Consumer medicine information

APO-Acamprosate

Acamprosate calcium

BRAND INFORMATION

Brand name

APO-Acamprosate

Active ingredient

Acamprosate calcium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Acamprosate.

What is in this leaflet

Read this leaflet carefully before taking your medicine. This leaflet answers some common questions about acamprosate. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

You can also download the most up to date leaflet from www.apotex.com.au.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

Keep this leaflet with your medicine. You may want to read it again.

What this medicine is used for

The name of your medicine is APO-Acamprosate Coated Tablets. It contains the active ingredient acamprosate calcium.

It is used to treat alcohol dependence. It helps people who are dependent on alcohol to abstain from drinking alcoholic beverages.

Alcohol dependence is an illness that can and should be treated. Drinking too much alcohol may harm your health and cause physical, psychological and social problems. If this happens to you, your doctor may advise you to stop drinking alcohol altogether.

If you drink too much alcohol, your body and nervous system adapt to its effects. When you suddenly stop drinking, you may experience some unpleasant symptoms (known as alcohol withdrawal syndrome or the "shakes"), which can last up to 2 weeks.

During alcohol withdrawal, you may feel shaky, have an upset stomach, a fast heart beat and high blood pressure. You may also feel anxious, down, or be in a bad mood.

Sometimes, you may see things that are not there, or suffer from a headache or not be able to sleep.

If these symptoms are severe, you may need observation in hospital.

After going through this difficult period, your doctor will encourage you to live without alcohol through counselling. Acamprosate, in combination with counselling from a general practitioner, psychiatrist, psychologist, or a drug and alcohol counsellor, will help you to stop yourself from starting to drink again.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

How it works

This medicine works by acting on certain chemical changes that have taken place in your brain over the time that you have been drinking alcohol.

There is no evidence that this medicine is addictive.

Use in children

This medicine should not be used in children.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You have or have had any of the following:
    - kidney impairment
    - severe liver problems.
  • You are pregnant.
    Acamprosate may affect your developing baby if you take it during pregnancy.
  • You are breastfeeding.
    Acamprosate may pass into human breast milk.
  • You are hypersensitive to, or have had an allergic reaction to, ac or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include: shortness of breath, wheezing, difficulty breathing or tightness in chest; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting; or hay fever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.

Before you start to take it

As this medicine does not treat the symptoms of alcohol withdrawal, it is recommended that you start this medicine:

  • after you have stopped drinking; and
  • as soon as the withdrawal symptoms have ended.

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • kidney disease
  • liver disease.
  1. You plan to become pregnant. Do not take this medicine whilst pregnant.
  2. You plan to breastfeed. Do not take this medicine whilst breastfeeding.
  3. You are planning to have surgery or an anaesthetic.
  4. You are currently receiving or are planning to receive dental treatment.
  5. You are taking or are planning to take any other medicines. This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Taking other medicines

Some medicines may interact with acamprosate, such as naltrexone.

How to take this medicine

Follow carefully all directions given to you by your doctor or pharmacist. Their instructions may be different to the information in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

The recommended dosages by patient weight are:

Over 60 kg:

2 tablets three times a day.

Under 60 kg:

2 tablets in the morning, 1 tablet at midday and 1 tablet at night.

Do not stop taking your medicine or change your dosage without first checking with your doctor or pharmacist.

How to take it

Swallow the tablets whole with a glass of water.

Do not break, crush or chew the tablets. The tablets have a special coating to prevent stomach upset.

When to take it

Take this medicine at the same time each day. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

This medicine should be taken with meals.

How long to take it for

This medicine is usually taken for one year.

Continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose, skip the missed dose and take your next dose at the usual time. Otherwise, take it as soon as you remember and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for missed doses. This may increase the chance of you experiencing side effects.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints to help you remember.

