Acamprosate Calcium

Name: Acamprosate Calcium

Uses for Acamprosate Calcium

Alcohol Dependence

Maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at the time acamprosate therapy is initiated.1 2 3 4 7

Should be used in conjunction with a comprehensive management program that includes psychosocial support.1

Therapeutic benefit not established in patients who have not undergone detoxification and have not achieved abstinence from alcohol ingestion.1

Efficacy not established for the promotion of abstinence from alcohol ingestion in patients who abuse multiple substances.1

Can be used in conjunction with naltrexone or disulfiram.7 8 9

Cautions for Acamprosate Calcium

Contraindications

  • Known hypersensitivity to acamprosate or any ingredient in the formulation.1

  • Severe renal impairment (Clcr <30mL/minute).1

Warnings/Precautions

General Precautions

Withdrawal Symptoms

Does not eliminate or diminish withdrawal symptoms.1

Suicide

Increased risk of suicide in substance abusers with or without depression.1

Suicidality (i.e., suicidal ideation, suicide attempt) and completed suicide reported.1

Monitor for symptoms of depression and suicidal thinking.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use caution.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 13

Evaluated in a limited number of adolescents 16–19 years of age.10

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1

Increased plasma concentrations in patients with renal impairment; assess renal function periodically since geriatric patients are more likely to have decreased renal function.1

Hepatic Impairment

Pharmacokinetics not altered in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).1 Safety and pharmacokinetics not evaluated in patients with severe hepatic impairment.13

Renal Impairment

Clearance decreased depending on degree of renal impairment.1

Dosage adjustment necessary in patients with Clcr 30–50 mL/minute.1 (See Renal Impairment under Dosage and Administration.)

Contraindicated in severe renal impairment (Clcr <30 mL/minute).1

Common Adverse Effects

Diarrhea1 2 3 4 5 6 and asthenia.1

Interactions for Acamprosate Calcium

Does not induce CYP isoenzymes 1A2 or 3A4; does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4.1

Concomitant use with anxiolytics, hypnotics and sedatives (including benzodiazepines), or nonopiate analgesics not associated with changes in safety profile.1

Specific Drugs

Drug

Interaction

Comments

Alcohol

Pharmacokinetic interaction unlikely1

Antidepressants

Antidepressants: Changes in weight (i.e., loss or gain) reported 1

Desipramine: No change in pharmacokinetics of the antidepressant1

Imipramine: No change in pharmacokinetics of the antidepressant1

Diazepam

Pharmacokinetic interaction unlikely1

Disulfiram

Pharmacokinetic interaction unlikely1

Naltrexone

Increased concentrations of acamprosate; no change in concentrations of naltrexone or its major metabolite, 6-β-naltrexol1

No dosage adjustment recommended1

Acamprosate Calcium Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 11%.1

Food

Food reduces peak plasma concentrations by 42% and AUC by 23%; effect not considered clinically important.1

Distribution

Plasma Protein Binding

Negligible.1

Elimination

Metabolism

Does not undergo metabolism.1

Elimination Route

Excreted principally in urine as unchanged drug.1

Half-life

20–33 hours.1

Special Populations

In patients with moderate or severe renal impairment, peak plasma concentrations are 2-fold or 4-fold higher, respectively, than in healthy individuals.1 Half-life is 1.8-fold or 2.6-fold longer in patients with moderate or severe renal impairment, respectively, than in healthy individuals.1

Warnings

Included as part of the PRECAUTIONS section.

Overdose

In all reported cases of acute overdosage with Campral (total reported doses of up to 56 grams of acamprosate calcium), the only symptom that could be reasonably associated with Campral was diarrhea. Hypercalcemia has not been reported in cases of acute overdose. A risk of hypercalcemia should be considered in chronic overdosage only. Treatment of overdose should be symptomatic and supportive.

What should i avoid while taking acamprosate (campral)?

Acamprosate can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Side effects

Clinical Trials Experience

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 Campral described elsewhere in labeling include suicidality and depression and acute kidney failure [see WARNINGS AND PRECAUTIONS]

The adverse event data described below reflect the safety experience in over 7000 patients exposed to Campral for up to one year, including over 2000 Campral-exposed patients who participated in placebocontrolled trials.

Adverse Events Leading To Discontinuation

In placebo-controlled trials of 6 months or less, 8% of Campral-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 Campral-treated patients. Only diarrhea was associated with the discontinuation of more than 1% of patients (2% of Campral-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 Campral-treated patients than in placebo-treated patients.

Common Adverse Events Reported In Controlled Trials

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. shows those events that occurred in any Campral 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.

