approved for medical use in the United States in 2017 and Europe in 2019.[1][2] In the United States a 2.5 ml bottle costs about 305 USD as of 2021.[4] It is also available as the combination netarsudil/latanoprost.[1] It is not commercially available in Europe and the United Kingdom as of 2021.[5]

Medical uses

Dosage

It is used at a dose of one drop per day.[2]

Contraindications

Netarsudil has no contraindications apart from known hypersensitivity to the drug.[2][6]

Side effects

The most common side effects are hyperaemia (increased blood flow associated with redness, in 51% of patients) in the conjunctiva, cornea verticillata (drug deposits in the cornea, in 17%), and eye pain (in 17%). All other side effects occur in fewer than 10% of people. Hypersensitivity reactions occur in fewer than 1%.[2][7]

Overdose

Overdosing netarsudil is unlikely because concentrations in the body are so low that they are generally not detectable.[7]

Interactions

No interaction studies have been done. The European label recommends to apply other eye drops at least five minutes before, and eye ointments at least five minutes after netarsudil drops.[2][6]

Pharmacology

AR-13503, the active metabolite

Mechanism of action

This drug's mechanism of action is not entirely clear. It inhibits the enzyme rho kinase. This appears to increase outflow of aqueous humor through the trabecular meshwork, and also to reduce pressure in the veins of the episcleral layer. The drug also inhibits the norepinephrine transporter.[2][6]

Pharmacokinetics

After instillation into the eye, netarsudil is cleaved by esterases in the cornea to AR-13503, which is the active metabolite. Concentrations reached in the blood plasma are so low that they are generally not detectable. To judge from animal models, the drug acts for at least 24 hours. Its elimination half-life is 16 to 17 hours (in rabbits).[6]

Chemistry

The drug is used in form of a salt, netarsudil dimesilate, which is a white to light yellow crystalline powder. It is a weak acid and moderately hygroscopic, freely soluble in water and soluble in methanol.[8]

History

The FDA considers it to be a first-in-class medication.[9]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Netarsudil Mesylate Monograph for Professionals". Drugs.com. Retrieved 12 November 2021.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Rhokiinsa EPAR". European Medicines Agency (EMA). 16 September 2019. Retrieved 27 September 2020.
  3. "Rhopressa- netarsudil solution/ drops". DailyMed. Retrieved 2 May 2021.
  4. "Rhopressa Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 12 November 2021.
  5. "Netarsudil". SPS - Specialist Pharmacy Service. 25 January 2016. Retrieved 12 November 2021.
  6. 6.0 6.1 6.2 6.3 "Netarsudil Mesylate Monograph for Professionals". American Society of Health-System Pharmacists. 16 November 2020. Retrieved 2 May 2021.
  7. 7.0 7.1 "Rhokiinsa Product Information" (PDF). European Medicines Agency (EMA). 2 December 2019.
  8. "Rhokiinsa: EPAR – Public assessment report" (PDF). European Medicines Agency. 3 December 2019.
  9. New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.

External links

External sites:
Identifiers: