Side Effects of Acamprosate
Acamprosate is generally well-tolerated with primarily gastrointestinal side effects, most notably diarrhea, and carries no risk of hepatotoxicity, making it particularly safe for patients with liver disease. 1, 2
Common Adverse Effects (≥3% and Greater than Placebo)
The FDA-approved labeling identifies the following common side effects based on controlled clinical trials involving over 7,000 patients: 2
Gastrointestinal effects:
- Diarrhea (most common, leading to discontinuation in 2% of patients vs. 0.7% with placebo) 2
- Nausea 2
- Flatulence 2
- Anorexia 2
Neuropsychiatric effects:
Dermatological effects:
General effects:
Serious Adverse Effects Requiring Monitoring
Suicidality and depression: Suicidal events (ideation, attempts, completed suicides) occurred more frequently with acamprosate than placebo (1.4% vs. 0.5% in studies ≤6 months; 2.4% vs. 0.8% in year-long studies), with completed suicides in 0.13% of acamprosate patients vs. 0.10% of placebo patients. 2 All patients must be monitored for emergence of depression or suicidal thinking, and families/caregivers should be educated to report such symptoms immediately. 2
Renal impairment: Acamprosate is renally excreted and requires dose reduction in moderate renal impairment (creatinine clearance 30-50 mL/min) and is contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min). 2 Acute kidney failure has been reported. 2
Rare extrapyramidal symptoms: One case report documented severe extrapyramidal symptoms in an elderly patient that developed two days after starting acamprosate and resolved within one week of discontinuation, potentially mediated through glutamatergic effects on dopamine levels in the ventral tegmental area. 3
Key Safety Advantages
No hepatotoxicity: Unlike naltrexone and disulfiram, acamprosate undergoes no hepatic metabolism and has no reported instances of hepatotoxicity, making it the preferred agent in patients with alcohol-associated liver disease according to the American Association for the Study of Liver Diseases. 1, 4
No abuse potential: Acamprosate demonstrates no hypnotic, antidepressant, anxiolytic, or muscle-relaxant effects and has no evidence of abuse potential. 5
Does not potentiate alcohol toxicity: The drug does not enhance acute or chronic toxic effects of alcohol. 5
Discontinuation Rates
In placebo-controlled trials ≤6 months, 8% of acamprosate patients discontinued due to adverse events versus 6% with placebo; in longer studies, discontinuation rates were equal at 7% for both groups. 2 Only diarrhea accounted for discontinuation in >1% of patients. 2
Important Clinical Caveats
Does not treat withdrawal: Acamprosate does not eliminate or diminish alcohol withdrawal symptoms and should only be initiated 3-7 days after last alcohol consumption, once withdrawal has resolved. 2, 6
Pregnancy considerations: Limited data show no fetal abnormalities with acamprosate use during pregnancy, though the decision to continue must be individualized weighing risks of the medication against risks of alcohol withdrawal syndrome. 1 Disulfiram is contraindicated and baclofen should be used with caution in pregnancy. 1