Xalatan®
Latanoprost 0.005% · ophthalmic solution
Antiglaucoma
Approved uses
Open-angle glaucoma or ocular hypertension
One drop in the affected eye(s) once daily in the evening; not to exceed once daily.
IOP falls 3 to 4 hours after dosing, peaks at 8 to 12 hours, and lasts 24 hours with a 6.7 mmHg drop.
OFF-LABELNot in the FDA label for this product
Chronic angle-closure glaucoma
0.005% solution, one drop once daily at 9 PM (trial regimen), 12 weeks.
RCT · n=275
Randomized, double-masked, multicenter 12-week trial in chronic angle-closure glaucoma (latanoprost n=137, timolol n=138): mean change in daily IOP was -8.2 mmHg versus -5.2 mmHg with timolol BID, difference -3.0 mmHg (95% CI -4.0 to -2.1, P<0.001), favoring latanoprost, and more patients reached each prespecified target IOP. The formulation studied was the preserved 0.005% solution.
Pediatric glaucoma
0.005% solution, one drop once daily at 8 PM (trial regimen, ages 0 to 18 years), 12 weeks.
RCT · n=137 · not superior
Phase 3, randomized, double-masked, 12-week multicenter trial, 137 treated (primary congenital and non-congenital glaucoma): mean IOP reduction at week 12 was 7.2 mmHg versus 5.7 mmHg with timolol, difference 1.5 mmHg (95% CI -0.8 to 3.7, P=0.21), meeting the noninferiority margin without demonstrating superiority; responder rates 60% versus 52% (P=0.33) and both agents well tolerated over 3 months. This label states pediatric safety and effectiveness are not established.
Contraindications
Known hypersensitivity to latanoprost, benzalkonium chloride, or any other ingredient in this product.
Available Forms0.005% (50 mcg/mL) ophthalmic solution, 2.5 mL fill in a 5 mL bottle, package of 1 bottle
Mechanism of ActionProstaglandin F2alpha analogue supplied as an isopropyl ester prodrug that corneal esterases hydrolyze to the active acid; IOP falls mainly through increased uveoscleral outflow, which class reviews attribute to matrix metalloproteinase remodeling that widens the spaces between ciliary muscle fibers. Onset is 3 to 4 hours after instillation, maximum effect at 8 to 12 hours, and IOP reduction persists at least 24 hours.
Warnings & Precautions
- Iris pigmentation: Brown pigmentation spreads concentrically from the pupil and increases as long as dosing continues, from increased melanin content in melanocytes rather than more melanocytes; it is likely permanent after discontinuation, so examine these patients regularly. Nevi and freckles of the iris appear unaffected, and the change may take months to years to become noticeable.
- Periorbital and lash changes: Eyelid skin darkening plus increased eyelash and vellus hair length, thickness, pigmentation, number, and misdirected growth in the treated eye; periorbital tissue pigmentation reported reversible in some patients, eyelash changes usually reversible upon discontinuation.
- Intraocular inflammation: Caution with a history of iritis or uveitis, and generally not for use with active intraocular inflammation, which may be exacerbated.
- Macular edema: Macular edema including cystoid macular edema has been reported; caution in aphakia, in pseudophakia with a torn posterior lens capsule, and with other known risk factors.
- Herpetic keratitis: Reactivation of herpes simplex keratitis has been reported; caution with a history of it, and avoid in active herpes simplex keratitis, which may be exacerbated.
- Bacterial keratitis: Reported with inadvertently contaminated multiple-dose containers, in most cases in patients with concurrent corneal disease or a disrupted ocular epithelial surface.
- Benzalkonium chloride: Preserved with 0.02% benzalkonium chloride, which may be absorbed by contact lenses; remove lenses before instillation and reinsert 15 minutes after.
- Prostaglandin duplication: Dosing more than once daily, or combining two or more prostaglandins or prostaglandin analogs, may decrease the IOP lowering effect or cause paradoxical IOP elevation.
- Thimerosal-containing drops: Precipitation occurs in vitro when thimerosal drops are mixed with this solution; separate concurrent topical drops by at least 5 minutes.
Common Side Effects
- Ocular, 5% to 15%: foreign body sensation 13%, punctate keratitis 10%, stinging 9%, conjunctival hyperemia 8%, blurred vision 8%, itching 8%, burning 7%, increased iris pigmentation 7% (n=460 vs timolol n=369 in three controlled trials).
- Ocular, 1% to 5%: excessive tearing 4%, eyelid discomfort or pain 4%, dry eye 3%, eye pain 3%, eyelid margin crusting 3%, eyelid erythema 3%, photophobia 2%, eyelid edema 1%, blepharitis 1%.
- Discontinuation: fewer than 1% stopped therapy for intolerance to conjunctival hyperemia.
- Ocular, postmarketing: intraocular inflammation (iritis/uveitis), macular edema including cystoid macular edema, herpes keratitis, keratitis, corneal edema and erosions, deepening of the eyelid sulcus, trichiasis, iris cyst, eyelid skin darkening, conjunctivitis, pseudopemphigoid of the conjunctiva.
- Systemic, 1% to 3%: upper respiratory infection, nasopharyngitis or influenza 3%, myalgia, arthralgia or back pain 1%, rash or allergic skin reaction 1%.
- Systemic, postmarketing: asthma and exacerbation of asthma, dyspnea, headache, dizziness, angina including unstable angina, palpitations, chest pain, nausea, vomiting, pruritus, toxic epidermal necrolysis.
Pregnancy & LactationPregnancy: No adequate and well-controlled studies in pregnant women. IV latanoprost given to pregnant rabbits and rats through organogenesis produced malformations, embryofetal lethality, and spontaneous abortion at clinically relevant doses, with post-implantation loss in rabbits at 1.3 times the maximum recommended human ophthalmic dose and cleft palate in rats at 3.2 times.
Lactation: Excretion in human milk is unknown; weigh the benefits of breastfeeding against maternal need and potential effects on the breastfed child.
Pediatric UseSafety and effectiveness not established in pediatric patients.