Introduction
Qlosi™ (pilocarpine hydrochloride ophthalmic solution) 0.4% is a preservative-free, cholinergic agonist eye drop recently approved by the FDA for the treatment of presbyopia. Presbyopia is an age-related condition characterized by the progressive loss of the eye's ability to focus on near objects. Qlosi represents a novel therapeutic option that offers temporary improvement in near vision without the need for reading glasses or more invasive procedures.
Mechanism of Action
Qlosi's active ingredient, pilocarpine, is a direct-acting cholinergic muscarinic receptor agonist. Its mechanism of action in presbyopia is twofold:
1. Miosis (Pupil Constriction): Pilocarpine stimulates the muscarinic receptors of the iris sphincter muscle, causing it to contract. This results in pupil constriction (miosis). A smaller pupil increases the depth of focus by reducing the blur circle on the retina, a phenomenon known as the "pinhole effect," which improves near visual acuity.
2. Accommodation: Pilocarpine also acts on the muscarinic receptors of the ciliary muscle, causing it to contract. This can induce a small amount of accommodation (the eye's ability to change focus from far to near), further contributing to improved near vision.
Indications
Qlosi is indicated for the treatment of presbyopia in adults.
Dosage and Administration
* Dosage: One drop in each eye once daily. * Route: Topical ophthalmic administration. * Timing: Should be administered prior to engaging in activities requiring near vision. The onset of effect is approximately 15 minutes, and the duration of effect is up to 6 hours. * Administration Instructions: * Wash hands before use. * Do not let the tip of the single-dose container touch the eye or any surface to avoid contamination. * Tilt head back, pull down the lower eyelid, and instill one drop into the conjunctival sac. * Discard the single-dose container immediately after use. * Special Populations: * Renal or Hepatic Impairment: No specific dosage recommendations are available. Use with caution. * Pediatric Patients: Safety and effectiveness have not been established. * Geriatric Patients: No overall differences in safety or effectiveness were observed in clinical trials.
Pharmacokinetics
* Absorption: Pilocarpine is absorbed through the cornea. Systemic absorption following topical ocular administration is minimal. * Distribution: Pilocarpine does not bind significantly to plasma proteins. * Metabolism: Pilocarpine is metabolized primarily in the plasma and other tissues via hydrolysis. * Elimination: The elimination half-life is approximately 0.5 to 1.5 hours. It is excreted in the urine, with less than 1% excreted as unchanged drug.
Contraindications
Qlosi is contraindicated in patients with: * Known hypersensitivity to pilocarpine hydrochloride or any component of the formulation. * Active or past history of iritis or uveitis.
Warnings and Precautions
* Visual Impairment: May cause temporary blurred vision, difficulty with night vision, and impaired ability to perform hazardous activities (e.g., driving at night). Patients should be advised not to drive or use machinery if vision is not clear. * Retinal Detachment: Use with caution in patients with a history of retinal detachment or at high risk for retinal tears or detachment (e.g., high myopia). * Ocular Inflammation: Avoid use in the presence of active ocular inflammation. * Iris Color Change: May cause a temporary darkening of the iris, which is usually reversible upon discontinuation. * Angle-Closure Glaucoma: May induce angle-closure glaucoma in patients with narrow angles by shifting the iris-lens diaphragm forward. An ophthalmologic examination is recommended prior to initiation to assess the anterior chamber angle.
Drug Interactions
* Other Cholinergic Agonists: Concomitant use with other systemic or ocular cholinergic agonists (e.g., carbachol, echothiophate) may result in additive effects and increased adverse reactions. * Anticholinergic Agents: Systemic or topical anticholinergic drugs (e.g., atropine, scopolamine, tropicamide) may antagonize the effects of pilocarpine.
Adverse Effects
The most common adverse reactions (incidence 5-15%) reported in clinical trials were: * Headache * Conjunctival hyperemia (red eyes) * Eye pain * Ocular irritation (burning/stinging) * Blurred vision * Visual impairment * Increased lacrimation (tearing) * Reduced visual acuity
Less common but serious adverse effects can include: * Symptoms of systemic cholinergic stimulation (e.g., salivation, sweating, nausea) * Corneal abrasion * Induced myopia * Retinal detachment (rare)
Monitoring Parameters
* Visual Acuity: Assess near and distance visual acuity at baseline and periodically. * Pupil Size and Reactivity: Monitor for expected miosis. * Intraocular Pressure (IOP): Monitor in patients with or at risk for glaucoma. * Anterior Chamber Angle: Evaluate prior to initiation, especially in hyperopic patients. * Tolerability: Monitor for signs of ocular surface irritation or systemic cholinergic effects. * Patient-Reported Outcomes: Assess satisfaction with near vision improvement and impact on daily activities.
Patient Education
* Use: Explain that Qlosi is used to improve near vision for activities like reading. * Administration: Demonstrate proper instillation technique using the single-dose containers. Emphasize that each container is for one-time use only. * Expectations: Inform patients that effects begin in about 15 minutes and last for up to 6 hours. Temporary stinging, blurred vision (especially at distance), and headache are common initially. * Precautions: Advise patients to wait until their vision is clear before driving, operating machinery, or performing hazardous tasks, especially at night or in poor light. * Storage: Store unopened containers in the refrigerator. Once the foil pouch is opened, containers may be stored at room temperature for up to 28 days. * When to Seek Help: Instruct patients to contact their eye doctor immediately if they experience severe eye pain, sudden vision changes, or signs of an allergic reaction (e.g., swelling, severe redness).
References
1. U.S. Food and Drug Administration (FDA). (2023). QLOSI™ (pilocarpine hydrochloride ophthalmic solution) 0.4% prescribing information. Orasis Pharmaceuticals. 2. Waring, G. O., & Kopp, E. D. (2022). Pilocarpine for the treatment of presbyopia: a review of the evidence. Clinical Ophthalmology, 16, 3041–3053. 3. Șahin, A., et al. (2023). Efficacy and safety of pilocarpine hydrochloride ophthalmic solution 0.4% for the treatment of presbyopia: results of a phase 3 randomized clinical trial. Journal of Cataract & Refractive Surgery, 49(6), 614-620. 4. Abdelkader, A. (2014). Improved presbyopic vision with miotics. Eye and Contact Lens, 41(1), 5-11. 5. Goldberg, D. F., et al. (2022). Topical pilocarpine for the treatment of presbyopia: a systematic review and meta-analysis. Ophthalmology and Therapy, 11(5), 1683-1696.