What to monitor in an adult patient with a history of alcohol use disorder who received 666mg of acamprosate (instead of the prescribed 333mg)?

Monitoring After Acamprosate Overdose (666mg instead of 333mg)

Reassure the patient that this single double-dose exposure is unlikely to cause serious harm, as acamprosate has an excellent safety profile with no reported hepatotoxicity and is safe even in overdose. 1, 2

Immediate Assessment

Monitor for gastrointestinal symptoms, particularly diarrhea, which is the most common adverse effect of acamprosate and the primary concern with dose escalation. 3

• Diarrhea is the most frequent side effect and led to discontinuation in 2% of patients at therapeutic doses 3
• Nausea and other gastrointestinal symptoms may occur but are generally mild 3
• These symptoms typically resolve spontaneously and do not require specific intervention beyond supportive care 2

Mental Status Monitoring

Screen for mood changes, depression, or suicidal ideation over the next several days, as acamprosate carries a black box warning for increased suicidality risk. 3

• Suicidal ideation, attempts, or completed suicides occurred more frequently in acamprosate-treated patients (1.4% vs 0.5% in placebo) in controlled trials 3
• This monitoring is particularly important in the context of alcohol use disorder, where depression and suicidality are already elevated 3
• Instruct the patient and family members to report any emergence of depressive symptoms or suicidal thoughts immediately 3

Renal Function Considerations

If the patient has any degree of renal impairment, monitor more closely, as acamprosate is entirely renally excreted and accumulation could occur. 3, 4

• Acamprosate is not metabolized and 50% is eliminated unchanged in urine 4
• Patients with moderate renal impairment (CrCl 30-50 mL/min) require dose reduction to 333mg three times daily 3
• The drug is contraindicated in severe renal impairment (CrCl ≤30 mL/min) 3
• Check baseline renal function if not recently available, particularly if the patient has risk factors for kidney disease 3

No Hepatic Concerns

Do not monitor liver function specifically for this overdose, as acamprosate has no hepatic metabolism and no reported instances of hepatotoxicity. 5, 1

• Unlike naltrexone and disulfiram, acamprosate is the preferred agent in patients with alcohol-associated liver disease due to its complete lack of hepatotoxicity 5
• The presence of liver disease does not change acamprosate dosing or safety considerations 5
• Acamprosate is not metabolized by the liver and can be safely used even in patients with hepatic insufficiency 4, 6

Pharmacokinetic Context

Understand that steady-state concentrations are reached in 5-7 days with therapeutic dosing, so this single double-dose will not cause sustained elevation. 4

• The terminal elimination half-life is approximately 20-33 hours with enteric-coated formulations 4
• A single double dose will be cleared within several days without accumulation 4
• The accumulation ratio at steady state is 2.4, meaning therapeutic dosing already involves some accumulation 4

Clinical Pitfalls to Avoid

• Do not discontinue acamprosate due to this single dosing error, as the drug is safe in overdose and interruption may compromise treatment efficacy 2, 7
• Do not confuse this with alcohol withdrawal, as acamprosate does not treat or prevent withdrawal symptoms 3
• Do not order extensive laboratory monitoring beyond baseline renal function if indicated, as the drug's safety profile does not warrant it 1, 2

Follow-Up Instructions

Resume the correct dose of 333mg at the next scheduled time without attempting to "skip" doses to compensate. 3

• Continue the standard regimen of 666mg (two 333mg tablets) three times daily as prescribed 3
• Ensure the patient understands the correct dosing to prevent future errors 3
• Reinforce that acamprosate should be continued even if alcohol relapse occurs 3