Bimatoprost

Description

Bimatoprost ophthalmic solution, 0.03%, is a synthetic prostamide analog exhibiting ocular hypotensive activity. The chemical name of bimatoprost is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-(1E,3S)-3-hydroxy-5-phenyl-1-pentenylcyclopentyl]-5-N-ethylheptenamide, with a molecular weight of 415.58 and a molecular formula of C25H37NO4. This compound is presented as a powder that is soluble in methanol and alcohol.

The ophthalmic solution is characterized as a clear, isotonic, colorless, sterile formulation with an osmolality of approximately 290 mOsmol/kg. Each milliliter of the solution contains 0.3 mg of bimatoprost as the active ingredient, along with inactive components including 0.05 mg/mL of benzalkonium chloride, disodium hydrogen phosphate heptahydrate, citric acid monohydrate, sodium chloride, 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.

Uses and Indications

Bimatoprost ophthalmic solution 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 pocket, and 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 drainage.

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

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 upon discontinuation of the medication. Monitoring for these effects is advisable, and patients should be counseled on what to expect during treatment.

No specific laboratory tests are recommended for monitoring the safety of this medication. However, healthcare providers should remain vigilant for any adverse effects and maintain open communication with patients regarding their treatment experience.

Side Effects

Most common adverse reaction observed in clinical trials is conjunctival hyperemia, occurring in 45% of patients.

In addition to conjunctival hyperemia, other adverse reactions may include pigmentation changes, which can affect the iris, periorbital tissue (eyelids), and eyelashes. Notably, iris pigmentation is likely to be permanent. Patients may also experience changes in their eyelashes, characterized by an increase in length, thickness, and number of lashes; these changes are usually reversible.

Hypersensitivity reactions have also been reported among participants, warranting careful monitoring.

Drug Interactions

Bimatoprost ophthalmic solution, 0.03% may be used in conjunction with other topical ophthalmic drug products aimed at lowering intraocular pressure. When administering multiple topical ophthalmic medications, it is recommended that they be applied at least five (5) minutes apart to ensure optimal efficacy and minimize potential interactions.

It is important to note that bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which can be absorbed by soft contact lenses, leading to discoloration. Therefore, contact lenses should be removed prior to the instillation of bimatoprost ophthalmic solution, 0.03%, and may be safely reinserted 15 minutes after administration. This practice helps to prevent any adverse effects related to the interaction between the solution and the contact lenses.

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

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.

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 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 higher than the recommended clinical dose, specifically at least 33 times the human exposure in mice and 94 times in rats, based on blood area under the curve (AUC) levels. Notably, these adverse effects were not observed at lower doses, specifically at 2.6 times the human exposure in mice and 47 times in rats.

In pre- and postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis through lactation resulted in reduced gestation length, decreased fetal body weight, increased fetal and pup mortality at doses at least 41 times the human systemic exposure at the recommended clinical dose. 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 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 approximately 47 times the human systemic exposure at the recommended human ophthalmic dose (RHOD). Similarly, in mice, the NOAEL for abortion and early delivery was 0.1 mg/kg/day, equating to about 2.6 times the human systemic exposure at the RHOD. No abnormalities were observed in rat or mouse fetuses at doses up to 0.6 mg/kg/day, which is significantly higher than the human exposure levels.

Healthcare professionals should weigh the potential risks and benefits when considering the use of bimatoprost in 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 (i.e., 1 mg/kg) 324 times the recommended human oral dose (RHOD) 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%, as well as any potential adverse effects on the breastfed child from this treatment.

Renal Impairment

There is no information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution and consider the lack of specific guidance when prescribing to patients with reduced kidney function.

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 bimatoprost ophthalmic solution, 0.03%, 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 via oral administration (by gavage) have demonstrated that doses up to 100 mg/kg/day did not result in any observable toxicity. Notably, this dosage, when converted to mg/m², is at least 70 times greater than the accidental ingestion of an entire bottle of bimatoprost ophthalmic solution, 0.03%, by a child weighing 10 kg. This information may provide some reassurance regarding the safety margin associated with potential accidental overdoses in pediatric populations.

Healthcare professionals are advised to monitor patients for any adverse effects and manage symptoms accordingly, as specific antidotes or treatments for bimatoprost overdose have not been established.

Nonclinical Toxicology

Bimatoprost was evaluated for its potential carcinogenic effects in long-term studies. It was found to be non-carcinogenic in both mice and rats when administered via oral gavage for 104 weeks at doses of up to 2 mg/kg/day and 1 mg/kg/day, respectively. These doses correspond to at least 192 and 291 times the human systemic exposure at the recommended human dose (RHOD), 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 at least 103 times the human systemic exposure at the RHOD, based on blood AUC levels.

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Patients should be informed about the potential for increased brown pigmentation of the iris, which may be permanent. They should also be made aware of the possibility of eyelid skin darkening, which may be reversible after discontinuation of bimatoprost ophthalmic solution, 0.03%.

It is important to discuss with patients the potential changes in eyelashes and vellus hair in the treated eye during the course of treatment with bimatoprost ophthalmic solution, 0.03%. 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. Patients should be reassured that eyelash changes are typically reversible upon discontinuation of treatment.

Healthcare providers should instruct patients to avoid allowing the tip of the dispensing container to come into contact with the eye, surrounding structures, fingers, or any other surface. This precaution is essential to prevent contamination of the solution by common bacteria that can cause ocular infections, which may lead to serious damage to the eye and potential loss of vision.

Patients should be advised to seek immediate medical advice if they develop any intercurrent ocular condition, such as trauma or infection, undergo ocular surgery, or experience any ocular reactions, particularly conjunctivitis and eyelid reactions, regarding the continued use of bimatoprost ophthalmic solution, 0.03%.

Additionally, it is crucial to inform patients that bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Patients should be instructed to remove their contact lenses prior to instillation of the solution and may reinsert them 15 minutes after administration.

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

Storage and Handling

Bimatoprost ophthalmic solution, 0.03% 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, the solution can be used until the expiration date indicated on the bottle. It is important to handle the product with care to ensure its integrity and effectiveness throughout its use.

Additional Clinical Information

Patients receiving treatment with bimatoprost ophthalmic solution, 0.03% should be informed about the potential for increased pigmentation, particularly of the iris. Regular examinations are recommended for patients who notice significant changes in iris pigmentation. Additionally, it is advised that contact lenses be removed before the administration of the solution and may be reinserted 15 minutes after application.

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)