Netarsudil

File:Netarsudil.svg
Systematic (IUPAC) name
[4-[(2S)-3-Amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate
Clinical data
Pronunciation	ne TAR soo dil
Trade names	Rhopressa, Rhokiinsa
AHFS/Drugs.com	monograph
MedlinePlus	a618014
Licence data	EMA:Link, US Daily Med:link
Legal status	US: ℞-only EU: Rx-only
Routes of administration	Eye drops, topical
Pharmacokinetic data
Metabolism	Esterases in the cornea
Metabolites	AR-13503 (active metabolite)
Biological half-life	16–17 hrs
Duration of action	≥ 24 hrs
Identifiers
CAS Number	1254032-66-0
ATC code	S01EX05 (WHO)
PubChem	CID: 66599893
DrugBank	DB13931
ChemSpider	34980598
UNII	W6I5QDT7QI
KEGG	D11030
Synonyms	AR-13324
Chemical data
Formula	C28H27N3O3
Molecular mass	453.54 g·mol−1
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

Netarsudil, sold under the brand name Rhopressa among others, is a medication for the treatment of glaucoma. 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. The European Medicines Agency approved it in 2019 for the same uses under the brand name Rhokiinsa.

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

Contraindications

Netarsudil has no contraindications apart from known hypersensitivity to the drug.

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%.

Overdose

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

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.

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.

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).

File:AR-13503 skeletal.svg

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.

See also

• Netarsudil/latanoprost, a combination drug