Class: Prostaglandin Analogs
VA Class: OP109
Molecular Formula: C26H40O5
CAS Number: 130209-82-4
Brands: Xalatan, Xelpros
Introduction
Ocular hypotensive agent; a synthetic analog of prostaglandin F2α (PGF2α).
Uses for Latanoprost
Ocular Hypertension and Glaucoma
Latanoprost 0.005%: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.
Appears to be more effective than unoprostone (not available in US), as effective as travoprost, and slightly less effective than bimatoprost in reducing IOP in patients with open-angle glaucoma or ocular hypertension.
May be more effective or at least as effective as twice-daily administration of timolol 0.5% in reducing IOP in patients with open-angle glaucoma or ocular hypertension. Appears to be more effective than thrice-daily administration of dorzolamide 2%.
Tolerance does not occur, and reduction in mean IOP is maintained for up to at least 24 months of therapy after initial stabilization.
Fixed-combination netarsudil 0.02% and latanoprost 0.005%: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension. When administered once daily, mean IOP reduction was approximately 1–3 mm Hg greater than that achieved with once-daily administration of either drug alone.
When selecting an initial ocular hypotensive agent, consider extent of the required IOP reduction, coexisting medical conditions, and drug characteristics (e.g., dosing frequency, adverse effects, cost). With single-agent regimens, the reduction in IOP is approximately 25–33% with topical prostaglandin analogs; 20–25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20–30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15–20% with topical carbonic anhydrase inhibitors.
A prostaglandin analog frequently is considered for initial therapy in the absence of other considerations (e.g., contraindications, cost considerations, intolerance, adverse effects, patient refusal) because of relatively greater activity, once-daily administration, and low frequency of systemic adverse effects; however, ocular adverse effects can occur.
Goal is to maintain an IOP at which visual field loss is unlikely to substantially reduce quality of life during the patient's lifetime.
Reduction of pretreatment IOP by ≥25% shown to slow progression of primary open-angle glaucoma. Set an initial target IOP (based on extent of optic nerve damage and/or visual field loss, baseline IOP at which damage occurred, rate of progression, life expectancy, and other considerations) and reduce IOP toward this goal. Adjust target IOP up or down as needed over course of disease.
Combination therapy with drugs from different therapeutic classes often required to control IOP.
Latanoprost Dosage and Administration
Administration
Ophthalmic Administration
Apply topically to the affected eye(s) as an ophthalmic emulsion (latanoprost) or ophthalmic solution (latanoprost alone or in fixed combination with netarsudil).
Avoid contamination of the dispensing container. (See Bacterial Keratitis under Cautions.)
Remove contact lenses before administering each dose; may reinsert lenses 15 minutes after the dose.
If more than one topical ophthalmic preparation is used, administer the preparations at least 5 minutes apart.
Dosage
Adults
Ocular Hypertension and Glaucoma
Ophthalmic
Latanoprost 0.005% ophthalmic solution or emulsion: One drop in the affected eye(s) once daily in the evening.
Netarsudil 0.02% and latanoprost 0.005% ophthalmic solution: One drop in the affected eye(s) once daily in the evening.
More frequent dosing may diminish the IOP-lowering effect of latanoprost or cause paradoxical elevation of IOP.
If target IOP not achieved, may initiate additional or alternative ocular hypotensive agents. (See Ocular Hypertension and Glaucoma under Uses.) However, concomitant use of ≥2 prostaglandin analogs not recommended.
If a dose is missed, continue the usual schedule with the next dose applied the following evening.
Special Populations
No special population dosage recommendations at this time.
Cautions for Latanoprost
Contraindications
- Known hypersensitivity to latanoprost or any ingredient in the formulation (e.g., benzalkonium chloride).
Warnings/Precautions
Pigmentation
Increased pigmentation of the iris and periorbital tissue (eyelid) reported. Pigmentation expected to increase as long as latanoprost is administered. Following discontinuance of therapy, pigmentation of the iris is likely to be permanent, while pigmentation of periorbital tissue reportedly is reversible in some patients. Long-term effects (i.e., beyond 5 years) of increased pigmentation are unknown.
Increased pigmentation of iris may not be evident until after several months to years of latanoprost therapy. May continue therapy in patients who develop noticeably increased iris pigmentation; however, examine these patients regularly.
Eyelash Changes
Possible gradual change in eyelashes and vellus hair in the treated eye, including increased length, thickness, pigmentation, and number of eyelashes and/or misdirected growth of eyelashes. Usually reversible upon discontinuance of therapy.
Intraocular Inflammation
Use with caution in patients with a history of intraocular inflammation (e.g., iritis, uveitis); use generally not recommended in patients with active intraocular inflammation since latanoprost may exacerbate inflammation.
Macular Edema
Macular edema, including cystoid macular edema, reported in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema; use with caution in such patients.
Herpetic Keratitis
Reactivation of herpes simplex keratitis reported. Use with caution in patients with a history of herpetic keratitis; avoid use in those with active herpes simplex keratitis since latanoprost may exacerbate inflammation.
Bacterial Keratitis
Bacterial keratitis reported with use of multiple-dose containers of topical ophthalmic preparations. Containers were inadvertently contaminated by patients, most of whom had concurrent corneal disease or disruption of the ocular epithelial surface.
Improper handling of ophthalmic solutions can result in contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions. (See Advice to Patients.)
Use with Contact Lenses
Remove contact lenses before administering each dose; may reinsert lenses 15 minutes after the dose.
Use of Fixed Combinations
When used in fixed combination with netarsudil, consider the cautions, precautions, and contraindications associated with netarsudil.
Specific Populations
Pregnancy
Category C.
Use only if potential benefits justify possible risks to the fetus.
Lactation
Not known whether latanoprost distributes into milk, affects the breast-fed infant, or affects milk production.
