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-1-pentenylcyclopentyl]-N-ethyl-5-heptenamide. The molecular weight of bimatoprost is 415.58, and its molecular formula is C25H37NO4. Bimatoprost is presented as a powder that is very soluble in ethyl alcohol and methyl alcohol, and slightly soluble in water.

The ophthalmic solution is a clear, isotonic, colorless, sterile formulation with an osmolality of approximately 290 mOsmol/kg. The active ingredient is bimatoprost at a concentration of 0.3 mg/mL, and it contains the preservative benzalkonium chloride at 0.05 mg/mL. Inactive ingredients include citric acid, purified water, sodium chloride, and sodium phosphate dibasic. 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 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. This ensures that each eyelid is treated effectively and safely.

Contraindications

Use of this product is contraindicated in individuals with a known hypersensitivity to any of its components. Due to the potential for severe allergic reactions, administration in such cases 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. Healthcare professionals are advised to closely monitor patients using these products together for any changes in their IOP to ensure effective management of their condition.

Additionally, patients should be informed about the potential for pigmentation changes associated with bimatoprost use. Specifically, pigmentation of the eyelids and iris may occur, with iris pigmentation likely to be permanent. It is essential for healthcare providers to discuss these risks with patients prior to initiating treatment, ensuring they are fully aware of the potential long-term effects on eye color and eyelid appearance.

Side Effects

Patients may experience a range of adverse reactions while using the product. The most common adverse reactions reported include eye pruritus, conjunctival hyperemia, and skin hyperpigmentation, with the latter occurring in approximately 3% to 4% of participants.

In addition to these common reactions, there are important considerations regarding the concurrent use of bimatoprost ophthalmic solution with other intraocular pressure (IOP)-lowering prostaglandin analogs. In ocular hypertensive patients, this combination may lead to a decreased IOP-lowering effect. Therefore, patients using these products together should be closely monitored for any changes in their IOP.

Furthermore, patients may experience pigmentation changes, specifically of the eyelids and iris. It is important to note that iris pigmentation is likely to be permanent. Hypersensitivity reactions have also been reported and should be taken into account when evaluating patient responses to the treatment.

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 has the potential to be absorbed by soft contact lenses, leading to discoloration. To mitigate this risk, patients are recommended to remove their contact lenses prior to the application of the solution and may reinsert them 15 minutes after application.

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 has been evaluated in pediatric patients, specifically in a sixteen-week double-masked, randomized, vehicle-controlled study. This study included adolescents aged 15 to 17 years with hypotrichosis and pediatric patients aged 5 to 17 years who were post-chemotherapy or had alopecia areata.

In adolescents with hypotrichosis (N=40), bimatoprost ophthalmic solution demonstrated a response rate of 73% (19 out of 26), compared to 7% (1 out of 14) for the vehicle, resulting in a significant difference of 66% (95% CI: 44%, 88%).

Among post-chemotherapy pediatric patients (N=16), the response rate for bimatoprost was 85% (11 out of 13), while the vehicle group had a 100% response rate (3 out of 3), yielding a difference of -15% (95% CI: -35%, 4%).

In pediatric patients with alopecia areata (N=15), bimatoprost ophthalmic solution showed a response rate of 44% (4 out of 9), compared to 33% (2 out of 6) for the vehicle, resulting in a difference of 11% (95% CI: -39%, 61%).

No new safety issues were observed in any of the pediatric populations studied.

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 elderly patients for any potential adverse effects, as individual responses may vary. It is essential to consider the overall health status and comorbidities of geriatric patients when prescribing, as these factors may influence treatment 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 its use. However, animal studies have shown that administration of bimatoprost during organogenesis can lead to adverse fetal outcomes. In embryofetal development studies, pregnant mice and rats receiving bimatoprost orally at doses significantly higher than human exposure experienced abortion and early delivery. Specifically, in mice, these effects were noted at doses at least 33 times the human exposure, while in rats, they were observed at doses 94 times 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, increased fetal and pup mortality, and decreased fetal body weight at doses at least 41 times the human systemic exposure. No adverse effects were observed at lower doses, specifically at 14 times the human exposure. 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 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.

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 benefits justify the potential risks to the fetus.

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

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in these patients 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 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 this 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 arise from an overdose. Common symptoms may include, but are not limited to, severe drowsiness, confusion, respiratory distress, or any other unusual clinical manifestations.