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively, go to the Accident and Emergency department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking this medicine

Things you must do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breastfeeding or are planning to breastfeed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects. Go to your doctor regularly for a check-up.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Take your medicine to treat any other condition unless your doctor tells you to.
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

Things to be careful of

Drinking alcohol while taking this medicine will not make you feel sick. However, you are advised not to drink alcohol at all during your treatment with this medicine. Even if you only drink a little alcohol, you run the risk of making your treatment fail.

Possible side effects

Tell your doctor as soon as possible if you do not feel well while you are taking acamprosate or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor if you notice any of the following:

  • diarrhoea
  • nausea (feeling sick), vomiting, upset stomach, wind
  • itching, skin rash
  • change in sex drive.

Other side effects not listed above may occur in some patients.

Allergic reactions

If you think you are having an allergic reaction to acamprosate, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • shortness of breath, wheezing, difficulty breathing or tightness in chest
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hay fever-like symptoms.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it. If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 30°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What APO-Acamprosate Enteric Coated Tablets looks like

333 mg enteric coated tablets:
White to off-white coloured, round-shaped, biconvex enteric coated tablets engraved with "APO" on one side and "300" on the other side.

Blister pack of 180 tablets.

Ingredients

Each enteric coated tablet contains 333 mg of acamprosate calcium as the active ingredient.

It also contains the following inactive ingredients:

  • Methylcellulose
  • hyprolose
  • Crospovidone
  • Magnesium Stearate
  • Methacrylic Acid Copolymer
  • Triethyl Citrate
  • purified talc
  • Sodium hydroxide.

This medicine is gluten-free, lactose-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

APO-Acamprosate 333 mg tablets (Blister Pack): AUST R 286652.

Sponsor

Arrotex Pharmaceuticals Pty Ltd
15 - 17 Chapel Street, Cremorne
VIC, Australia, 3121
www.arrotex.com.au

APO and APOTEX are registered trade marks of Apotex Inc.

This leaflet was last updated in:
February 2023.

Published by MIMS March 2023

BRAND INFORMATION

Brand name

APO-Acamprosate

Active ingredient

Acamprosate calcium

Schedule

S4

 

1 Name of Medicine

Acamprosate calcium.

2 Qualitative and Quantitative Composition

Each enteric coated tablet contains 333 mg acamprosate calcium as the active ingredient.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White to off-white coloured, round-shaped, biconvex, enteric coated tablets, engraved with "APO" on one side and "300" on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

APO-Acamprosate Tablets are intended for oral administration.

Dosage.

Treatment with acamprosate calcium should be initiated as soon as possible after the withdrawal period and should be maintained if the patient relapses. The recommended period of treatment is 1 year.
Acamprosate calcium enteric coated tablets should be taken with meals, and swallowed whole.
Based on the clinical results the daily dose is fixed according to body weight:
For adults weighing 60 kg or more, the dose is 2 tablets taken three times daily (i.e. 2 tablets in the morning, at midday and at night).
In adults weighing less than 60 kg, the dose is 2 tablets in the morning, 1 tablet at midday and 1 tablet at night.
Lower doses might be ineffective. The efficacy and safety of higher doses have not been established.

4.3 Contraindications

Acamprosate calcium enteric coated tablets are contraindicated in:
patients with a known hypersensitivity to the medicine;
pregnant or breastfeeding women;
renal insufficiency (serum creatinine > 120 micromol/L);
severe hepatic failure (Child-Pugh Classification C).

4.4 Special Warnings and Precautions for Use

Acamprosate does not constitute treatment for the withdrawal period.
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 respective symptoms.
Each tablet contains 33.3 mg of calcium. In preclinical studies, various signs of toxicity were observed, including diarrhoea, hyperkeratosis and dysplasia of the stomach, soft tissue calcification, and increased deaths due to renal and cardiac lesions in the rat.

Use in hepatic impairment.

The safety and efficacy of acamprosate calcium enteric coated tablets has not been established in patients with severe hepatic failure (Child-Pugh Classification C).

Use in the elderly.

