Besivance (Page 2 of 2)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to determine the carcinogenic potential of besifloxacin have not been performed.

No in vitro mutagenic activity of besifloxacin was observed in an Ames test (up to 3.33 mcg/plate) on bacterial tester strains Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA. However, it was mutagenic in S. typhimurium strain TA102 and E. coli strain WP2(pKM101). Positive responses in these strains have been observed with other quinolones and are likely related to topoisomerase inhibition.

Besifloxacin induced chromosomal aberrations in CHO cells in vitro and it was positive in an in vivo mouse micronucleus assay at oral doses ≥ 1500 mg/kg. Besifloxacin did not induce unscheduled DNA synthesis in hepatocytes cultured from rats given the test compound up to 2,000 mg/ kg by the oral route. In a fertility and early embryonic development study in rats, besifloxacin did not impair the fertility of male or female rats at oral doses of up to 500 mg/kg/day. This is over 10,000 times higher than the recommended total daily human ophthalmic dose.

14 CLINICAL STUDIES

In a randomized, double-masked, vehicle controlled, multicenter clinical trial, in which patients 1-98 years of age were dosed 3 times a day for 5 days, Besivance™ was superior to its vehicle in patients with bacterial conjunctivitis. Clinical resolution was achieved in 45% (90/198) for the Besivance™ treated group versus 33% (63/191) for the vehicle treated group (difference 12%, 95% CI 3% — 22%). Microbiological outcomes demonstrated a statistically significant eradication rate for causative pathogens of 91% (181/198) for the Besivance™ treated group versus 60% (114/191) for the vehicle treated group (difference 31%, 95% CI 23% — 40%). Microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

16 HOW SUPPLIED/STORAGE AND HANDLING

Besivance™ (besifloxacin ophthalmic suspension) 0.6%, is supplied as a sterile ophthalmic suspension in a white low density polyethylene (LDPE) bottle with a controlled dropper tip and tan polypropylene cap. Tamper evidence is provided with a shrink band around the cap and neck area of the package.

5 mL in 7.5 mL bottle

NDC 54868-6282-0


Storage:
Store at 15°- 25°C (59° — 77°F). Protect from Light.

Invert closed bottle and shake once before use.

Rx Only

17 PATIENT COUNSELING INFORMATION

Patients should be advised to avoid contaminating the applicator tip with material from the eye, fingers or other source.

Although Besivance™ is not intended to be administered systemically, quinolones administered systemically have been associated with hypersensitivity reactions, even following a single dose. Patients should be advised to discontinue use immediately and contact their physician at the first sign of a rash or allergic reaction.

Patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Besivance™ or other antibacterial drugs in the future.

Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with Besivance™.

Patients should be advised to thoroughly wash hands prior to using Besivance™.

Patients should be instructed to invert closed bottle (upside down) and shake once before each use. Remove cap with bottle still in the inverted position. Tilt head back, and with bottle inverted, gently squeeze bottle to instill one drop into the affected eye(s).


MANUFACTURER INFORMATION

Manufactured by: Bausch & Lomb Incorporated
Tampa, Florida 33637
©Bausch & Lomb Incorporated

U.S. Patent No. 6,685,958
U.S. Patent No. 6,699,492
U.S. Patent No. 5,447,926

Besivance™ is a trademark of Bausch & Lomb Incorporated

*DuraSite is a trademark of InSite Vision Incorporated

April 2009

Relabeling and Repackaging by:
Physicians Total Care, Inc.
Tulsa, OK 74146

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

NDC 54868-6282-0

Besivance -- besifloxacin ophthalmic suspension, 0.6% label
(click image for full-size original)

Besivance

besifloxacin ophthalmic suspension, 0.6%

Rx only
Sterile

FOR OPHTHALMIC USE ONLY.

5 mL

BESIVANCE
besifloxacin suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-6282(NDC:24208-446)
Route of Administration OPHTHALMIC DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BESIFLOXACIN (BESIFLOXACIN) BESIFLOXACIN 6 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
BENZALKONIUM CHLORIDE
POLYCARBOPHIL
MANNITOL
POLOXAMER 407
SODIUM CHLORIDE
EDETATE DISODIUM
SODIUM HYDROXIDE
WATER
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54868-6282-0 1 BOTTLE, DROPPER (BOTTLE) in 1 CARTON contains a BOTTLE, DROPPER
1 5 mL in 1 BOTTLE, DROPPER This package is contained within the CARTON (54868-6282-0)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022308 07/13/2011
Labeler — Physicians Total Care, Inc. (194123980)
Establishment
Name Address ID/FEI Operations
Physicians Total Care, Inc. 194123980 relabel, repack

Revised: 04/2009 Physicians Total Care, Inc.

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