SUMMARY OF PRODUCT CHARACTERISTICS,
LABELLING AND PACKAGE LEAFLET
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SUMMARY OF PRODUCT CHARACTERISTICS
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1. NAME OF THE MEDICINAL PRODUCT
Acamprosate 333 mg Gastro-resistant Tablets.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each gastro-resistant tablet contains acamprosate calcium 333.0 mg as the active ingredient.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Gastro-resistant tablet.
White, round, biconvex coated tablet with “M” over “AC” printed in black ink on one side of the tablet and blank on the other side.
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
Posology
Adults within the age range 18-65 years - 2 tablets three times daily with meals (2 tablets in the 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).
Paediatric population and older people Acamprosate should not be administered to children, adolescents and the elderly.
Duration of treatment 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.
Method of administration
For oral use. Swallow this tablet whole. Do not chew or crush the tablet as this may damage the gastro-resistant coating.
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4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Breast-feeding women (see section 4.6) Patients with renal impairment (serum creatinine >120 micromol/l)
4.4 Special warnings and precautions for use
The safety and efficacy of acamprosate has not been established in patients younger than 18 years or older than 65 years. Acamprosate is therefore not recommended for use in these populations.
The safety and efficacy of acamprosate 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.
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.
In clinical trials, acamprosate has been safely administered in combination with antidepressants, anxiolytics, hypnotics and sedatives, and non-opioid analgesics.
No change in the frequency of clinical and/or biological adverse reactions has been shown when acamprosate is used concomitantly with disulfiram, oxazepam, tetrabamate or meprobamate.
Pharmacokinetic studies have been completed and show no interaction between acamprosate and diazepam, imipramine.
There is no information available on the concomitant administration of acamprosate with diuretics.
4.6 Fertility, pregnancy and lactation
Pregnancy There are no adequate data from the use of acamprosate in pregnant women. Animal studies do not indicate any evidence of foetotoxicity or tetragenicity. Acamprosate must therefore only be used during pregnancy after a careful benefit/risk assessment, when the patient cannot abstain from drinking alcohol without being treated with acamprosate and when there is consequently a risk of foetotoxicity or teratogenicity due to alcohol.
Breast-feeding It is known that acamprosate is excreted in the milk of lactating animals. It is not known whether acamprosate is excreted in human milk. There are no adequate data from the use of acamprosate in infants. Acamprosate must therefore not be used in breastfeeding women.
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If a breastfeeding woman cannot abstain from drinking alcohol without being treated with acamprosate, a decision must be made whether to discontinue breast-feeding or to discontinue Acamprosate, taking into account the importance of the medicinal product to the woman.
Fertility In animal studies, no adverse effects on fertility were observed. Whether or not acamprosate affects the fertility in humans is unknown.
4.7 Effects on ability to drive and use machines
Acamprosate has no influence on the ability to drive and use machines.
4.8 Undesirable effects
According to information collected during clinical trials and spontaneous reports since marketing authorisation, the following adverse reactions may occur under treatment with Acamprosate.
The following definitions apply to the frequency terminology used hereafter: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Immune system disorders: Very rare: Hypersensitivity reactions including urticaria, angio-oedema or anaphylactic reactions.
Psychiatric disorders: Common: Decreased libido. Uncommon: Increased libido.
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.
Reproductive system and breast disorders: Common: Frigidity or impotence.
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 [to be completed nationally]
4.9 Overdose
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.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
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Pharmacotherapeutic group: Drugs used in addictive disorders, drugs used in alcohol dependence, ATC code: N07BB03
Mechanism of action 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.
Pharmacodynamic effects 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
Absorption 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.
Oral absorption shows considerable variability and is usually less than 10% of the ingested drug in the first 24 hours.
Distribution Acamprosate is not protein bound.
Biotransformation The drug is not metabolised significantly.
Elimination The drug is excreted in the urine.
Linearity There is a linear relationship between creatinine clearance values and total apparent plasma clearance, renal clearance and plasma half-life of acamprosate.
Hepatic impairment 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
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Tablet Core: Glycerol dibehenate Cellulose, microcrystalline Hypromellose Silica, Colloidal anhydrous Magnesium stearate
Tablet seal coating: Hypromellose
Tablet gastro-resistant coating: Methacrylic acid-ethyl acrylate copolymer Talc Propylene glycol
Printing Ink: Shellac Iron oxide black (E172) Propylene glycol (E1520) Ammonium hydroxide (E527)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
PVC blister in packs of 84, 168 and multipacks containing 168 (2 packs of 84) tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
[To be completed nationally]
8. MARKETING AUTHORISATION NUMBER(S)
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[To be completed nationally]
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
[To be completed nationally]
10. DATE OF REVISION OF THE TEXT
[To be completed nationally]
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LABELLING
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARDBOARD CARTON
1. NAME OF THE MEDICINAL PRODUCT
Acamprosate 333 mg Gastro-resistant Tablets. acamprosate calcium
2. STATEMENT OF ACTIVE SUBSTANCE
Each tablet contains 333 mg acamprosate calcium.
