Zolymbus

Description

ZOLYMBUS contains bimatoprost, a synthetic prostamide analog with ocular hypotensive activity, intended for topical ophthalmic use. The chemical name of bimatoprost is 5-Heptenamide, 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-ylcyclopentyl]-N-ethyl, (5Z)-. It has a molecular weight of 415.58 and a molecular formula of C25H37NO4. Bimatoprost is presented as a crystalline powder that is very soluble in ethyl alcohol and methyl alcohol, and slightly soluble in water.

ZOLYMBUS is formulated as a sterile, colorless, opalescent ophthalmic gel with an osmolality of approximately 300 mOsmol/kg. Each container contains 0.03 mg of bimatoprost along with inactive ingredients that include carbomer, polyethylene glycol, sodium acetate trihydrate, sorbitol, sodium hydroxide, and water for injection. The pH of the formulation ranges from 6.9 to 7.9.

Uses and Indications

ZOLYMBUS™ 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 ZOLYMBUS™.

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 hand hygiene before administering the drop. The patient should tilt their head back, pull down the lower eyelid to create a pocket, and instill the drop into the pocket without touching the dropper tip to the eye or eyelid to avoid contamination. After administration, patients should close their eyes gently and may apply pressure to the inner corner of the eye for one to two minutes to enhance absorption and minimize systemic absorption.

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 cases may pose significant health risks.

Warnings and Precautions

Pigmentation changes may occur with the use of this medication, specifically affecting the iris, periorbital tissue (eyelids), and eyelashes. 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 may include increased length, thickness, and number of lashes. These changes are typically reversible; however, monitoring for any unexpected or concerning effects is advisable.

No specific laboratory tests are required for the safe use of this medication. Nonetheless, healthcare providers should remain vigilant and assess patients regularly for any adverse effects or changes in their condition.

In the event of any severe reactions or concerns, patients should be advised to seek emergency medical assistance promptly. Furthermore, if patients experience any troubling symptoms, they should be instructed to discontinue use and consult their healthcare provider for further evaluation and guidance.

Side Effects

Most common adverse reactions observed in clinical trials include conjunctival hyperemia, reported in 14% of patients, and eye irritation, which occurred in 11% of participants.

In addition to these common reactions, pigmentation changes have been noted, including pigmentation of the iris, periorbital tissue (eyelid), and eyelashes. It is important to note that iris pigmentation is likely to be permanent.

Patients may also experience changes in eyelashes, characterized by a gradual increase in length, thickness, and number of lashes. These changes are typically reversible.

Hypersensitivity reactions have been reported, although specific frequency data for these events is not provided.

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

Drug Interactions

There are currently no documented drug interactions associated with 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 Zolymbus (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 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 for any potential age-related changes that may affect individual patient responses to treatment. 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 ZOLYMBUS (bimatoprost ophthalmic gel) 0.01% in pregnant women. Based on post-marketing experience, there is no increase in the risk of major birth defects or miscarriages associated with bimatoprost. However, animal studies have shown that administration of bimatoprost during organogenesis in pregnant mice and rats resulted in abortion and early delivery at doses significantly higher than human exposure levels. Specifically, in mice, these effects were observed at doses at least 33 times the human exposure to bimatoprost solution 0.03%, while in rats, the threshold was 94 times the human exposure.

In pre- and 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. No adverse effects were noted in rat offspring at exposures estimated at 14 times the human exposure to bimatoprost solution 0.03%.

Due to the potential risks observed in animal studies, ZOLYMBUS should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. The background risk of major birth defects and miscarriage in the general U.S. population is estimated to be 2 to 4% and 15 to 20%, respectively, for clinically recognized pregnancies. Given that animal reproductive studies may not always predict human response, healthcare professionals should carefully consider these factors when prescribing ZOLYMBUS to pregnant patients.

Lactation

It is not known whether topical ocular treatment with ZOLYMBUS 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 of 1 mg/kg, which is 970 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 ZOLYMBUS and any potential adverse effects on the breastfed child from ZOLYMBUS.

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

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 and consider general principles of management in cases of suspected overdose.