The safety and efficacy of acamprosate calcium enteric coated tablets has not been established in patients older than 65 years. Acamprosate calcium enteric coated tablets should not be administered to the elderly.

Paediatric use.

The safety and efficacy of acamprosate calcium enteric coated tablets has not been established in patients younger than 18 years. Acamprosate calcium enteric coated tablets should not be administered to children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The concomitant intake of alcohol and acamprosate calcium does not affect the pharmacokinetics of either alcohol or acamprosate.
Administering acamprosate calcium with food diminishes the bioavailability of the medicine compared with its administration in the fasting state.
Pharmacokinetic studies show no interaction between acamprosate calcium and diazepam, disulfiram or imipramine.
Since pharmaco-interaction studies have not been performed with all psychotropic medicines, when acamprosate is administered simultaneously with such medicines, it is advisable to monitor the patient carefully for possible interactions.
Co-administration of naltrexone with acamprosate produced a 25% increase in AUC and a 33% increase in Cmax of acamprosate; however, this finding has limited clinical impact so that no adjustment of dosage is necessary in such patients. The pharmacokinetics of naltrexone and its major metabolite 6-beta-naltrexol were unaffected following co-administration with acamprosate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No adverse effects on fertility or reproduction were observed in male or female mice administered acamprosate at oral doses up to 2400 mg/kg daily (approximately 6 times human exposure at the maximum recommended clinical dose, based on BSA), prior to and throughout mating and gestation.
In an equivalent study in rats, no effects were seen at daily oral doses up to 1000 mg/kg (approximately 5 times human exposure at the maximum recommended clinical dose, based on BSA).
(Category B2)
Acamprosate crosses the placenta and is distributed into fetal tissue following oral administration to pregnant rats. Acamprosate administered during organogenesis was not teratogenic in mice, rats or rabbits at daily oral doses up to 2400 mg/kg, 2000 mg/kg and 1000 mg/kg, respectively (approximately 6, 10 and 9 times human exposure at the maximum recommended clinical dose, based on BSA). The safety of acamprosate calcium has not been established in pregnant women. Acamprosate calcium enteric coated tablets should not be administered to pregnant women (see Section 4.3 Contraindications).
Acamprosate calcium is excreted in the milk of lactating animals. Safe use of acamprosate calcium has not been demonstrated in lactating women. Acamprosate calcium enteric coated tablets must not be administered to breastfeeding women (see Section 4.3 Contraindications).
If a breastfeeding woman cannot abstain from drinking alcohol without being treated with acamprosate, a decision must be made whether to discontinue nursing or to discontinue acamprosate calcium enteric coated tablets, taking into account the importance of the medicinal product to the woman.

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 Adverse Effects (Undesirable Effects)

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

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 suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems and contact Arrotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Symptoms.

Acute overdosage with acamprosate is usually benign. In all reported cases, the only symptom which could be reasonably ascribed to acamprosate overdose was diarrhoea. A risk of hypercalcaemia should be considered in chronic overdosage only.

Treatment.

Treatment of overdosage should be symptomatic and supportive.
For information on the management of overdose contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Acamprosate calcium has a chemical structure similar to that of amino acid neuromediators, such as taurine or gamma-aminobutyric acid (GABA), including an acetylation to facilitate passage across the blood brain barrier. Pharmacodynamic studies have been unable to confirm any specific neuromodulatory effect via amino acid receptors. If acamprosate is administered to rats during the induction of ethanol-dependence, the elevation of extracellular brain glutamate concentrations seen during ethanol withdrawal is decreased. In studies in rats and dogs, there was inconclusive evidence of significant distribution of acamprosate into the brain following oral administration of radiolabelled medicine.
Animal experimental studies have demonstrated that acamprosate calcium decreases the voluntary intake of drinking water containing alcohol without affecting food and total fluid intake. The mechanism for this effect in rats is unclear.

Clinical trials.

