What is the recommended use and dosage of acamprosate (Campral) for treating alcohol dependence?

Acamprosate for Alcohol Dependence

Acamprosate is the only pharmacological intervention with sufficient high-quality evidence demonstrating superiority over placebo for maintaining abstinence in detoxified alcohol-dependent patients, and should be initiated 3-7 days after the last alcohol consumption once withdrawal symptoms have resolved. 1, 2, 3

Recommended Dosage

Standard dosing is 666 mg (two 333 mg tablets) three times daily for a total of 1998 mg per day. 3

• For patients weighing less than 60 kg, reduce the dose by one-third to 1332 mg daily (one 333 mg tablet three times daily) 2, 3
• Dosing may be done without regard to meals, though taking with meals is suggested for patients who regularly eat three meals daily 3
• For patients with moderate renal impairment (creatinine clearance 30-50 mL/min), use 333 mg three times daily 3
• Contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min) 3

Critical Timing for Initiation

Acamprosate must be started only after detoxification is complete and the patient has achieved abstinence—not immediately after sobering up. 2, 3

• Initiate 3-7 days after the last alcohol consumption and only after withdrawal symptoms have resolved 2
• The drug is ineffective in patients who have not undergone detoxification or achieved abstinence prior to treatment 3
• This timing is critical because acamprosate's mechanism is maintaining rather than inducing remission 1, 2

Treatment Duration

Continue treatment for 3-6 months minimum, with potential extension up to 12 months. 2

• Treatment should be maintained even if the patient relapses during therapy 3
• Evidence supports efficacy up to 12 months, with the 2020 BMJ network meta-analysis showing acamprosate as the only intervention with moderate-quality evidence for maintaining abstinence up to 12 months 1
• Long-term follow-up data (27 months) demonstrates sustained benefit beyond the active treatment period 4

Mechanism and Clinical Effects

Acamprosate modulates N-methyl-D-aspartic acid (NMDA) receptor transmission and has structural similarities to gamma-aminobutyric acid (GABA) 2, 5

• Reduces withdrawal symptoms and alcohol craving by promoting balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters 1, 5
• Decreases the rate of relapse, maintains abstinence, and reduces severity of relapse when it occurs 1, 2
• More effective at maintaining abstinence than inducing it 1, 2

Evidence Base

The 2020 BMJ systematic review and network meta-analysis found acamprosate to be the only intervention with sufficient high-quality evidence (moderate certainty) to conclude superiority over placebo for maintaining abstinence in primary care settings. 1

• This analysis included 17 trials with 2,268 participants receiving acamprosate 1
• Acamprosate showed an odds ratio of 1.77 (95% CI 1.50-2.10) for maintaining abstinence compared to placebo 1
• The absolute probability of maintaining abstinence was 59% with acamprosate versus 45% with placebo 1
• Dropout rates were favorable: 42% with acamprosate versus 50% with placebo (OR 0.73,95% CI 0.62-0.86) 1

Comparison to Other Agents

Unlike naltrexone and disulfiram, evidence for acamprosate's efficacy in maintaining abstinence is more robust, and it has unique advantages in patients with liver disease. 1

• The 2020 BMJ analysis found insufficient evidence to recommend naltrexone or disulfiram for maintaining abstinence in detoxified patients 1
• Acamprosate is not metabolized by the liver, making it suitable for patients with alcoholic liver disease 2, 5
• The American College of Gastroenterology specifically recommends acamprosate (or naltrexone) in combination with counseling for patients with alcohol-induced liver disease 1

Essential Combination with Psychosocial Support

Acamprosate must be used as part of a comprehensive psychosocial treatment program—this is an FDA requirement and guideline recommendation. 3

• All clinical trials demonstrating efficacy included concomitant psychosocial/behavioral therapies 6, 4
• The drug's efficacy is more pronounced when combined with counseling and support 1

Safety Profile and Tolerability

Acamprosate is generally well tolerated with minimal adverse effects 3, 4

• Most common adverse event is diarrhea, which is typically mild and transient 6, 4
• Withdrawal rates due to adverse events are similar to placebo 6, 7
• No abuse potential, no hypnotic, antidepressant, anxiolytic, or muscle-relaxant effects 6
• Does not potentiate toxic effects of alcohol and is not impacted by ongoing alcohol use 5
• Contains sodium sulfite, which may cause allergic reactions in susceptible individuals 3

Drug Interactions

Acamprosate has minimal drug interactions and does not affect cytochrome P450 metabolism. 3

• No effect on CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 systems 3
• Pharmacokinetics unaffected by co-administration with alcohol, disulfiram, or diazepam 3
• When combined with naltrexone, acamprosate levels increase by 25-33%, but no dosage adjustment is needed 3

Common Pitfalls to Avoid

Starting acamprosate immediately after sobering up or before complete detoxification significantly reduces efficacy. 2, 3

• The drug works by maintaining abstinence, not inducing it—patients must be abstinent at initiation 1, 2, 3
• Failing to combine with psychosocial support undermines treatment effectiveness 2, 3
• Discontinuing treatment prematurely (before 3-6 months) limits optimal benefit 2
• Not adjusting dose for patients <60 kg or those with moderate renal impairment 2, 3
• Using in patients with severe renal impairment (contraindicated) 3

Special Populations

Acamprosate requires no dosage adjustment in hepatic impairment but requires careful consideration in renal impairment. 3

• Mild to moderate hepatic impairment (Child-Pugh A and B): No dosage adjustment needed 3
• Moderate renal impairment (CrCl 30-50 mL/min): Reduce to 333 mg three times daily 3
• Severe renal impairment (CrCl ≤30 mL/min): Contraindicated 3
• Elderly patients likely have higher plasma concentrations due to age-related decline in renal function 3
• Not evaluated in pediatric populations 3