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Latisse为全球首个获得FDA核准的睫毛增长液。
Latisse睫毛增长液的效果让人激动，但其使用方法和副作用也值得注意，所以规定其上市后购买必须有医生处方。
Latisse睫毛增长液的有效成分bimatroprost，是一种中枢神经抑制剂，原先是Allergan公司用于治疗青光眼处方药Lumigan的有效成分。Lumigan的使用者发现它有促进睫毛生长的副作用，于是Latisse（bimatoprost ophthalmic solution 0.03%）应运而生，用来治疗眼睑稀毛症。Latisse是一种结构类似前列腺素的化合物，撷取自脂肪酸，可用来结合前列腺素受体，这些受体分布于毛发上，与毛囊发育及生长有关。
Latisse睫毛增长液使用方法：以经过消毒的一次性涂抹棒（两眼各用一根），将Latisse涂在上睫毛根部，每天涂抹一次。
Latisse睫毛增长液注意事项：使用8～16周睫毛会有明显增长，一旦停止，睫毛将逐渐恢复到从前的样子。使用时注意不要涂抹在上睫毛根部以外的地方，否则可能促进其他部位的毛发生长。
Latisse睫毛增长液副作用：临床试验中常见的不良反应为眼睛发红（3.6%）、眼珠颜色加深（3.6%）、眼皮色素沉淀（2.9%）。眼皮色素沉淀可能是可逆性，但眼珠颜色可能会永久加深。
LATISSE™
(bimatoprost) Ophthalmic Solution 0.03%
DRUG DESCRIPTION
LATISSE™ (bimatoprost ophthalmic solution) 0.03% is a synthetic prostaglandin analog. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C25H37NO4. Its chemical structure is:
Bimatoprost is a powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. LATISSE™ is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.
Contains: Active: bimatoprost 0.3 mg/mL;
Preservative: benzalkonium chloride 0.05 mg/mL;
Inactives: sodium chloride; sodium phosphate, dibasic; citric acid; and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 - 7.8.
INDICATIONS
LATISSE™ (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness.
DOSAGE AND ADMINISTRATION
Ensure the face is clean, makeup and contact lenses are removed. Once nightly, place one drop of LATISSE™ (bimatoprost ophthalmic solution) 0.03% on the disposable sterile applicator supplied with the package and apply evenly along the skin of the upper eyelid margin at the base of the eyelashes. The upper lid margin in the area of lash growth should feel lightly moist without runoff. Blot any excess solution runoff outside the upper eyelid margin with a tissue or other absorbent cloth. Dispose of the applicator after one use. Repeat for the opposite eyelid margin using a new sterile applicator.
Do not reuse applicators and do not use any other brush/applicator to apply LATISSE™ .
Do not apply to the lower eyelash line (see WARNINGS AND PRECAUTIONS, and PATIENT INFORMATION).
Additional applications of LATISSE™ will not increase the growth of eyelashes.
Upon discontinuation of treatment, eyelash growth is expected to return to its pre-treatment level.
HOW SUPPLIED
Dosage Forms And Strengths
Bimatoprost ophthalmic solution 0.3 mg/mL.
LATISSE™ (bimatoprost ophthalmic solution) 0.03% is supplied sterile in opaque white low density polyethylene dispenser bottles and tips with turquoise polystyrene caps accompanied by 60 sterile, disposable applicators:3 mL in a 5 mL bottle NDC 0023-3616-03
Storage: LATISSE™ should be stored at 2° to 25°C (36° to 77°F).
SIDE EFFECTS
The following information is based on clinical trial results from a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment.
The most frequently reported adverse events were eye pruritis, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and erythema of the eyelid. These events occurred in less than 4% of patients.
Adverse reactions reported with bimatoprost ophthalmic solution (LUMIGAN®) for the reduction of intraocular pressure include, ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, blepharitis, cataract, superficial punctuate keratitis, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, conjunctival edema, abnormal hair growth, iritis, infections (primarily colds and upper respiratory tract infections), headaches, , and asthenia.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Effects on Intraocular Pressure
Bimatoprost ophthalmic solution (LUMIGAN®) lowers intraocular pressure (IOP) when instilled directly to the eye in patients with elevated IOP. In clinical trials, in patients with or without elevated IOP, LATISSE™ lowered IOP, however, the magnitude of the reduction was not cause for clinical concern.
In ocular hypertension studies with LUMIGAN®, it has been shown that exposure of the eye to more than one dose of bimatoprost daily may decrease the intraocular pressure lowering effect. In patients using LUMIGAN® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE™ may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN® for IOP reduction should only use LATISSE™ after consulting with their physician and should be monitored for changes to their intraocular pressure (see PATIENT INFORMATION).
Iris Pigmentation
Increased iris pigmentation has occurred when the same formulation of bimatoprost ophthalmic solution (LUMIGAN®) was instilled directly onto the eye. Although iridal pigmentation was not reported in clinical studies with LATISSE™ , patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent.
The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. The long term effects of increased pigmentation are not known. Iris color changes seen with administration of bimatoprost ophthalmic solution may not be noticeable for several months to years. 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. Treatment with LATISSE™ solution can be continued in patients who develop noticeably increased iris pigmentation.
Patients who receive treatment with LATISSE™ should be informed of the possibility of increased pigmentation (see PATIENT INFORMATION).
Lid Pigmentation
Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes. The pigmentation is expected to increase as long as bimatoprost is administered, but has been reported to be reversible upon discontinuation of bimatoprost in most patients.
Hair Growth Outside the Treatment Area
There is the potential for hair growth to occur in areas where LATISSE™ solution comes in repeated contact with the skin surface. It is important to apply LATISSE™ only to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying sterile applicators, and to carefully blot any excess LATISSE™ from the eyelid margin to avoid it running onto the cheek or other skin areas (see PATIENT INFORMATION).
