DARIFENACIN tablet, film coated, extended release

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

DARIFENACIN HYDROBROMIDE (UNII: CR02EYQ8GV) (DARIFENACIN - UNII:APG9819VLM)

Διαθέσιμο από:

Aurobindo Pharma Limited

INN (Διεθνής Όνομα):

DARIFENACIN HYDROBROMIDE

Σύνθεση:

DARIFENACIN 7.5 mg

Οδός χορήγησης:

ORAL

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

Darifenacin extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Darifenacin extended-release tablets are contraindicated in patients with, or at risk for, the following conditions: - urinary retention - gastric retention, or - uncontrolled narrow-angle glaucoma. Risk Summary There are no available data on darifenacin extended-release tablets use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal studies, darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 and 28 times the maximum recommended human dose (MRHD) of 15 mg, respectively. Effects on embryofetal development were observed following administration of darifenacin during pregnancy (dilated ureter and/or kidney pelvis in rabbits at about 9 times the MRHD, post-implantation loss in rabbits at about 28 times, and delayed ossification in rats at about 59 times) and during pregnancy and lactation (developmental delays in rats at about 17 times the MRHD), which was associated with maternal toxicity (see Data). Dystocia was observed in rat dams at about 17 times the MRHD. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryofetal development studies were conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) and rabbits (0, 3, 10, and 30 mg/kg/day) during the period of organogenesis (gestation days 6 to 17 in the rat and gestation days 6 to 18 in the rabbit). Darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 times and 28 times, respectively (doses up to 50 and 30 mg/kg/day, respectively) the maximum recommended human dose [MRHD] of 15 mg. At approximately 59 times the MRHD in pregnant rats, there was a delay in the ossification of the sacral and caudal vertebrae (associated with a decrease in maternal and pup body weight gains) which was not observed at an exposure approximately 13 times the AUC at the MRHD. At five times the AUC (3 mg/kg/day), there were no effects on dams or pups.   In pregnant rabbits, an exposure of darifenacin approximately 28 times the AUC at the MRHD of 15 mg (30 mg/kg/day) was shown to increase post-implantation loss (associated with decreased maternal body weight gain), with a no effect level at 10 mg/kg/day (9 times the AUC at the MRHD). Dilated ureter and/or kidney pelvis was also observed in offspring at this highest dose along with urinary bladder dilation consistent with the pharmacological action of darifenacin, with one case observed at the mid dose of 10 mg/kg/day (9 times the MRHD ). No effect was observed at the lowest dose of 3 mg/kg/day ((approximately 2.8 times the AUC at the MRHD). A pre- and post-natal development study was conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) throughout gestation and lactation. Decreased body weight gain and dystocia were observed in dams at 10 mg/kg/day (approximately 17 times the MRHD) and above. Slight developmental delays (surface righting reflex, incisor eruption, eyelid opening, vaginal opening, preputial separation) were observed in pups at these doses. At 5 times the AUC at the MRHD (3 mg/kg/day), there were no effects on dams or pups. Risk Summary There are no data on the presence of darifenacin in human milk, the effects on the breastfed infant, or the effects of darifenacin extended-release tablets on milk production. Darifenacin is present in rat milk [see Data]. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for darifenacin and any potential adverse effects on the breastfed child from darifenacin or from the underlying maternal conditions. Data After a single oral dose of 14 C radiolabeled darifenacin to lactating rats, darifenacin was detected in maternal milk. The safety and effectiveness of darifenacin extended-release tablets in pediatric patients have not been established. In the fixed-dose, placebo-controlled, clinical studies, 30% of patients treated with darifenacin extended-release tablets were over 65 years of age. No overall differences in safety or efficacy were observed between patients over 65 years (n = 207) and younger patients less than 65 years (n = 464). No dose adjustment is recommended for elderly patients [see Clinical Pharmacology (12.3) and Clinical Studies (14)] . Subjects with severe hepatic impairment (Child-Pugh C) have not been studied, therefore darifenacin extended-release tablets are not recommended for use in these patients [see Dosage and Administration (2) and Warnings and Precautions (5.6)] . The daily dose of darifenacin extended-release tablets should not exceed 7.5 mg once daily for patients with moderate hepatic impairment (Child-Pugh B) [see Dosage and Administration (2) and Warnings and Precautions (5.6)] . After adjusting for plasma protein binding, unbound darifenacin exposure was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment than subjects with normal hepatic function. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A). A study of subjects with varying degrees of renal impairment (creatinine clearance between 10 and 136 mL/min) demonstrated no clear relationship between renal function and darifenacin clearance. No dose adjustment is recommended for patients with renal impairment [see Clinical Pharmacology (12.3)] . No dose adjustment is recommended based on gender [see Clinical Pharmacology (12.3) and Clinical Studies (14)] .