In an extensive clinical research programme, acamprosate proved its efficacy as an adjuvant to psycho-social therapy over long treatment periods of up to one year, independent of the country where the trial was performed and the type of psycho-social programme applied.
The primary outcome criteria was abstinence, defined as no alcohol intake whatsoever. In the combined efficacy analysis which pooled data from 3338 weaned alcohol dependent patients, despite this very stringent definition (more reliable from a standardisation point of view), the clinical data demonstrated that:
there is a doubling of the absolute abstinence rate after one year treatment when compared to placebo with 22% of the acamprosate treated patients remaining completely abstinent for one year compared to 12% in the placebo group;
patient compliance to remain in the treatment was statistically significantly different from Day 90 onwards with 50% retention rate in patients on acamprosate compared with 40% on placebo at the end of the one year treatment period;
the drink-free periods (Cumulative Abstinent Duration calculated as a fraction of the total abstinent days over the total duration of exposure to treatment) were much longer in the active treatment group in 11 of 12 comparative studies: 53.3 ± 38.5% in acamprosate group compared to 40 ± 35.4% in the placebo group;
there is no overt rebound drinking after termination of treatment and no signs of medicine withdrawal.

5.2 Pharmacokinetic Properties

Absorption.

Oral absorption shows considerable variability and is usually less than 10% of the ingested medicine in the first 24 hours.
Acamprosate calcium absorption across the gastrointestinal tract is moderate, slow and sustained and varies substantially from person to person. Food reduces the oral absorption of acamprosate calcium.

Distribution.

After a single acamprosate dose of 2 x 333 mg tablets, peak plasma concentrations of approximately 200 nanogram/mL are reached after 5 to 7 hours and longer. After a 15 minute infusion of 666 mg of acamprosate, the volume of distribution is on average 72 ± 3 L.
Steady-state levels of acamprosate calcium are achieved by the seventh day of dosing. Acamprosate calcium is not protein bound.

Metabolism and excretion.

The medicine 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 calcium. After oral dosing of 666 mg of acamprosate, the apparent elimination half life ranged from 13 to 28.4 hours.

Hepatic dysfunction.

The pharmacokinetics of acamprosate calcium are not altered by hepatic dysfunction.

5.3 Preclinical Safety Data

Genotoxicity.

Acamprosate showed no evidence of genotoxicity in a series of assays for gene mutations (bacterial and mammalian cells) and chromosomal damage (human lymphocytes in vitro and micronucleus formation in vivo).

Carcinogenicity.

In carcinogenicity studies, mice and rats were administered acamprosate in the diet for 91 and 104 weeks, respectively. In mice, there was no evidence of an increased incidence of tumours at doses up to 400 mg/kg/day, a dose which approximates the human exposure at the maximum recommended clinical dose, based on body surface area (BSA). In male rats, there was an increased incidence of adrenal phaeochromocytomas at 400 mg/kg/day (approximately twice human exposure at the maximum recommended clinical dose, based on BSA). Dietary calcium can lead to adrenal medullary proliferative disease in rats but there is no evidence that increased dietary calcium poses a risk of increased adrenal medullary lesions in humans.

6 Pharmaceutical Particulars

6.1 List of Excipients

Methylcellulose, hyprolose, crospovidone, magnesium stearate, methacrylic acid copolymer, triethyl citrate, purified talc, sodium hydroxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

APO-Acamprosate tablets.

333 mg tablets.

Blister (Alu/PVC) of 180 tablets (AUST R 286652).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Acamprosate calcium is a white, odourless or practically odourless powder with a bitter taste. It is freely soluble in water, practically insoluble in absolute ethanol and dichloromethane. The parameters such as Log P/ Partition coefficient is -3.57 and pKa value is 1.8.

Chemical structure.


Chemical Name: Calcium bis[3-(acetylamino) propane-1-sulphonate].
Molecular Formula: C10H20N2O8S2Ca.
Molecular Weight: 400.5.

CAS number.

77337-76-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes