Bimatoprost

Description

Bimatoprost ophthalmic solution, 0.03%, is a synthetic prostaglandin analog designed for ophthalmic use. The chemical name of bimatoprost is (Z)-7-[(1R, 2R, 3R, 5S)-3, 5-Dihydroxy-2-(1E, 3S)-3-hydroxy-5-phenyl-1pentenyl cyclopentenyl]-5-N-ethylheptenamide, with a molecular weight of 415.58 and a molecular formula of C25H37NO4. This formulation appears as a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

Each milliliter of bimatoprost ophthalmic solution contains 0.3 mg of bimatoprost as the active ingredient, along with 0.05 mg/mL of benzalkonium chloride as a preservative. Inactive ingredients include sodium chloride, sodium phosphate dibasic, citric acid, and water for injection. The pH of the solution is adjusted with sodium hydroxide and/or hydrochloric acid, maintaining a range of 6.8 to 7.8 throughout its shelf life. Bimatoprost is a powder that is soluble in methanol and alcohol.

Uses and Indications

Bimatoprost ophthalmic solution, for topical ophthalmic use, is indicated for the treatment of hypotrichosis of the eyelashes. This medication promotes eyelash growth, resulting in increased length, thickness, and darkness of the eyelashes.

There are no teratogenic or nonteratogenic effects associated with the use of this drug.

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, a new sterile applicator must be used to repeat the application process.

Contraindications

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

Warnings and Precautions

Concurrent administration of Bimatoprost ophthalmic solution with other 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 these products together are monitored closely for any alterations in their IOP to ensure effective management of their condition.

Patients should be informed that the use of Bimatoprost may lead to pigmentation changes in the eyelids and iris. It is important to note that any increase in iris pigmentation is likely to be permanent, and patients should be counseled accordingly regarding this potential side effect.

Healthcare professionals are advised to remain vigilant in monitoring patients for these effects and to provide appropriate guidance on the use of Bimatoprost in conjunction with other ocular therapies.

Side Effects

Most common adverse reactions observed in patients include eye pruritus, conjunctival hyperemia, and skin hyperpigmentation, with an incidence of approximately 3% to 4%.

In addition to these common reactions, patients may experience pigmentation of the eyelids and iris, with iris pigmentation likely to be permanent. Hypersensitivity reactions have also been reported. These adverse reactions should be monitored in patients receiving treatment.

Drug Interactions

Concurrent administration of bimatoprost ophthalmic solution with intraocular pressure (IOP)-lowering prostaglandin analogs may result in a diminished IOP-lowering effect in ocular hypertensive patients. It is advised that patients using these products together be closely monitored for any changes in their IOP.

In patients receiving LUMIGAN or other prostaglandin analogs for elevated IOP, the use of bimatoprost ophthalmic solution 0.03% may interfere with the intended reduction of IOP. Therefore, it is recommended that patients consult their physician before using bimatoprost ophthalmic solution 0.03% in conjunction with prostaglandin analogs. Monitoring of IOP is essential in these cases.

Bimatoprost ophthalmic solution 0.03% contains benzalkonium chloride, which can be absorbed by soft contact lenses, potentially leading to discoloration. It is recommended that contact lenses be removed prior to the application of bimatoprost ophthalmic solution and may be reinserted 15 minutes after administration.

Packaging & NDC

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

Pediatric Use

The use of bimatoprost ophthalmic solution 0.03% has been evaluated in pediatric patients, specifically in a sixteen-week double-masked, randomized, vehicle-controlled study. This study included adolescents aged 15-17 years with hypotrichosis, as well as pediatric patients aged 5-17 years who were post-chemotherapy or had alopecia areata. No new safety issues were identified during the study.

In terms of efficacy, results from the Global Eyelash Assessment (GEA) indicated that among adolescents with hypotrichosis, 73% (19 out of 26) demonstrated at least a 1-grade increase from baseline 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 increase from baseline at month 4.

The age ranges for pediatric use are as follows: adolescents with hypotrichosis (15-17 years), post-chemotherapy pediatric patients (5-17 years), and alopecia areata pediatric patients (5-17 years).

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 bimatoprost ophthalmic solution 0.03% in pregnant women. Postmarketing experience does not indicate an increased risk of major birth defects or miscarriages associated with the use of bimatoprost. However, animal studies have demonstrated potential risks. In embryofetal development studies, administration of bimatoprost to pregnant mice and rats during organogenesis resulted in abortion and early delivery at oral doses significantly higher than those expected from topical ophthalmic administration. Specifically, these adverse effects were observed at doses at least 33 times (mice) or 94 times (rats) the human exposure based on the area under the curve (AUC) following topical administration.

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. No adverse effects were noted in rat offspring at exposures estimated at 14 times the human exposure.

Given that animal reproductive studies may not always predict human responses, bimatoprost ophthalmic solution 0.03% should be used during pregnancy only if the potential benefits justify the potential risks 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 approximately 47 times the human systemic exposure, while the NOAEL for postnatal development was 0.1 mg/kg/day, estimated at 14 times the human exposure. Therefore, healthcare professionals should carefully consider the risks and benefits when prescribing this medication to pregnant patients.