Intraocular Inflammation
LATISSE™ solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.
Macular Edema
Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution (LUMIGAN®) for elevated IOP. LATISSE™ should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.
Contamination of LATISSE™ or Applicators
The LATISSE™ bottle must be kept intact during use. It is important to use LATISSE™ solution as instructed, by placing one drop on the single-use-per eye applicator. The bottle tip should not be allowed to contact any other surface since it could become contaminated. The accompanying sterile applicators should only be used on one eye and then discarded since reuse of applicators increases the potential for contamination and infections. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products (see PATIENT INFORMATION)
Use with Contact Lenses
LATISSE™ contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration (see PATIENT INFORMATION)
Patient Counseling Information
Nightly Application
Patients should be informed that LATISSE™ (bimatoprost ophthalmic solution) should be applied every night using only the accompanying sterile applicators. They should start by ensuring their face is clean, all makeup is removed, and their contact lenses removed (if applicable). Then carefully place one drop of LATISSE™ solution on the disposable sterile applicator and brush cautiously along the skin of the upper eyelid margin at the base of the eyelashes. If any LATISSE™ solution gets into the eye proper, it will not cause harm. The eye should not be rinsed.
Additional applications of LATISSE™ will not increase the growth of eyelashes.
Patients should be informed not to apply to the lower eyelash line. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material.
The onset of effect is gradual but is not significant in the majority of patients until 2 months. Patients should be counseled that the effect is not permanent and can be expected to gradually return to the original level upon discontinuation of treatment with LATISSE™ .
Handling the Bottle and Applicator
Patients should be instructed that the LATISSE™ bottle must be maintained intact and to avoid allowing the tip of the bottle or applicator to contact surrounding structures, fingers, or any other unintended surface in order to avoid contamination of the bottle or applicator by common bacteria known to cause ocular infections. Patients should also be instructed to only use the applicator supplied with the product once and then discard since reuse could result in using a contaminated applicator. Serious infections may result from using contaminated solutions or applicators.
Potential for Intraocular Pressure Effects
LATISSE™ may lower intraocular pressure although not to a level that will cause clinical harm.
In patients using LUMIGAN® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE™ may interfere with the desired reduction in IOP. Patients using prostaglandin analogs for IOP reduction should only use LATISSE™ after consulting with their physician.
Potential for Eyelid Skin Darkening
Patients should be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of LATISSE™ .
Potential for Iris Darkening
Although iridal pigmentation was not reported in clinical studies with LATISSE™ , patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent. Increased iris pigmentation has occurred when the same formulation of bimatoprost ophthalmic solution (LUMIGAN®) was instilled directly onto the eye
Potential for Unexpected Hair Growth or Eyelash Changes
Patients should be informed of the possibility of hair growth occurring outside of the target treatment area if LATISSE™ repeatedly touches the same area of skin outside the treatment area. They should also be informed of the possibility of disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or directionof eyelash growth. Eyelash changes are likely reversible upon discontinuation of treatment.
When to Seek Physician Advice
Patients should be advised that if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of LATISSE™ . Patients on IOP-lowering medications should not use LATISSE™ without prior consultation with their physician.
Use with Contact Lenses
Patients should be advised that LATISSE™ solution contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of LATISSE™ and may be reinserted 15 minutes following its administration.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (approximately 192 and 291 times the recommended human exposure based on blood AUC levels after topical corneal and/or conjunctival sac administration respectively) for 104 weeks.
Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.
Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day.
Use In Specific Populations
Pregnancy
Pregnancy Category C
Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure (based on blood AUC levels after topical ophthalmic administration to the cornea or conjunctival sac).
At doses at least 41 times the maximum intended human exposure, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced.
There are no adequate and well-controlled studies of bimatoprost ophthalmic solution 0.03% administration in pregnant women. Because animal reproductive studies are not always predictive of human response, LATISSE™ should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether LATISSE™ solution is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when LATISSE™ is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No overall clinical differences in safety or effectivenesshave been observed between elderly and other adult patients.
OVERDOSE
No information provided.
CONTRAINDICATIONS
Hypersensitivity
LATISSE™ is contraindicated in patients with hypersensitivity to bimatoprost or any other ingredient in this product.
CLINICAL PHARMACOLOGY
Mechanism of Action
Bimatoprost is a structural prostaglandin analog. Although the precise mechanism of action is unknown the growth of eyelashes is believed to occur by increasing the percent of hairs in, and the duration of the anagen or growth phase.
Pharmacokinetics
Absorption
After one drop of bimatoprost ophthalmic solution 0.03% was administered once daily into both eyes (cornea and/or conjunctival sac) of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean Cmax and AUC0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng•hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time.
Distribution
Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma.
Metabolism
Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation. Bimatoprost then undergoes oxidation, N-deethylation, and glucuronidation to form a diverse variety of metabolites.
Elimination
Following an intravenous dose of radiolabeled bimatoprost (3.12 µg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.
Clinical Studies
LATISSE™ solution was evaluated for its effect on overall eyelash prominence in a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment. The primary efficacy endpoint in this study was an increase in overall eyelash prominence as measured by at least a 1-grade increase on the 4-point Global Eyelash Assessment (GEA) scale, from baseline to the end of the treatment period (week 16). LATISSE™ was more effective than vehicle as measured by the GEA score, with statistically significant differences seen at 8-week, 12-week, and 16-week (primary endpoint) treatment durations.
中文参考商品译名:
LATISSE0.03%眼用溶液 3毫升/瓶
生产厂家中文参考译名:
ALLERGAN
生产厂家英文名:
ALLERGAN | 
