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 can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

. 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 respo ...

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

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

in people with open-angle glaucoma or

ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and ...

. 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 pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

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 prototype drug 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 medic ...

Contraindications

Netarsudil has no contraindications apart from known

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

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 (widenin ...

(increased blood flow associated with redness, in 51% of patients) in the

conjunctiva In the anatomy of the eye, the conjunctiva (: conjunctivae) 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 gobl ...

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 transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, 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 Rho-associated protein kinase or Rho-associated coiled-coil 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 ...

. This appears to increase outflow of

aqueous humor The aqueous humour is a transparent water-like fluid similar to blood 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 po ...

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 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 In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

s in the

to AR-13503, which is the

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

. Concentrations reached in the

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

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 (elimination half-life, pharmacological 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 blood plasma. ...

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

Chemistry

The drug is used in form of a salt, netarsudil di mesilate, 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 (chemistry), absorption or adsorption from the surrounding Natural environment, environment, which is usually at normal or room temperature. If water mol ...

, freely soluble in water and soluble in

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

References

External links

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