Consumer medicine information

Amcal Strong Pain Relief Extra Tablets

Paracetamol; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Amcal Strong Pain Relief Extra

Active ingredient

Paracetamol; Codeine phosphate hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amcal Strong Pain Relief Extra Tablets.

What is in this Leaflet?

This leaflet answers some common questions about Amcal Strong Pain Relief Extra Tablets. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Amcal Strong Pain Relief Extra Tablets against the benefits this medicine is expected to have for you.

Keep this information with the medicine. You may need to read it again.

What are Amcal Strong Pain Relief Extra Tablets used for

This medicine may be addictive if taken for more than a few days at a time.

Amcal Strong Pain Relief Extra Tablets are used to relieve moderate to severe pain.

Amcal Strong Pain Relief Extra Tablets contain paracetamol and codeine phosphate hemihydrate. Paracetamol and codeine phosphate hemihydrate work together to stop the pain messages from getting through to the brain. Paracetamol also acts in the brain to reduce fever.

Your doctor or pharmacist may have given you this medicine for another use.

If you want more information, ask your doctor.

Before you take Amcal Strong Pain Relief Extra Tablets

When you must not take it

You should not take Amcal Strong Pain Relief Extra Tablets if you are allergic to paracetamol or codeine or any of the ingredients listed under ‘Product Description”. The symptoms of an allergic reaction may include a rash, asthma attack or hay fever.

Do not take this medicine if you have any of the following conditions:

  • acute breathing difficulties such as bronchitis, unstable asthma or emphysema
  • chronic constipation
  • diarrhoea caused by antibiotics or poisoning

Do not take this medicine if you regularly drink large quantities of alcohol.

Do not take codeine during labour, especially if the baby is premature. The medicine may produce withdrawal effects in the newborn baby.

Ask your doctor or pharmacist about taking Amcal Strong Pain Relief Extra Tablets if you are breastfeeding. A small amount of codeine passes into the breast milk. It may cause breathing problems in newborn infants.

Amcal Strong Pain Relief Extra Tablets may be used during pregnancy. However, ask your pharmacist or doctor about the risks and benefits of taking Amcal Strong Pain Relief Extra Tablets while you are pregnant.

Do not take Amcal Strong Pain Relief Extra tablets during label, especially if the baby is premature.

This medicine may produce withdrawal effects in the newborn baby.

Do not use Amcal Strong Pain Relief Extra tablets if you are breastfeeding or planning to breastfeed.

Do not use Amcal Strong Pain Relief Extra Tablets in children under 12 years.

Ask your doctor about taking Amcal Strong Pain Relief Extra Tablets if you are over 65 years of age and have kidney or respiratory problems.

Do not use it after the expiry date (EXP) printed on the pack. If you take it after the expiry date it may have no effect at all, or worse, have an entirely unexpected effect.

Do not use Amcal Strong Pain Relief Extra Tablets if the packaging is torn or shows signs of tampering.

Before you start to take it

Do not take Amcal Strong Pain Relief Extra Tablets with other medicines containing paracetamol or codeine, unless advised to do so by a doctor.

You must tell your doctor if:

