Latisse

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-pentenylcyclopentyl]-N-ethyl-5-heptenamide. The molecular weight of LATISSE is 415.58, and its molecular formula is C25H37NO4. Bimatoprost is presented as a powder that 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. The formulation contains bimatoprost as the active ingredient at a concentration of 0.3 mg/mL, along with the preservative benzalkonium chloride at 0.05 mg/mL. Inactive ingredients include sodium chloride, sodium phosphate dibasic, citric acid, and purified water. Sodium hydroxide and/or hydrochloric acid may be used to adjust the pH, which ranges from 6.8 to 7.8 during its shelf life.

Uses and Indications

LATISSE® is indicated for the treatment of hypotrichosis of the eyelashes, specifically to enhance their growth in terms of length, thickness, and darkness.

There are no teratogenic or nonteratogenic effects associated with the use of LATISSE®.

Dosage and Administration

The recommended dosage involves applying the solution nightly directly to the skin of the upper eyelid margin at the base of the eyelashes. Healthcare professionals should instruct patients to use the accompanying applicators for this application.

After application, any excess solution that extends beyond the eyelid margin should be blotted away to ensure proper dosing. It is essential to dispose of the applicator after a single use to maintain sterility and prevent contamination.

For the opposite eyelid margin, the application should be repeated using a new sterile applicator to ensure safety and efficacy.

Contraindications

Use of this product is contraindicated in patients with hypersensitivity to any component of the formulation. Due to the potential for severe allergic reactions, administration in such cases may pose significant health risks.

Warnings and Precautions

Concurrent administration of LATISSE® with intraocular pressure (IOP)-lowering prostaglandin analogs in patients with ocular hypertension may result in a diminished IOP-lowering effect. It is imperative that patients utilizing both LATISSE® and these prostaglandin analogs are closely monitored for any alterations in their IOP to ensure effective management of their condition.

Additionally, the use of LATISSE® may lead to pigmentation changes in the eyelids and the iris. It is important to note that any changes in iris pigmentation are likely to be permanent. Healthcare professionals should inform patients of this potential side effect and consider it when discussing treatment options. Regular follow-up assessments may be warranted to monitor for these changes.

Side Effects

Most commonly reported adverse reactions in clinical trials included eye pruritus, conjunctival hyperemia, and skin hyperpigmentation, each occurring in less than 4% of patients. Other frequently reported reactions encompassed ocular irritation, dry eye symptoms, and periorbital erythema. Additional adverse reactions observed in clinical trials included foreign body sensation, hair growth abnormalities, iris hyperpigmentation, ocular dryness, visual disturbances, ocular burning, eye pain, blepharitis, cataracts, superficial punctate keratitis, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, conjunctival edema, iritis, and infections primarily related to colds and upper respiratory tract infections. Headaches and asthenia were also reported.

Postmarketing experience has identified several additional adverse reactions. These include dry skin of the eyelid and/or periocular area, eye swelling, eyelid edema, hordeolum, and local hypersensitivity reactions. Increased lacrimation, madarosis (temporary loss of a few eyelashes), and trichorrhexis (temporary eyelash breakage) have also been noted. Changes associated with periorbital fat atrophy, such as skin tightness leading to deepening of the eyelid sulcus and eyelid ptosis, were reported. Other reactions included rash (macular and erythematous), skin discoloration (periorbital), skin exfoliation of the eyelid and/or periorbital area, trichiasis, and blurred vision.

It is important to note that concurrent administration of LATISSE® and intraocular pressure (IOP)-lowering prostaglandin analogs in ocular hypertensive patients may reduce the IOP-lowering effect. Patients using these products together should be closely monitored for any changes in IOP. Additionally, pigmentation of the eyelids and iris may occur, with iris pigmentation likely to be permanent. Hypersensitivity reactions have also been documented.

Drug Interactions

Concurrent administration of LATISSE with intraocular pressure (IOP)-lowering prostaglandin analogs may result in a diminished IOP-lowering effect. It is advisable for healthcare providers to monitor patients for any changes in their IOP during such concurrent use.

LATISSE contains benzalkonium chloride, which has the potential to be absorbed by soft contact lenses, leading to discoloration. To mitigate this risk, it is recommended that patients remove their contact lenses prior to the application of LATISSE. Contact lenses may be safely reinserted 15 minutes after the application.

Packaging & NDC

The table below lists all NDC Code configurations of Latisse (bimatoprost), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The use of LATISSE® has been evaluated in a sixteen-week double-masked, randomized, vehicle-controlled study involving pediatric patients aged 5 to 17 years who were post-chemotherapy or had alopecia areata, as well as adolescents aged 15 to 17 years with hypotrichosis without associated medical conditions.

