Bimatoprost

Description

Bimatoprost ophthalmic solution 0.03% is a synthetic prostaglandin analog indicated for ophthalmic use. The chemical name of bimatoprost is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-(1E,3S)-3-hydroxy-5-phenyl-1-pentenylcyclopentyl]-N-ethyl-5-heptenamide, with a molecular weight of 415.58 and a molecular formula of C25H37NO4.

This formulation appears as a clear, isotonic, colorless, sterile ophthalmic solution 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 0.05 mg/mL of benzalkonium chloride NF as a preservative. Inactive ingredients include citric acid USP, purified water USP, sodium chloride USP, and sodium phosphate USP, dibasic. The pH of the solution is maintained between 6.8 and 7.8, with hydrochloric acid and/or sodium hydroxide used for pH adjustment. Bimatoprost is a powder that exhibits high solubility in ethyl alcohol and methyl alcohol, and slight solubility in water.

Uses and Indications

Bimatoprost ophthalmic solution is indicated for the treatment of hypotrichosis of the eyelashes, specifically to enhance their growth in terms of length, thickness, and darkness.

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, the procedure should be repeated using a new sterile applicator to ensure safety and efficacy.

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. Healthcare professionals are advised to closely monitor patients using these products together for any alterations in their IOP to ensure optimal therapeutic outcomes.

Additionally, it is important to note that the use of bimatoprost may lead to pigmentation changes in the eyelids and iris. Such pigmentation of the iris is likely to be permanent. Clinicians should inform patients about this potential side effect and consider it when discussing treatment options. Regular follow-up assessments may be warranted to evaluate any changes in pigmentation and to address patient concerns.

Side Effects

In clinical trials, the most common adverse reactions observed in patients included eye pruritus, conjunctival hyperemia, and skin hyperpigmentation, each with an incidence of approximately 3% to 4%.

Additionally, pigmentation of the eyelids and iris may occur, with iris pigmentation likely to be permanent. Patients may also experience hypersensitivity reactions. These adverse reactions should be monitored, and patients should be informed of the potential for these effects during treatment.

Drug Interactions

Concurrent administration of bimatoprost ophthalmic solution with intraocular pressure (IOP)-lowering prostaglandin analogs, such as LUMIGAN, may result in a diminished IOP-lowering effect. Patients utilizing these medications together should be closely monitored for any alterations in their IOP.

In clinical studies involving ocular hypertension, it has been observed that administering more than one dose of bimatoprost daily can further reduce its efficacy in lowering IOP. Therefore, patients receiving treatment with LUMIGAN or other prostaglandin analogs should consult their physician before using bimatoprost ophthalmic solution. Continuous monitoring of IOP is recommended to ensure the desired therapeutic effect is maintained.

Additionally, bimatoprost ophthalmic solution contains benzalkonium chloride, which can be absorbed by soft contact lenses, potentially leading to discoloration. It is advised that contact lenses be removed prior to the application of the solution and may be reinserted 15 minutes after administration to avoid any adverse effects.

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 aged 5 to 17 years who are post-chemotherapy or have alopecia areata, as well as in adolescents aged 15 to 17 years with hypotrichosis. A sixteen-week double-masked, randomized, vehicle-controlled study demonstrated no new safety issues in these populations.

In the study, 73% of adolescents with hypotrichosis (19 out of 26) exhibited at least a 1-grade increase from baseline in the Global Eyelash Assessment at month 4. Among post-chemotherapy pediatric patients, 85% (11 out of 13) achieved a similar increase. In contrast, 44% of pediatric patients with alopecia areata (4 out of 9) showed at least a 1-grade increase from baseline at month 4.

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

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 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, doses at least 33 times the human exposure resulted in these outcomes, while in rats, doses at least 94 times the human exposure were associated with similar effects. No adverse effects were noted at lower doses, specifically 2.6 times the human exposure in mice and 47 times in rats.

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 doses estimated 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 response, 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

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

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 information regarding overdosage, healthcare professionals are advised to exercise caution and consider general principles of management in cases of suspected overdose.

