Bimatoprost

Description

Bimatoprost ophthalmic solution, 0.03% 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 415.6 g/mol, 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 clear, isotonic, colorless, and sterile, with an osmolality of approximately 290 mOsmol/kg. The active ingredient in this formulation is bimatoprost at a concentration of 0.3 mg/mL. Inactive ingredients include benzalkonium chloride at 0.05 mg/mL, citric acid, sodium chloride, sodium phosphate dibasic, and water for injection. Sodium hydroxide and/or hydrochloric acid may be used to adjust the pH, which ranges from 6.8 to 7.8 during 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.

Limitations of Use: There are no teratogenic or nonteratogenic effects associated with the use of this medication as per the available data.

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 to avoid touching the dropper tip to any surface, including the eye, to maintain sterility.

Contraindications

Use is contraindicated in patients with a known hypersensitivity to the active substance or any of the excipients in the formulation.

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.

No specific laboratory tests are recommended for monitoring during the use of this medication. However, healthcare providers should remain vigilant for any adverse effects and counsel patients on the importance of reporting any unexpected changes or concerns.

In the event of severe side effects or reactions, patients should seek emergency medical assistance. Furthermore, if patients experience any significant issues related to the medication, they are advised to discontinue use and consult their healthcare provider for further guidance.

Side Effects

Most patients in clinical trials experienced conjunctival hyperemia, which was reported in 45% of participants. This was the most common adverse reaction observed.

Additionally, pigmentation changes may occur, affecting the iris, periorbital tissue (eyelid), and eyelashes. Notably, iris pigmentation is likely to be permanent.

Patients may also experience changes in their eyelashes, including a gradual increase in length, thickness, and number of lashes; these changes are usually reversible.

Hypersensitivity reactions have been reported, indicating that some patients may experience allergic responses.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted 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 when 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. However, based on postmarketing experience, there is no increase in the risk of major birth defects or miscarriages associated with its use.

Embryofetal developmental studies in pregnant mice and rats have shown that 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, as determined by blood area under the curve (AUC) levels. Notably, these adverse effects were not observed at lower doses, specifically at 2.6 times (mice) and 47 times (rats) the human exposure at the recommended clinical dose.

In pre- and postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis through 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 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.

Due to the limitations of animal reproductive studies in predicting human response, bimatoprost ophthalmic solution, 0.03%, should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. In embryofetal development studies, abortion was observed in pregnant rats at an oral dose of 0.6 mg/kg/day (94 times the human systemic exposure at the recommended human ophthalmic dose), with a No Observed Adverse Effect Level (NOAEL) for abortion identified at 0.3 mg/kg/day (47 times the human systemic exposure). Similarly, in mouse studies, abortion and early delivery occurred at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure), with a NOAEL for these effects at 0.1 mg/kg/day (2.6 times the human systemic exposure). No abnormalities were observed in fetuses from either species at doses up to 0.6 mg/kg/day.

In summary, while there is no direct evidence of teratogenic effects in humans, the potential risks associated with bimatoprost use during pregnancy necessitate careful consideration and should only be undertaken when the benefits outweigh the risks.

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 (i.e., 1 mg/kg) 324 times the recommended human oral dose (RHOD) on a m2g/m 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 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 absence of specific overdosage information, it is essential for healthcare professionals to remain vigilant and consider general principles of management in cases of suspected overdose.

Healthcare providers should monitor patients closely for any signs or symptoms that may arise from an overdose of the medication. Common symptoms may include, but are not limited to, altered mental status, cardiovascular instability, and gastrointestinal disturbances.

In the event of an overdose, it is recommended that healthcare professionals initiate supportive care immediately. This may involve maintaining the patient's airway, breathing, and circulation, as well as providing symptomatic treatment as necessary.

Additionally, contacting a poison control center or a medical toxicologist for guidance on specific management strategies is advisable. It is crucial to gather as much information as possible regarding the substance involved, the amount ingested, and the time of exposure to facilitate appropriate treatment decisions.

Documentation of the incident and ongoing monitoring of the patient’s clinical status are also critical components of effective overdose management.

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 at least 192 and 291 times the human systemic exposure at the recommended human dose (RHOD), respectively, based on blood AUC levels.

In terms of mutagenicity, bimatoprost demonstrated a lack of mutagenic or clastogenic activity. This was confirmed through various assays, including the Ames test, the mouse lymphoma test, and in vivo mouse micronucleus tests, all of which yielded negative results.

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 at least 103 times the human systemic exposure at the RHOD, based on blood AUC levels.

Postmarketing Experience

Postmarketing experience has identified several events reported voluntarily or through surveillance programs. There is a potential for increased brown pigmentation of the iris, which may be permanent. Additionally, there is a possibility of eyelid skin darkening, which may be reversible after discontinuation of bimatoprost ophthalmic solution, 0.03%. Changes in eyelashes and vellus hair in the treated eye have also been observed during treatment with bimatoprost ophthalmic solution, 0.03%. These changes may lead to disparities between eyes in terms of length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are generally reversible upon discontinuation of treatment.

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 with bimatoprost ophthalmic solution, 0.03%. 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 develop any intercurrent ocular condition, such as trauma or infection, undergo ocular surgery, or experience any ocular reactions, particularly conjunctivitis or eyelid reactions. This is crucial for determining the continued use of bimatoprost ophthalmic solution, 0.03%.

It is also important to inform patients that bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which can be absorbed by soft contact lenses. Patients should be instructed to remove their contact lenses prior to instillation of the solution and may reinsert them 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, 0.03%, is supplied sterile in white opaque polypropylene bottles, which are equipped with translucent polypropylene droppers and turquoise opaque polypropylene caps.

This product should be stored at temperatures ranging from 2°C to 25°C (36°F to 77°F). Once opened, the solution can be used until the expiration date indicated on the bottle.

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. Clinicians should advise patients to remove contact lenses prior to the instillation of the solution and that lenses may be reinserted 15 minutes after administration.

FDA Insert (PDF)

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

View full prescribing information (PDF)