Acamprosate calcium is a white, odorless or nearly odorless powder. It is freely soluble in water, and practically insoluble in absolute ethanol and dichloromethane.
Each tablet contains acamprosate calcium 333 mg, equivalent to 300 mg of acamprosate. Inactive ingredients in tablets include: crospovidone, microcrystalline cellulose, magnesium silicate, sodium starch glycolate, colloidal anhydrous silica, magnesium stearate, talc, propylene glycol and Eudragit L 30 D or equivalent. Sulfites were used in the synthesis of the drug substance and traces of residual sulfites may be present in the drug product.
The mechanism of action of acamprosate in maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. and studies in animals have provided evidence to suggest acamprosate may interact with glutamate and GABA neurotransmitter systems centrally, and has led to the hypothesis that acamprosate restores this balance.
Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent animals in a dose-dependent manner and that this effect appears to be specific to alcohol and the mechanisms of alcohol dependence.
Acamprosate calcium has negligible observable central nervous system (CNS) activity in animals outside of its effects on alcohol dependence, exhibiting no anticonvulsant, antidepressant, or anxiolytic activity.
The administration of acamprosate calcium is not associated with the development of tolerance or dependence in animal studies.
Campral ()
The efficacy of 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 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. 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 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 over placebo.
Use of does not eliminate or diminish withdrawal symptoms.
Physicians are advised to discuss the following issues with patients for whom they prescribe .
Any psychoactive drug may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy does not affect their ability to engage in such activities.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.
Patients should be advised to notify their physician if they are breast-feeding.
Patients should be advised to continue therapy as directed, even in the event of relapse and should be reminded to discuss any renewed drinking with their physician.
Patients should be advised that has been shown to help maintain abstinence only when used as a part of a treatment program that includes counseling and support.
The concomitant intake of alcohol and does not affect the pharmacokinetics of either alcohol or acamprosate.
Pharmacokinetic studies indicate that administration of disulfiram or diazepam does not affect the pharmacokinetics of acamprosate. Co-administration of naltrexone with produced a 25% increase in AUC and a 33% increase in the C of acamprosate. No adjustment of dosage is recommended in such patients.
The pharmacokinetics of naltrexone and its major metabolite 6-beta-naltrexol were unaffected following co-administration with .
Other concomitant therapies: In clinical trials, the safety profile in subjects treated with concomitantly with anxiolytics, hypnotics and sedatives (including benzodiazepines), or non-opioid analgesics was similar to that of subjects taking placebo with these concomitant medications. Patients taking concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone.
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 MRHD 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 bacterial reverse point mutation assay (Ames assay) or an mammalian cell gene mutation test using Chinese Hamster Lung V79 cells. No clastogenicity was observed in an chromosomal aberration assay in human lymphocytes and no chromosomal damage detected in an 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 maximum recommended human daily oral dose on a mg/m 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 maximum recommended human daily oral dose on a mg/m basis) had no effect on fertility.
Forty-one of the 4234 patients in double-blind, placebo-controlled, clinical trials of were 65 years of age or older, while none were 75 years of age or over. There were too few patients in the ≥65 age group to evaluate any differences in safety or effectiveness for geriatric patients compared to younger patients.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (See , , and ).
The adverse event data described below reflect the safety experience in over 7000 patients exposed to for up to one year, including over 2000 -exposed patients who participated in placebo-controlled trials.
Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with in 20 clinical trials (4461 patients treated with , 3526 of whom received the maximum recommended dose of 1998 mg/day for up to one year in duration). This listing does not include those events already listed above; events for which a drug cause was considered remote; event terms which were so general as to be uninformative; and events reported only once which were not likely to be acutely life-threatening.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the summary of adverse events in controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
Opaque HDPE bottles of 180-NDC #0456-3330-01Dose Pak of 180-NDC #0456-3330-6010 X 10 Unit Dose-NDC #0456-3330-63
Storage:Store at 25ºC (77ºF); excursions permitted to 15º - 30ºC (59º - 86ºF).
Manufactured by:Merck Santé s.a.s.Subsidiary of Merck KGaA, Darmstadt, Germany37, rue Saint-Romain69008 Lyon, France
Manufactured for: Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc.St. Louis, MO 63045
Revised: 12/2010
