Acamprosate

Acamprosate: Drug information
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(For additional information see “Acamprosate: Patient drug information”)

Brand Names: U.S. Campral®
Brand Names: Canada Campral®
Pharmacologic Category GABA Agonist/Glutamate Antagonist
Dosing: Adult Alcohol abstinence: Oral: 666 mg 3 times/day (a lower dose may be effective in some patients). Note: Treatment should be initiated as soon as possible following the period of alcohol withdrawal, when the patient has achieved abstinence and should be maintained if patient relapses.
Dosing: Geriatric Refer to adult dosing.
Dosing: Renal Impairment
Clcr 30-50 mL/minute: 333 mg 3 times/day

Clcr <30 mL/minute: Contraindicated in severe renal impairment.

Dosing: Hepatic Impairment
Mild-to-moderate impairment: No dosage adjustments are recommended.

Severe impairment: There are no dosage adjustments provided in manufacturer’s labeling.

Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, delayed release, enteric coated, oral, as calcium:

Campral®: 333 mg [contains calcium 33 mg/tablet, sulfites]

Generic Equivalent Available: U.S. No
Administration May be administered without regard to meals (administered with meals during clinical trials to possibly increase compliance). Tablet should be swallowed whole; do not crush or chew.
Use Maintenance of alcohol abstinence
Adverse Reactions Significant Note: Many adverse effects associated with treatment may be related to alcohol abstinence; reported frequency range may overlap with placebo.
>10%: Gastrointestinal: Diarrhea (10% to 17%)

1% to 10%:

Cardiovascular: Chest pain, edema (peripheral), hypertension, palpitation, syncope, vasodilatation

Central nervous system: Insomnia (6% to 9%), anxiety (5% to 8%), depression (4% to 8%), dizziness (3% to 4%), pain (2% to 4%), paresthesia (2% to 3%), abnormal thinking, amnesia, chills, headache, somnolence, tremor

Dermatologic: Pruritus (3% to 4%), rash

Endocrine & metabolic: Libido decreased

Gastrointestinal: Anorexia (2% to 5%), nausea (3% to 4%), flatulence (1% to 4%), xerostomia (1% to 3%), abdominal pain, appetite increased, constipation, dyspepsia, taste perversion, vomiting, weight gain

Genitourinary: Impotence

Neuromuscular & skeletal: Weakness (5% to 7%), arthralgia, back pain, myalgia

Ocular: Abnormal vision

Respiratory: Bronchitis, cough increased, dyspnea, pharyngitis, rhinitis

Miscellaneous: Diaphoresis (2% to 3%), flu-like syndrome, infection, suicide attempt

<1% (Limited to important or life-threatening): Agitation, allergic reaction, alopecia, anemia, angina, AST/ALT increased, asthma, bilirubinemia, colitis, confusion, creatinine increased, deafness, diabetes mellitus, duodenal ulcer, encephalopathy, eosinophilia, epistaxis, exfoliative dermatitis, fever, gastrointestinal hemorrhage, gout, hallucinations, hemorrhage, hepatitis, hostility, hyperglycemia, hyperuricemia, hypesthesia, hyponatremia, hypotension, hypothyroidism, leukopenia, liver cirrhosis, liver function tests abnormal, lymphadenopathy, lymphocytosis, MI, neuralgia, neurosis, ophthalmitis, pancreatitis, photosensitivity, pneumonia, postural hypotension, psychosis, pulmonary embolus, rectal hemorrhage, renal calculus, renal failure, seizure, suicidal ideation, suicide completion, tachycardia, thrombocytopenia, urticaria, withdrawal syndrome

Contraindications Hypersensitivity to acamprosate or any component of the formulation; severe renal impairment (Clcr <30 mL/minute) Warnings/Precautions
Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Suicidal ideation/attempt: Attempted and completed suicides have occurred in acamprosate-treated patients; use with caution in suicidal ideation. Monitor for depression and/or suicidal thinking.

Disease-related concerns:

• Alcohol dependence: Appropriate use: Should be used as part of a comprehensive program to treat alcohol dependence. Treatment should be initiated as soon as possible following the period of alcohol withdrawal, when the patient has achieved abstinence. Acamprosate does not eliminate or diminish the symptoms of alcohol withdrawal.

• Renal impairment: Use with caution in patients with moderate renal impairment (Clcr 30-50 mL/minute). Contraindicated in patients with severe renal impairment (Cllcr 30 mL/minute).

Dosage form specific issues:

• Sulfites: Traces of sulfites may be present in the formulation.

Special populations:

• Geriatrics: Use caution due to the age-related decrease in renal function.

Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
There are no known significant interactions.
Ethanol/Nutrition/Herb Interactions
Ethanol: Abstinence is required during treatment. Ethanol does not affect the pharmacokinetics of acamprosate; however, the continued use of ethanol will decrease desired efficacy of acamprosate.

Food: Food decreases absorption of acamprosate (not clinically significant).

Pregnancy Risk Factor C (show table)
Pregnancy Implications Teratogenic effects have been observed in animal studies. No adequate or well-controlled studies in pregnant women; use only if potential benefit outweighs possible risk to the fetus.
Lactation Excretion in breast milk unknown/use caution
Dietary Considerations Abstinence is required during treatment. May be taken without regard to meals. Each 333 mg tablet contains 33 mg of elemental calcium.
Pricing: U.S. (www.drugstore.com)
Tablet, EC (Campral)

333 mg (180): $162.99

International Brand Names Acampral (KP); Acamprol (IN); Aotal (FR); Campral (AR, AT, AU, BE, BG, BR, CH, CN, CZ, DE, DK, EE, ES, FI, GB, GR, HN, IE, IT, MT, MX, NL, NO, PL, PT, RU, SE, SG, SK, TR)
Mechanism of Action Mechanism not fully defined. Structurally similar to gamma-amino butyric acid (GABA), acamprosate appears to increase the activity of the GABA-ergic system, and decreases activity of glutamate within the CNS, including a decrease in activity at N-methyl D-aspartate (NMDA) receptors; may also affect CNS calcium channels. Restores balance to GABA and glutamate activities which appear to be disrupted in alcohol dependence. During therapeutic use, reduces alcohol intake, but does not cause a disulfiram-like reaction following alcohol ingestion. Insignificant CNS activity, outside its effect on alcohol dependence, was observed including no anxiolytic, anticonvulsant, or antidepressant activity.
Pharmacodynamics/Kinetics
Distribution: Vd: 1 L/kg

Protein binding: Negligible

Metabolism: Not metabolized

Bioavailability: 11%

Half-life elimination: 20-33 hours

Excretion: Urine (as unchanged drug)

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REFERENCES
Brasser SM, McCaul ME, and Houtsmuller EJ, “Alcohol Effects During Acamprosate Treatment: A Dose-Response Study in Humans,” Alcohol Clin Exp Res, 2004, 28(7):1074-83. [PubMed 15252294]
Graham R, Wodak AD, and Whelan G, “New Pharmacotherapies for Alcohol Dependence,” Med J Aust, 2002, 177(2):103-7. [PubMed 12098353]
Overman GP, Teter CJ, and Guthrie SK, “Acamprosate for the Adjunctive Treatment of Alcohol Dependence,” Ann Pharmacother, 2003, 37(7-8):1090-9. [PubMed 12841823]