Latanoprost, an analog of prostaglandin F2alpha, is a prodrug used to reduce elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Studies have shown that latanoprost administered once daily is at least as effective as timolol in lowering intraocular pressure. When latanoprost and timolol were used in combination, a complete or almost complete additive effect in reducing intraocular pressure has been observed. Treatment has been associated with increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-Instruct the patient on proper instillation of the eye solution.
-Wash hands before and after use.
-Remove contact lenses before instilling ophthalmic drops. Lenses may be reinserted 15 minutes after drug administration.
-Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close eyes for 1 to 2 minutes. Do not blink.
-Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
-Latanoprost may be used concomitantly with other ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart. In vitro studies have shown precipitation occurs when ophthalmic drugs that contain thimerosal are mixed with latanoprost.
-A delivery aid (i.e., Xal-Ease) is available for administering the ophthalmic solution.
Ocular adverse reactions experienced by patients treated with latanoprost during clinical trials included ocular pain (3% to 55%), ocular irritation (7% to 55%), foreign body sensation (2% to 13%), ocular hyperemia (41%), conjunctival hyperemia (8% to 15%), ocular discharge (12%), ocular pruritus (5% to 8%), blurred vision or visual impairment (4% to 8%), and punctate keratitis (1% to 10%). Adverse reactions reported in 1% to 5% of patients include xerophthalmia (3%), lacrimation (4%), conjunctival edema (1%), eyelid crusting (3%), blepharedema (1% to 3%), blepharitis (1% to 3%), eyelid discomfort (4%), and photophobia (2%). Iridal discoloration was reported in 7% of patients; however, this adverse event happens slowly and may not be noticeable for several months to several years. This change is caused by an increase in the amount of brown pigment in the iris due to an increased number of melanosomes in melanocytes. The increase in brown pigment has not been shown to progress further upon discontinuation of treatment, however, the resultant color change may be permanent. Latanoprost may gradually change eyelashes and vellus hair; these changes include increased length, thickness, pigmentation, number of lashes or hairs (hypertrichosis), and misdirected growth of lashes. During clinical trials, 11% of drug recipients had increased eyelash growth, 8% had eyelash thickening, and 1% had eyelash discoloration. Eyelid skin darkening (eyelid skin hyperpigmentation) has also been reported. Corneal edema, corneal erosion, keratitis, herpes keratitis, ocular inflammation (iritis and uveitis), periorbital and lid changes resulting in deepening of the eyelid sulcus, trichiasis, iris cyst, conjunctivitis, pseudopemphigoid of the ocular conjunctiva, and macular edema (including cystoid macular edema) have been reported during postmarketing experience with latanoprost.
Asthma or asthma exacerbations (bronchospasm) and dyspnea have been reported during postmarketing experience with latanoprost.
Infection (i.e., upper respiratory tract infection, naso-pharyngitis, influenza) was reported in 3% of patients receiving latanoprost during clinical trials. Cases of herpes keratitis have been reported with postmarketing use.
Postmarketing use of latanoprost has been associated with cases of palpitations, unstable angina, and chest pain (unspecified).
Myalgia, arthralgia, musculoskeletal pain, and back pain were reported in 1% of patients during latanoprost clinical trials.
Rash and other allergic skin reactions were reported at a rate of 1% during latanoprost clinical trials. Cases of pruritus and toxic epidermal necrolysis have been reported during postmarketing use of latanoprost.
Dizziness and headache have been reported during postmarketing experience with latanoprost.
Nausea and vomiting have been reported during postmarketing experience with latanoprost.
Latanoprost should not be used in patients with closed-angle glaucoma, or inflammatory or neovascular glaucoma. There is limited experience with latanoprost in these patients.
Latanoprost should be used with caution in patients with aphakia, pseudophakic patients with a torn posterior lens capsule, and patients with known risk factors for macular edema. Macular edema, including cystoid macular edema, has been reported during treatment with this drug.
Recipients of latanoprost may experience a gradual increase in pigmentation (i.e., brown coloration) of the iris and periorbital tissue (eyelids), which may not be noticeable for several months to years. Patients who develop increased pigmentation may continue to receive treatment; however, these patients should be examined regularly as they may develop photophobia or be more sensitive to sunlight (UV) exposure. After discontinuing latanoprost, the change in iris color is likely to be permanent, while the pigmentation change in the periorbital tissue may be reversible in some patients. Eyelash changes (i.e., increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes) has also been associated with the use of latanoprost. Eyelash changes are usually reversible upon treatment discontinuation. Inform drug recipients of the possibility of iridal and eyelid discoloration, and of the potential for eyelash changes.
