Acamprosate Calcium: Package Insert and Label Information (Page 3 of 3)

Special Populations

Gender

Acamprosate calcium delayed-release tablets do not exhibit any significant pharmacokinetic differences between male and female subjects.

Age

The pharmacokinetics of acamprosate calcium delayed-release tablets have not been evaluated in a geriatric population. However, since renal function diminishes in elderly patients and acamprosate is excreted unchanged in urine, acamprosate plasma concentrations are likely to be higher in the elderly population compared to younger adults.

Pediatrics

The pharmacokinetics of acamprosate calcium delayed-release tablets have not been evaluated in a pediatric population.

Renal Impairment

Peak plasma concentrations after administration of a single dose of 2 x 333 mg acamprosate calcium delayed-release tablets to patients with moderate or severe renal impairment were about 2-fold and 4-fold higher, respectively, compared to healthy subjects. Similarly, elimination half-life was about 1.8-fold and 2.6-fold longer, respectively, compared to healthy subjects. There is a linear relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate. A dose of 1 x 333 mg acamprosate calcium delayed-release tablets, three times daily, is recommended in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min, [see Use in Specific Populations (8.6) ].

Acamprosate calcium delayed-release tablets are contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Warnings and Precautions (5.1), and Use in Specific Populations (8.6)].

Hepatic Impairment

Acamprosate is not metabolized by the liver and the pharmacokinetics of acamprosate calcium delayed-release tablets are not altered in patients with mild to moderate hepatic impairment (groups A and B of the Child-Pugh classification). No adjustment of dosage is recommended in such patients.

Alcohol-Dependent Subjects

A cross-study comparison of acamprosate calcium delayed-release tablets at doses of 2 x 333 mg three times daily indicated similar pharmacokinetics between alcohol-dependent subjects and healthy subjects.

Drug-Drug Interactions

Acamprosate had no inducing potential on the cytochrome CYP1A2 and 3A4 systems, and in vitro inhibition studies suggest that acamprosate does not inhibit in vivo metabolism mediated by cytochrome CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4. The pharmacokinetics of acamprosate calcium delayed-release tablets were unaffected when co-administered with alcohol, disulfiram or diazepam. Similarly, the pharmacokinetics of ethanol, diazepam and nordiazepam, imipramine and desipramine, naltrexone and 6-beta naltrexol were unaffected following co-administration with acamprosate calcium delayed-release tablets. However, co-administration of acamprosate calcium delayed-release tablets with naltrexone led to a 33% increase in the Cmax and a 25% increase in the AUC of acamprosate. No adjustment of dosage is recommended in such patients.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Dietary administration of acamprosate calcium for 2 years to Sprague-Dawley rats at doses of 25, 100 and 400 mg/kg/day (up to 3 times the maximum recommended human daily (MRHD) oral dose on an AUC basis) and CD-1 mice at doses of 400, 1200 and 3600 mg/kg/day (up to 25 times the MRHD on an AUC basis) showed no evidence of increased tumor incidence.

Acamprosate calcium was negative in all genetic toxicology studies conducted. Acamprosate calcium demonstrated no evidence of genotoxicity in an in vitro bacterial reverse point mutation assay (Ames assay) or an in vitro mammalian cell gene mutation test using Chinese Hamster Lung V79 cells. No clastogenicity was observed in an in vitro chromosomal aberration assay in human lymphocytes and no chromosomal damage detected in an in vivo mouse micronucleus assay.

Acamprosate calcium had no effect on fertility after treatment for 70 days prior to mating in male rats and for 14 days prior to mating, throughout mating, gestation and lactation in female rats at doses up to 1000 mg/kg/day (approximately 4 times the MRHD oral dose on a mg/m2 basis). In mice, acamprosate calcium administered orally for 60 days prior to mating and throughout gestation in females at doses up to 2400 mg/kg/day (approximately 5 times the MRHD oral dose on a mg/m2 basis) had no effect on fertility.