Περίληψη προϊόντος:

Darifenacin Extended-Release Tablets, 7.5 mg are white colored, round convex, film-coated tablets debossed with “Z” on one side and “22” on other side.             Bottles of 30                                                   NDC 65862-861-30             Bottles of 90                                                   NDC 65862-861-90             Bottles of 500                                                 NDC 65862-861-05             Bottles of 1,000                                              NDC 65862-861-99 Darifenacin Extended-Release Tablets, 15 mg are light peach colored, round convex, film-coated tablets debossed with “Z” on one side and “23” on other side.             Bottles of 30                                                   NDC 65862-862-30             Bottles of 90                                                   NDC 65862-862-90             Bottles of 500                                                 NDC 65862-862-05             Bottles of 1,000                                              NDC 65862-862-99 Storage Store at 20° to 25°C (68° to 77° F) [see USP Controlled Room Temperature]. Protect from light. Keep this and all drugs out of the reach of children.

Καθεστώς αδειοδότησης:

Abbreviated New Drug Application

Αρχείο Π.Χ.Π.

DARIFENACIN - DARIFENACIN TABLET, FILM COATED, EXTENDED RELEASE
AUROBINDO PHARMA LIMITED
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DARIFENACIN EXTENDED-
RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR DARIFENACIN
EXTENDED-RELEASE TABLETS.
DARIFENACIN EXTENDED-RELEASE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2004
INDICATIONS AND USAGE
Darifenacin extended-release tablets are a muscarinic antagonist
indicated for the treatment of overactive
bladder with symptoms of urge urinary incontinence, urgency and
frequency (1)
DOSAGE AND ADMINISTRATION
The recommended starting dose of darifenacin extended-release tablets
is 7.5 mg once daily. Based upon
individual response, the dose may be increased to 15 mg once daily, as
early as two weeks after starting
therapy (2)
The daily dose of darifenacin extended-release tablets should not
exceed 7.5 mg in the following patients:
Patients with moderate hepatic impairment (Child-Pugh B) (2, 8.6)
Patients taking potent CYP3A4 inhibitors (2, 7.1)
Darifenacin extended-release tablets are not recommended for use in
patients with severe hepatic
impairment (Child-Pugh C) (2, 8.6)
Darifenacin extended-release tablets may be taken with or without
food. The tablet should be swallowed
whole with water and not chewed, divided or crushed (2)
DOSAGE FORMS AND STRENGTHS
Extended-release tablets 7.5 mg and 15 mg (3)
CONTRAINDICATIONS
Darifenacin extended-release tablets are contraindicated in patients
with, or at risk for, the following
conditions (4):
urinary retention,
gastric retention, or
uncontrolled narrow-angle glaucoma.
WARNINGS AND PRECAUTIONS
Darifenacin extended-release tablets should be administered with
caution to patients with clinically
significant bladder outflow obstruction because of the risk of urinary
retention (5.1)
Darifenacin extended-release tablets should be administered with
caution to patients with
gastrointestinal obstructive disorders because of the risk of gastric