Bimatoprost

Description

Bimatoprost ophthalmic solution, 0.03%, is a synthetic prostaglandin analog. Its chemical name 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. Bimatoprost is presented as a powder that is soluble in methanol and alcohol. The ophthalmic solution is clear, isotonic, colorless, and sterile, with an osmolality of approximately 290 mOsmol/kg.

The formulation contains bimatoprost as the active ingredient at a concentration of 0.3 mg/mL, along with the preservative benzalkonium chloride at 0.05 mg/mL. 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, and it ranges from 6.8 to 7.8 during its shelf-life.

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 and minimize potential side effects. 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. This ensures that each eyelid is treated effectively while adhering to safety protocols.

Contraindications

Use of this product is contraindicated in individuals with a known 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.

No additional general precautions or laboratory tests have been specified for the safe use of Bimatoprost ophthalmic solution. Healthcare professionals should remain vigilant in monitoring patients for any adverse effects or changes in their ocular health during treatment.

Side Effects

Patients may experience a range of adverse reactions while using the medication. The most common adverse reactions reported include eye pruritus, conjunctival hyperemia, and skin hyperpigmentation, with an incidence of approximately 3% to 4%.

In addition to these common reactions, there are other important considerations. Pigmentation of the eyelids and iris may occur, with iris pigmentation likely to be permanent. Hypersensitivity reactions have also been noted among patients.

Healthcare professionals should monitor patients for these adverse reactions and provide appropriate guidance regarding their management.

Drug Interactions

Concurrent administration of Bimatoprost ophthalmic solution with other intraocular pressure (IOP)-lowering prostaglandin analogs may result in a diminished IOP-lowering effect. It is advisable for healthcare providers to monitor patients for any changes in their IOP during such combination therapy.

Additionally, Bimatoprost ophthalmic solution contains benzalkonium chloride, which can be absorbed by soft contact lenses, potentially leading to discoloration. To mitigate this risk, patients are instructed to remove their contact lenses prior to the application of the solution and may reinsert them 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 and 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.

These findings suggest that bimatoprost ophthalmic solution 0.03% may be effective in improving eyelash growth in the specified pediatric populations, with no significant safety concerns noted.

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 has not indicated an increase in the 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) and 94 times (rats) the human exposure based on the area under the curve (AUC) following topical administration.

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. Conversely, 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 0.03% 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, corresponding to 47 times the human systemic exposure, while in mice, the NOAEL for abortion and early delivery was 0.1 mg/kg/day, equating to 2.6 times the human exposure. No abnormalities were observed in fetuses at doses up to 0.6 mg/kg/day in both species.

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 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 treatment.

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 assessment of renal function may be warranted to ensure safe and effective use of the medication in 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 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 overdosage information, it is essential for healthcare professionals to remain vigilant regarding the potential for overdose with any medication. In cases where an overdose is suspected, immediate medical attention should be sought.

Healthcare providers are advised to monitor patients closely for any signs or symptoms that may indicate an overdose. Common symptoms may include, but are not limited to, altered mental status, cardiovascular instability, and gastrointestinal disturbances.

Management of an overdose typically involves supportive care, which may include the following steps:

1. Assessment: Conduct a thorough evaluation of the patient's clinical status, including vital signs and level of consciousness.

2. Supportive Care: Provide symptomatic treatment as necessary, which may involve intravenous fluids, oxygen supplementation, or other interventions based on the patient's needs.

3. Decontamination: If the overdose is recent, consider gastrointestinal decontamination methods, such as activated charcoal, if appropriate and within the recommended time frame.

4. Consultation: Engage with a poison control center or toxicology specialist for guidance on specific antidotes or advanced management strategies, if applicable.

It is crucial for healthcare professionals to document the incident thoroughly and report any adverse events to the appropriate regulatory authorities. Continuous education on the signs of overdose and the management protocols is recommended to ensure patient safety.

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 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. This dose 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, with the likelihood of permanence.

