Acamprosate

U.S. BRAND NAMES — Campral®

PHARMACOLOGIC CATEGORY
GABA Agonist/Glutamate Antagonist

DOSING: ADULTS — Alcohol abstinence: Oral: 666 mg 3 times/day (a lower dose may be effective in some patients).
Adjustment in patients with low body weight (unlabeled): A lower dose (4 tablets/day) may be considered in patients with low body weight (eg, <60 kg).

Note: Treatment should be initiated as soon as possible following the period of alcohol withdrawal, when the patient has achieved abstinence.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr 30-50 mL/minute: Initial dose should be reduced to 333 mg 3 times/day.

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

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, enteric coated, delayed release, as calcium:
Campral®: 333 mg [contains calcium 33 mg and sulfites]

DOSAGE FORMS: CONCISE
Tablet, enteric coated, delayed release:
Campral®: 333 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — May be administered without regard to meals. 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: Syncope, palpitation, edema (peripheral)
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%), headache, somnolence, amnesia, tremor, chills
Dermatologic: Pruritus (3% to 4%), rash
Endocrine & metabolic: Weight gain, libido decreased
Gastrointestinal: Anorexia (2% to 5%), flatulence (1% to 3%), nausea (3% to 4%), abdominal pain, dry mouth (1% to 3%), vomiting, dyspepsia, constipation, appetite increased, taste perversion
Genitourinary: Impotence
Neuromuscular & skeletal: Weakness (5% to 7%), back pain, myalgia, arthralgia
Ocular: Abnormal vision
Respiratory: Rhinitis, dyspnea, pharyngitis, bronchitis
Miscellaneous: Diaphoresis (2% to 3%), suicide attempt

<1%, postmarketing, and/or case reports (limited to important or life-threatening): Angina, asthma, exfoliative dermatitis, gastrointestinal hemorrhage, hallucinations, hypothyroidism, MI, ophthalmitis, pancreatitis, photosensitivity, psychosis, pulmonary embolus, renal calculus, renal failure, seizure, suicidal ideation, suicide attempts, suicide completion

CONTRAINDICATIONS — Hypersensitivity to acamprosate or any component of the formulation; severe renal impairment (Clcr <30 mL/minute)

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: 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).

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Dosage form specific issues: Sulfites: Traces of sulfites may be present in the formulation.

DRUG INTERACTIONS — 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 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 — May be taken without regard to meals. Each 333 mg tablet contains 33 mg of elemental calcium.

PRICING — (data from drugstore.com)
Tablet, EC (Campral)
333 mg (180): $148.39

Tablet, EC (Campral Dose Pak)
333 mg (180): $159.10

CANADIAN BRAND NAMES — Campral®

INTERNATIONAL BRAND NAMES — Acampral (KP); Aotal (FR); Campral (AR, AT, AU, BE, BG, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, MX, NL, NO, PL, PT, RU, SE, 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.

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)