What is the recommended dosing schedule for acamprosate (Campral) in an adult patient with alcohol use disorder and potentially impaired renal (kidney) function?

Acamprosate Dosing Schedule

The standard dosing regimen for acamprosate is 666 mg (two 333 mg tablets) taken three times daily, with dose reduction to 333 mg three times daily required for patients with moderate renal impairment (creatinine clearance 30-50 mL/min), and the medication is contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min). 1

Standard Dosing for Adults with Normal Renal Function

• Acamprosate should be administered as 666 mg (two 333 mg tablets) three times daily, totaling 1,998 mg per day 2, 1
• The three-times-daily (TID) dosing schedule is necessary to maintain therapeutic plasma concentrations throughout the day 2
• Steady-state plasma concentrations are reached within 5-7 days of initiating therapy 1, 3
• Treatment should be initiated as soon as possible after alcohol withdrawal and continued as part of a comprehensive management program that includes psychosocial support 1

Critical Consideration: Renal Function Assessment

Because acamprosate is exclusively renally excreted without hepatic metabolism, renal function must be assessed before initiating therapy and monitored during treatment. 2, 4, 1

Dosing Adjustments Based on Renal Function:

• Normal renal function (CrCl >50 mL/min): 666 mg three times daily (standard dose) 1
• Moderate renal impairment (CrCl 30-50 mL/min): Reduce dose to 333 mg (one tablet) three times daily 1
• Severe renal impairment (CrCl ≤30 mL/min): Acamprosate is contraindicated 1

The pharmacokinetic rationale for these adjustments is compelling: peak plasma concentrations are approximately 2-fold higher in moderate renal impairment and 4-fold higher in severe renal impairment compared to patients with normal renal function 1. The elimination half-life similarly increases 1.8-fold and 2.6-fold, respectively 1.

Timing and Food Considerations

• Acamprosate can be taken without regard to meals, though food decreases bioavailability by approximately 23-42% 1
• This food effect is not considered clinically significant and does not require dosage adjustment 1
• The medication should be taken at consistent times throughout the day to maintain steady plasma levels 3
• The enteric-coated formulation should not be crushed or chewed 1

Advantages in Liver Disease

Acamprosate is particularly advantageous for patients with alcohol-associated liver disease because it has no hepatic metabolism and no reported instances of hepatotoxicity, unlike naltrexone and disulfiram which undergo hepatic metabolism and can cause liver damage 2, 4

• No dosage adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh classes A and B) 1
• This makes acamprosate the preferred pharmacotherapy option in patients with alcohol-associated liver disease who have normal or moderately impaired renal function 2

Common Pitfalls to Avoid

• Do not use acamprosate in patients with severe renal impairment (CrCl ≤30 mL/min), as this is an absolute contraindication due to excessive drug accumulation 1
• Do not forget to reduce the dose in moderate renal impairment—failure to adjust can lead to unnecessarily high plasma concentrations 1
• Do not assume hepatic dosing adjustments are needed—acamprosate requires no modification for liver disease, which is a key advantage over other alcohol use disorder medications 1, 5
• Ensure patients understand the three-times-daily schedule is necessary—twice-daily dosing is inadequate for maintaining therapeutic levels 2, 3

Safety and Tolerability

• Acamprosate is generally well tolerated with the most common adverse effects being diarrhea (16% vs 10% placebo) and flatulence (3% vs 2% placebo) 5
• The medication has a low propensity for drug interactions and does not affect the metabolism of other commonly used medications 1, 5
• No clinically significant interactions occur with alcohol, disulfiram, diazepam, naltrexone, or imipramine 1, 3