Acamprosate

Acamprosate is thought to reduce drinking by modulating brain GABA (gamma-aminobutyric acid) and glutamate function which is implicated in withdrawal symptoms. The drug only reaches desired levels in the brain after one to two weeks.  

Meta-analyses of randomised controlled trials indicate acamprosate is effective in maintaining abstinence from alcohol and reducing the risk of returning to any drinking with a number needed to treat (NNT) of 12 over placebo.

Based on available evidence, acamprosate is a suitable treatment option for patients with AUD (usually moderate to severe), who are medically stable and are willing to comply with the dosing regimen.

Acamprosate has been suggested to be more effective for patients with an abstinence goal rather than preventing excessive drinking in non-abstinent patients, however this remains to be ascertained as it may be due to a lack of studies evaluating these specific outcomes.

Acamprosate is contraindicated in patients with a known hypersensitivity to the drug, renal insufficiency or severe hepatic failure (Childs Pugh classification C). 

There is an absence of well controlled studies and therefore it should not be administered to women who are pregnant or breastfeeding. 

• Acamprosate is a safe medicine with regards to pharmacological interactions.
• Acamprosate does not interact with alcohol.
• Tetracyclines may be rendered inactive by the calcium component in acamprosate.

Acamprosate dosing is recommended to begin 3-7 days after the patient’s last drink, and after resolution of any acute withdrawal symptoms.  Starting acamprosate at the beginning of detoxification versus after completion of detoxification has not been shown to improve treatment outcomes. Starting acamprosate after the resolution of withdrawal symptoms may prevent the possibility of worsening of withdrawal symptoms and to distinguish between side-effects and withdrawal symptoms.  

Medical history should be taken, as per Chapter 4. Physical examination may include assessment for signs of chronic liver disease and hepatic failure. Investigations may include tests of kidney function (urea and electrolytes), since 90 percent of acamprosate is excreted through the kidney, and liver function tests.

Acamprosate is formulated in tablets of 333mg, with the recommended dose for adults being 1998mg with meals (six tablets/day, orally in three doses: 2; 2; 2). Adults under 60kg should take 1332 mg/day (four tablets/day in three doses: 2; 1; 1).

In individuals with moderate renal dysfunction (creatinine clearance 30 to 50 ml/min) an initial dose of 333mg three times daily is recommended by the manufacturer.

Acamprosate is available in tablets. It is subsidised by the Pharmaceutical Benefit Scheme.

The usual treatment period is 3-6 months. However, the decision on the duration of treatment should be made on a case-by-case basis between the patient and doctor, based on side effects, history of relapse, social and family circumstances and other individual factors.

Acamprosate is usually well tolerated. Its predominantly gastrointestinal adverse effects, commonly diarrhoea, usually resolve spontaneously within days. Mild abdominal pain, rash or isolated pruritus, parasthesiae, altered libido and confusion have been reported at low frequencies.

The following strategies are recommended:

• Patient education about expected side effects and duration.
• Distinguishing between prolonged alcohol withdrawal symptoms and side effects of acamprosate by beginning treatment once more pronounced features of withdrawal have subsided (after first 3-5 days).

Treatment should continue even if the patient lapses; psychosocial relapse prevention techniques should be used to deal with the lapse or relapse.

The clinician should regularly monitor the patient’s progress and attend to physical, mental health and social issues as they arise.

Some patients will have difficulty adhering to a medication regime that involves taking tablets three times a day for prolonged periods (see below for strategies).

There is no evidence of a withdrawal syndrome following the use of acamprosate or of developing dependence. Psychosocial relapse prevention interventions should continue beyond the end of pharmacotherapy.