Description for Zolymbus
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 is 415.58 and molecular formula is C25H37NO4. Its chemical structure is:
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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.
Warnings for Zolymbus
Included as part of the PRECAUTIONS section.
Precautions for Zolymbus
Pigmentation
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.
Eyelash Changes
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.
Intraocular Inflammation
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
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 Lens Use
Contact lenses should be removed prior to the administration of ZOLYMBUS and may be reinserted 15 minutes after administration.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
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).
Patient Information for Zolymbus
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.
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. ©2024, Laboratoires Théa.
All rights reserved. ZOLYMBUS is a trademark of Laboratoires Théa.
OVERDOSAGE
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/m2 is 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.
Contraindications for Zolymbus
ZOLYMBUS is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [see Adverse Reactions (6.2)].
Clinical Pharmacology for Zolymbus
Mechanism of Action
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.
Pharmacokinetics
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 Cmax values 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
MetabolismBimatoprost 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.
ExcretionFollowing 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.
Patient Information for Zolymbus
ZOLYMBUS (zoh LIM bus)
(bimatoprost ophthalmic gel) 0.01%
for topical ophthalmic use
Read this Instructions for Use before using your ZOLYMBUS and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.
Important Information You Need to Know Before Using ZOLYMBUS:
- ZOLYMBUS is for use in the eye. Do not swallow ZOLYMBUS.
- ZOLYMBUS single-dose containers are packaged in a foil pouch.
- Do not use the ZOLYMBUS single-dose containers if the foil pouch is already opened when you receive it.
- Write down the date you open the foil pouch in the space provided on the pouch.
- Use 1 drop of ZOLYMBUS in your affected eye or eyes each evening.
- If you use other eye medicines dropped into the eye (topically applied ophthalmic medicines), use the medicines at least 5 minutes before or 5 minutes after the use of ZOLYMBUS.
- Do not open the ZOLYMBUS single-dose container until you are ready to use the eye drops.
Please follow these instructions to use ZOLYMBUS:
| Step 1. | Wash your hands and sit or stand comfortably. | |
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| Step 6. | Place the tip of the single-dose container close to, but not touching your eye. |  |
| Step 7. | Squeeze the single-dose container gently so that only 1 drop goes into your eye, then release the lower eyelid. If the drop misses your eye completely, try again. |
- If your healthcare provider has told you to use ZOLYMBUS drops in both eyes, repeat Step 5 to Step 7 for your other eye.
- Each single-dose container contains enough drops for both eyes.
- Throw away the single-dose container after use. Do not keep it to use it again even if there is product left in the container. To lessen the chance of infection, a new single-dose container must be opened each time you are ready to use ZOLYMBUS.
- Place the folded foil pouch back in the carton. The unopened single-dose containers must be used within 14 days after opening the foil pouch. Protect from light.
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.
This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.
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