Lanotan

Lanotan

latanoprost

Manufacturer:

Bausch & Lomb

Distributor:

DKSH
Full Prescribing Info
Contents
Latanoprost.
Description
Active Ingredient: Latanoprost 0.005% (each mL contains 50 μg of latanoprost).
The active ingredient in LANOTAN is latanoprost, a prostaglandin F analogue. Its chemical name is isopropyl-(Z)-7[(1R,2R,3R,5S)3,4-dihydroxy-2[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate. Its molecular formula is C26H40O5.
Latanoprost is a colorless to slightly yellow oil that is very soluble in acetonitrile and freely soluble in acetone, ethanol, ethyl acetate, isopropranol, methanol and octanol. It is practically insoluble in water.
Active ingredient: Latanoprost (0.005% Each mL contains 50 μg of latanoprost).
Clear colorless sterile ophthalmic solution.
Lanotan is supplied as a sterile, isotonic, buffered aqueous solution of latanoprost with a pH of approximately 6.7 and an osmolality of approximately 267 mOsmol/kg. Each ml of lanotan contains 50 micrograms of latanoprost. Benzalkonium chloride, 0.02% is added as a preservative.
Excipients/Inactive Ingredients: Sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous and water for injection.
One drop contains approximately 1.5 µg of latanoprost.
Action
Pharmacology: Pharmacodynamics: Latanoprost is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and man suggest that the main mechanism of action is increased uveoscleral outflow. Elevated IOP represents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
Pharmacokinetics: Absorption: Latanoprost is absorbed through the cornea where the isopropyl ester prodrug is hydrolyzed to the acid form to become biologically active. Studies in man indicate that the peak concentration in the aqueous humor is reached about two hours after topical administration.
Distribution: The distribution volume in humans is 0.16 ± 0.02 L/kg. The acid of latanoprost can be measured in aqueous humor during the first 4 hours, and in plasma only during the first hour after local administration.
Metabolism: Latanoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to the biologically active acid. The active acid of latanoprost reaching the systemic circulation is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation.
Excretion: The elimination of the acid of latanoprost from human plasma is rapid (t½=17 min) after both intravenous and topical administration. Systemic clearance is approximately 7 mL/min/kg. Following hepatic β-oxidation, the metabolites are mainly eliminated via the kidneys. Approximately 88% and 98% of the administered dose is recovered in the urine after topical and intravenous dosing, respectively.
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Latanoprost was not mutagenic in bacteria, in mouse lymphoma or in mouse micronucleus tests.
Chromosome aberrations were observed in vitro with human lymphocytes.
Latanoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 170 µg/kg/day (approximately 2,800 times the recommended maximum human dose) for up to 20 and 24 months, respectively.
Additional in vitro and in vivo studies on unscheduled DNA synthesis in rats were negative.
Latanoprost has not been found to have any effect on male or female fertility in animal studies.
Indications/Uses
Lanotan is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Dosage/Direction for Use
The recommended dosage is one drop (1.5 µg) in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal.
Administration: The dosage of lanotan should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including lanotan is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure lowering effect or cause paradoxical elevations in IOP. Reduction of the intraocular pressure starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours and persists for up to 24 hours or longer. Lanotan may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
Overdosage
Apart from ocular irritation and conjunctival or episcleral hyperemia, the ocular effects of latanoprost administered at high doses are not known. Intravenous administration of large doses of latanoprost in monkeys has been associated with transient bronchoconstriction; however, in 11 patients with bronchial asthma treated with latanoprost, bronchoconstriction was not induced. Intravenous infusion of up to 3 µg/kg in healthy volunteers produced mean plasma concentrations 200 times higher than during clinical treatment and no adverse reactions were observed. Intravenous dosages of 5.5 to 10 µg/kg caused abdominal pain, dizziness, fatigue, hot flushes, nausea and sweating.
If overdosage with Latanoprost ophthalmic eye drops occurs, treatment should be symptomatic.
Information for Patients (see Warnings and Precautions): Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of Lanotan.
Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with Lanotan. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment.
Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients also should be advised that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should immediately seek their physician's advice concerning the continued use of the multiple-dose container.
Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should immediately seek their physician's advice.
Patients should also be advised that Lanotan contains benzalkonium chloride, which may be absorbed by contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of Lanotan.
If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
Contraindications
Known hypersensitivity to latanoprost, benzalkonium chloride or any other ingredients in this product.
Warnings
