Netarsudil

Netarsudil, sold under the brand name Rhopressa among others, is a medication for the treatment of glaucoma.[1][2][3] In the United States, in December 2017, the Food and Drug Administration (FDA) approved a 0.02% ophthalmic solution for the lowering of elevated intraocular pressure in people with open-angle glaucoma or ocular hypertension.[4][5] The European Medicines Agency approved it in 2019 for the same uses under the brand name Rhokiinsa.[2]

Netarsudil
Clinical data
Pronunciationne TAR soo dil
Trade namesRhopressa, Rhokiinsa
Other namesAR-13324
AHFS/Drugs.comMonograph
MedlinePlusa618014
License data
Routes of
administration		Eye drops, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismEsterases in the cornea
MetabolitesAR-13503 (active metabolite)
Elimination half-life16–17 hrs
Duration of action≥ 24 hrs
Identifiers
IUPAC name
  • [4-[(2S)-3-Amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ECHA InfoCard100.251.524
Chemical and physical data
FormulaC28H27N3O3
Molar mass453.542 g·mol−1
3D model (JSmol)
SMILES
  • Cc1ccc(c(c1)C)C(=O)OCc2ccc(cc2)[C@@H](CN)C(=O)Nc3ccc4cnccc4c3
InChI
  • 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

The FDA considers it to be a first-in-class medication.[6]

Contraindications

Netarsudil has no contraindications apart from known hypersensitivity to the drug.[2][7]

Adverse 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][8]

Overdose

Overdosing netarsudil is unlikely because concentrations in the body are so low that they are generally not detectable.[8]

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][7]

Pharmacology

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][7]

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).[7]

AR-13503, the active metabolite

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.[9]

See also

References
  1. "Rhopressa- netarsudil solution/ drops". DailyMed. Retrieved 2 May 2021.
  2. "Rhokiinsa EPAR". European Medicines Agency (EMA). 16 September 2019. Retrieved 27 September 2020.
  3. Dasso L, Al-Khaled T, Sonty S, Aref AA (2018). "Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date". Clinical Ophthalmology. Auckland, N.Z. 12: 1939–1944. doi:10.2147/OPTH.S154001. PMC 6177382. PMID 30323550.
  4. "Rhopressa (netarsudil) Ophthalmic Solution". U.S. Food and Drug Administration (FDA). 29 January 2018. Retrieved 3 June 2020.
  5. "Aerie (AERI) Gets Early FDA Approval for Lead Drug Rhopressa". 19 December 2017.
  6. New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
  7. "Netarsudil Mesylate Monograph for Professionals". American Society of Health-System Pharmacists. 16 November 2020. Retrieved 2 May 2021.
  8. "Rhokiinsa Product Information" (PDF). European Medicines Agency (EMA). 2 December 2019.
  9. "Rhokiinsa: EPAR – Public assessment report" (PDF). European Medicines Agency. 3 December 2019.
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