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 (CrCl ≤30 mL/min). 1
Standard Dosing for Normal Renal Function
For patients weighing ≥60 kg with normal renal function, administer 666 mg (two 333 mg tablets) three times daily, totaling 1,998 mg per day. 2, 3, 1
For patients weighing <60 kg, reduce the dose by one-third to 1,332 mg daily (444 mg three times daily). 2, 4
The three-times-daily dosing schedule is necessary to maintain therapeutic plasma concentrations throughout the day, with steady-state reached within 5-7 days. 3, 1, 5
Dosing may be done without regard to meals, though food decreases bioavailability by approximately 23-42%; this reduction is not clinically significant and requires no adjustment. 1, 5
Critical Dosing Adjustments for Renal Impairment
Acamprosate is exclusively renally excreted without hepatic metabolism, making renal function assessment mandatory before initiating therapy. 3, 1
Moderate Renal Impairment (CrCl 30-50 mL/min)
Reduce dose to 333 mg three times daily (total 999 mg/day). 1
Peak plasma concentrations are approximately 2-fold higher in moderate renal impairment compared to normal renal function, with elimination half-life prolonged 1.8-fold. 1
There is a linear relationship between creatinine clearance and total apparent plasma clearance of acamprosate. 1
Severe Renal Impairment (CrCl ≤30 mL/min)
Acamprosate is absolutely contraindicated in severe renal impairment. 1
Peak plasma concentrations are 4-fold higher and elimination half-life is 2.6-fold longer compared to normal renal function, creating unacceptable drug accumulation. 1
Advantages in Liver Disease
Acamprosate is the preferred pharmacotherapy for alcohol dependence in patients with liver disease because it has no hepatic metabolism and no reported hepatotoxicity, unlike naltrexone and disulfiram. 2, 3
No dosage adjustment is required for hepatic impairment (Child-Pugh A and B), as acamprosate is not metabolized by the liver. 1
This makes acamprosate particularly valuable for patients with alcohol-associated liver disease who have adequate renal function. 3
Timing of Initiation
Treatment must be initiated 3-7 days after the last alcohol consumption, only after withdrawal symptoms have completely resolved. 2, 4, 1
Acamprosate does not treat withdrawal and should never be started during active withdrawal. 2
The patient must be detoxified and abstinent before starting therapy. 2
Full therapeutic dose can be started immediately without titration, unlike medications such as gabapentin. 4
Treatment Duration
Continue treatment for a minimum of 3-6 months, with potential extension up to 12 months. 2, 4
Maintain treatment even if the patient relapses to alcohol use. 1
Clinical benefit emerges over 3-12 months of consistent use alongside psychosocial interventions. 2
Common Pitfalls to Avoid
Do not use acamprosate in patients with CrCl ≤30 mL/min – this is an absolute contraindication due to dangerous drug accumulation. 1
Always calculate creatinine clearance before prescribing – elderly patients are at particular risk for unrecognized renal impairment. 1
Do not start during active withdrawal – wait until withdrawal has fully resolved (3-7 days post-last drink). 2, 4
Monitor for suicidality, as suicidal ideation and attempts occur more frequently with acamprosate (1.4-2.4%) compared to placebo (0.5-0.8%). 1