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 re ...

. 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 federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) approved a 0.02% ophthalmic solution for the lowering of elevated

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response fu ...

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 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 medica ...

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 ...

to the drug.

Adverse effects

The most common side effects are

hyperaemia Hyperaemia (also hyperemia) is the increase of blood flow to different tissues in the body. It can have medical implications but is also a regulatory response, allowing change in blood supply to different tissues through vasodilation. Clinically, ...

(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 epitheli ...

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 ...

(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 ...

, 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 The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...

through the

trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...

, and also to reduce pressure in the veins of the

episcleral layer The episclera is the outermost layer of the sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen ...

. The drug also inhibits the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

Pharmacokinetics

After instillation into the eye, netarsudil is cleaved by

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

s 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 ...

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.

References

External links

* * {{Portal bar , Medicine Ophthalmology drugs Isoquinolines Benzoate esters