Netarsudil, sold under the brand name Rhopressa among others, is a medication for the treatment of

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

. In the United States, in December 2017, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(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 The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

approved it in 2019 for the same uses under the brand name Rhokiinsa. The FDA considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Contraindications

Netarsudil has no contraindications apart from known

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

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 The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...

cornea verticillata Cornea verticillata, also called vortex keratopathy or whorl keratopathy, is a condition characterised by corneal deposits at the level of the basal epithelium forming a faint golden-brown whorl pattern. It is seen in Fabry disease or in case of ...

(drug deposits in the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

, 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 Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton. ROCKs ( ...

. 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 episclera is the outermost layer of the sclera (the white of the eye).Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company, 1990. It is composed of loose, fibrous, elastic tissue and atta ...

. The drug also inhibits the norepinephrine transporter.

Pharmacokinetics

After instillation into the eye, netarsudil is cleaved by esterases in the

to AR-13503, which is the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

. Concentrations reached in the

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...

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 Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is 16 to 17 hours (in rabbits). AR-13503 skeletal

Chemistry

The drug is used in form of a salt, netarsudil di

mesilate In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group ...

, which is a white to light yellow crystalline powder. It is a weak acid and moderately

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance ...

, freely soluble in water and soluble in

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...

References

External links

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