14 CLINICAL STUDIES

The efficacy of acamprosate calcium delayed-release tablets in the maintenance of abstinence was supported by three clinical studies involving a total of 998 patients who were administered at least one dose of acamprosate calcium delayed-release tablets or placebo as an adjunct to psychosocial therapy. Each study was a double-blind, placebo-controlled trial in alcohol-dependent patients who had undergone inpatient detoxification and were abstinent from alcohol on the day of randomization. Study durations ranged from 90 days to 360 days. Acamprosate calcium delayed-release tablets proved superior to placebo in maintaining abstinence, as indicated by a greater percentage of subjects being assessed as continuously abstinent throughout treatment.

In a fourth study, the efficacy of acamprosate calcium delayed-release tablets was evaluated in alcoholics, including patients with a history of polysubstance abuse and patients who had not undergone detoxification and were not required to be abstinent at baseline. This study failed to demonstrate superiority of acamprosate calcium delayed-release tablets over placebo.

16 HOW SUPPLIED/STORAGE AND HANDLING

Acamprosate Calcium Delayed-Release Tablets are available containing 333 mg of acamprosate calcium, USP (equivalent to 300 mg of acamprosate).

The 333 mg tablets are white, enteric-coated, round, unscored tablets imprinted with M over AC in black ink on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-6333-80
bottles of 180 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

17 PATIENT COUNSELING INFORMATION

17.1 Information for Patients

Physicians are advised to discuss the following issues with patients for whom they prescribe acamprosate calcium delayed-release tablets.

Renal Impairment

A lower dose is recommended for patients with moderate renal impairment. Acamprosate calcium delayed-release tablets are contraindicated in patients with severe renal impairment (creatinine clearance of ≤ 30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

Suicidality and Depression

Families and caregivers of patients being treated with acamprosate calcium delayed-release tablets should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s health care provider [see Warnings and Precautions (5.2) ].

Alcohol Withdrawal

Use of acamprosate calcium delayed-release tablets does not eliminate or diminish withdrawal symptoms [see Warnings and Precautions (5.3) ].

Pregnancy and Breast Feeding

Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy.
Advise patients to notify their physician if they are breast feeding.

Relapse to Drinking

Advise patients to continue acamprosate calcium delayed-release tablets therapy as directed, even in the event of relapse and remind them to discuss any renewed drinking with their physicians.
Advise patients that acamprosate calcium delayed-release tablets have been shown to help maintain abstinence only when used as a part of a treatment program that includes counseling and support.

Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Manufactured in India by:
Mylan Laboratories Limited
Hyderabad—500 096, India

Revised: 7/2019
MX:ACMPDR:R7

75068772

PRINCIPAL DISPLAY PANEL — 333 mg

NDC 0378-6333-80

Acamprosate
Calcium
Delayed-Release
Tablets
333 mg

Rx only 180 Tablets

Each enteric-coated tablet contains
333 mg of acamprosate calcium
(equivalent to 300 mg of acamprosate).

Usual Dosage: See accompanying
prescribing information.

Keep this and all medication out of
the reach of children.

Store at 20° to 25°C (68° to 77°F). [See
USP Controlled Room Temperature.]

Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX6333SS3

Dispense in a tight, light-resistant
container as defined in the USPusing a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Acamprosate Calcium Delayed-Release Tablets 333 mg Bottle Label
(click image for full-size original)
ACAMPROSATE CALCIUM acamprosate calcium enteric-coated tablet, delayed release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0378-6333
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACAMPROSATE CALCIUM (ACAMPROSATE) ACAMPROSATE CALCIUM 333 mg
Inactive Ingredients
Ingredient Name Strength
AMMONIA
FERROSOFERRIC OXIDE
SILICON DIOXIDE
GLYCERYL DIBEHENATE
HYPROMELLOSE, UNSPECIFIED
MAGNESIUM STEARATE
METHACRYLIC ACID — METHYL METHACRYLATE COPOLYMER (1:1)
MICROCRYSTALLINE CELLULOSE
PROPYLENE GLYCOL
SHELLAC
TALC
Product Characteristics
Color WHITE Score no score
Shape ROUND Size 10mm
Flavor Imprint Code M;AC
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0378-6333-80 180 TABLET, DELAYED RELEASE in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA200142 09/24/2014
Labeler — Mylan Pharmaceuticals Inc. (059295980)

Revised: 07/2019 Mylan Pharmaceuticals Inc.

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