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 demonstrates high solubility in ethyl alcohol and methyl alcohol, while being slightly soluble in water.

The ophthalmic solution is characterized as a clear, isotonic, colorless, sterile formulation with an osmolality ranging from approximately 270 to 320 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, sodium chloride, sodium phosphate dibasic (heptahydrate), citric acid monohydrate, and water for injection. The pH of the solution is adjusted using 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 0.03% 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 systemic absorption.

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 may include increased length, thickness, and number of lashes. These changes are typically reversible upon discontinuation of the medication. It is advisable for healthcare providers to monitor patients for these effects and discuss any concerns with them.

Currently, there are no specific laboratory tests recommended for monitoring the safety or efficacy of this medication. However, healthcare professionals should remain vigilant and assess patients regularly for any adverse effects or changes in their condition.

In the event of any concerning symptoms or side effects, patients should be encouraged to communicate with their healthcare provider for further evaluation and guidance.

Side Effects

In clinical trials, the most common adverse reaction observed among participants was conjunctival hyperemia, reported in 45% of subjects. Additionally, pigmentation changes may occur, affecting the iris, periorbital tissue (eyelid), and eyelashes. Notably, iris pigmentation is likely to be permanent, while changes to eyelashes, including increased length, thickness, and number, are usually reversible. Hypersensitivity reactions have also been reported in some patients.

Drug Interactions

Bimatoprost ophthalmic solution 0.03% may be administered concurrently with other topical ophthalmic medications aimed at reducing intraocular pressure. When utilizing multiple topical ophthalmic agents, it is recommended that they be applied at least five minutes apart to ensure optimal efficacy and minimize potential interactions.

The formulation of bimatoprost ophthalmic solution 0.03% includes benzalkonium chloride, a preservative that can be absorbed by soft contact lenses, potentially leading to discoloration. Therefore, it is advised that contact lenses be removed prior to the application of bimatoprost ophthalmic solution 0.03%. Contact lenses may be safely reinserted 15 minutes after the administration of the solution to avoid any adverse effects related to lens discoloration.

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 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 bimatoprost. However, data from embryofetal developmental studies in pregnant mice and rats indicate potential risks. Administration of bimatoprost during organogenesis resulted in abortion and early delivery at oral doses that were at least 33 times (mice) or 94 times (rats) the human exposure at the recommended clinical dose, based on blood area under the curve (AUC) levels. No adverse effects were observed at lower doses, specifically at 2.6 times (mice) and 47 times (rats) the human exposure at the recommended clinical dose.

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

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 (47 times the human systemic exposure at the recommended human ophthalmic dose), while in mice, the NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure at the recommended human ophthalmic dose). No abnormalities were observed in fetuses from either species at doses up to 0.6 mg/kg/day.

Healthcare professionals should carefully consider the risks and benefits when prescribing bimatoprost 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 (1 mg/kg) that is 324 times the recommended human dose (RHOD) on a body surface area 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 infant 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

There is no information available regarding the use of this medication in patients with hepatic impairment. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions specified for individuals with compromised liver function. Healthcare professionals should exercise clinical judgment when considering the use of this medication in patients with liver problems, as the absence of data does not preclude the need for careful evaluation and monitoring based on individual patient circumstances.

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 dose, 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 suggests a significant margin of safety in the context of potential accidental exposure.

Healthcare professionals are advised to monitor patients for any adverse effects and manage symptoms accordingly, given the lack of specific overdose data in humans.

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 at least 192 and 291 times the human systemic exposure at the recommended highest observed dose (RHOD), respectively, based on blood area under the curve (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.

Additionally, bimatoprost did not impair fertility in male or female rats when administered 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. Additionally, they should be made aware of the possibility of eyelid skin darkening, which may be reversible upon 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. 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 after stopping the 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 experience any intercurrent ocular conditions, such as trauma or infection, undergo ocular surgery, or develop any ocular reactions, particularly conjunctivitis or eyelid reactions, regarding the continued use of bimatoprost ophthalmic solution 0.03%.

It is also crucial to inform patients that bimatoprost ophthalmic solution 0.03% contains benzalkonium chloride, which can be absorbed by soft contact lenses. Therefore, contact lenses should be removed prior to the instillation of the solution and may be reinserted 15 minutes after administration.

Finally, patients should be advised that if they are using more than one topical ophthalmic drug, they should 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 ensure that the product is kept in its original container to protect it from contamination and to preserve its stability.

Additional Clinical Information

Patients receiving treatment with bimatoprost ophthalmic solution 0.03% should be informed about the potential for increased pigmentation as a side effect. Additionally, it is important for patients to remove contact lenses prior to the instillation of the solution and to wait at least 15 minutes before reinserting them.

FDA Insert (PDF)

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

View full prescribing information (PDF)