Acamprosate Dosing for Alcohol Dependence
The recommended dose of acamprosate is 666 mg (two 333 mg tablets) taken three times daily, for a total daily dose of 1,998 mg in patients weighing ≥60 kg. 1
Standard Dosing Regimen
- For patients ≥60 kg: 666 mg (two 333 mg tablets) three times daily (total 1,998 mg/day) 2, 1
- For patients <60 kg: Reduce dose by one-third to 1,332 mg/day 2, 3
- Dosing schedule: Three times daily, which can be taken with or without meals, though taking with meals was used in clinical trials 1
Critical Timing Considerations
Acamprosate must be initiated 3-7 days after the last alcohol consumption and only after withdrawal symptoms have completely resolved. 2, 3, 1 This timing is essential because:
- Acamprosate works by maintaining abstinence rather than inducing it 3
- Starting too early (immediately after sobering up) reduces efficacy 3
- The drug reaches therapeutic concentrations within 1-2 weeks of starting treatment 2
Duration of Treatment
- Standard treatment period: 3-6 months 3
- Extended treatment: Can continue up to 12 months 3
- Important: Continue acamprosate even if the patient relapses during treatment 1
Dose Adjustments for Renal Impairment
Moderate renal impairment (CrCl 30-50 mL/min): Reduce to 333 mg three times daily 1
Severe renal impairment (CrCl ≤30 mL/min): Acamprosate is contraindicated 1
Key Advantages in Liver Disease
Acamprosate has no hepatic metabolism and no reported hepatotoxicity, making it particularly suitable for patients with alcohol-associated liver disease. 2 This is a critical distinction from naltrexone and disulfiram, which undergo hepatic metabolism and carry hepatotoxicity concerns 2
Essential Treatment Context
- Acamprosate must be part of a comprehensive psychosocial treatment program 1, 3
- The number needed to treat to prevent return to any drinking is approximately 12 2
- Steady-state plasma concentrations are reached after 5-7 days of treatment 4
Common Pitfalls to Avoid
- Do not start before complete detoxification: The drug is ineffective if withdrawal is not complete 3, 1
- Do not use as monotherapy: Always combine with psychosocial support 3, 1
- Do not discontinue prematurely: Minimum 3-6 months needed for optimal results 3
- Do not forget dose adjustment: Reduce dose by one-third in patients <60 kg 2, 3
Pharmacokinetic Profile
- Absorption: Rapid but limited via paracellular route in GI tract 4
- Distribution: Moderate volume of approximately 20L 4
- Metabolism: None—excreted unchanged 4
- Elimination: 50% renal, 50% possibly biliary 4
- Half-life: Terminal elimination half-life is prolonged with enteric-coated formulation 4
Alternative Dosing Considerations
While a reduced frequency regimen (500 mg twice daily) has been shown to be bioequivalent to the traditional three-times-daily dosing 5, the standard FDA-approved regimen of 666 mg three times daily should be used as first-line given the robust clinical trial data supporting this dosing schedule 1, 6, 7.