  • You have allergies to any ingredients listed under “Product Description” at the end of this leaflet.
  • You have any of these conditions:
    - Liver or kidney problems
    - Difficulty breathing, wheezing, chronic cough, asthma or other chronic breathing conditions
    - You drink large quantities of alcohol
    - You have a history or drug or alcohol abuse
    - Recent surgery on the stomach or intestines
    - Head injury
    - Enlarged prostate
    - Low blood pressure
    - Underactive thyroid
  • You should tell your pharmacist or doctor if you are using any other medicines including any of the following medicines:
    - Any medicines causing sleepiness
    - Tranquillisers (medicines for anxiety and nerves)
    - Medicines which thin the blood (e.g. warfarin)
    - Medicines to treat epilepsy
    - Metoclopramide, a medicine used to control nausea and vomiting
    - Chloramphenicol, an antibiotic used to treat ear and eye infections
    - Medicines used to relieve stomach cramps or spasms
    - Medicines used to prevent travel sickness
    - Medicines used to treat Parkinson’s disease
    - Medicines used to treat high blood pressure
    - Medicines for diarrhoea, such as kaolin, pectin and loperamide
    - Monoamine oxidase inhibitors, medicines used to treat depression, if taken within the last 14 days
    - Quinidine, a medicine used to treat abnormal or irregular heart beat
    - Phenothiazines and antipsychotic agents, medicines used to treat mental disorders
    - Other opioids, used to treat pain or suppress coughs
    - Alcohol
    - If you are an Ultra‐rapid metaboliser of CYP2D6
    - If you are aged below 18 years of age and have had your tonsils or adenoids removed to treat sleep apnoea

These medicines may be affected by Amcal Strong Pain Relief Extra Tablets or affect how well Amcal Strong Pain Relief Extra Tablets work.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

You should also tell your pharmacist or doctor about any other medicines that you have bought without a prescription from either your pharmacy, supermarket or health food shop.

If you have not told your pharmacist or doctor about any of these things, tell him/her before you take any Amcal Strong Pain Relief Extra Tablets.

How to take Amcal Strong Pain Relief Extra Tablets

The label on your pack Amcal Strong Pain Relief Extra Tablets will tell you how to take your medicine and how often. If you are unsure about the directions ask your doctor or pharmacist.

How much to take

The usual dose of Amcal Strong Pain Relief Extra Tablets is:

Adults and children over 12 years: 2 tablets.

This dosage may be repeated in 4‐6 hours if necessary. You should not take more than 8 tablets in a 24‐hour period.

How long to take it

Adults: Do not take this medicine for longer than a few days at a time unless advised to by a doctor.

Children aged over 12 years: Do not take this medicine for longer than 48 hours at a time, unless advised to by a doctor.

Keep to the recommended dose. If Amcal Strong Pain Relief Extra Tablets are not adequately controlling your pain, do not increase the dose. Please see your doctor.

How to take it

Swallow tablets whole with a little water or other liquid.

The directions given to you by your doctor may be different from the information in this leaflet. If you are unsure what dose to take, ask your doctor.

If you forget to take it

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the dose you missed, and take your next dose when you are meant to. Do not take a double dose to make up for the dose missed.

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

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Amcal Strong Pain Relief Extra Tablets.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention because of the risk of delayed, serious liver damage with an overdose of paracetamol.

Keep telephone numbers of these places handy.

If you take too many tablets you may feel nauseous, light headed, dizzy or drowsy.

While you are taking Amcal Strong Pain Relief Extra Tablets

Things you must do

Take Amcal Strong Pain Relief Extra Tablets exactly as your pharmacist or doctor has told you to.

Tell all your doctors, dentists and pharmacists that you are taking Amcal Strong Pain Relief Extra Tablets.

Tell your doctor if you become pregnant while taking Amcal Strong Pain Relief Extra Tablets.

Things you must NOT do

Do not use this medicine to treat any other complaint unless your doctor says it is safe. Do not give this medicine to anyone else even if they have the same symptoms as you.

Adults: Do not take this medicine for longer than a few days at a time unless advised to by a doctor.

Children aged over 12 years: Do not take this medicine for longer than 48 hours at a time, unless advised to by a doctor.

Do not take more than the recommended dose unless your doctor tells you to.

Things to be careful of

Amcal Strong Pain Relief Extra Tablets may cause dizziness or drowsiness in some people, especially after the first dose.

If affected do not drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or drowsy. Children should not ride bikes if affected and should be supervised to avoid potential harm. Do not drink alcohol.

Drinking alcohol increases the likelihood of becoming drowsy.

