Acamprosate

Acamprosate is used to help maintain abstinence in alcohol dependence after detoxification. It reduces craving and the unpleasant symptoms of early abstinence, and it is started as soon as possible after withdrawal, while the patient is still abstinent. It works only with psychosocial support. It is not metabolised by the liver, so it can be used in liver disease, but it is contraindicated in severe kidney impairment.

Classification. Anti-craving agent for alcohol dependence, glutamate modulator.

Mechanism. Modulates glutamatergic NMDA receptor activity and restores balance between excitatory and inhibitory signalling that is disrupted by chronic alcohol use.

Pharmacokinetics. Poorly absorbed orally (bioavailability about 11%); food reduces absorption by about 20%. Not metabolised and not bound to plasma proteins. Excreted unchanged in urine. Half-life about 20 to 33 hours. Steady state in about 7 days.

All regimens are oral with no loading dose.

Maintenance of abstinence in alcohol dependence, adults.

• Weight over 60 kg: 666 mg (two 333 mg tablets) three times daily.
• Weight 60 kg or under: 666 mg in the morning, 333 mg at midday and 333 mg at night.
• Start as soon as possible after alcohol withdrawal and continue even if the patient relapses.
• Duration: up to 12 months, with psychosocial support.

Dose limits. Kidney impairment with creatinine clearance 30 to 50 mL/min: 333 mg three times daily. Creatinine clearance under 30 mL/min: contraindicated. Liver impairment: no adjustment. Older adults: no formal adjustment but check kidney function.

Contraindications. Creatinine clearance 30 mL/min or lower, hypersensitivity, pregnancy, breastfeeding.

Serious adverse effects. Suicidal ideation and behaviour (rare), depression, severe skin reactions (rare), hypersensitivity reactions, mania or hypomania (rare).

Common adverse effects. Diarrhoea, nausea, vomiting, abdominal pain, pruritus, rash, reduced or increased libido, anxiety, dizziness.

Interactions. No clinically important cytochrome interactions. Naltrexone raises acamprosate levels modestly and can be combined with it. Alcohol does not interact, but continued drinking reduces the benefit.

Common prescribing errors. Starting before detoxification is complete; giving to patients with severe kidney impairment; using the wrong dose for body weight; stopping after a lapse; using without psychosocial support.

Special groups.

• Pregnancy: contraindicated.
• Breastfeeding: contraindicated.
• Children: not established.
• Older adults: check kidney function.
• Kidney impairment: reduce the dose to 333 mg three times daily if creatinine clearance is 30 to 50 mL/min; contraindicated at 30 mL/min or lower.
• Liver impairment: no adjustment, so it is useful in alcohol-related liver disease.

Formulations. Enteric-coated tablets 333 mg. Swallow whole with water, at mealtimes, with three doses spaced across the day.

Baseline. Kidney function, alcohol history and abstinence status, mood and suicide risk, pregnancy status.

Monitoring. Review adherence, craving and alcohol use weekly at first and then monthly. Check kidney function periodically and mood at each visit.

Stopping. No taper is needed; stop after the planned course.

Referral and escalation. Refer to addiction services for repeated relapse or comorbid mental illness. Suicidal thoughts or a severe skin reaction needs the drug stopped and urgent review.