ACAMPROSATE CALCIUM- acamprosate calcium tablet, delayed release
Zydus Lifesciences Limited
Acamprosate calcium delayed-release tablets are indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with acamprosate calcium delayed-release tablets should be part of a comprehensive management program that includes psychosocial support.
The efficacy of acamprosate calcium delayed-release tablets in promoting abstinence has not been demonstrated in subjects who have not undergone detoxification and not achieved alcohol abstinence prior to beginning acamprosate calcium delayed-release tablets treatment. The efficacy of acamprosate calcium delayed-release tablets in promoting abstinence from alcohol in polysubstance abusers has not been adequately assessed.
Although dosing may be done without regard to meals, dosing with meals was employed during clinical trials and is suggested in those patients who regularly eat three meals daily.
Treatment with acamprosate calcium delayed-release tablets should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence, and should be maintained if the patient relapses. Acamprosate calcium delayed-release tablets should be used as part of a comprehensive psychosocial treatment program.
For patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min), a starting dose of one 333 mg tablet taken three times daily is recommended. Acamprosate calcium delayed-release tablets are contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Contraindications (4.2), Warnings and Precautions (5.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
Acamprosate calcium is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
Treatment with acamprosate calcium in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min) requires a dose reduction [see Dosage and Administration (2.1)]. Acamprosate calcium is contraindicated in patients with severe renal impairment (creatinine clearance of ≤30 mL/min) [see Dosage and Administration (2.1), Contraindications (4.2), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].
In controlled clinical trials of acamprosate calcium, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) were infrequent overall, but were more common in acamprosate calcium-treated patients than in patients treated with placebo (1.4% vs. 0.5% in studies of 6 months or less; 2.4% vs. 0.8% in year-long studies). Completed suicides occurred in 3 of 2272 (0.13%) patients in the pooled acamprosate group from all controlled studies and 2 of 1962 patients (0.10%) in the placebo group. Adverse events coded as “depression” were reported at similar rates in acamprosate calcium-treated and placebo-treated patients. Although many of these events occurred in the context of alcohol relapse, and the interrelationship between alcohol dependence, depression and suicidality is well-recognized and complex, no consistent pattern of relationship between the clinical course of recovery from alcoholism and the emergence of suicidality was identified. Alcohol-dependent patients, including those patients being treated with acamprosate calcium, should be monitored for the development of symptoms of depression or suicidal thinking. Families and caregivers of patients being treated with acamprosate calcium 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.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinically significant serious adverse reactions associated with acamprosate calcium described elsewhere in labeling include suicidality and depression and acute kidney failure [see Warnings and Precautions (5.2), and Adverse Reactions (6.2)].
The adverse event data described below reflect the safety experience in over 7000 patients exposed to acamprosate calcium for up to one year, including over 2000 acamprosate calcium-exposed patients who participated in placebo-controlled trials.
In placebo-controlled trials of 6 months or less, 8% of acamprosate calcium-treated patients discontinued treatment due to an adverse event, as compared to 6% of patients treated with placebo. In studies longer than 6 months, the discontinuation rate due to adverse events was 7% in both the placebo-treated and the acamprosate calcium-treated patients. Only diarrhea was associated with the discontinuation of more than 1% of patients (2% of acamprosate calcium-treated vs. 0.7% of placebo-treated patients). Other events, including nausea, depression, and anxiety, while accounting for discontinuation in less than 1% of patients, were nevertheless more commonly cited in association with discontinuation in acamprosate calcium-treated patients than in placebo-treated patients.
Common adverse events were collected spontaneously in some controlled studies and using a checklist in other studies. The overall profile of adverse events was similar using either method. Table 1 shows those events that occurred in any acamprosate calcium treatment group at a rate of 3% or greater and greater than the placebo group in controlled clinical trials with spontaneously reported adverse events. The reported frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed, without regard to the causal relationship of the events to the drug.
|Body System/ Preferred Term||Number of Patients (%) with Events|
|Acamprosate Calcium 1332 mg/day||Acamprosate Calcium 1998 mg/day *||Acamprosate Calcium Pooled †||Placebo|
|Number of patients in Treatment Group||397||1539||2019||1706|
|Number (%) of patients with an AE||248 (62%)||910 (59%)||1231 (61%)||955 (56%)|
|Body as a Whole||121 (30%)||513 (33%)||685 (34%)||517 (30%)|
|Accidental Injury ‡||17 (4%)||44 (3%)||70 (3%)||52 (3%)|
|Asthenia||29 (7%)||79 (5%)||114 (6%)||93 (5%)|
|Pain||6 (2%)||56 (4%)||65 (3%)||55 (3%)|
|Digestive System||85 (21%)||440 (29%)||574 (28%)||344 (20%)|
|Anorexia||20 (5%)||35 (2%)||57 (3%)||44 (3%)|
|Diarrhea||39 (10%)||257 (17%)||329 (16%)||166 (10%)|
|Flatulence||4 (1%)||55 (4%)||63 (3%)||28 (2%)|
|Nausea||11 (3%)||69 (4%)||87 (4%)||58 (3%)|
|Nervous System||150 (38%)||417 (27%)||598 (30%)||500 (29%)|
|Anxiety §||32 (8%)||80 (5%)||118 (6%)||98 (6%)|
|Depression||33 (8%)||63 (4%)||102 (5%)||87 (5%)|
|Dizziness||15 (4%)||49 (3%)||67 (3%)||44 (3%)|
|Dry mouth||13 (3%)||23 (1%)||36 (2%)||28 (2%)|
|Insomnia||34 (9%)||94 (6%)||137 (7%)||121 (7%)|
|Paresthesia||11 (3%)||29 (2%)||40 (2%)||34 (2%)|
|Skin and Appendages||26 (7%)||150 (10%)||187 (9%)||169 (10%)|
|Pruritus||12 (3%)||68 (4%)||82 (4%)||58 (3%)|
|Sweating||11 (3%)||27 (2%)||40 (2%)||39 (2%)|
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.