Acamprosate Dosing in Renal Impairment
For patients with moderate renal impairment (creatinine clearance 30-50 mL/min), reduce the dose to 333 mg three times daily (total 999 mg/day); acamprosate is contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min). 1
Standard Dosing for Normal Renal Function
- The recommended dose is 666 mg (two 333 mg tablets) three times daily, totaling 1,998 mg per day 2, 1
- This three-times-daily schedule maintains therapeutic plasma concentrations throughout the day 2
- Steady-state concentrations are reached within 5-7 days of dosing 3, 1
Dose Adjustments Based on Renal Function
Critical consideration: Because acamprosate is exclusively renally excreted without any hepatic metabolism, renal function must be assessed before initiating therapy 2, 1
Moderate Renal Impairment (CrCl 30-50 mL/min)
- Reduce dose to 333 mg three times daily (999 mg/day total) 3, 1
- Peak plasma concentrations are approximately 2-fold higher compared to patients with normal renal function 1
- Elimination half-life is approximately 1.8-fold longer 1
Severe Renal Impairment (CrCl ≤30 mL/min)
- Acamprosate is contraindicated 1
- Peak concentrations are 4-fold higher and half-life is 2.6-fold longer compared to normal renal function 1
- There is a linear relationship between creatinine clearance and total plasma clearance 1
Additional Dosing Considerations
Body Weight Adjustments
- Patients weighing ≥60 kg: full dose of 1,998 mg/day 3
- Patients weighing <60 kg: reduce by one-third to 1,332 mg/day (two 333 mg tablets twice daily) 3
Timing of Initiation
- Treatment should begin 3-7 days after the last alcohol consumption, once withdrawal symptoms have resolved 3, 1
- Patients must be detoxified and abstinent before starting 3
- Acamprosate does not treat withdrawal and should only be initiated after withdrawal has resolved 3
Advantages in Alcohol-Associated Liver Disease
Acamprosate is the preferred pharmacotherapy option for patients with alcohol-associated liver disease who have normal or moderately impaired renal function 2
- No hepatic metabolism and no reported hepatotoxicity 2, 3
- Unlike naltrexone (contraindicated in alcoholic liver disease) and disulfiram (avoided in severe liver disease), acamprosate requires no dose adjustment for hepatic impairment 3, 1, 4
- Pharmacokinetics are not altered in patients with mild to moderate hepatic impairment (Child-Pugh A and B) 1
Treatment Duration and Monitoring
- Typical treatment period is 3-6 months, though can extend to 12 months 3
- Clinical benefit emerges over 3-12 months of consistent use alongside psychosocial interventions 3
- Treatment should be maintained even if the patient relapses 1
- Renal function must be monitored during treatment 2
Common Pitfall to Avoid
The most critical error is failing to assess renal function before prescribing acamprosate, as the drug's exclusive renal excretion makes dose adjustment or contraindication mandatory in renal impairment 2, 1. Additionally, do not initiate acamprosate during active withdrawal or before abstinence is achieved 3, 1.