Latanoprost should be used with caution in patients with active intraocular inflammation (e.g., iritis, uveitis). Use of latanoprost in these patient may exacerbate inflammation.
Instruct drug recipients to remove contact lenses before instilling latanoprost ophthalmic drops. Lenses may be reinserted 15 minutes after drug administration. The ophthalmic solution is formulated with the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.
The use of multiple dose containers of ophthalmic products has been associated with bacterial keratitis. Inadvertent contamination of the latanoprost containers may increase the risk of infection in ocular surgery patients, or in patients who develop an ocular infection or ocular trauma, including corneal abrasion. If there is any damage to the ocular epithelial surface, latanoprost should be used with caution. Reactivation of herpes simplex keratitis has been reported during latanoprost therapy. Use caution in patients with a history of herpetic keratitis; avoid use in patients with active herpes simplex keratitis due to the potential for exacerbation of inflammation.
No adequate and well-controlled studies have been conducted to evaluate the use of latanoprost during human pregnancy. In animal studies involving rats and rabbits, the administration of intravenous latanoprost (at clinically relevant doses) throughout the period of organogenesis resulted in malformations, embryofetal lethality, and spontaneous abortion. In rabbits, intravenous latanoprost given on gestation days 6 through 18 resulted in post-implantation loss due to late resorption [1.3-times maximum recommended human ophthalmic dose (RHOD)], spina bifida and abortion (32-times RHOD), and total litter loss due to early resorption (324-times RHOD). In rats, intravenous latanoprost given on gestation days 6 through 15 resulted in cleft palate (3.2-times RHOD), brain porencephalic cysts (162-times RHOD), and skeletal anomalies (811-times RHOD). In an observational study involving 11 pregnant women taking latanoprost for glaucoma, there were no congenital anomalies in 9 cases with complete follow-up, 1 case was lost to follow-up, and 1 case experienced an early spontaneous abortion. Limited experience in human pregnancy has not resulted in clinically significant risk to the fetus. A minimal amount of drug reaches systemic circulation after ophthalmic administration, suggesting exposure of the drug to the fetus is low.
According to the manufacturer, it is not known whether latanoprost or its metabolites are excreted in breast milk. Because systemic plasma concentrations of latanoprost are low and the half-life is short after ophthalmic administration, clinically significant amounts of the drug would not be expected to be excreted in breast-milk. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. According to the manufacturer, caution should be exercised when latanoprost is administered during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Safety and efficacy of latanoprost have not been established in the pediatric population (i.e., neonates, infants, children, or adolescents).
Latanoprost should be used cautiously in patients with renal disease (e.g., renal failure, renal impairment) or hepatic disease. There have been no studies on safe use in these patients.
For the reduction of increased intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension:
Ophthalmic dosage (0.005% solution and emulsion):
Adults: 1 drop (1.5 mcg) applied to each affected eye once daily in the evening. More frequent administration may decrease the intraocular pressure-lowering effect or cause paradoxical elevations in intraocular pressure.
Maximum Dosage Limits:
-Adults
1 drop/day per affected eye.
-Geriatric
1 drop/day per affected eye.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Latanoprost should be used with caution in patients with hepatic impairment; data are lacking in these patients.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Latanoprost should be used with caution in patients with renal impairment; data are lacking in these patients.
Intermittent hemodialysis
No dosage adjustment is needed.
*non-FDA-approved indication
There are no drug interactions associated with Latanoprost products.
Latanoprost is a selective agonist at a subtype of prostaglandin receptors known as the FP receptor. By acting on the FP receptor, latanoprost increases the outflow of aqueous humor, thereby reducing intraocular pressure. According to the manufacturer, studies in both animals and man suggest that increased uveoscleral outflow is the primary mechanism of action.
Latanoprost is administered topically to the eye as an isopropyl ester prodrug. Once in systemic circulation, the biologically active latanoprost acid is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4- tetranor metabolites via fatty acid beta-oxidation with an elimination half-life of 17 minutes. The metabolites are mainly eliminated by the kidneys, with 88% of the topically administered dose being recovered in the urine.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
Following ocular administration, latanoprost is absorbed through the cornea where the isopropyl ester prodrug is hydrolyzed to the acid form to become biologically active. Peak aqueous humor concentrations are reached about 2 hours after topical administration. Reduction of intraocular pressure starts approximately 3 to 4 hours after administration and peaks after 8 to 12 hours. Plasma levels of the acid of latanoprost can only be measured during the first hour after local administration.