Campral EC

1. Name Of The Medicinal Product

Campral EC

2. Qualitative And Quantitative Composition

Each tablet contains acamprosate (I.N.N.) calcium 333.0 mg as the active ingredient.

3. Pharmaceutical Form

Enterocoated tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Posology And Method Of Administration

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).

Children and the Elderly:

Acamprosate should not be administered to children and the elderly.

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.

4.3 Contraindications

Acamprosate is contraindicated:

− in patients with a known hypersensitivity to the drug

− in pregnant women and lactating women

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

− in cases with severe hepatic failure (Childs- Pugh Classification C)

4.4 Special Warnings And Precautions For Use

Acamprosate does not constitute treatment for the withdrawal period.

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.

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.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The concomitant intake of alcohol and acamprosate does not affect the pharmacokinetics of either alcohol or acamprosate. Administering acamprosate with food diminishes the bioavailability of the drug compared with its administration in the fasting state. Pharmacokinetic studies have been completed and show no interaction between acamprosate and diazepam, disulfiram or imipramine. There is no information available on the concomitant administration of acamprosate with diuretics.

4.6 Pregnancy And Lactation

Although animal studies have not shown any evidence of foetotoxicity or teratogenicity, the safety of acamprosate has not been established in pregnant women. Acamprosate should not be administered to pregnant women.

Acamprosate is excreted in the milk of lactating animals. Safe use of acamprosate has not been demonstrated in lactating women. Acamprosate should not be administered to breast feeding women.

4.7 Effects On Ability To Drive And Use Machines

Acamprosate should not impair the patient's ability to drive or operate machinery.

4.8 Undesirable Effects

The following definitions apply to the frequency terminology used hereafter: very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Gastrointestinal disorders:

Very common: Diarrhoea

Common: Abdominal pain, nausea, vomiting

Skin and subcutaneous tissue disorders:

Common: Pruritus, maculo-papular rash

Rare: Bullous skin reactions

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

4.9 Overdose

Five cases of overdose associated with acamprosate therapy have been reported in humans, including one patient who ingested 43g of acamprosate. After gastric lavage all patients had an uneventful recovery. Diarrhoea was observed in two cases. No case of hypercalcaemia was reported in the course of these overdoses. However, should this occur, the patients should be treated for acute hypercalcaemia.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

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.

5.2 Pharmacokinetic Properties

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.

5.3 Preclinical Safety Data

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.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Crospovidone (KOLLIDON CL)

Microcrystalline cellulose (AVICEL PH 101)

Magnesium silicate (COMPRESSIL)

Sodium starch glycolate (EXPLOTAB)

Anhydrous colloidal silica (AEROSIL 200)

Magnesium stearate

Anionic copolymer of methacrylic and acrylic acid ethyl ester (EUDRAGIT L30 D)

Talc

Propylene glycol

6.2 Incompatibilities

None known

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

None

6.5 Nature And Contents Of Container

Aluminium/PVC sheets of blisters presented in cartons of 168 tablets.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Merck Santé s.a.s

37 rue Saint Romain

69379 Lyon Cedex 08

France

8. Marketing Authorisation Number(S)

MA 13466/0001

9. Date Of First Authorisation/Renewal Of The Authorisation

18 December 1995 (first authorization)

10. Date Of Revision Of The Text

16 November 2007

LEGAL CATEGORY

POM