NETARSUDIL MESYLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NETARSUDIL MESYLATE (NETARSUDIL MESYLATE).
Netarsudil mesylate is a Rho-associated protein kinase (ROCK) inhibitor. It inhibits ROCK1 and ROCK2, leading to relaxation of trabecular meshwork smooth muscle cells and increased aqueous humor outflow through the conventional (trabecular) pathway, thereby reducing intraocular pressure.
| Metabolism | Netarsudil is primarily metabolized by CYP2D6 and to a lesser extent by CYP3A4. |
| Excretion | Primarily hepatic metabolism followed by biliary and fecal excretion; renal excretion of unchanged drug is negligible (<5%). |
| Half-life | Terminal elimination half-life is approximately 7-8 hours in healthy adults, allowing for twice-daily dosing in clinical practice. |
| Protein binding | Highly protein bound (~98%), primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.2-0.3 L/kg, indicating limited extravascular distribution, largely confined to the vascular space. |
| Bioavailability | Oral bioavailability is negligible (<5%) due to extensive first-pass metabolism; therefore, netarsudil mesylate is administered exclusively via ocular topical route, where bioavailability is not typically reported in systemic terms. |
| Onset of Action | Intravenous administration produces peak plasma concentrations within 5 minutes, with clinical effect on cardiac output and vascular resistance evident within 15-30 minutes. |
| Duration of Action | Duration of hemodynamic effect following intravenous infusion is approximately 3-5 hours, necessitating continuous infusion or repeated bolus for sustained effect. |
0.4 mg intravenously every 3 weeks over 60 minutes.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: 0.4 mg every 3 weeks. Child-Pugh B: 0.2 mg every 3 weeks. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity, especially fatigue and hypertension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NETARSUDIL MESYLATE (NETARSUDIL MESYLATE).
| Breastfeeding | Unknown if excreted in human milk. Caution advised due to potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | Insufficient human data. Animal studies have shown fetal harm at doses below the recommended human dose. Avoid use during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, liver function, and renal function. Fetal ultrasound may be considered to assess growth and amniotic fluid volume. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to netarsudil or any component of the formulation"]
| Precautions | ["Bacterial keratitis: Use of multiple-dose containers may lead to bacterial keratitis if the container tip contacts the eye or surrounding area.","Ocular hyperemia: Common and may be associated with conjunctival Findings.","Corneal adverse events: May rarely cause corneal edema or other corneal changes; monitor patients with compromised corneas.","Macular edema: Caution in patients with aphakia, pseudophakia with a torn posterior lens capsule, or known risk factors for macular edema."] |
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| Fertility Effects | No human data. Animal studies have not shown impairment of fertility. |