Latanoprost has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes, and growth of eyelashes. Pigmentation is expected to increase as long as Latanoprost is administered. After discontinuation of Latanoprost, pigmentation of the iris is likely to be permanent while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The effects of increased pigmentation beyond 5 years are not known.
Special Precautions
General: Latanoprost ophthalmic eye drops may gradually increase the pigmentation of the iris. The eye color change is due to increased melanin content in the stromal melanocytes of the iris rather than to an increase in the number of melanocytes. This change may not be noticeable for several months to years (see Warnings). Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with Latanoprost can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.
During clinical trials, the increase in brown iris pigment has not been shown to progress further upon discontinuation of treatment, but the resultant color change may be permanent.
Eyelid skin darkening, which may be reversible, has been reported in association with the use of Latanoprost (see Warnings).
Latanoprost may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation of treatment.
Latanoprost should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation.
Macular edema, including cystoid macular edema, has been reported during treatment with Latanoprost. These reports have mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Latanoprost should be used with caution in patients who do not have an intact posterior capsule or who have known risk factors for macular edema.
There is limited experience with Latanoprost in the treatment of angle closure, inflammatory or neovascular glaucoma.
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface (see Precautions and Information for Patients).
Contact lenses should be removed prior to the administration of Latanoprost, and may be reinserted 15 minutes after administration (see Precautions and Information for Patients).
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Use in Elderly: No overall differences in safety or effectiveness have been observed between elderly and younger patients.
Use In Pregnancy & Lactation
Pregnancy: Teratogenic Effects: Pregnancy category: C.
Reproduction studies have been performed in rats and rabbits. In rabbits an incidence of 4 of 16 dams had no viable fetuses at a dose that was approximately 80 times the maximum human dose, and the highest non embryocidal dose in rabbits was approximately 15 times the maximum human dose.
There are no adequate and well-controlled studies in pregnant women. Latanoprost should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Latanoprost is administered to a nursing woman.
Adverse Reactions
Adverse events referred to in other sections: Eyelash changes (increased length, thickness, pigmentation, and number of lashes); eyelid skin darkening; intraocular inflammation (iritis/uveitis); iris pigmentation changes; and macular edema, including cystoid macular edema (see Warnings and Precautions).
Controlled Clinical Trials: The ocular adverse events and ocular signs and symptoms reported in 5 to 15% of the patients on latanoprost ophthalmic eye drops in the three 6-month, multi-center, double-masked, active­ controlled trials were blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctuate epithelial keratopathy.
Local conjunctival hyperemia was observed; however, less than 1% of the patients treated with latanoprost required discontinuation of therapy because of intolerance to conjunctival hyperemia.
In addition to the previously listed ocular events/signs and symptoms, the following were reported in 1 to 4% of the patients: Dry eye, excessive tearing, eye pain, lid crusting, lid discomfort/pain, lid edema, lid erythema, and photophobia.
The following events were reported in less than 1% of the patients: Conjunctivitis, diplopia and discharge from the eye.
During clinical studies, there were extremely rare reports of the following: Retinal artery embolus, retinal detachment, and vitreous hemorrhage from diabetic retinopathy.
The most common systemic adverse events seen with Latanoprost were upper respiratory tract infection/cold/flu, which occurred at a rate of approximately 4%. Chest pain/angina pectoris, muscle/joint/back pain, and rash/allergic skin reaction each occurred at a rate of 1 to 2%.
Clinical Practice: The following events have been identified during postmarketing use of Latanoprost in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to Latanoprost, or a combination of these factors, include: Asthma and exacerbation of asthma; corneal edema and erosions; dyspnea; eyelash and vellus hair changes (increased length, thickness, pigmentation, and number); eyelid skin darkening; herpes keratitis; intraocular inflammation (iritis/uveitis); keratitis; macular edema, including cystoid macular edema; misdirected eyelashes sometimes resulting in eye irritation; dizziness, headache, and toxic epidermal necrolysis; periorbital and lid changes resulting in deepening of the eyelid sulcus.
Drug Interactions
In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with Latanoprost. If such drugs are used they should be administered at least five (5) minutes apart.
Storage
Protect from light. Store unopened bottle(s) under refrigeration at 2° to 8°C (36° to 46°F). During shipment to the patient, the bottle may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 8 days. Once a bottle is opened for use, it may be stored at room temperature up to 25°C (77°F) for 6 weeks.
ATC Classification
S01EE01 - latanoprost ; Belongs to the class of prostaglandin analogues. Used in the treatment of glaucoma.
Presentation/Packing
Ophth soln 50 mcg/mL x 2.5 mL.
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