Acamprosate Dosing Above 666mg Per Dose
No, you should not prescribe acamprosate at doses higher than 666mg per individual dose (three times daily), as the maximum approved daily dose is 1998 mg/day for patients ≥60 kg, administered as 666mg three times daily. 1
Standard Dosing Guidelines
The established dosing protocol for acamprosate is weight-based and clearly defined:
- For patients ≥60 kg: 666 mg (two 333 mg tablets) three times daily, totaling 1,998 mg per day 1, 2
- For patients <60 kg: Reduce dose by one-third to 1,332 mg daily (444 mg three times daily) 1, 3
- For moderate renal impairment (CrCl 30-50 mL/min): 333 mg three times daily 1
Evidence on Higher Doses
While one exploratory U.S. study examined a 3g daily dose (1000mg three times daily) versus the standard 2g dose, this higher dose showed only modest numerical improvements in abstinence rates (60.7% vs 56.1% abstinent days) without achieving statistical significance in primary analysis. 4 This exploratory dose has never been FDA-approved and should not be used in clinical practice.
The pharmacokinetic profile demonstrates that acamprosate exhibits dose-independent kinetics at the standard 666mg three-times-daily dosing, with steady-state achieved in 5-7 days and an accumulation ratio of 2.4. 5 There is no established evidence that exceeding standard dosing improves clinical outcomes sufficiently to justify off-label use.
Key Clinical Considerations
Liver disease does not require dose adjustment: The presence of liver disease, including severe alcoholic liver disease, does not change acamprosate dosing or safety considerations, making it the preferred agent in this population due to complete lack of hepatotoxicity. 6, 1 This is a critical advantage over naltrexone and disulfiram, which are contraindicated in hepatic insufficiency. 6
Renal function is the primary dosing determinant: Unlike hepatic metabolism, acamprosate is eliminated unchanged in urine, making renal function the sole factor requiring dose modification. 5, 7
Common Pitfalls to Avoid
- Do not increase doses beyond approved limits seeking enhanced efficacy—the evidence does not support this practice 4
- Do not confuse total daily dose with per-dose amount: The 1998 mg daily dose is divided into three 666mg doses, not given as a single dose 1
- Do not adjust dosing for liver disease: This is unnecessary and may lead to underdosing in patients who would benefit from standard therapy 6, 1