Usage
- Ripasudil is prescribed for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. It is used as adjunctive therapy in patients insufficiently responsive to topical beta-blockers or prostaglandin analogues, or as monotherapy when other IOP-lowering medications are contraindicated or not tolerated.
- Pharmacological Classification: Rho-kinase inhibitor, Antiglaucoma agent.
- Mechanism of Action: Ripasudil inhibits Rho-kinase, thereby increasing aqueous humor outflow through the trabecular meshwork and Schlemm’s canal, the conventional outflow pathway. It also modulates the behavior of trabecular meshwork cells and Schlemm’s canal endothelial cell permeability, disrupting tight junctions and further facilitating outflow.
Alternate Names
- Ripasudil hydrochloride hydrate (active ingredient)
- K-115 (developmental code name)
- Brand Name: Glanatec (ophthalmic solution 0.4%)
How It Works
- Pharmacodynamics: Ripasudil lowers IOP by enhancing aqueous humor outflow through the conventional outflow pathway. It relaxes trabecular meshwork and Schlemm’s canal endothelial cells, leading to increased outflow facility.
- Pharmacokinetics:
- Absorption: Administered as ophthalmic solution, with rapid ocular penetration and some systemic absorption.
- Metabolism: Primarily metabolized to M1 (isoquinoline ring position 1 hydroxylated form).
- Elimination: Predominantly renal excretion, with rapid clearance. Half-life is approximately 0.45 hours.
- Mode of Action: Ripasudil selectively inhibits ROCK-1 and ROCK-2 (Rho-kinase isoforms). This inhibition leads to cytoskeletal changes in trabecular meshwork cells, reducing cell contractility and increasing outflow facility.
- Receptor Binding, Enzyme Inhibition: Selective inhibition of Rho-kinase. No significant interaction with other receptors or enzymes, including serine-threonine protein kinases, has been observed.
- Elimination Pathways: Primarily renal excretion of ripasudil and its metabolite M1.
Dosage
Standard Dosage
Adults:
- One drop in the affected eye(s) twice daily.
Children:
- Safety and efficacy not established in pediatric patients. No dosing recommendations are available.
Special Cases:
- Elderly Patients: No specific dose adjustment is typically required. Monitor for potential side effects.
- Patients with Renal Impairment: Use with caution. Monitor renal function and adjust dose as necessary.
- Patients with Hepatic Dysfunction: Use with caution. Monitor liver function and adjust dose as necessary.
- Patients with Comorbid Conditions: Evaluate potential drug interactions and adjust treatment accordingly.
Clinical Use Cases
- Specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not available. The standard dosage is generally applied unless contraindicated.
Dosage Adjustments
- Dose adjustments might be necessary based on patient response and tolerance, as well as in cases of renal or hepatic dysfunction.
Side Effects
Common Side Effects
- Conjunctival hyperemia (redness)
- Conjunctivitis
- Blepharitis (eyelid inflammation)
- Eye irritation
- Ocular discomfort (abnormal sensation in eye)
- Conjunctival hemorrhage
Rare but Serious Side Effects
- Allergic reactions (e.g., rash, itching, swelling)
Long-Term Effects
- Potential for allergic conjunctivitis and blepharitis with long-term use.
Adverse Drug Reactions (ADR)
- Severe allergic reactions requiring immediate discontinuation of treatment and medical intervention.
Contraindications
- Hypersensitivity to ripasudil or any component of the formulation.
Drug Interactions
- Limited information available. Potential interaction with pilocarpine, which can interfere with ripasudil-induced IOP reduction. When using multiple ophthalmic medications, administer with at least a 5-minute interval. Caution is advised when combining with other drugs that affect IOP or ocular health.
Pregnancy and Breastfeeding
- Pregnancy: Safety not established. Use only if potential benefit outweighs potential risk.
- Breastfeeding: Ripasudil is excreted in breast milk in animal studies. Avoid use or discontinue breastfeeding while using ripasudil.
Drug Profile Summary
- Mechanism of Action: Rho-kinase inhibitor, increases aqueous outflow.
- Side Effects: Conjunctival hyperemia, conjunctivitis, blepharitis, eye irritation.
- Contraindications: Hypersensitivity.
- Drug Interactions: Potential interaction with pilocarpine.
- Pregnancy & Breastfeeding: Safety not established. Avoid use or discontinue breastfeeding.
- Dosage: 1 drop twice daily in the affected eye(s).
- Monitoring Parameters: Intraocular pressure, signs of ocular irritation or inflammation.
Popular Combinations
- Ripasudil can be used in combination with other IOP-lowering medications, such as timolol or latanoprost, when monotherapy is insufficient. Timolol reduces aqueous humor production, while latanoprost increases uveoscleral outflow. This combination can provide additive IOP-lowering effects.
Precautions
- General Precautions: Assess for allergies, pre-existing eye conditions, and concurrent medications.
- Specific Populations: Caution advised in pregnant/breastfeeding women, children, and patients with hepatic/renal impairment.
- Lifestyle Considerations: Advise patients to avoid driving or operating machinery if blurred vision occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ripasudil?
A: The standard dosage is one drop in the affected eye(s) twice daily.
Q2: What is the mechanism of action of Ripasudil?
A: It is a Rho-kinase inhibitor that increases aqueous humor outflow through the trabecular meshwork and Schlemm’s canal.
Q3: What are the common side effects of Ripasudil?
A: Common side effects include conjunctival hyperemia, conjunctivitis, blepharitis, and eye irritation.
Q4: Is Ripasudil safe to use during pregnancy or breastfeeding?
A: Safety has not been established. Avoid use or discontinue breastfeeding.
Q5: Can Ripasudil be used with other glaucoma medications?
A: Yes, it can be used as adjunctive therapy with beta-blockers like timolol or prostaglandin analogues like latanoprost.
Q6: How should Ripasudil be administered?
A: Instill one drop into the conjunctival sac of the affected eye(s), being careful not to touch the tip of the bottle to the eye or any other surface.
Q7: What should a patient do if they miss a dose of Ripasudil?
A: Apply the missed dose as soon as remembered. If it is almost time for the next dose, skip the missed dose and continue with the regular schedule.
Q8: Are there any contraindications to using Ripasudil?
A: Known hypersensitivity to ripasudil or any of its components.
Q9: What should I monitor in patients taking Ripasudil?
A: Intraocular pressure, signs of ocular irritation or inflammation, and any allergic reactions.
Q10: Does Ripasudil have any effect on driving ability?
A: Ripasudil might cause transient blurred vision. Advise patients to avoid driving or operating machinery until their vision clears.