Lactation

It is not known whether topical ocular treatment with bimatoprost ophthalmic solution 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 of 1 mg/kg, which is 324 times the recommended human ophthalmic dose on a mg/m² basis; however, no animal data is available at clinically relevant doses.

The developmental and health benefits of breastfeeding should be considered alongside the mother’s clinical need for bimatoprost ophthalmic solution 0.03% and any potential adverse effects on the breastfed child from 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 information regarding overdosage, healthcare professionals are advised to exercise caution and adhere to general principles of management in cases of suspected overdose.

It is essential to monitor the patient closely for any potential symptoms that may arise from an overdose. Symptoms can vary widely depending on the substance involved and the individual patient's response.

In the event of an overdose, immediate medical attention should be sought. Healthcare providers should initiate supportive care, which may include monitoring vital signs, providing symptomatic treatment, and ensuring the patient's safety.

If available, consultation with a poison control center or a medical toxicologist is recommended to guide further management and treatment options.

Documentation of the incident, including the substance involved, the amount taken, and the time of ingestion, is crucial for effective management and follow-up care.

Nonclinical Toxicology

Bimatoprost was evaluated for its potential carcinogenic effects 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 human systemic exposure following the topical 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 a lack of mutagenic or clastogenic activity 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 approximately 103 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on blood AUC levels.

Postmarketing Experience

Postmarketing experience with bimatoprost ophthalmic solution, 0.03%, includes reports of various adverse events following its use. Darkening of the eyelid skin has been observed, which may be reversible. Additionally, increased brown pigmentation of the iris has been reported, and this change is likely to be permanent.

There have been instances of hair growth occurring in areas of the skin that frequently come into contact with the solution. To minimize the risk of hair growth outside the intended treatment area, it is advised to blot any excess solution outside the upper eyelid margin with a tissue or absorbent material.

Variations in eyelash characteristics, such as length, thickness, fullness, pigmentation, number of hairs, and direction of growth, may occur between the eyes. These differences are generally expected to resolve upon discontinuation of the solution.

The most commonly reported side effects include an itching sensation in the eyes and eye redness, affecting approximately 4% of patients. Other less common side effects may occur, typically localized to the skin near the application site or within the eyes, including skin darkening, eye irritation, dryness, and redness of the eyelids.

Patients are advised to seek medical attention if they develop a new ocular condition, experience a sudden decrease in visual acuity, undergo ocular surgery, or encounter any ocular reactions, particularly conjunctivitis or eyelid reactions. It is important to note that any darkening of the iris is not expected to reverse and is likely to be permanent.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) prior to using bimatoprost ophthalmic solution, 0.03%. It is important to inform patients that this solution 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 their contact lenses if applicable.

When applying the solution, patients should carefully place one drop of bimatoprost ophthalmic solution, 0.03% 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 solution inadvertently gets into the eye, it will not cause harm, and the eye should not be rinsed. Patients should be counseled that additional applications 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.

It is essential to inform patients that the effects of bimatoprost ophthalmic solution, 0.03% are not permanent and will gradually return to the original level upon discontinuation of treatment. Patients should be instructed to maintain the integrity of the bimatoprost ophthalmic solution bottle and to avoid allowing the tip of the bottle or applicator to contact surrounding structures, fingers, or any unintended surfaces to prevent contamination by common bacteria that can cause ocular infections. They should also be advised to use the supplied applicator only once and then discard it, as reuse could lead to contamination.

Patients should be made aware of the potential for serious infections resulting from the use of contaminated solutions or applicators. Additionally, they should be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of the solution, and the potential for increased brown iris pigmentation, which is likely to be permanent. Patients should also be cautioned that hair growth may occur outside the target treatment area if the solution repeatedly touches the same area of skin outside the treatment area.

Patients should be advised to seek their physician’s advice immediately 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. Those on intraocular pressure (IOP)-lowering medications should not use bimatoprost ophthalmic solution, 0.03% without prior consultation with their physician.

Finally, patients should be informed that bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Therefore, contact lenses should be removed prior to the application of the solution and may be reinserted 15 minutes after administration.

Storage and Handling

Bimatoprost ophthalmic solution, 0.03%, is supplied in a sterile, opaque white low-density polyethylene round screw neck bottle, which is equipped with tips made of high-density polyethylene. Each bottle is sealed with a turquoise opaque screw cap and is accompanied by sterile, disposable applicators.

For optimal preservation of the product's integrity, it should be stored at a temperature range of 2° to 25°C (36° to 77°F). Proper handling and storage conditions are essential to maintain the efficacy and safety of the solution.

Additional Clinical Information

Bimatoprost ophthalmic solution 0.03% should be applied exclusively to the skin of the upper eyelid margin at the base of the eyelashes using the provided sterile applicators. Patients are advised of the potential for increased brown iris pigmentation, which is likely to be permanent. It is essential to keep the bottle intact during use and to prevent the bottle tip from contacting any surfaces to avoid contamination. Each sterile applicator is intended for single use on one eye only, and should be discarded afterward to minimize the risk of contamination and infections. Additionally, patients should remove contact lenses prior to application and may reinsert them 15 minutes after administration.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bimatoprost as submitted by Alembic Pharmaceuticals Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)