Latanoprost TOA Ophthalmic Solution 0.005% w/v

Latanoprost.

Active substance: Latanoprost.
Strength: 0.05 mg in 1 mL.
Latanoprost is a colorless to light yellow and viscous oil. It is very soluble in acetonitrile and N,N-dimethylacetamide, freely soluble in ethanol (99.5), practically insoluble in water.
Chemical name: (+)-Isopropyl(Z)-7-[(1R, 2R, 3R, 5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate.
Molecular formula: C₂₆H₄₀O₅.
Molecular weight: 432.59.
pH: 6.5-6.9.
Osmotic pressure ratio: 0.9-1.0.
Excipients/Inactive Ingredients: Sodium chloride, dibasic sodium phosphate hydrate, sodium dihydrogen phosphate, polysorbate 80, disodium edetate hydrate, benzalkonium chloride concentrated solution 50, pH adjuster.

Pharmacology: Bioequivalence study: After a single instillation of LATANOPROST TOA OPHTHALMIC SOLUTION 0.005% W/V or its standard preparation (ophthalmic solution 0.005%) was administered into the conjunctival sac of both eyes of healthy adult men, the IOP was measured, and the obtained parameters (maximum IOP difference between before and after instillation, area under the curve of IOP versus time area under IOP curve) were statistically analyzed. As a result, bioequivalence of both drugs was confirmed. (See Table 1 and Figures 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Parameters of IOP, maximum IOP difference, and area under the curve of IOP versus time may vary depending on the test conditions of subject selection, the number of IOP measurements, and the measurement time of IOP.

Glaucoma and ocular hypertension.

One drop in the affected eye(s) once daily.
Precautions regarding Dosage and Administration: The dosage of latanoprost should not exceed once daily since it has been shown that more frequent administration may decrease the intraocular pressure lowering effect.

This product is contraindicated in the following patients: Patients with hypersensitivity to any ingredients in this product.

To be used as directed by physician.
Careful Administration: This product should be administered with special caution in the following patients: (1) Aphakic patients, pseudophakic patients with a torn posterior lens capsule. [Macular edema, including cystoid macular edema and the decreased visual acuity associated with macular edema, have been reported.]
(2) Patients with active or a history of bronchial asthma. [Asthmatic attack may be exacerbated or induced (see Other Precautions as follows).]
(3) Patients with intraocular inflammation (iritis/uveitis). [Elevated intraocular pressure (IOP) has been reported.]
(4) Patients potentially with latent herpes virus infection. [Herpetic keratitis has been reported.]
(5) Pregnant, parturient, nursing women (see Use in Pregnancy & Lactation).
Important Precautions: (1) When this product is administered, the iris pigmentation may occur (due to increased melanin content). Before using this product, patients who receive treatment should be well informed of the possibility of the iris pigmentation and the change in iris color. It is reported that pigmentation is expected to increase gradually and stops after discontinuation of treatment. However, the resultant pigmentation is likely to be permanent. In addition, iris color change due to the iris pigmentation may occur. In particular, the treatment of one eye may cause iris color difference between the right and left eyes. The pigmentation of the iris has been reported predominantly in patients with brown-based irises. The change in iris color is mild and may not be detected clinically. (See Clinically Significant Adverse Reactions under Adverse Reactions.)
(2) Corneal epithelium disorder (superficial punctate keratitis, filamentary keratitis, corneal erosion) may occur during administration of this product. The patients should be adequately instructed to immediately consult a doctor if the subjective symptoms of eye stinging, itching, and eye pain persist.
(3) This product should be administered with special caution in the patients with angle-closure glaucoma due to an insufficient clinical experience.
(4) Since blurred vision may temporarily occur after administration of the product, patients should be warned not to operate machinery or drive a car until the symptom disappears.
Other Precautions: (1) In overseas reports, retinal artery occlusion, detached retina, and vitreous hemorrhage associated with diabetic retinopathy have been reported as adverse events locally in the eyes, and upper respiratory tract infection, common cold, influenza, myalgia, arthralgia, low back pain, chest pain, angina, rash, and allergic skin reaction have been reported as systemic adverse events.
(2) Infused intravenously in doses (2 μg/kg) of latanoprost in monkeys caused transient increased airway resistance. However, it has been reported that instillation of latanoprost in 11 patients with moderate bronchial asthma at 7 times the recommended clinical dose (recommended dose is 1.5 μg/eye) had no effect on lung function.
Use in the Elderly: Generally elderly patients have declined physiological functions and this product should be administered with caution.
Use in Children: The safety of this product in pediatric patients has not been established. (No clinical data are available for premature infants, newborns, and infants. Very limited clinical data are available for children.)

Pregnant women: This product should be used in pregnant women or women who may be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment. [The safety of this product during pregnancy has not been established. Reproduction studies have been performed in rabbits. In the study of administration during organogenesis in rabbits, increased incidences of abortion and late resorption and reduce in fetal weight were observed when latanoprost was given by intravenous administration at a dose that was approximately 80 times the clinical dose (5 μg/kg/day).]
Nursing mothers: Administration of this product should be avoided in breastfeeding mothers. If the use of this product is unavoidable, the patient should discontinue breastfeeding. [An animal study (in rats, i.v.) has shown that the drug was excreted in breast milk.]

Since studies which could clarify the frequency of incidence on adverse reactions have not been conducted, the frequency of incidence on adverse reactions associated with the administration of this product is unknown.
Clinically Significant Adverse Reactions (Frequency unknown): Iris pigmentation: Since iris pigmentation may occur, patients should be examined regularly. If iris pigmentation occurs, use of this product may be discontinued according to patient's clinical condition. (See Important Precautions under Precautions.)
Other Adverse Reactions: See Table 2.

Click on icon to see table/diagram/image

Precautions for co-administration: See Table 3.

Click on icon to see table/diagram/image

Route of administration: Ophthalmic use only.
Precautions regarding dispensing: Patients should be instructed the following: 1) Instill the product with care not to touch the eye with the dropper tip.
2) If the solution exceeds to the eyelid skin during instilling the product, wipe off any excess solution immediately.
3) If this product is used with other ophthalmic solution, they should be administered at least 5 minutes apart.
4) Since this product contains benzalkonium chloride and it may discolor contact lenses, contact lenses should be removed before instillation of the product and may be reinserted after 15 minutes or more.
Precautions for handling: The residual solution of the product should not be used four weeks after opening.
Stability study: The long-term stability study (25°C, 60% RH, three years) of LATANOPROST TOA OPHTHALMIC SOLUTION 0.005% W/V filled in polyethylene containers demonstrated that this product remains stable for three years under the usual distribution conditions in the market.

Antiglaucoma Preparations

S01EE01 - latanoprost ; Belongs to the class of prostaglandin analogues. Used in the treatment of glaucoma.

P₁S₁S₃