Lumigan

Description

LUMIGAN (bimatoprost ophthalmic solution) 0.01% is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-(1E,3S)-3-hydroxy-5-phenyl-1-pentenylcyclopentyl]-5-N-ethylheptenamide. The molecular weight of bimatoprost is 415.58, and its molecular formula is C25H37N O4. Bimatoprost is a powder that is very soluble in ethyl alcohol and methyl alcohol, and slightly soluble in water.

LUMIGAN 0.01% is presented as 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 0.1 mg/mL. Inactive ingredients include benzalkonium chloride at 0.2 mg/mL, sodium chloride, sodium phosphate, dibasic, citric acid, and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust the pH, which ranges from 6.8 to 7.8 during its shelf life.

Uses and Indications

LUMIGAN 0.01% is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

The recommended dosage for administration is one drop in the affected eye(s) once daily in the evening. Healthcare professionals should instruct patients to ensure proper technique when administering the drop to maximize efficacy and minimize potential contamination. It is advised that patients tilt their head back, pull down the lower eyelid to create a small pocket, and then instill the drop without touching the eye or eyelid with the dropper tip. After administration, patients should close their eyes gently and may apply pressure to the inner corner of the eye to prevent systemic absorption.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to any of its components. Due to the potential for severe allergic reactions, administration in such cases may pose significant health risks.

Warnings and Precautions

Pigmentation of the iris, periorbital tissue (eyelid), and eyelashes may occur with the use of this medication. It is important to note that iris pigmentation is likely to be permanent. Healthcare professionals should inform patients about this potential side effect to ensure they are adequately prepared for any changes.

In addition to pigmentation changes, patients may experience a gradual alteration in their eyelashes, which can include increased length, thickness, and number of lashes. These changes are typically reversible; however, monitoring for any unexpected or concerning effects is advisable.

No specific laboratory tests are required for the safe use of this medication. Nonetheless, healthcare providers should remain vigilant and assess patients regularly for any adverse effects or changes in their condition.

In the event of any severe reactions or concerns, patients should be advised to seek emergency medical assistance promptly. Furthermore, if patients experience any unexpected symptoms or side effects, they should be instructed to discontinue use and consult their healthcare provider for further evaluation.

Side Effects

Common adverse reactions observed in patients include conjunctival hyperemia, which occurred in 31% of participants, along with conjunctival edema, conjunctival hemorrhage, eye irritation, eye pain, eye pruritus, erythema of the eyelid, eyelids pruritus, growth of eyelashes, hypertrichosis, instillation site irritation, punctate keratitis, skin hyperpigmentation, blurred vision, and reduced visual acuity.

In addition to these common reactions, postmarketing experience has revealed other adverse effects, including asthma-like symptoms, dizziness, dry eye, dyspnea, eye discharge, eye edema, foreign body sensation, headache, hypersensitivity reactions (which may include signs and symptoms of eye allergy and allergic dermatitis), hypertension, increased lacrimation, and periorbital and lid changes. The latter may be associated with periorbital fat atrophy, leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos, and eyelid retraction. Photophobia has also been reported.

It is important to note that hypersensitivity reactions are mentioned in the contraindications section. Additionally, pigmentation changes may occur, including pigmentation of the iris, periorbital tissue (eyelid), and eyelashes, with iris pigmentation likely to be permanent. Patients may also experience gradual changes to their eyelashes, including increased length, thickness, and number of lashes, which are usually reversible.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

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

Pediatric Use

Use in pediatric patients below the age of 16 years is not recommended due to potential safety concerns. Specifically, there is an increased risk of pigmentation changes associated with long-term chronic use in this population. Healthcare professionals should exercise caution when considering treatment options for children and adolescents under 16 years of age.

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 LUMIGAN (bimatoprost ophthalmic solution) 0.01% in pregnant women. Postmarketing experience does not indicate an increased risk of major birth defects or miscarriages associated with bimatoprost. However, animal studies have demonstrated potential risks. In embryofetal developmental studies, administration of bimatoprost to pregnant mice and rats during organogenesis resulted in abortion and early delivery at oral doses significantly exceeding human exposure levels. Specifically, these adverse effects were observed at doses at least 33 times (mice) or 94 times (rats) the human exposure to bimatoprost 0.03% dosed bilaterally once daily, based on blood area under the curve (AUC) levels. No adverse effects were noted at lower doses, specifically at 2.6 times (mice) and 47 times (rats) the human exposure.

In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis through lactation resulted in reduced gestation length, decreased fetal body weight, and increased fetal and pup mortality at doses at least 41 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily. No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure.

Due to the limitations of animal reproductive studies in predicting human response, LUMIGAN 0.01% 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 (47 times the human systemic exposure), while in mice, the NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure). No abnormalities were observed in fetuses at doses up to 0.6 mg/kg/day in both species.

Lactation

It is not known whether topical ocular treatment with LUMIGAN® 0.01% 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 of 1 mg/kg, which is 970 times the recommended human 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 LUMIGAN® 0.01% and any potential adverse effects on the breastfed infant from the use of this medication.

