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DEXTENZA(dexamethasone ophthalmic insert)0.4mg,for intracanalicular(四)
l-shaped, resorbable, sterile insert forintracanalicular use. DEXTENZA contains 0.4 mg dexamethasone in a polyethylene glycol (PEG) based hydrogel conjugated withfluorescein. DEXTENZA does not contain an antimicrobial preservative. The active ingredient is represented by the chemicalstructure:
The chemical name for dexamethasone is 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. It has a molecularformula of C22H29FO5 and a molecular weight of 392.47 g/mol. Dexamethasone is a crystalline powder.
Each DEXTENZA contains: Active ingredients: 0.4 mg dexamethasone. Inactive ingredients: 4-arm polyethylene glycol (PEG) Nhydroxysuccinimidylglutarate (20K), trilysine acetate, N-hydroxysuccinimide-fluorescein, sodium phosphate dibasic, sodiumphosphate monobasic, water for injection.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Dexamethasone, a corticosteroid, has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting indecreased edema, fibrin deposition, capillary leakage and migration of inflammatory cells.
12.3 Pharmacokinetics
Plasma samples were obtained from 16 healthy volunteers prior to insertion of DEXTENZA and on Day 1 (at 1, 2, 4, 8, 16 hours), 2(24 hours), 4, 8, 15, 22 and 29 following the insertion of DEXTENZA.
Plasma concentrations of dexamethasone were detectable (above 50 pg/mL, the lower limit of quantification of the assay) in 11% ofsamples (21 of 189), and ranged from 0.05 ng/mL to 0.81 ng/mL.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies in animals have been conducted to determine whether DEXTENZA has the potential for carcinogenesis.
Dexamethasone was not mutagenic in the Ames/Salmonella assay, both with and without metabolic activation. Dexamethasone wasgenotoxic in two in vitro assays using human lymphocytes (chromosomal aberration assay and sister chromatid exchange assay) andwas genotoxic in two mouse in vivo assays (micronucleus assay and sister chromatid exchange assay).
Fertility studies have not been conducted in animals using DEXTENZA.
14 CLINICAL STUDIES
In two randomized, multicenter, double-masked, parallel group, vehicle-controlled trials, patients received DEXTENZA or its vehicleimmediately upon completion of cataract surgery. In both trials, DEXTENZA had a higher incidence of subjects who were pain free atall post-operative days. Results are shown in Table 1.
Table 1: Percentage of Pain-Free Patients
Study 1 Study 2
Dextenza
(N=164)
Vehicle
(N=83)
Dextenza
(N=161)
Vehicle
(N=80)
Visit n (%) n (%) Difference (95% CI) n (%) n (%) Difference (95% CI)
Day 2 116 (71%) 38 (46%) 25% (12%, 38%) 105 (65%) 32 (40%) 25% (12%, 38%)
Day 4 127 (77%) 43 (52%) 26% (13%, 38%) 117 (73%) 39 (49%) 24% (11%, 37%)
Day 8 131 (80%) 36 (43%) 37% (24%, 49%) 124 (77%) 47 (59%) 18% ( 6%, 31%)
16 HOW SUPPLIED/STORAGE AND HANDLING
DEXTENZA is supplied sterile in a foam carrier within a foil laminate pouch containing:
NDC 70382-204-10 Carton containing 10 pouches (10 inserts)
NDC 70382-204-01 Carton containing 1 pouch (1 insert)
Do not use if pouch has been damaged or broken.
DEXTENZA is intended for single dose only.
Storage: Store refrigerated, between 2°C and 8°C (36˚F and 46˚F). Do not freeze. Protect from light, keep in package until use.
17 PATIENT COUNSELING INFORMATION
Advise patients to consul |
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