3. LIST OF EXCIPIENTS
4. PHARMACEUTICAL FORM AND CONTENTS
Gastro-resistant tablet.
84 gastro-resistant tablets 168 gastro-resistant tablets
5. METHOD AND ROUTE OF ADMINISTRATION
For oral use.
Tablets should be swallowed whole and not chewed or crushed.
Read the package leaflet before use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
8. EXPIRY DATE
EXP
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9. SPECIAL STORAGE CONDITIONS
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
Batch/Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Acamprosate 333 mg Gastro-resistant Tablets.
17. UNIQUE IDENTIFIER – 2D BARCODE
2D barcode carrying the unique identifier included
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
PC: {number} SN: {number} NN: {number}
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARDBOARD CARTON OF MULTIPACK
1. NAME OF THE MEDICINAL PRODUCT
Acamprosate 333 mg Gastro-resistant Tablets. acamprosate calcium
2. STATEMENT OF ACTIVE SUBSTANCE
Each tablet contains 333 mg acamprosate calcium.
3. LIST OF EXCIPIENTS
4. PHARMACEUTICAL FORM AND CONTENTS
Gastro-resistant tablet.
Multipack: 168 (2 packs of 84) gastro-resistant tablets
5. METHOD AND ROUTE OF ADMINISTRATION
For oral use.
Tablets should be swallowed whole and not chewed or crushed.
Read the package leaflet before use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
8. EXPIRY DATE
EXP
9. SPECIAL STORAGE CONDITIONS
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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
Batch/Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Acamprosate 333 mg Gastro-resistant Tablets.
17. UNIQUE IDENTIFIER – 2D BARCODE
2D barcode carrying the unique identifier included
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
PC: {number} SN: {number} NN: {number}
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INNER CARDBOARD CARTON OF MULTIPACK
1. NAME OF THE MEDICINAL PRODUCT
Acamprosate 333 mg Gastro-resistant Tablets. acamprosate calcium
2. STATEMENT OF ACTIVE SUBSTANCE
Each tablet contains 333 mg acamprosate calcium.
3. LIST OF EXCIPIENTS
4. PHARMACEUTICAL FORM AND CONTENTS
Gastro-resistant tablet.
84 gastro-resistant tablets Component of a multipack, can’t be sold separately.
5. METHOD AND ROUTE OF ADMINISTRATION
For oral use.
Tablets should be swallowed whole and not chewed or crushed.
Read the package leaflet before use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7. OTHER SPECIAL WARNING(S), IF NECESSARY
8. EXPIRY DATE
EXP
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9. SPECIAL STORAGE CONDITIONS
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
Batch/Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
17. UNIQUE IDENTIFIER – 2D BARCODE Kommentiert [ZM1]: This inner cardboard carton of multipack must have the poits 17,18 but empty , via guideline 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
PVC BLISTER
1. NAME OF THE MEDICINAL PRODUCT
Acamprosate 333 mg Gastro-resistant Tablets. acamprosate calcium
2. NAME OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
3. EXPIRY DATE
EXP
4. BATCH NUMBER
Batch/Lot
5. OTHER
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PACKAGE LEAFLET
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Package leaflet: Information for the patient
Acamprosate 333 mg Gastro-resistant Tablets
acamprosate calcium
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet 1. What Acamprosate is and what it is used for 2. What you need to know before you take Acamprosate 3. How to take Acamprosate 4. Possible side effects 5. How to store Acamprosate 6. Contents of the pack and other information
1. What Acamprosate is and what it is used for
Acamprosate is a medicine which acts on the central nervous system (the brain and the spinal cord). Acamprosate is used for the treatment of alcohol dependence. It helps to maintain abstinence in alcohol-dependent patients. Acamprosate in combination with counselling will help you to not drink alcohol. It does this by acting on the chemical changes that have taken place in the brain during the years that you have been drinking alcohol. It does not prevent the harmful effects of continuous alcohol abuse.
2. What you need to know before you take Acamprosate
Do not take Acamprosate: - if you are allergic to acamprosate or any of the other ingredients of this medicine (listed in section 6). - if you are breast-feeding. - if you suffer from severe kidney disease.
Warnings and precautions
Talk to your doctor or pharmacist before taking Acamprosate.
Acamprosate is not recommended for use: - if you are a patient below the age 18 years or if you are above the age 65 years. - if you suffer from severe liver disease.
