inetics
The pharmacokinetic exposure to loteprednol etabonate following topical bilateral ocular administration of onedrop three times daily of LOTEMAX® SM for up to two weeks (Day 15) was eva luated in 18 healthy adultsubjects. Plasma concentrations of loteprednol etabonate were analyzed using a validated LC/MS/MS methodand the lower limit of quantitation for loteprednol etabonate was 0.05 ng/mL. The mean (± SD) Cmax values forloteprednol etabonate in plasma were 0.13 (± 0.06) ng/mL on Day 1 after a single dose and 0.16 (± 0.06) ng/mLafter the last dose on Day 15 of the study. The mean (± SD) AUCt values for loteprednol etabonate in plasmawere 0.15 (± 0.15) hr•ng/mL on Day 1 after a single dose and 0.35 (± 0.32) hr•ng/mL after the last dose on Day15.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been conducted to eva luate the carcinogenic potential of loteprednoletabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, orin the chromosomal aberration test in human lymphocytes, or in vivo in the mouse micronucleus assay.
Treatment of male and female rats with 25 mg/kg/day of loteprednol etabonate (533 times the RHOD based onbody surface area, assuming 100% absorption) prior to and during mating caused preimplantation loss anddecreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (106 timesthe RHOD).
14 CLINICAL STUDIES
In two randomized, multicenter, double-masked, parallel group, vehicle-controlled trials in patients whounderwent cataract extraction with intraocular lens implantation, LOTEMAX® SM administered three timesdaily to the affected eye beginning the day after cataract surgery was more effective compared to its vehicle inresolving anterior chamber inflammation and pain following surgery. In these studies, LOTEMAX® SM hadstatistically significantly higher rates of subjects with complete clearing of anterior chamber cells and ofsubjects who were pain free at post-operative Day 8 compared to vehicle. Results are shown in the followingtable.
Proportion of Subjects with Complete Clearing of Anterior Chamber Cells and Proportion of Subjectswith Complete Resolution of Pain at Post-Operative Day 8.
Outcome
Study 1 Study 2
LOTEMAX® SM
N=171
n (%)
Vehicle
N=172
n (%)
Difference
(95 CI)
%
LOTEMAX® SM
N=200
n (%)
Vehicle
N=199
n (%)
Difference
(95% CI)
%
Cells 49
(29%)
16
(9%)
19 (11,
27)
61
(31%)
40
(20%) 10 (2, 19)
Pain 125
(73%)
82
(48%)
25 (15,
35)
151
(76%)
99
(50%) 26 (17, 35)
16 HOW SUPPLIED/STORAGE AND HANDLING
LOTEMAX® SM (loteprednol etabonate ophthalmic gel) 0.38% is a sterile ophthalmic submicron gel suppliedin a white low-density polyethylene plastic bottle with a white controlled drop tip and a pink polypropylene capin the following size: 5 g in a 10 mL bottle (NDC 24208-507-07)
Use only if imprinted neckband is intact.
Storage: Store upright at 15º to 25ºC (59º to 77ºF). After opening, LOTEMAX® SM can be used until theexpiration date on the bottle.
17 PATIENT COUNSELING INFORMATION
Administration
Invert closed bottle and shake once to fill tip before instilling drops.
Risk of Contamination
Advise patients not to allow the dropper tip to touch any surface, as t |