In this study, no new safety issues were identified. Among adolescents with hypotrichosis, 73% (19 out of 26) demonstrated at least a 1-grade increase from baseline in the Global Eyelash Assessment at month 4. For post-chemotherapy pediatric patients, 85% (11 out of 13) achieved a similar increase, while 44% (4 out of 9) of pediatric patients with alopecia areata showed at least a 1-grade improvement at the same time point.

These findings support the efficacy of LATISSE® in enhancing eyelash prominence in the specified pediatric populations.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, have not demonstrated any overall clinical differences in safety or effectiveness compared to younger adult patients. Therefore, no specific dosage adjustments are necessary for this population based on age alone.

However, healthcare providers should remain vigilant in monitoring geriatric patients for any potential age-related changes that may affect drug metabolism and response. It is essential to consider individual patient factors, including comorbidities and concurrent medications, when prescribing to elderly patients to ensure optimal therapeutic outcomes.

Pregnancy

There are no adequate and well-controlled studies of LATISSE (bimatoprost ophthalmic solution) 0.03% in pregnant women. However, based on postmarketing experience, there is no increase in the risk of major birth defects or miscarriages associated with bimatoprost use.

Embryofetal development studies in pregnant mice and rats have shown that administration of bimatoprost during organogenesis can lead to abortion and early delivery at oral doses significantly higher than those expected from topical ophthalmic administration. Specifically, in mice, doses at least 33 times the human exposure resulted in these adverse effects, while in rats, doses at least 94 times the human exposure were required. No adverse effects were observed at lower doses (2.6 times in mice and 47 times in rats the human exposure).

In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis through lactation resulted in reduced gestation length, increased fetal and pup mortality, and decreased fetal body weight at doses at least 41 times the human systemic exposure. No adverse effects were noted at exposures estimated at 14 times the human exposure.

Due to the potential risks observed in animal studies, LATISSE 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. The No Observed Adverse Effect Level (NOAEL) for abortion in rats was determined to be 0.3 mg/kg/day, which corresponds to 47 times the human systemic exposure, while in mice, the NOAEL was 0.1 mg/kg/day, equating to 2.6 times the human exposure. No abnormalities were observed in fetuses at doses up to 0.6 mg/kg/day in both species.

Healthcare professionals should carefully consider the risks and benefits when prescribing LATISSE to pregnant patients.

Lactation

It is not known whether topical ocular treatment with LATISSE® 0.03% could result in sufficient systemic absorption to produce detectable quantities in human milk. In animal studies, bimatoprost has been shown to be present in the breast milk of lactating rats at an intravenous dose (1 mg/kg) that is 324 times the recommended human ophthalmic dose (on a mg/m² basis); however, no animal data is available at clinically relevant doses.

Healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the mother’s clinical need for LATISSE® 0.03% and any potential adverse effects on the breastfed child from the use of this medication.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the absence of specific overdosage information, it is essential for healthcare professionals to remain vigilant and prepared for potential scenarios involving overdose.

Healthcare providers should be aware that the clinical presentation of an overdose may vary depending on the substance involved and the individual patient’s characteristics. Symptoms of overdose can range from mild to severe and may include altered mental status, cardiovascular instability, respiratory distress, and gastrointestinal disturbances.

In the event of suspected overdosage, immediate medical evaluation is recommended. Healthcare professionals should assess the patient's vital signs and conduct a thorough clinical examination. Supportive care should be initiated as necessary, which may include airway management, intravenous fluids, and monitoring of vital parameters.

If specific antidotes or treatments are available for the substance involved, they should be administered according to established protocols. Consultation with a poison control center or a medical toxicologist may also be beneficial in managing the case effectively.

It is crucial to document all findings and interventions in the patient's medical record to ensure continuity of care and facilitate further management.

Nonclinical Toxicology

Bimatoprost was evaluated for its potential carcinogenic effects in both mice and rats. The results indicated that bimatoprost was not carcinogenic when administered via oral gavage for a duration of 104 weeks at doses of up to 2 mg/kg/day in mice and 1 mg/kg/day in rats. These doses correspond to 192 and 291 times the human systemic exposure following the topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on blood AUC levels.

In terms of mutagenicity, bimatoprost demonstrated no mutagenic or clastogenic effects in several assays, including the Ames test, the mouse lymphoma test, and in vivo mouse micronucleus tests.

Regarding reproductive toxicity, bimatoprost did not impair fertility in male or female rats at doses up to 0.6 mg/kg/day, which is 103 times the human systemic exposure following the topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on blood AUC levels.