If you drink too much alcohol, your body and in particular your nervous system adapt to the effects of alcohol. When you then suddenly stop drinking you may experience some unpleasant symptoms
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known as alcohol withdrawal syndrome. You should take Acamprosate as soon as possible after the withdrawal period.
Because patients who suffer from alcohol dependence often also suffer from depression and are at risk of thinking about suicide, it is recommended that you be monitored for symptoms of depression and thoughts of committing suicide.
Other medicines and Acamprosate
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Acamprosate has often been given to patients together with other medicines that are used to treat alcohol withdrawal or maintain abstinence. So far, acamprosate does not seem to interfere with the effects of other medicines, however if you are prescribed diuretics (water tablets) talk to your doctor.
Acamprosate with alcohol
Drinking alcohol while taking Acamprosate does not make you feel sick, however do not drink alcohol at all during your treatment with Acamprosate. Even if you drink a small amount of alcohol you run the risk of making your treatment fail and you may end up drinking heavily again.
Pregnancy and breast-feeding
Pregnancy: If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Breast-feeding: If you are breastfeeding, do not take Acamprosate because it is not known whether this medicine passes into breast milk.
Driving and using machines Acamprosate has no influence on the ability to drive and use machines.
3. How to take Acamprosate
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Dosage: Adults within the age range 18-65 years: - If you weigh 60kg or more, the recommended dose is 6 tablets a day: 2 tablets in the morning, 2 tablets at noon and 2 tablets in the evening with meals.
- If you weigh less than 60kg, the recommended dose is 4 tablets a day: 2 in the morning, 1 at noon and 1 in the evening with meals.
Duration of treatment: It is recommended that you keep taking Acamprosate for one year.
Method of administration
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Swallow this tablet whole. Do not chew or crush the tablet as this may damage the gastro-resistant coating.
If you take more Acamprosate than you should
If you take too many tablets, call your doctor or hospital casualty department immediately. You may experience symptoms of diarrhoea such as frequent loose or watery stools, abdominal cramps, stomach pains, fever, feeling sick and vomiting.
If you forget to take Acamprosate
Do not take a double dose to make up for a forgotten dose. If you forget to take a dose, take it as soon as you remember it and then take the next dose at the right time.
If you stop taking Acamprosate
Talk to your doctor before you stop taking the tablets and follow their advice.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. If you notice any of the following serious side effects, stop taking acamprosate and contact your doctor immediately:
Very rare (may affect up to 1 in 10,000 people) severe allergic reaction causing a rash, itching or hives (urticaria) on the skin, swelling of the face, lips, tongue or other parts of the body (angioedema) or shortness of breath, trouble breathing with rash, swelling, wheezing and feeling faint (anaphylaxis reaction)
Other side effects include:
Very common (may affect more than 1 in 10 people) diarrhoea
Common (may affect up to 1 in 10 people) stomach ache feeling sick (nausea) vomiting excessive gas in the stomach or bowel (flatulence) spotty red skin rash decreased sexual desire (libido)
Uncommon (may affect up to 1 in 100 people) increased sexual desire (libido)
Not known (frequency cannot be estimated from the available data) blistering rash characterised by patches of skin filled fluid (vesiculo-bullous eruptions)
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.
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Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via [to be completed nationally]. By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store Acamprosate
Keep this medicine out of the sight and reach of children.
This medicinal product does not require any special storage conditions.
Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
What Acamprosate contains
The active substance is acamprosate calcium. Each gastro-resistant tablet contains 333 mg acamprosate calcium.
The other ingredients are glycerol dibehenate, microcrystalline cellulose, hypromellose, silica colloidal anhydrous and magnesium stearate. The coating includes hypromellose, methacrylic acid- ethyl acrylate copolymer, talc, propylene glycol. The printing ink contains shellac, iron oxide black (E172), propylene glycol (E1520) and ammonium hydroxide (E527).
What Acamprosate looks like and contents of the pack
Acamprosate gastro-resistant tablets are white, round, biconvex coated tablet with “M” over “AC” printed in black ink on one side of the tablet and blank on the other side.
Acamprosate is available in blister packs of 84, 168 and in a multipack of 168 comprising of 2 cartons, each containing 84 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
[To be completed nationally]
Manufacturer
Generics [UK] Ltd, Station Close, Potters Bar, Hertfordshire, EN6 1TL, UK
Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland.
Mylan Hungary Kft, H-2900 Komárom Mylan útca 1, Hungary
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This medicinal product is authorised in the Member States of the EEA under the following names:
Slovakia – Acamprosat Mylan 333mg United Kingdom - Acamprosate 333 mg Gastro-resistant Tablets
This leaflet was last revised in {MM/YYYY}.
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