What is the recommended dosing of acamprosate (Campral) for a patient with alcohol dependence and potential impaired renal function?

Acamprosate Dosing

For patients with normal renal function and body weight ≥60 kg, administer acamprosate 666 mg (two 333 mg tablets) three times daily for a total of 1,998 mg/day; for patients <60 kg, reduce the dose by one-third to 1,332 mg/day (one 333 mg tablet twice daily plus one tablet once daily). 1

Standard Dosing by Body Weight

• Patients ≥60 kg: 666 mg (two 333 mg tablets) three times daily = 1,998 mg/day total 2, 3, 4, 1
• Patients <60 kg: Reduce dose by one-third to 1,332 mg/day (typically one 333 mg tablet three times daily) 2, 3
• The three-times-daily dosing schedule is necessary to maintain therapeutic plasma concentrations throughout the day 4

Dosing in Renal Impairment

Renal function assessment is critical before initiating acamprosate because it is exclusively renally excreted without hepatic metabolism. 4, 1

• Moderate renal impairment (CrCl 30-50 mL/min): Reduce to 333 mg three times daily (999 mg/day total) 1
• Severe renal impairment (CrCl ≤30 mL/min): Acamprosate is contraindicated 1
• Peak plasma concentrations are approximately 2-fold higher in moderate renal impairment and 4-fold higher in severe renal impairment compared to normal renal function 1

Timing of Initiation

Initiate acamprosate 3-7 days after the last alcohol consumption, once the patient has achieved abstinence and withdrawal symptoms have resolved. 2, 3, 1

• Acamprosate does not treat alcohol withdrawal and should never be started during active withdrawal 3
• Treatment should be maintained even if the patient relapses to drinking 1

Treatment Duration and Pharmacokinetics

• Standard treatment duration: 3-6 months, though can extend up to 12 months 2, 3
• Steady-state plasma concentrations are reached within 5-7 days of initiating therapy 3, 1, 5
• The desired therapeutic concentration is achieved within 1-2 weeks 2

Administration Considerations

• Dosing may be done without regard to meals, though dosing with meals was used in clinical trials and is suggested for patients who regularly eat three meals daily 1
• Food decreases bioavailability by approximately 23-42%, but this is not clinically significant and requires no dose adjustment 1, 5

Safety Advantages in Liver Disease

Acamprosate is the preferred pharmacotherapy for alcohol-dependent patients with liver disease because it has no hepatic metabolism and no reported hepatotoxicity, unlike naltrexone and disulfiram. 3, 4

• No dosage adjustment is needed in patients with mild to moderate hepatic impairment (Child-Pugh A and B) 2, 1
• Acamprosate is particularly advantageous for patients with alcohol-associated liver disease who have normal or moderately impaired renal function 4

Critical Pitfalls to Avoid

• Never use acamprosate in severe renal impairment (CrCl ≤30 mL/min) - it is absolutely contraindicated due to 4-fold higher drug exposure 1
• Never initiate during active alcohol withdrawal - wait until withdrawal has resolved (3-7 days post-cessation) 2, 3, 1
• Always assess renal function before starting and monitor during treatment, as acamprosate is 100% renally excreted 4, 1
• Acamprosate must be combined with psychosocial support and counseling to be effective 3, 1