Healthcare providers should be aware that the clinical presentation of an overdose may vary depending on the substance involved and the individual patient’s characteristics. Symptoms may include, but are not limited to, altered mental status, cardiovascular instability, respiratory distress, and gastrointestinal disturbances.

In the event of an overdose, it is recommended that healthcare professionals take the following actions:

1. Assessment: Conduct a thorough assessment of the patient, including vital signs and a detailed history of the substance involved, dosage, and time of ingestion.

2. Supportive Care: Initiate supportive care measures as necessary, which may include airway management, oxygen supplementation, intravenous fluids, and monitoring of vital signs.

3. Decontamination: If appropriate and within a reasonable time frame, consider decontamination methods such as activated charcoal, provided the patient is alert and able to protect their airway.

4. Consultation: Engage with a poison control center or toxicology expert for guidance on specific antidotes or additional management strategies tailored to the substance involved.

5. Monitoring: Continuous monitoring of the patient is crucial to identify any evolving symptoms or complications that may arise during the course of treatment.

In summary, while specific overdosage information is not available, healthcare professionals should employ a systematic approach to assessment and management, ensuring patient safety and optimal care outcomes.

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 estimated human systemic exposure to bimatoprost solution 0.03%, 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, which is at least 103 times the recommended human exposure to bimatoprost solution 0.03%, based on blood AUC levels.

Postmarketing Experience

Postmarketing experience with bimatoprost medicines, including ZOLYMBUS, has identified several adverse events reported through voluntary reporting and surveillance programs. The following side effects have been documented in patients using these medications topically in the eye:

Asthma-like symptoms, dizziness, and shortness of breath (dyspnea) have been noted. Ocular effects include eye discharge (eye mucus), inflammation of the eye (eye edema), and signs and symptoms of eye allergy, as well as allergic inflammation of the skin (allergic dermatitis). Other reported systemic effects include headache and hypertension.

Additionally, changes in the periorbital area have been observed, such as loss of fat leading to skin tightness, deepening of the eyelid crease (eyelid sulcus), drooping eyelid (eyelid ptosis), and sunken eye (enophthalmos). Eyelid retraction and sensitivity to light (photophobia) have also been reported.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use, to ensure they understand the proper use of ZOLYMBUS (bimatoprost ophthalmic gel).

It is important to inform patients about the potential for increased brown pigmentation of the iris, which may be permanent. Additionally, patients should be made aware of the possibility of eyelid skin darkening, which may be reversible after discontinuation of ZOLYMBUS.

Patients should also be informed that changes in eyelashes and vellus hair in the treated eye may occur during treatment. These changes can lead to differences between the eyes in terms of length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Typically, eyelash changes are reversible upon discontinuation of treatment.

Patients should be advised that ZOLYMBUS is a sterile gel that does not contain a preservative. The drops are supplied in a single-dose container, and the gel from one container should be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the single-dose container is opened, patients should discard the open container and any remaining contents immediately after use. A new single-dose container should be opened for each application of ZOLYMBUS.

Patients should be instructed to seek their physician’s advice regarding the continued use of ZOLYMBUS if they develop an intercurrent ocular condition, such as trauma or infection, undergo ocular surgery, or experience any ocular reactions, particularly conjunctivitis and eyelid reactions.

It is essential to advise patients to remove contact lenses prior to the administration of ZOLYMBUS. Lenses may be reinserted 15 minutes after the administration of the gel.

Patients should also be informed that if they are using more than one topical ophthalmic drug, the medications should be administered at least five (5) minutes apart to ensure proper absorption and effectiveness.

Finally, patients should be advised that if they miss a dose, they should continue with the next dose as scheduled without doubling up.

Storage and Handling

The product is supplied in single-dose containers, which are packaged in a protective foil pouch. It is essential to store the product at a temperature range of 20°C to 30°C (68°F to 86°F) and to protect it from light. The product should remain in its original pouch until use.

Once the pouch is opened, the single-dose containers may be stored within the opened foil pouch for a maximum of 14 days at the same temperature range of 20°C to 30°C (68°F to 86°F). Patients are advised to note the date of opening in the designated space on the pouch. Any unused containers must be discarded 14 days after the pouch has been opened. Additionally, any unused portion of the single-dose container should also be discarded.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)