Rhopressa
Rhopressa Uses, Dosage, Side Effects, Food Interaction and all others data.
A Rho kinase inhibitor with norepinephrine transport inhibitory activity that reduces production of aqueous
As of December 18, 2017 the FDA approved Aerie Pharmaceutical's Rhopressa (netarsudil ophthalmic solution) 0.02% for the indication of reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Acting as both a rho kinase inhibitor and a norepinephrine transport inhibitor, Rhopressa is a novel glaucoma medication in that it specifically targets the conventional trabecular pathway of aqueous humour outflow to act as an inhibitor to the rho kinase and norepinephrine transporters found there as opposed to affecting protaglandin F2-alpha analog like mechanisms in the unconventional uveoscleral pathway that many other glaucoma medications demonstrate.
Aqueous humour flows out of the eye via two pathways: 1) the conventional trabecular pathway and 2) the unconventional uveoscleral pathway. And, although it has been shown that the conventional trabecular pathway accounts for most aqueous outflow due to various pathologies, most medications available for treating glaucoma target the uveoscleral pathway for treatment and leave the diseased trabecular pathway untreated and unhindered in its progressive deterioration and dysfunction .
| Trade Name | Rhopressa |
| Availability | Prescription only |
| Generic | Netarsudil |
| Netarsudil Other Names | Netarsudil |
| Related Drugs | epinephrine ophthalmic, latanoprost ophthalmic, timolol ophthalmic, brimonidine ophthalmic, pilocarpine ophthalmic, Xalatan, Lumigan |
| Weight | 0.02%, |
| Type | Ophthalmic solution |
| Formula | C28H27N3O3 |
| Weight | Average: 453.542 Monoisotopic: 453.205241741 |
| Protein binding | The active metabolite of netarsudil, AR-13503 is highly protein bound in plasma, at approximately 60% bound. As AR-13503 is considered to bind less extensively to plasma proteins as its parent netarsudil, the % protein binding of netarsudil may be at least 60% or higher . |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Rhopressa is a rho kinase inhibitor used to reduce intraocular pressure in patients with open angle glaucoma or ocular hypertension.
Rhopressa is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension .
Rhopressa is also used to associated treatment for these conditions: Increased Intra Ocular Pressure (IOP)
How Rhopressa works
The medical condition glaucoma is a leading cause of progressive visual impairment and blindness across the world with primary open-angle glaucoma (POAG) being the major type of glaucoma .
Elevated intraocular pressure (IOP) resulting from increased resistance to aqueous humor outflow is considered a major risk for the development and progression of POAG, but various clinical studies have demonstrated that the reduction and tight control of IOP can delay or prevent POAG and the vision loss associated with it. Ordinary physiological IOP results from aqueous humor produced by the ocular ciliary body and its outflow through two main outflow pathways: the conventional (trabecular) and the unconventional (uveoscleral) pathways .
Under ordinary physiological conditions, diagnostic tracers have shown that the conventional trabecular pathway accounts for up to 90% of aqueous humor outflow. Through this pathway, aqueous humor drains from the anterior chamber sequentially through the uveal and corneoscleral meshwork beams, juxtacanalicular connective tissue (JCT) region, and inner wall (IW) endothelial cells of Schlemm's canal (SC) until finally entering the lumen of SC. From there aqueous humor drains into the collector channels, intravascular plexus, epscleral veins, and finally into the blood circulation .
In glaucomatous eyes, elevated IOP is the result of abnormally increased resistance to aqueous outflow in the conventional trabecular pathway due to apparent increases in the contractile tone and stiffness of the trabecular pathway meshwork (TM), changes in extracellular matrix composition, and/or a decrease in the conductance of the IW endothelial cells of SC .
Subsequently, as a rho kinase inhibitor, the novelty of netarsudil lies in its ability or specificity to apply its mechanism of action directly and specifically at the diseased TM of the conventional trabecular outflow pathway. In particular, rho kinases are serine/threonine kinases that function as important downstream effectors of Rho GTPase. Such activity in the TM and SC drives actomysin contraction, promotes extracellular matrix production, and increases cell stiffness. Acting as an inhibitor of rho kinase, netarsudil consequently reduces cell contraction, decreases the expression of fibrosis-related proteins, and reduces cell stiffness in the TM and SC cells. As a result, netarsudil has been able to demonstrate increases in trabecular outflow facility, increases in the effective filtration area of the TM, cause expansion of the TM tissue, and dilate episcleral veins .
Furthermore, netarsudil is also believed to possess inhibitory action against the norepinephrine transporter (NET). Such inhibition of the NET prevents reuptake of norepinephrine at noradrenergic synapses, which results in an increase in the strength and duration of endogenous norepinephrine signaling. As a consequence of this enhanced signaling, norepinephrine-induced vasoconstriction that can reduce blood flow to the ciliary body may subsequently be responsible for a mechanism in which the formation of aqueous humor may be delayed, prolonged, or reduced as well .
Toxicity
The most common adverse reaction associated with netarsudil dosed once daily in controlled clinical studies was conjunctival hyperemia which was reported by 53% of patients. Other common adverse affects reported (about 20%) include corneal verticillata, instillation site pain, and even conjunctival hemorrhage. Still other reactions include instillation site erythema, corneal staining, blurred vision, increased lacrimiation, erythema of eyelid, and reduced visual acuity being reported by 5-10% of patients in clinical studies .
When using multiple dose containers of topical ophthalmic products there is a possibilty of contaminating the containers with agents that may cause bacterial keratitis by patients who in many cases have a concurrent corneal disease or a disruption of the ocular epithelial surface .
Although systemic exposure to netarsudil from ocular administration is low, there is no formal available data on the safe use of netarsudil in pregnant women .
There is no formal data available on whether significant netarsudil levels could be present in human milk following ocular administration, on the effects on the breastfed enfant, or on the effects on milk production .
The safety and effectiveness of using netarsudil in pediatric patients below the age of 18 years have not been established .
No overall differences in safety or effectiveness have been observed between elderly and other aduly patients .
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of netarsudil. Rhopressa was not mutagenic in the Ames test, in the mouse lymphoma test, or in the in vivo rat micronucleus test. Studies to evaluate the effects of netarsudil on male or female fertility in animals have not been performed .
Food Interaction
No interactions found.Volume of Distribution
As netarsudil and its active metabolite demonstrate a high degree of protein binding , it is expected to exhibit a low volume of distribution.
Elimination Route
The systemic exposure of netarsudil and its active metabolite, AR-13503, after topical ocular administration of netarsudil opthalmic solution 0.02% once daily (one drop bilaterally in the morning) for eight days in 18 healthy subjects demonstrated no quantifiable plasma concentrations of netarsudil (lower limit of quantitation [LLOQ] 0.100 ng/mL) post dose on Day 1 and Day 8. Only one plasma concentration at 0.11 ng/mL for the active metabolite was observed for one subject on Day 8 at 8 hours post dose .
Half Life
The half-life of netarsudil incubated in vitro with human corneal tissue is 175 minutes .
Clearance
The clearance of netarsudil is strongly influenced by its low plasma concetrations following topical administration and absorption and high protein binding in human plasma inn .
Elimination Route
Clinical studies assessing the in vitro metabolism of netarsudil using corneal tissue from humans, human plasma, and human liver microsomes and microsomal S9 fractions demonstrated that netarsudil metabolism occurs through esterase activity. Subsequent metabolism of netarsudil's esterase metabolite, AR-13503, was not detectable. In fact, esterase metabolism in human plasma was not detected during a 3 hour incubation .
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