Acamprosate

• Alcohol Use Disorder
• Alcohol Dependence
• Maintaining Sobriety

Acamprosate is a medication used in the treatment of alcohol use disorder to help maintain abstinence in patients who have stopped drinking. It works by helping to restore the brain's chemical balance disrupted by chronic alcohol use, reducing the discomfort and cravings associated with alcohol withdrawal.

Mechanism of Action

Acamprosate's exact mechanism of action is not fully understood, but it is thought to work by modulating glutamatergic neurotransmission. Chronic alcohol exposure causes adaptive changes in the brain, including upregulation of NMDA glutamate receptors and downregulation of GABA receptors. When alcohol use stops, the resulting glutamatergic hyperexcitability contributes to withdrawal symptoms and craving. Acamprosate is believed to act as a functional glutamate antagonist, reducing this hyperexcitability by interacting with both NMDA receptors and metabotropic glutamate receptors. It may also modulate calcium channels and enhance GABAergic inhibition, helping restore normal neuronal function.

Available Formulations

Acamprosate is available as enteric-coated, delayed-release tablets containing 333 mg of acamprosate calcium. The enteric coating protects the medication from stomach acid degradation and improves bioavailability. The tablets should be swallowed whole and not crushed, cut, or chewed.

Medical Uses

Acamprosate is FDA-approved for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. It is most effective when combined with psychosocial support programs including counseling, support groups, and behavioral therapy. The medication does not treat acute alcohol withdrawal and should not be used until withdrawal symptoms have resolved. Clinical trials have shown that acamprosate increases the proportion of patients maintaining complete abstinence and reduces drinking days in those who relapse.

Dosing Guidelines

The recommended dose is 666 mg (two 333 mg tablets) taken three times daily, for a total daily dose of 1998 mg. The medication may be taken with or without food, though taking with meals may help with adherence to the three-times-daily dosing schedule. Treatment should be initiated as soon as possible after withdrawal symptoms have subsided and abstinence has been achieved. Treatment duration is typically 12 months, though some patients may benefit from longer treatment. Dose reduction is required in patients with moderate renal impairment.

Important Safety Information

Acamprosate is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min). Patients with moderate renal impairment require dose reduction to 333 mg three times daily. The medication should be used with caution in patients with a history of depression or suicidal ideation, as depression and suicidal events have been reported. Unlike disulfiram, acamprosate does not produce an unpleasant reaction with alcohol consumption, so patients must be committed to abstinence.

Drug Interactions

Acamprosate has minimal drug interactions. It is not metabolized by the liver and does not inhibit or induce cytochrome P450 enzymes. Coadministration with naltrexone increases acamprosate exposure but dose adjustment is not required. The medication can be safely combined with antidepressants, anxiolytics, and other medications commonly used in patients with alcohol use disorder. Food decreases absorption but does not significantly affect overall efficacy when taken consistently.

Special Populations

Acamprosate has not been adequately studied in pregnancy and should be used only if the potential benefit justifies the potential risk to the fetus. It is unknown whether acamprosate is excreted in human breast milk; caution should be exercised when administering to nursing mothers. Safety and efficacy have not been established in pediatric patients. Elderly patients with normal renal function do not require dose adjustment, though renal function should be assessed before starting therapy. Patients with hepatic impairment do not require dose adjustment.