Renal Impairment

Dosage adjustments may be necessary for patients with renal impairment. Regular monitoring of renal function is essential. For patients with a creatinine clearance of less than 30 mL/min, a reduced dose should be administered. It is recommended to perform renal function tests prior to initiation of treatment and periodically during the course of therapy.

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 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 event of an overdose with LUMIGAN (bimatoprost ophthalmic solution) 0.01%, there is currently no available information regarding overdosage in humans. Should an overdose occur, the recommended course of action is to provide symptomatic treatment as necessary.

Toxicity studies conducted in mice and rats, where doses of up to 100 mg/kg/day were administered via oral gavage, did not indicate any signs of toxicity. It is important to note that this dosage is significantly higher—at least 210 times greater—than the potential accidental ingestion of an entire bottle of LUMIGAN 0.01% by a child weighing 10 kg.

Healthcare professionals should remain vigilant and monitor for any adverse effects, although the likelihood of toxicity appears to be low based on animal studies.

Nonclinical Toxicology

Bimatoprost was evaluated for its carcinogenic potential in long-term studies conducted in mice and rats. The results indicated that bimatoprost was not carcinogenic when administered via oral gavage for 104 weeks at doses of up to 2 mg/kg/day in mice and 1 mg/kg/day in rats. These doses correspond to approximately 192 and 291 times the estimated human systemic exposure to bimatoprost 0.03% when dosed 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.

Furthermore, bimatoprost did not impair fertility in male or female rats at doses up to 0.6 mg/kg/day, which is at least 103 times the recommended human exposure to bimatoprost 0.03% dosed bilaterally once daily, based on blood AUC levels.

Postmarketing Experience

During postapproval use of LUMIGAN® 0.01%, several adverse reactions have been reported voluntarily from a population of uncertain size. Due to the nature of these reports, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following reactions have been identified for inclusion based on their seriousness, frequency of reporting, or possible connection to LUMIGAN®:

• Asthma-like symptoms

• Dizziness

• Dry eye

• Dyspnea

• Eye discharge

• Eye edema

• Foreign body sensation

• Headache

• Hypersensitivity, including signs and symptoms of eye allergy and allergic dermatitis

• Hypertension

• Increased lacrimation

• Periorbital and lid changes associated with periorbital fat atrophy, leading to skin tightness

• Deepening of the eyelid sulcus

• Eyelid ptosis

• Enophthalmos

• Eyelid retraction

• Photophobia

These events reflect the range of experiences reported in the postmarketing setting.

Patient Counseling

Healthcare providers should advise patients 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 LUMIGAN® (bimatoprost ophthalmic solution) 0.01%.

It is important to inform patients of the possibility of changes in eyelashes and vellus hair in the treated eye during treatment with LUMIGAN® 0.01%. These changes may lead to differences between the eyes in terms of length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Healthcare providers should reassure patients that eyelash changes are usually reversible upon discontinuation of treatment.

Patients should be instructed to avoid allowing the tip of the dispensing container to come into contact with the eye, surrounding structures, fingers, or any other surface to prevent contamination of the solution by common bacteria that can cause ocular infections. Serious damage to the eye and potential loss of vision may result from using contaminated solutions.

Healthcare providers should advise patients that if they develop an intercurrent ocular condition, such as trauma or infection, undergo ocular surgery, or experience any ocular reactions—particularly conjunctivitis and eyelid reactions—they should seek their physician’s advice immediately regarding the continued use of LUMIGAN® 0.01%.

Patients should also be informed that LUMIGAN® 0.01% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Therefore, contact lenses should be removed prior to instillation of LUMIGAN® 0.01% and may be reinserted 15 minutes after administration.

Finally, healthcare providers should advise patients that if they are using more than one topical ophthalmic drug, the drugs should be administered at least five (5) minutes apart to ensure proper absorption and effectiveness.

Storage and Handling

LUMIGAN 0.01% is supplied in a container that allows for easy dispensing. It should be stored at a temperature range of 2°C to 25°C (36°F to 77°F) to maintain its efficacy.

Once opened, LUMIGAN 0.01% can be used until the expiration date indicated on the bottle. It is important to ensure that the product is kept in its original container to protect it from light and contamination.

Additional Clinical Information

Postmarketing experience has revealed several adverse reactions associated with the use of LUMIGAN® 0.01%. Clinicians should be aware that patients may report asthma-like symptoms, dizziness, dry eye, dyspnea, and eye discharge. Other noted reactions include eye edema, foreign body sensation, headache, and hypersensitivity reactions, which may manifest as signs of eye allergy and allergic dermatitis.

Additionally, hypertension, increased lacrimation, and changes around the periorbital area, such as periorbital fat atrophy leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos, eyelid retraction, and photophobia have also been identified. These findings underscore the importance of monitoring patients for these potential effects during treatment.

FDA Insert (PDF)

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

View full prescribing information (PDF)