It is essential to monitor the patient closely for any potential symptoms that may arise from an overdose. Symptoms can vary widely depending on the substance involved and the individual patient's response.

In the event of an overdose, immediate medical attention should be sought. Healthcare providers should initiate supportive care and symptomatic treatment as necessary. This may include monitoring vital signs, providing respiratory support, and administering intravenous fluids if indicated.

Additionally, it is recommended to contact a poison control center or consult relevant toxicology resources for guidance on specific management strategies tailored to the substance involved.

Documentation of the incident, including the amount and timing of the substance taken, is crucial for effective management and follow-up care.

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 192 and 291 times the human systemic exposure following the 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.

Furthermore, bimatoprost did not impair fertility in male or female rats at doses up to 0.6 mg/kg/day, which is 103 times the human systemic exposure following the 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 has identified several adverse events reported voluntarily or through surveillance programs.

Use of bimatoprost ophthalmic solution 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, any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material.

Variations in eyelash characteristics, such as length, thickness, fullness, pigmentation, number of hairs, and direction of growth, may occur between eyes. These differences typically resolve upon discontinuation of the solution. 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 of the eyes, and redness of the eyelids. Patients are advised to seek medical advice if they develop a new ocular condition, 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

Patients should be advised to read the FDA-approved patient labeling (Patient Information) thoroughly. It is important to inform them that bimatoprost ophthalmic solution should be applied every night using only the accompanying sterile applicators. Patients should begin by ensuring their face is clean, removing all makeup, and taking out their contact lenses if applicable. They should then carefully place one drop of bimatoprost ophthalmic solution on the disposable sterile applicator and brush 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.

Patients should be made aware that additional applications of bimatoprost ophthalmic solution will not enhance eyelash growth. They must not apply the solution to the lower eyelash line, and 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. It should be communicated that the effects are not permanent and will gradually return to baseline levels upon discontinuation of treatment.

Healthcare providers should instruct patients to keep the bimatoprost ophthalmic solution bottle intact and to 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. Patients should be advised to use the supplied applicator only once and then discard it, as reuse could lead to contamination. Serious infections may arise from using contaminated solutions or applicators.

Patients should be informed that bimatoprost ophthalmic solution may lower intraocular pressure, although not to a level that would cause clinical harm. For patients using LUMIGAN or other prostaglandin analogs for elevated intraocular pressure, it is crucial to consult with their physician before using bimatoprost ophthalmic solution, as it may interfere with the desired reduction in intraocular pressure.

Counsel patients about the potential for eyelid skin darkening, which may be reversible after discontinuation of the solution, and the possibility of increased brown iris pigmentation, which is likely to be permanent. They should also be informed about the risk of hair growth occurring outside the target treatment area if the solution repeatedly touches the skin outside the treatment area. Additionally, patients should be made aware of the potential for disparity between eyes in terms of length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth, with changes likely reversible upon discontinuation.

Patients should be advised to seek their physician’s advice immediately if they develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, undergo ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions. Those on intraocular pressure-lowering medications should not use bimatoprost ophthalmic solution without prior consultation with their physician.

Finally, patients should be informed that bimatoprost ophthalmic solution contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. They should remove their contact lenses prior to application and may reinsert them 15 minutes after administration.

Storage and Handling

Bimatoprost ophthalmic solution 0.03% is supplied sterile in white low-density polyethylene dispenser bottles, which are equipped with tips and turquoise caps. Each package includes sterile disposable applicators to ensure proper application.

For optimal storage, the product should be maintained at a temperature range of 2° to 25°C (36° to 77°F). It is essential to adhere to these temperature guidelines to preserve the integrity and efficacy of the solution.

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 regarding the possibility of increased brown iris pigmentation, which is likely to be a permanent change.

Patients must be instructed to keep the solution bottle intact during use and to avoid contact between the bottle tip and any surfaces to prevent contamination. Each sterile applicator is intended for single use on one eye only and should be discarded afterward to minimize the risk of infection. Additionally, patients should remove contact lenses prior to application and may reinsert them 15 minutes after administration.

FDA Insert (PDF)

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

View full prescribing information (PDF)