Besobrial

Acamprosate is indicated as therapy to maintain abstinence in alcohol-dependent patients. It should be combined with counselling.

Posology

Adults within the age range 18-65 years:

- 2 tablets three times daily with meals (2 tablets morning, noon and night) in subjects weighing 60kg or more.

- In subjects weighing less than 60kg, 4 tablets divided into three daily doses with meals (2 tablets in the morning, 1 at noon and 1 at night).

Older people

Acamprosate should not be used in older people

Paediatric population

Acamprosate should not be used in children

The recommended treatment period is one year. Treatment with acamprosate should be initiated as soon as possible after the withdrawal period and should be maintained if the patient relapses.

Acamprosate does not prevent the harmful effects of continuous alcohol abuse. Continued alcohol abuse negates the therapeutic benefit, therefore acamprosate treatment should only be initiated after weaning therapy, once the patient is abstinent from alcohol.

−

− Lactating women

− In cases of renal insufficiency (serum creatinine >120 micromol/L)

The safety and efficacy of Besobrial has not been established in patients younger than 18 years or older than 65 years. Besobrial is therefore not recommended for use in these populations.

The safety and efficacy of Besobrial has not been established in patients with severe liver insufficiency (Childs-Pugh Classification C).

Because the interrelationship between alcohol dependence, depression and suicidality is well-recognised and complex, it is recommended that alcohol-dependent patients, including those treated with acamprosate, be monitored for such symptoms.

Abuse and dependence

Non-clinical studies suggest that acamprosate has little or no abuse potential. No evidence of dependence on acamprosate was found in any clinical study thus demonstrating that acamprosate has no significant dependence potential.

Besobrial has no influence on the ability to drive and use machines.

According to information collected during clinical trials and spontaneous reports since marketing authorization, the following adverse reactions may occur under treatment with Besobrial.

The following definitions apply to the frequency terminology used hereafter:

very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare (> 1/10,000, < 1/1,000), very rare (< 1/10,000, including isolated cases), frequency not known (cannot be estimated from the available data)

Gastrointestinal disorders:

Very common: Diarrhoea

Common: Abdominal pain, nausea, vomiting, flatulence

Skin and subcutaneous tissue disorders:

Common: Pruritus, maculo-papular rash

Not known: Vesiculo-bullous eruptions

Immune system disorders:

Very rare: Hypersensitivity reactions including urticaria, angio-oedema or anaphylactic reactions.

Reproductive system and breast disorders:

Common: Frigidity or impotence.

Psychiatric disorders:

Common: Decreased libido

Uncommon: Increased libido

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Acute overdose is usually mild. In the reported cases, the only symptom, which can be reasonably related to overdose is diarrhoea. No case of hypercalcaemia has ever been reported. Treatment of overdose is directed to symptoms.

Acamprosate (calcium acetylhomotaurinate) has a chemical structure similar to that of amino acid neuromediators, such as taurine or gamma-amino-butyric acid (GABA), including an acetylation to permit passage across the blood brain barrier. Acamprosate may act by stimulating GABAergic inhibitory neurotransmission and antagonising excitatory amino-acids, particularly glutamate. Animal experimental studies have demonstrated that acamprosate affects alcohol dependence in rats, decreasing the voluntary intake of alcohol without affecting food and total fluid intake.

Acamprosate absorption across the gastrointestinal tract is moderate, slow and sustained and varies substantially from person to person. Food reduces the oral absorption of acamprosate. Steady state levels of acamprosate are achieved by the seventh day of dosing. Acamprosate is not protein bound.

Oral absorption shows considerable variability and is usually less than 10% of the ingested drug in the first 24 hours. The drug is excreted in the urine and is not metabolised significantly. There is a linear relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate.

The kinetics of acamprosate are not modified in group A or B of the Child-Pugh classification of impaired liver function, a population which is likely to be part of the target population for acamprosate. This is in accordance with the absence of hepatic metabolism of the drug.

In the preclinical studies, signs of toxicity are related to the excessive intake of calcium and not to acetylhomotaurine. Disorders of phosphorus/calcium metabolism have been observed including diarrhoea, soft tissue calcification, renal and cardiac lesions. Acamprosate had no mutagenic or carcinogenic effect, nor any teratogenic or adverse effects on the male or female reproductive systems of animals. Detailed in vitro and in vivo research on acamprosate to detect genetic and chromosomal mutations has not produced any evidence of potential genetic toxicity.

Not applicable

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.