Starting Dose of Acamprosate for Alcohol Use Disorder
The recommended starting dose of acamprosate for adult patients with AUD is 666 mg (two 333 mg tablets) taken three times daily, totaling 1,998 mg per day. 1
Standard Dosing Protocol
For patients weighing ≥60 kg:
- Administer 666 mg (two 333 mg tablets) three times daily 2, 1
- Total daily dose: 1,998 mg 3, 1
- The three-times-daily schedule is necessary to maintain therapeutic plasma concentrations throughout the day 3
For patients weighing <60 kg:
- Reduce dose by one-third to 1,332 mg daily (one 333 mg tablet three times daily) 4
- This weight-based adjustment optimizes efficacy while minimizing side effects 5
Critical Timing Considerations
Treatment initiation requires the patient to be abstinent first:
- Start acamprosate 3-7 days after the last alcohol consumption, once withdrawal symptoms have resolved 4, 1
- The patient must complete detoxification and achieve abstinence before beginning therapy 1
- Acamprosate does not treat alcohol withdrawal and is ineffective if started during active drinking 4
Common pitfall: Starting acamprosate too early during or immediately after withdrawal reduces efficacy, as the medication is designed to maintain abstinence, not induce it 4.
Dosing Adjustments for Renal Impairment
Acamprosate is exclusively renally excreted, making renal function assessment mandatory before initiation: 3, 1
- Normal renal function (CrCl >50 mL/min): Standard dose of 666 mg three times daily 1
- 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
Critical consideration: Unlike naltrexone and disulfiram, acamprosate has no hepatic metabolism, making it the preferred option for patients with alcohol-associated liver disease who have adequate renal function 2, 3.
Administration Guidelines
Dosing can be done without regard to meals, though taking with meals may improve tolerability: 1
- Clinical trials employed dosing with meals 1
- Consider meal-based dosing for patients who regularly eat three meals daily to enhance adherence 1
- Food decreases absorption but this does not significantly impact clinical efficacy 5
Steady-state plasma concentrations are reached within 5-7 days of consistent dosing 4, 5
Treatment Duration and Continuation
Continue acamprosate even if the patient relapses to drinking: 1
- Maintain treatment through relapse episodes 1
- Typical treatment duration is 3-6 months, though it can extend to 12 months 4
- Clinical benefit emerges over sustained use of 3-12 months alongside psychosocial interventions 4
Acamprosate must be combined with comprehensive psychosocial support for optimal outcomes 1, 6
Safety Profile Relevant to Dosing
Most common side effects are gastrointestinal:
- Diarrhea occurs in 16% of patients (versus 10% with placebo) 7
- Flatulence in 3% (versus 2% with placebo) 7
- Most adverse events are mild to moderate and transient 7
No hepatotoxicity risk: Acamprosate has no reported instances of liver toxicity, making it particularly safe for patients with alcohol-associated liver disease 2, 3, 7
Alternative Dosing Considerations
While the FDA-approved regimen is 666 mg three times daily, some evidence suggests alternative approaches:
- A 3,000 mg daily dose showed trends toward higher abstinence rates (60.7% abstinent days) compared to standard 2,000 mg dose (56.1%) in one trial, though this higher dose is not FDA-approved 8
- Reduced frequency dosing (e.g., twice daily with higher strength tablets) may be bioequivalent but lacks robust clinical efficacy data 9
Recommendation: Stick with the FDA-approved 666 mg three times daily regimen, as it has the strongest evidence base and regulatory approval 1, 6.