There have been instances of hair growth in areas of the skin that frequently come into contact with the solution. Variations in eyelash characteristics, such as length, thickness, fullness, pigmentation, number of hairs, and direction of growth between eyes, are generally expected to resolve upon discontinuation of the product.

The most frequently reported side effects include an itching sensation in the eyes and eye redness, occurring in approximately 4% of patients. Other less common side effects may manifest on the skin near the application site or in the eyes, including skin darkening, eye irritation, dryness, and redness of the eyelids.

Patients are advised to seek medical attention if they develop new ocular conditions, experience a sudden decrease in visual acuity, undergo ocular surgery, or encounter any ocular reactions, particularly conjunctivitis or eyelid reactions. Upon cessation of bimatoprost ophthalmic solution, eyelashes are anticipated to revert to their previous appearance over several weeks to months, while eyelid skin darkening is also expected to reverse within a similar timeframe. In contrast, 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 starting treatment with 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. They should begin by ensuring their face is clean, removing all makeup, and taking out contact lenses if applicable.

Patients should be instructed to 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. It is essential to communicate that additional applications will not increase eyelash growth 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.

The onset of effect is gradual, with significant results typically not observed until approximately two months. Patients should be counseled that the effects of the treatment are not permanent and will gradually return to baseline upon discontinuation of bimatoprost ophthalmic solution, 0.03%. They must be instructed to maintain the integrity of the solution bottle and avoid contact between the tip of the bottle or applicator and any surrounding structures, fingers, or unintended surfaces to prevent contamination by bacteria that can cause ocular infections.

Patients should only use the supplied applicator once and then discard it, as reuse could lead to contamination. They should be informed about the potential for eyelid skin darkening, which may be reversible after discontinuation, and the possibility of increased brown iris pigmentation, which is likely to be permanent. Additionally, patients should be made aware that hair growth may occur outside the intended treatment area if the solution repeatedly touches skin outside the upper eyelid margin.

If patients develop a new ocular condition, experience a sudden decrease in visual acuity, undergo ocular surgery, or have any ocular reactions, particularly conjunctivitis or eyelid reactions, they should seek their physician’s advice regarding the continued use of bimatoprost ophthalmic solution, 0.03%. It is also important to inform patients that this solution contains benzalkonium chloride, which may be absorbed by and discolor soft contact lenses. Therefore, contact lenses should be removed prior to application and may be reinserted 15 minutes after administration.

Patients should be reminded to read the Patient Information that accompanies bimatoprost ophthalmic solution, 0.03%, before starting treatment and each time they receive a refill, as there may be new information. They should not use the solution if they are allergic to any of its ingredients. Bimatoprost ophthalmic solution, 0.03%, is intended solely for application on the skin of the upper eyelid margins at the base of the eyelashes and should not be applied to the lower eyelid.

For patients using LUMIGAN® or other products in the same class for elevated intraocular pressure (IOP), or those with a history of abnormal IOP, it is crucial to use bimatoprost ophthalmic solution, 0.03%, only under close supervision by their physician. If treatment is discontinued, patients can expect their eyelashes to return to their previous appearance over several weeks to months, and any eyelid skin darkening is anticipated to reverse within a similar timeframe. However, any darkening of the iris is not expected to reverse and is likely to be permanent.

Storage and Handling

Bimatoprost ophthalmic solution, 0.03%, is supplied sterile in an 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 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, utilizing the provided sterile applicators. Clinicians should instruct patients to carefully blot any excess solution to prevent it from running onto the cheek or other areas of the skin.

Patients must be counseled regarding the possibility of increased brown iris pigmentation, which is likely to be permanent. It is crucial for patients to keep the bottle intact during use and to apply the solution as directed, using one drop on a single-use applicator for each eye. The bottle tip should not come into contact with any surfaces to avoid contamination. Additionally, patients should remove contact lenses prior to application and may reinsert them 15 minutes after administration. Reuse of applicators is discouraged to minimize the risk of contamination and infections.

FDA Insert (PDF)

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

View full prescribing information (PDF)