What are the potential side effects of acamprosate (acamprosate calcium) in adults with a history of alcohol use disorder, particularly those with impaired renal function?

Acamprosate Side Effects

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

Primary Side Effect Profile

Gastrointestinal Effects

• Diarrhea is the most common side effect and represents the primary tolerability concern with acamprosate therapy 1, 2
• Other frequent gastrointestinal effects include vomiting, dyspepsia, constipation, and increased appetite 3
• Nausea, gastroenteritis, gastritis, and dysphagia occur less commonly 3

Common Non-GI Side Effects (≥1/100 patients)

• Headache, abdominal pain, back pain, and infection are frequently reported 3
• Flu syndrome, chest pain, and chills occur commonly 3
• Psychiatric effects include insomnia, anxiety, depression, and decreased libido 3
• Dizziness, paresthesia, somnolence, amnesia, and abnormal thinking may occur 3
• Asthenia (weakness) and peripheral edema are reported 3

Critical Safety Advantages

Hepatic Safety

• Acamprosate has NO hepatic metabolism and NO reported instances of hepatotoxicity, making it the preferred agent in patients with alcohol-associated liver disease 4, 1
• The American Association for the Study of Liver Diseases explicitly recommends acamprosate as the preferred agent in patients with alcohol-associated liver disease due to its lack of hepatotoxicity 1, 5
• This contrasts sharply with naltrexone (contraindicated in liver disease) and disulfiram (should be avoided in severe alcoholic liver disease) 1, 5
• A 2024 pilot randomized controlled trial in liver transplant recipients demonstrated that acamprosate was safe with similar adverse event rates compared to standard of care (92.3% vs. 90.0%), including grade 3 adverse events (53.9% vs. 60.0%), with no grade 4 or 5 adverse events reported 6

Renal Considerations

• Acamprosate is excreted entirely renally without metabolism, requiring dose adjustment in renal impairment 4
• For patients with moderate renal impairment (CrCl 30-50 mL/min), reduce dose to 333 mg three times daily 7
• Acamprosate is contraindicated in severe renal impairment (CrCl <30 mL/min) 1
• Acute kidney failure has been reported in at least 3 patients temporally associated with acamprosate treatment in postmarketing surveillance 3

Less Common but Notable Adverse Events

Cardiovascular Effects (1/100 to 1/1000 patients)

• Palpitation and syncope occur infrequently 3
• Hypotension, tachycardia, angina pectoris, and myocardial infarction have been reported 3

Psychiatric Effects

• Suicide attempt is listed as a frequent adverse event 3
• Suicidal ideation, confusion, hallucinations, and psychosis occur infrequently 3
• Depression and anxiety are common, though distinguishing these from underlying alcohol use disorder symptoms is challenging 3

Metabolic Effects

• Peripheral edema and weight gain occur frequently 3
• Hyperglycemia, elevated liver enzymes (SGOT, SGPT), and gout occur infrequently 3

Rare but Serious Events (<1/1000 patients)

• Sudden death, heart failure, and cardiomyopathy have been reported 3
• Pancreatitis, gastrointestinal hemorrhage, and hepatitis (rare) 3
• Convulsions, encephalopathy, and manic reaction 3
• Pulmonary embolus 3

Drug Interaction Profile

• Acamprosate has an excellent drug interaction profile with no clinically significant interactions with alcohol, diazepam, disulfiram, or naltrexone 3, 8
• This low propensity for drug interactions enhances its safety profile, particularly in patients taking multiple medications 2

Special Population Considerations

Pregnancy (Category C)

• Acamprosate produced dose-related teratogenic effects in rats at doses approximately equal to the human dose and in rabbits at 3 times the human dose 3
• Malformations included hydronephrosis, malformed iris, retinal dysplasia, and retroesophageal subclavian artery 3
• The decision to use acamprosate during pregnancy must weigh medication risks against risks of alcohol withdrawal syndrome, with limited data showing no fetal abnormalities in some cases 1
• Disulfiram is contraindicated and baclofen should be used with caution in pregnancy 1

Lactation

• Acamprosate is excreted in breast milk in animal studies 3

Common Pitfalls to Avoid

• Never initiate acamprosate during active alcohol withdrawal - it does not treat withdrawal and should only be started 3-7 days after last alcohol consumption once withdrawal has resolved 1, 7
• Monitor renal function closely, particularly in patients with baseline renal impairment or those at risk for acute kidney injury 3
• Do not discontinue treatment prematurely - continue for at least 3-6 months for optimal results 7
• Always combine acamprosate with psychosocial support, as medication alone is insufficient 1, 5

Overall Tolerability Assessment

• Acamprosate has an excellent tolerability and safety profile compared to other FDA-approved treatments for alcohol dependence 8, 2
• The number needed to treat is approximately 12 to prevent return to any drinking, demonstrating meaningful clinical efficacy 4, 5
• Most adverse events are mild to moderate in severity, with diarrhea being the primary reason for discontinuation 1, 2