Zolymbus Gel
FDA Label NDC 82584-010

ZOLYMBUS™ is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

The recommended dosage is one drop in the affected eye(s) once daily in the evening. ZOLYMBUS should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may lessen the IOP lowering effect.

Reduction of the IOP starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

ZOLYMBUS may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

If one dose is missed, treatment should continue with the next dose as normal.

The gel from one single-dose container is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the single-dose container is opened, discard the open container and the remaining contents immediately after administration.

Ophthalmic gel: 0.01% bimatoprost as a colorless, opalescent gel in a single-dose container.

ZOLYMBUS is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [see Adverse Reactions (6.2)] .

Bimatoprost has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known.

Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with ZOLYMBUS can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

ZOLYMBUS may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.

Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. ZOLYMBUS should be used with caution in patients with active intraocular inflammation (e.g., iritis/uveitis) because inflammation may be exacerbated.

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic products. ZOLYMBUS should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

Contact lenses should be removed prior to the administration of ZOLYMBUS and may be reinserted 15 minutes after administration.

The following adverse reactions are described elsewhere in the labeling:

• Pigmentation including blepharal pigmentation and iris hyperpigmentation [see Warnings and Precautions (5.1)]
• Eyelash Changes [see Warnings and Precautions (5.2)]
• Intraocular Inflammation [see Warnings and Precautions (5.3)]
• Macular Edema [see Warnings and Precautions (5.4)]
• Hypersensitivity [see Contraindications (4)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In the two clinical trials conducted with ZOLYMBUS (bimatoprost ophthalmic gel) 0.01% comparing it to preserved bimatoprost ophthalmic solution 0.01%, the most frequently reported ocular adverse reactions were conjunctival hyperemia (14%), eye irritation (11%), eye pruritus (9%) and foreign body sensation in eyes (8%). Other adverse drug reactions (reported in 1% to 6% of patients) with ZOLYMBUS in the studies included dry eye, abnormal sensation in eye, lacrimation increased, eye pain, and vision blurred.

The following adverse reactions have been identified during post-approval use of topical bimatoprost products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to bimatoprost, or a combination of these factors include: asthma-like symptoms, dizziness, dry eye, dyspnea, eye discharge, eye edema, foreign body sensation, headache, hypersensitivity including signs and symptoms of eye allergy and allergic dermatitis, hypertension, lacrimation increased, periorbital and lid changes associated with periorbital fat atrophy leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos, and eyelid retraction; and photophobia.

Risk Summary
There are no adequate and well-controlled studies of ZOLYMBUS (bimatoprost ophthalmic gel) 0.01% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost post-marketing experience.

In embryofetal developmental studies, administration of bimatoprost to pregnant mice and rats during organogenesis, resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure to bimatoprost solution 0.03% dosed bilaterally once daily (based on blood area under the curve [AUC] levels). These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure to bimatoprost 0.03% dosed bilaterally once daily (based on blood AUC levels).

In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily (based on blood AUC levels). No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure to bimatoprost solution 0.03% dosed bilaterally once daily (based on blood AUC levels).

Because animal reproductive studies are not always predictive of human response 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 for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data
Animal Data
In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC). No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day.

In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily based on AUC).

In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC. The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, based on AUC).

Risk Summary
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 breast milk of lactating rats at an intravenous dose (i.e., 1 mg/kg) 970 times the recommended human ophthalmic dose (on a mg/m ²basis), however, no animal data is available at clinically relevant doses.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOLYMBUS and any potential adverse effects on the breastfed child from ZOLYMBUS.

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

No information is available on overdosage in humans. If overdose with ZOLYMBUS occurs, treatment should be symptomatic.

In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m ²is at least 90 times higher than the accidental dose of the entire content of a pack of ZOLYMBUS (30 x 0.3 g single-dose containers; 9 g) for a 10 kg child.

ZOLYMBUS contains bimatoprost, a synthetic prostamide analog with ocular hypotensive activity, for topical ophthalmic use. The chemical name is 5-Heptenamide, 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2- [(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-N-ethyl, (5Z)-, with the molecular weight 415.58 and molecular formula is C ₂₅H ₃₇NO ₄. Its chemical structure is:

Chemical Structure (Zolymbus 01)

Bimatoprost is a crystalline powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. ZOLYMBUS is a sterile, colorless, opalescent ophthalmic gel with an osmolality of approximately 300 mOsmol/kg.

Each container contains 0.03 mg of bimatoprost and the following inactive ingredients: carbomer, polyethylene glycol, sodium acetate trihydrate, sorbitol, sodium hydroxide and water for injection with a pH range from 6.9 to 7.9.

ZOLYMBUS does not contain a preservative.

Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

Absorption
After one drop of bimatoprost ophthalmic gel 0.01% was administered once daily to both eyes of 20 healthy participants for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (5 pg/mL) in most subjects within 30 minutes after dosing. Mean C _maxvalues were similar on days 1 and 14 at 0.021 ng/mL and 0.028 ng/mL, respectively, indicating that a steady state was reached. There was no significant systemic drug accumulation over time.

Distribution
Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma.

Elimination
Metabolism
Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.

Excretion
Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

Carcinogenesis
Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses up to 2 mg/kg/day and 1 mg/kg/day, respectively (192 and 291 times the estimated human systemic exposure to bimatoprost solution 0.03% dosed bilaterally once daily, respectively, based on blood AUC levels).

Mutagenesis
Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.

Impairment of Fertility
Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure to bimatoprost solution 0.03% dosed bilaterally once daily based on blood AUC levels).

In a 12-week clinical trial of patients with open-angle glaucoma or ocular hypertension with a mean baseline IOP of 23 to 24 mmHg, the IOP-lowering effect of ZOLYMBUS once daily (in the evening) was non-inferior to preserved bimatoprost ophthalmic solution 0.01%.

ZOLYMBUS (bimatoprost ophthalmic gel) 0.01% is supplied as a colorless, opalescent gel in blow-fill-seal single-dose container packaged in foil pouches.
10 single-dose containers per pouch.

NDC 82584-010-30; Carton of 30 single-dose containers

Storage: 

Store at 20°C to 30°C (68°F to 86°F).

Protect from light. Store in the original pouch. After the pouch is opened, the single-dose containers may be stored in the opened foil pouch for up to 14 days at 20°C to 30°C (68°F to 86°F).
Patient should be advised to write down the date the foil pouch is opened in the space provided on the pouch.
Discard any unused containers 14 days after first opening the pouch.

Single-dose container. Discard unused portion.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Potential for Pigmentation
Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Also inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of ZOLYMBUS (bimatoprost ophthalmic gel).

Potential for Eyelash Changes
Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with ZOLYMBUS. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment.

Handling the Container
Advise patients that ZOLYMBUS is a sterile gel that does not contain a preservative. The drops are supplied in a single-dose container. The gel from one single-dose container is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the single-dose container is opened, discard the open container and the remaining contents immediately after administration. Open a new single-dose container every time you use ZOLYMBUS.

When to Seek Physician Advice
Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of ZOLYMBUS.

Contact Lens Use
Advise patients that contact lenses should be removed prior to administration of ZOLYMBUS. Lenses may be reinserted 15 minutes following administration of ZOLYMBUS.

Use with Other Ophthalmic Drugs
Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

If a Dose is Missed
Advise patients that if one dose is missed, treatment should continue with the next dose as normal.

Manufactured for: Thea Pharma Inc.Waltham, MA 02451.
U.S. Patent N°. 10,314,780. ©2025, Laboratoires Théa. All rights reserved. ZOLYMBUS™ is a trademark of Laboratoires Théa.

NDC 82584-010-30

ZOLYMBUS™

(bimatoprost ophthalmic gel)

0.01%

Contains:

Active:bimatoprost 0.1 mg/g.

Inactive ingredients:carbomer, sodium acetate 

trihydrate, polyethylene glycol, sodium hydroxide (for

pH adjustment), sorbitol and water for injection.

Recommended Dosage:one drop in the a­ffected eye(s) 

once daily in the evening.

Single-dose container. Discard unused portion.

Storage:Store at 20°C to 30°C (68°F to 86°F).

See Prescribing Information.

30 single-dose containers: 3 pouches x 10 single-dose

containers (0.3 g each).

Store in the original pouch. After the pouch is opened, the 

single-dose containers may be stored in the opened foil

pouch for up to 14 days.

Discard any unused containers 14 days after first 

opening the pouch.

Manufactured for Thea Pharma Inc.

Waltham, MA 02451

U.S. Patent N°. 10,314,780. ©2024, Laboratoires Théa.

All rights reserved. ZOLYMBUS™ is a trademark of 

Laboratoires Théa.

Théa Logo

Carton (Zolymbus 06)

NDC 82584-010-81

Recommended Dosage:one drop in the affected eye(s) once daily in the evening.
Single-dose container. Discard unused portion.
See carton for inactive ingredients.
Storage:Store at 20°C to 30°C (68°F to 86°F).
Protect from light. Store in the original pouch. After the pouch is opened, the single-use containers may be stored in the
opened foil pouch for up to 14 days.
Discard any unused containers 14 days after first opening the pouch.
Write down the date you open the pouch.                                  __ / __ / __

ZOLYMBUS™
(bimatoprost ophthalmic gel) 0.01%
For Topical Ophthalmic Use
10 single-dose containers (0.3 g each)
Rx only
Sterile - Contains no preservatives
Manufactured for Thea Pharma Inc.
Waltham, MA 02451

Théa Logo

Lot:

EXP:

Pouch (Zolymbus 07)