Latanoprost ophthalmic solution or emulsion: Use with caution.
Netarsudil and latanoprost fixed-combination ophthalmic solution: Consider developmental and health benefits of breast-feeding along with the mother's clinical need for the drugs and any potential adverse effects of the drugs on the breast-fed infant.
Pediatric Use
Safety and efficacy not established in pediatric patients.
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults.
Common Adverse Effects
Latanoprost ophthalmic solution: Foreign body sensation, punctate keratitis, ocular stinging, conjunctival hyperemia, blurred vision, ocular pruritus, ocular burning, increased pigmentation of the iris.
Latanoprost ophthalmic emulsion: Eye pain/stinging upon instillation, ocular hyperemia, conjunctival hyperemia, eye discharge, eyelash growth or thickening, ocular pruritus.
Netarsudil and latanoprost ophthalmic solution: Conjunctival hyperemia, instillation site pain, corneal verticillata, conjunctival hemorrhage, ocular pruritus, decreased visual acuity, increased lacrimation, instillation site discomfort, blurred vision.
Interactions for Latanoprost
Specific Drugs
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Drug |
Interaction |
Comments |
|
Thimerosal |
Ophthalmic preparations containing thimerosal: Precipitation occurs when admixed with latanoprost ophthalmic solution or emulsion |
Administer latanoprost and thimerosal-containing preparations ≥5 minutes apart |
Latanoprost Pharmacokinetics
Absorption
Bioavailability
Approximately 1% of a topically applied dose penetrates the human eye; remaining portion is absorbed into systemic circulation through blood vessels in the conjunctiva and mucous membranes of the nose, pharynx, esophagus, and GI tract.
Prodrug; absorbed through the cornea following ocular instillation and rapidly hydrolyzed to active form (latanoprost acid). Peak aqueous humor concentrations of latanoprost acid occur within 2 hours.
Onset
Reduction in IOP generally occurs within 3–4 hours after topical application and peaks within 8–12 hours.
Duration
Effects on IOP generally persist for up to 24 hours or longer.
Following long-term therapy (i.e., 6 months), pharmacologic effects may persist for at least 14 days after the drug is discontinued.
Distribution
Extent
The volume of distribution of latanoprost acid in humans following ocular or IV administration is 0.36 or 0.16 L/kg, respectively. Latanoprost acid can be measured in aqueous humor during the first 4 hours, and in plasma only during the first hour after ocular instillation.
Not known whether the drug or its metabolites distribute into milk in humans.
Elimination
Metabolism
Rapidly hydrolyzed by esterases in the cornea and plasma to biologically active form (latanoprost acid).
Systemically absorbed latanoprost acid is metabolized in the liver.
Elimination Route
Metabolites are excreted principally in urine; however, biliary excretion also may occur. Unchanged latanoprost or latanoprost acid generally are not recovered in urine or feces. Following topical administration of radiolabeled latanoprost to the eye, 88% of the dose was eliminated in urine.
Half-life
The elimination half-life of latanoprost acid from aqueous humor is approximately 3 hours.
Following topical application to the eye, the plasma elimination half-life of latanoprost acid is approximately 17 minutes.
Stability
Storage
Ophthalmic
Emulsion
Latanoprost: Store at 2–25°C and protect from light; may use opened bottle until the manufacturer's labeled expiration date. During shipping, may be maintained at up to 40°C for ≤8 days.
Solution
Latanoprost: Store unopened bottle at 2–8°C and protect from light. During shipping, may be maintained at up to 40°C for ≤8 days. May store opened bottle at room temperature for ≤6 weeks; do not expose opened bottle to temperatures >25°C.
Netarsudil and latanoprost: Store at 2–8°C and protect from light; may use opened bottle until the manufacturer's labeled expiration date. During shipping, may be maintained at up to 40°C for ≤14 days.
Actions
- Selective prostanoid agonist.
- Appears to reduce IOP by increasing uveoscleral outflow of aqueous humor.
Advice to Patients
- Importance of not exceeding once-daily dosing; more frequent administration may decrease IOP-lowering effect of latanoprost.
- Risk of permanent increase in brown pigmentation of the iris; risk of darkening of the skin around the eyes (eyelid), which may be reversible after discontinuance of latanoprost.
- Risk of changes in eyelashes and vellus hair in the treated eye. Potential for disparity between eyes in length, thickness, pigmentation, or number of eyelashes or vellus hairs and/or direction of eyelash growth. Eyelash changes usually are reversible after discontinuance of latanoprost.
- Importance of learning and adhering to proper administration techniques to avoid contamination of the ophthalmic preparation with common bacteria that can cause ocular infections. Instruct patients that the tip of the dispensing container should not touch the eye or surrounding structures, fingers, or any other surface. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic preparations.
- Advise patients to immediately contact their clinician for advice regarding continued use of the ophthalmic preparation if an intercurrent ocular condition (e.g., trauma, infection) or ocular reaction (particularly conjunctivitis and eyelid reaction) develops or ocular surgery is planned.
- Importance of removing contact lenses before administering each dose and delaying reinsertion for at least 15 minutes after the dose.
- If using more than one topical ophthalmic preparation, importance of administering the preparations at least 5 minutes apart.
- Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
- Importance of women informing clinicians if they are or intend to become pregnant or plan to breast-feed.
- Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
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Latanoprost |
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Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|
Ophthalmic |
Emulsion |
0.005% |
Xelpros |
Sun |
|
Solution |
0.005%* |
Latanoprost Ophthalmic Solution |
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Xalatan |
Pfizer |
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Latanoprost Combinations |
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Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|
Ophthalmic |
Solution |
0.005% with Netarsudil Mesylate 0.02% (of netarsudil) |
Rocklatan |
Aerie |