Zylet: Package Insert and Label Information (Page 2 of 2)

12.3 Pharmacokinetics

In a controlled clinical study of ocular penetration, the levels of loteprednol etabonate in the aqueous humor were found to be comparable between LOTEMAX^® and ZYLET treatment groups.

Results from a bioavailability study in normal volunteers established that plasma levels of loteprednol etabonate and Δ¹ cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times.

The results were obtained following the ocular administration of one drop in each eye of 0.5% loteprednol etabonate ophthalmic suspension 8 times daily for 2 days or 4 times daily for 42 days. This study suggests that limited (<1 ng/mL) systemic absorption occurs with 0.5% loteprednol etabonate.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate or tobramycin.

Mutagenesis

Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma TK assay, a chromosome aberration test in human lymphocytes, or in an in vivo mouse micronucleus assay.

Impairment of Fertility

Oral treatment of female and male rats with 25 mg/kg/day of loteprednol etabonate (67 times the RHOD based on body surface area, assuming 100% absorption) prior to and during mating caused preimplantation loss and decreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (13 times the RHOD). Subcutaneous administration of male and female rats with tobramycin did not affect mating behavior or cause impairment of fertility at 100 mg/kg/day (450 times the RHOD based on body surface area, assuming 100% absorption).

16 HOW SUPPLIED/STORAGE AND HANDLING

ZYLET (loteprednol etabonate and tobramycin ophthalmic suspension) 0.5%/0.3% is supplied in a white low density polyethylene plastic bottle with a white controlled drop tip and a white polypropylene cap in the following sizes:

NDC 24208-358-05 5 mL fill in a 7.5 mL bottle

NDC 24208-358-10 10 mL fill in a 10 mL bottle

USE ONLY IF IMPRINTED NECKBAND IS INTACT.

Storage: Store upright at 15ºC to 25ºC (59ºF to 77ºF). PROTECT FROM FREEZING. SHAKE VIGOROUSLY BEFORE USING. After opening, ZYLET can be used until the expiration date on the bottle.

17 PATIENT COUNSELING INFORMATION

Risk of Contamination

This product is sterile when packaged. Advise patients not to allow the dropper tip to touch any surface, as this may contaminate the suspension.

Risk of Secondary Infection

Advise patients to consult a physician if pain develops, redness, itching or inflammation becomes aggravated.

Contact Lens Wear

As with all ophthalmic preparations containing benzalkonium chloride, advise patients not to wear soft contact lenses when using ZYLET.

Distributed by:
Bausch & Lomb Americas Inc.
Bridgewater, NJ 08807 USA
Manufactured by:
Bausch & Lomb Incorporated
Tampa, FL 33637 USA
ZYLET and LOTEMAX are trademarks of Bausch & Lomb Incorporated or its affiliates.

© 2022 Bausch & Lomb Incorporated or its affiliates

9007709 (FOLDED)
9004409 (FLAT)

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

NDC 24208-358-10
BAUSCH + LOMB
Zylet _®
( loteprednol etabonate
and tobramycin ophthalmic
suspension) 0.5%/0.3%
Sterile

FOR TOPICAL
OPHTHALMIC
USE ONLY
Rx only

10 mL

9528905AB35809

ZYLET loteprednol etabonate and tobramycin suspension/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:24208-358 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LOTEPREDNOL ETABONATE (LOTEPREDNOL) LOTEPREDNOL ETABONATE 5 mg in 1 mL TOBRAMYCIN (TOBRAMYCIN) TOBRAMYCIN 3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength GLYCERIN POVIDONE, UNSPECIFIED WATER TYLOXAPOL BENZALKONIUM CHLORIDE SULFURIC ACID SODIUM HYDROXIDE EDETATE DISODIUM

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:24208-358-10 1 BOTTLE, DROPPER in 1 CARTON contains a BOTTLE, DROPPER 1 10 mL in 1 BOTTLE, DROPPER This package is contained within the CARTON (24208-358-10) 2 NDC:24208-358-05 1 BOTTLE, DROPPER in 1 CARTON contains a BOTTLE, DROPPER 2 5 mL in 1 BOTTLE, DROPPER This package is contained within the CARTON (24208-358-05) 3 NDC:24208-358-01 1 BOTTLE, DROPPER in 1 CARTON contains a BOTTLE, DROPPER 3 1 mL in 1 BOTTLE, DROPPER This package is contained within the CARTON (24208-358-01)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050804 12/14/2004

Labeler — Bausch & Lomb Incorporated (196603781)

Establishment
Name	Address	ID/FEI	Operations
Bausch & Lomb Incoporated		079587625	MANUFACTURE (24208-358)

Revised: 04/2022 Bausch & Lomb Incorporated