Management of an overdose should be guided by the clinical presentation of the patient. Supportive care is paramount, and symptomatic treatment should be initiated as necessary. Healthcare professionals should also consider contacting a poison control center for additional guidance on the management of overdose cases.

It is crucial to document any instances of overdose and report them to the appropriate regulatory authorities as part of ongoing pharmacovigilance efforts.

Nonclinical Toxicology

Bimatoprost was evaluated for its carcinogenic potential in both mice and rats. In these studies, it was administered via oral gavage for a duration of 104 weeks at doses of up to 2 mg/kg/day for mice and 1 mg/kg/day for rats. The results indicated that bimatoprost was not carcinogenic at these doses, which correspond to 192 and 291 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.

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 at doses up to 0.6 mg/kg/day. This dose is equivalent to 103 times the human systemic exposure following the same topical ophthalmic administration of bimatoprost 0.03%.

Postmarketing Experience

Bimatoprost ophthalmic solution has been associated with several postmarketing experiences reported voluntarily or through surveillance programs.

The use of bimatoprost may lead to darkening of the eyelid skin, which is generally reversible. In contrast, increased brown pigmentation of the iris is likely to be permanent. Additionally, hair growth may occur in areas of the skin that frequently come into contact with the solution. To minimize this risk, 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 typically resolve upon discontinuation of the product. The most commonly 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. It is important to note that any darkening of the iris is not expected to reverse and is likely to be permanent.

Patient Counseling

Advise patients to read the FDA-approved patient labeling (Patient Information) thoroughly to understand the proper use of bimatoprost ophthalmic solution. 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 their contact lenses if applicable.

Patients should carefully place one drop of bimatoprost ophthalmic solution on the disposable sterile applicator and brush it cautiously along the skin of the upper eyelid margin at the base of the eyelashes. It is important to inform patients that if any solution gets into the eye, it will not cause harm, and the eye should not be rinsed. Additionally, counsel patients that extra applications of the solution will not enhance eyelash growth.

Instruct patients not to apply the solution to the lower eyelash line and to blot any excess solution outside the upper eyelid margin with a tissue or other absorbent material. Explain that the onset of effect is gradual, with significant results typically not observed until about two months. Patients should be made aware that the effects are not permanent and will gradually return to baseline levels upon discontinuation of the treatment.

Emphasize the importance of maintaining the integrity of the bimatoprost ophthalmic solution bottle. Patients should 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. Instruct patients to use the supplied applicator only once and then discard it, as reuse could lead to contamination and serious infections.

Inform patients about the potential for eyelid skin darkening, which may be reversible after discontinuation of the solution. Advise them of the possibility of increased brown iris pigmentation, which is likely to be permanent, and that this has been observed with the administration of bimatoprost solution. Patients should also be made aware of the risk of hair growth occurring outside the target treatment area if the solution repeatedly touches skin outside the treatment area.

Counsel patients regarding the possibility of differences between eyes in terms of eyelash length, thickness, pigmentation, and direction of growth, noting that these changes are likely reversible upon discontinuation of treatment. Advise patients to seek immediate medical advice if they 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.

Patients on intraocular pressure (IOP)-lowering medications should not use bimatoprost ophthalmic solution without prior consultation with their physician. Inform patients that the 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.

If patients discontinue the use of bimatoprost ophthalmic solution, they can expect their eyelashes to return to their previous appearance over several weeks to months. Any eyelid skin darkening is also expected to reverse after several weeks to months, while any darkening of the iris is not expected to reverse and is likely permanent. Patients should inform their physician that they are using bimatoprost ophthalmic solution, especially if they have a history of eye pressure problems, and should also notify anyone conducting an eye pressure screening.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at a temperature range of 2° to 25°C (36° to 77°F) to maintain its integrity and efficacy. Proper container requirements must be adhered to, ensuring that the product is kept in a suitable environment. Special handling needs should be observed to prevent any compromise to the product's quality during storage and transportation.

Additional Clinical Information

Bimatoprost ophthalmic solution 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 counsel patients on the possibility of increased brown iris pigmentation, which is likely to be a permanent change. It is essential for patients to blot any excess solution from the eyelid margin to prevent it from running onto the cheek or other areas of the skin.

Additionally, the integrity of the bimatoprost ophthalmic solution bottle must be maintained during use, ensuring it does not come into contact with any surfaces to prevent contamination. Patients are advised to remove contact lenses prior to application and may reinsert them 15 minutes after administering the solution.

FDA Insert (PDF)

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

View full prescribing information (PDF)