Bimatoprost

Description

Bimatoprost 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 g/mol, and its molecular formula is C25H37NO4. It appears as a white to off-white powder, soluble in methanol and alcohol.

Bimatoprost is formulated as an ophthalmic solution at a concentration of 0.01%. This solution is clear, isotonic, colorless, and sterile, with an osmolality of approximately 290 mOsmol/kg (ranging from 260 mOsmol/kg to 330 mOsmol/kg). Each mL of Bimatoprost ophthalmic solution 0.01% contains 0.1 mg of Bimatoprost and 0.15 mg of Benzalkonium chloride. Inactive ingredients in each mL include citric acid monohydrate, sodium chloride, sodium phosphate dibasic heptahydrate, 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 is a prostaglandin analog 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 the use of this drug.

Dosage and Administration

The recommended dosage for administration is one drop in the affected eye(s) once daily in the evening. It is essential for healthcare professionals to instruct patients to follow this dosing schedule consistently to achieve optimal therapeutic outcomes. Prior to administration, patients should be advised to wash their hands thoroughly.

To apply the drop, patients should tilt their head back, pull down the lower eyelid to create a small pocket, and then instill one drop into the pocket without touching the dropper tip to the eye or surrounding areas to avoid contamination. After instillation, patients should close their eyes gently and may apply pressure to the inner corner of the eye for a few moments to enhance absorption.

Healthcare professionals should ensure that patients understand the importance of adhering to the prescribed dosing regimen and the proper technique for administration.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to any of its components.

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.

While no specific laboratory tests are required for monitoring, healthcare providers should remain vigilant for any adverse effects and counsel patients on the importance of reporting any unexpected changes.

In the event of severe side effects or concerns, patients should be advised to seek immediate medical attention and to communicate any issues to their healthcare provider promptly.

Side Effects

In clinical trials, the most common adverse reaction observed among participants was conjunctival hyperemia, reported in 31% of subjects.

Additionally, pigmentation changes may occur, including pigmentation of the iris, periorbital tissue (eyelid), and eyelashes. It is important to note that iris pigmentation is likely to be permanent.

Participants may also experience changes in their eyelashes, characterized by a gradual increase in length, thickness, and number of lashes. These changes are usually reversible upon discontinuation of treatment.

Hypersensitivity reactions have also been reported, warranting careful monitoring in patients receiving this treatment.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary at this time.

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, it is essential for healthcare providers to remain vigilant when prescribing to geriatric patients, as individual responses may vary. Continuous monitoring for any potential adverse effects or changes in efficacy is recommended to ensure optimal therapeutic outcomes in this demographic.

Pregnancy

There are no adequate and well-controlled studies of bimatoprost ophthalmic solution 0.01% in pregnant women. Post-marketing 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 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 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.

Given that animal reproductive studies may not always predict human responses, bimatoprost ophthalmic solution 0.01% 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), 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

There are no adequate and well-controlled studies of bimatoprost ophthalmic solution 0.01% in nursing mothers. In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length, decreased fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels). However, no adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels).

Due to the lack of human data and the potential risks identified in animal studies, bimatoprost ophthalmic solution 0.01% should be administered to lactating mothers only if the potential benefit justifies the potential risk to the nursing infant.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

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 0.01%, 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.

Toxicological 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. This threshold is significantly higher—at least 210 times greater—than the potential accidental ingestion of an entire bottle of bimatoprost ophthalmic solution 0.01% by a child weighing 10 kg.

Healthcare professionals should remain vigilant for any symptoms that may arise from an overdose and manage them accordingly, although the likelihood of significant toxicity appears to be low based on animal studies.

Nonclinical Toxicology

Bimatoprost was evaluated for its carcinogenic potential in long-term studies involving mice and rats. The results indicated that bimatoprost did not exhibit carcinogenicity 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 192 and 291 times the estimated human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, respectively, based on blood AUC levels.

In terms of mutagenicity, bimatoprost was found to be non-mutagenic and non-clastogenic. This conclusion was supported by results from the Ames test, the mouse lymphoma test, and in vivo mouse micronucleus tests, all of which demonstrated no mutagenic effects.

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

Postmarketing Experience

No specific postmarketing experience details are available in the extracted data. As such, there are no reported adverse events or 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 0.01%.

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 0.01%. 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. Patients should be reassured that eyelash changes are typically reversible upon discontinuation of the 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. 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.

In the event that patients develop an intercurrent ocular condition, such as trauma or infection, undergo ocular surgery, or experience any ocular reactions—particularly conjunctivitis or eyelid reactions—they should be advised to seek their physician’s guidance regarding the continued use of bimatoprost ophthalmic solution 0.01%.

Patients should also be informed that bimatoprost ophthalmic solution 0.01% 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, 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 0.01% is supplied in a container that allows for easy dispensing. It should be stored at a temperature range of 2° to 25°C (36° 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 container is kept tightly closed when not in use to prevent contamination and preserve the integrity of the product.

Additional Clinical Information

Patients receiving treatment with bimatoprost ophthalmic solution 0.01% should be informed about the potential for increased pigmentation, particularly in 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 can be reinserted 15 minutes after application.

FDA Insert (PDF)

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

View full prescribing information (PDF)