Can Acamprosate (Campral) be prescribed to an adult patient with a history of alcohol dependence during withdrawal?

Acamprosate Should NOT Be Prescribed During Active Alcohol Withdrawal

Acamprosate must be initiated only after withdrawal has completely resolved—specifically 3-7 days following the last alcohol consumption—and should never be started during active withdrawal. 1, 2, 3

Timing of Initiation: The Critical Window

The FDA label explicitly states that acamprosate should be "initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence" 3. This is not merely a suggestion but reflects the drug's mechanism of action and clinical efficacy profile:

• Acamprosate does not treat withdrawal symptoms and provides no benefit during the acute withdrawal phase 1
• The drug works by maintaining abstinence rather than inducing it, making it ineffective when started before complete detoxification 1, 2
• Treatment should begin 3-7 days after the last episode of alcohol consumption, once withdrawal symptoms have resolved 1, 2

Why This Timing Matters: Mechanism and Efficacy

Acamprosate modulates NMDA receptor transmission and restores the balance between glutamate and GABA neurotransmission that has been disrupted by chronic alcohol exposure 2, 4. However, this mechanism is designed for maintenance of abstinence, not acute withdrawal management:

• The drug's efficacy has not been demonstrated in subjects who have not undergone detoxification and achieved abstinence prior to beginning treatment 3
• Clinical trials consistently show acamprosate is effective for maintaining abstinence and preventing relapse, but not for managing acute withdrawal 5, 4
• The number needed to treat is 12 to prevent relapse to drinking, but only when initiated after detoxification 1

The Proper Clinical Algorithm

Step 1: Manage acute withdrawal with benzodiazepines (the gold standard for alcohol withdrawal syndrome) 6

Step 2: Complete the detoxification process and ensure the patient has achieved abstinence 2, 3

Step 3: Wait 3-7 days after the last alcohol consumption to allow withdrawal symptoms to fully resolve 1, 2

Step 4: Initiate acamprosate at the appropriate dose:

• For patients ≥60 kg: 666 mg (two 333 mg tablets) three times daily 1, 2
• For patients <60 kg: reduce dose by one-third to 1332 mg/day 1, 2
• For moderate renal impairment (CrCl 30-50 mL/min): 333 mg three times daily 3

Step 5: Continue treatment for 3-6 months (up to 12 months), combined with comprehensive psychosocial support 1, 2, 3

Evidence Addressing Early Initiation

One Spanish study attempted to initiate acamprosate during withdrawal rather than after detoxification 7. While this study found acamprosate did not cause unwanted effects when given during withdrawal, the standard of care remains to wait until withdrawal has resolved, as this approach has been validated in the majority of clinical trials and is reflected in FDA labeling 3.

Common Pitfalls to Avoid

• Starting acamprosate immediately after sobering up reduces efficacy since the drug's primary mechanism is maintaining abstinence, not inducing it 2
• Delaying appropriate benzodiazepine therapy by attempting to use acamprosate for withdrawal management, which it cannot do 1, 6
• Failing to wait the full 3-7 days after last alcohol consumption before initiating treatment 1, 2
• Not combining acamprosate with psychosocial support, which is essential for optimal outcomes 1, 2, 3

Key Safety Advantage for Post-Withdrawal Use

Unlike naltrexone and disulfiram, acamprosate has no hepatotoxicity risk and is not metabolized by the liver, making it the preferred agent for patients with alcohol-associated liver disease once they have completed withdrawal 1, 4. This is particularly important since many alcohol-dependent patients have comorbid liver disease 4.