Postmarketing Experience

During postapproval use of LATISSE®, several adverse reactions have been reported voluntarily or through surveillance programs. These include dry skin of the eyelid and/or periocular area, eye swelling, eyelid edema, and hordeolum. Additionally, local allergic reactions characterized by hypersensitivity, increased lacrimation, and madarosis have been noted, with reports of temporary loss of eyelashes and temporary eyelash breakage (trichorrhexis).

Other reported events include periorbital and lid changes associated with periorbital fat atrophy, leading to skin tightness, deepening of the eyelid sulcus, and eyelid ptosis. Skin reactions such as rash (including macular and erythematous), periorbital skin discoloration, and skin exfoliation of the eyelid and/or periorbital area have also been documented. Furthermore, trichiasis and blurred vision have been reported.

Due to the voluntary nature of these reports from a population of uncertain size, it is not always possible to reliably estimate the frequency of these events or establish a causal relationship to drug exposure.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) prior to starting treatment with LATISSE® (bimatoprost ophthalmic solution). It is important to inform patients that LATISSE® should be applied every night using only the accompanying sterile applicators. Patients should begin by ensuring their face is clean, removing all makeup, and taking out contact lenses if applicable.

When applying LATISSE®, patients should carefully place one drop of the solution on the disposable sterile applicator and brush it cautiously along the skin of the upper eyelid margin at the base of the eyelashes. If any LATISSE® solution inadvertently gets into the eye, it will not cause harm, and the eye should not be rinsed. Patients should be informed that additional applications of LATISSE® will not increase the growth of eyelashes and that the solution should not be applied to the lower eyelash line. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material.

Counsel patients that the onset of effect is gradual, with significant results typically not observed until approximately 2 months. It is essential to communicate that the effects of LATISSE® are not permanent; upon discontinuation of treatment, eyelashes are expected to gradually return to their original appearance.

Patients should be instructed to maintain the LATISSE® bottle intact and to avoid allowing the tip of the bottle or applicator to contact surrounding structures, fingers, or any unintended surface to prevent contamination by common bacteria known to cause ocular infections. They should only use the supplied applicator once and then discard it, as reusing it could lead to contamination and serious infections.

Inform patients that LATISSE® may lower intraocular pressure, although not to a clinically harmful level. For patients using LUMIGAN® or other prostaglandin analogs for elevated intraocular pressure, it is crucial to consult with their physician before using LATISSE®, as it may interfere with the desired reduction in IOP.

Patients should be made aware of the potential for eyelid skin darkening, which may be reversible after discontinuation of LATISSE®, and the possibility of increased brown iris pigmentation, which is likely to be permanent. Additionally, inform patients about the risk of hair growth occurring outside 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 terms of length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth, with changes likely reversible upon discontinuation of treatment.

Advise patients to seek immediate medical advice if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, undergo ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions.

Patients should be informed that LATISSE® solution contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Therefore, contact lenses should be removed prior to application of LATISSE® and may be reinserted 15 minutes after administration.

If a patient stops using LATISSE®, their eyelashes are expected to return to their previous appearance over several weeks to months. Any eyelid skin darkening is also expected to reverse after several weeks to months, while any darkening of the iris is not expected to reverse and is likely permanent. The recommended dosage is one application nightly to the skin of the upper eyelid margin at the base of the eyelashes only. If a dose is missed, patients should not attempt to “catch up” but should simply apply LATISSE® solution the next evening. Lastly, remind patients not to allow the tip of the bottle or applicator to contact surrounding structures, fingers, or any unintended surface to avoid contamination.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It is essential to store the product at a temperature range of 2º to 25ºC (36º to 77ºF) to maintain its efficacy and stability. Proper container requirements must be adhered to, ensuring that the product is kept in a suitable environment. Special handling needs should be observed to prevent exposure to conditions outside the recommended temperature range.

Additional Clinical Information

During postmarketing surveillance of LATISSE®, several adverse reactions have been reported. Clinicians should be aware that patients may experience dry skin of the eyelid and/or periocular area, eye swelling, and eyelid edema. Other identified reactions include hordeolum, local hypersensitivity reactions, increased lacrimation, and madarosis, which is a temporary loss of eyelashes.

Additionally, temporary eyelash breakage (trichorrhexis), changes in the periorbital area associated with fat atrophy and skin tightness, and eyelid ptosis have been noted. Patients may also report rashes (macular and erythematous), periorbital skin discoloration, skin exfoliation of the eyelid and/or periorbital area, trichiasis, and blurred vision. Clinicians should monitor for these effects and manage them accordingly.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Latisse as submitted by Allergan, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)