Table 1: Events Occurring at a Rate of at Least 3% and Greater than Placebo in any Campral Treatment Group in Controlled Clinical Trials with Spontaneously Reported Adverse Events

Body System/
Preferred Term
  Number of Patients (%) with Events
Campral 1332 mg/day Campral 1998 mg/day 1 Campral Pooled 2 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%)
†*includes events coded as &ldquolfracture” by sponsor;
††**includes events coded as &ldquolnervousness” by sponsor includes 258 patients treated with acamprosate calcium 2000 mg/day, using a different dosage strength and regimen.1
includes all patients in the first two columns as well as 83 patients treated with acamprosate calcium 3000 mg/day, using a different dosage strength and regimen.2

Concomitant Therapies

In clinical trials, the safety profile in subjects treated with Campral 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 Campral concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone.

Other Events Observed During The Premarketing Evaluation Of Campral

Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with Campral in 20 clinical trials (4461 patients treated with Campral, 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.

Body as a Whole -Frequent: headache, abdominal pain, back pain, infection, flu syndrome, chest pain, chills, suicide attempt; Infrequent: fever, intentional overdose, malaise, allergic reaction, abscess, neck pain, hernia, intentional injury; Rare: ascites, face edema, photosensitivity reaction, abdomen enlarged, sudden death.

Cardiovascular System -Frequent: palpitation, syncope; Infrequent: hypotension, tachycardia, hemorrhage, angina pectoris, migraine, varicose vein, myocardial infarct, phlebitis, postural hypotension; Rare: heart failure, mesenteric arterial occlusion, cardiomyopathy, deep thrombophlebitis, shock.

Digestive System - Frequent : vomiting, dyspepsia, constipation, increased appetite; Infrequent: liver function tests abnormal, gastroenteritis, gastritis, dysphagia, eructation, gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage, liver cirrhosis, esophagitis, hematemesis, nausea and vomiting, hepatitis; Rare: melena, stomach ulcer, cholecystitis, colitis, duodenal ulcer, mouth ulceration, carcinoma of liver. �

Endocrine System -Rare: goiter, hypothyroidism.

Hemic and Lymphatic System -Infrequent: anemia, ecchymosis, eosinophilia, lymphocytosis, thrombocytopenia; Rare: leukopenia, lymphadenopathy, monocytosis.

Metabolic and Nutritional Disorders -Frequent - peripheral edema, weight gain; Infrequent: weight loss, hyperglycemia, SGOT increased, SGPT increased, gout, thirst, hyperuricemia, diabetes mellitus, avitaminosis, bilirubinemia; Rare:alkaline phosphatase increased, creatinine increased, hyponatremia, lactic dehydrogenase increased.

Musculoskeletal System -Frequent - myalgia, arthralgia; Infrequent: leg cramps; Rare: rheumatoid arthritis, myopathy.

Nervous System -Frequent -somnolence, libido decreased, amnesia, thinking abnormal, tremor, vasodilatation, hypertension; Infrequent: convulsion, confusion, libido increased, vertigo, withdrawal syndrome, apathy, suicidal ideation, neuralgia, hostility, agitation, neurosis, abnormal dreams, hallucinations, hypesthesia; Rare: alcohol craving, psychosis, hyperkinesia, twitching, depersonalization, increased salivation, paranoid reaction, torticollis, encephalopathy, manic reaction.

Respiratory System -Frequent: rhinitis, cough increased, dyspnea, pharyngitis, bronchitis; Infrequent: asthma, epistaxis, pneumonia; Rare: laryngismus, pulmonary embolus.

Skin and Appendages -Frequent: rash; Infrequent: acne, eczema, alopecia, maculopapular rash, dry skin, urticaria, exfoliative dermatitis, vesiculobullous rash; Rare: psoriasis.

Special Senses -Frequent : abnormal vision, taste perversion; Infrequent: tinnitus, amblyopia, deafness; Rare: ophthalmitis, diplopia, photophobia.

Urogenital System -Frequent : impotence; Infrequent - metrorrhagia, urinary frequency, urinary tract infection, sexual function abnormal, urinary incontinence, vaginitis; Rare: kidney calculus, abnormal ejaculation, hematuria, menorrhagia, nocturia, polyuria, urinary urgency.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Campral. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious Adverse Events Observed During the Non-US Postmarketing Evaluation Of Campral (acampros ate calcium)

The serious adverse event of acute kidney failure has been reported to be temporally associated with Campral treatment in at least 3 patients and is not described elsewhere in the labeling.

Read the entire FDA prescribing information for Campral (Acamprosate Calcium)

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