Codeine may be habit forming if taken in high doses for extended periods of time. Too much paracetamol may cause delayed, serious liver damage. Please ask your doctor or pharmacist if you are concerned about this.

About 8% of people are poor metabolisers of codeine. Amcal Strong Pain Relief Extra Tablets may not work as well if you are one of those people.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking Amcal Strong Pain Relief Extra Tablets.

Like other medicines, Amcal Strong Pain Relief Extra Tablets can cause some side effects. If they occur, they are most likely minor and temporary. However, sometimes they are serious and need medical treatment.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your pharmacist or doctor if you notice any of the following and they worry you:

Stomach problems such as:

  • Nausea
  • Vomiting
  • Stomach pain
  • Constipation

If you are taking Amcal Strong Pain Relief Extra Tablets regularly, you may also need to take laxatives to prevent constipation.

Difficulty thinking or working because of:

  • Dizziness
  • Drowsiness

Be careful driving or operating machinery until you know how Amcal Strong Pain Relief Extra Tablets affect you.

The above list includes the more common side effects of your medicine. They are usually mild.

Tell your doctor as soon as possible if you notice any of the following:

  • cough suppression
  • unusual or extreme mood swings
  • flushing of the face
  • fast heart beat.
  • The above list includes serious side effects that may require medical attention. Serious side effects are rare for low doses of this medicine and when used for a short period of time.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

If you believe Amcal Strong Pain Relief Extra Tablets are not working well for you, do not increase the dose. Please see your pharmacist or doctor.

Some people may get other side effects not listed above.

Tell your pharmacist or doctor you notice anything else that making you feel unwell.

After taking Amcal Strong Pain Relief Extra Tablets

Storage

Keep your tablets in the blister pack until it is time to take them.

If you take the tablets out of the box or the blister pack, they will not keep well.

Keep Amcal Strong Pain Relief Extra Tablets in a cool dry place where the temperature stays below 30°C.

Heat and dampness can destroy some medicines.

Do not leave Amcal Strong Pain Relief Extra Tablets in the car on hot days.

Do not store Amcal Strong Pain Relief Extra Tablets or any other medicine in the bathroom or near a sink.

Keep Amcal Strong Pain Relief Extra Tablets where young 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 the tablets, ask your pharmacist what to do with any tablets that are left over.

This is not all the information that is available on Amcal Strong Pain Relief Extra Tablets. If you have any more questions or are not sure about anything, ask your doctor or pharmacist.

Product Description

Amcal Strong Pain Relief Extra Tablets come as white to off white capsule shaped uncoated tablets, plain on one side and break line on the other side.

It is available in packs of 20 and 40* tablets.

* Not all pack sizes may be marketed.

Active ingredients:

Each tablet contains:

Paracetamol 500 mg
Codeine Phosphate Hemihydrate 15 mg

Other ingredients:

Starch — Potato, Lactose, Povidone, Docusate Sodium, Silica ‐ colloidal anhydrous, Magnesium Stearate.

Amcal Strong Pain Relief Extra Tablets do not contain any gluten, sucrose, tartrazine or any azo dyes.

Name and Address of the sponsor

Amcal Strong Pain Relief Extra Tablets are supplied in Australia by:

Sigma Company Limited
3 Myer Place
Rowville VIC 3178

AUST R 208319

This leaflet was updated in June 2021.

Published by MIMS September 2021

BRAND INFORMATION

Brand name

Amcal Strong Pain Relief Extra

Active ingredient

Paracetamol; Codeine phosphate hemihydrate

Schedule

S4

 

1 Name of Medicine

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg.

2 Qualitative and Quantitative Composition

Actives.

Each tablet contains paracetamol 500 mg and codeine phosphate hemihydrate 15 mg.

Excipients.

Starch - potato, lactose monohydrate, povidone, docusate sodium, silica colloidal anhydrous, magnesium stearate.

3 Pharmaceutical Form

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are white to off-white, capsule-shaped, uncoated tablets, plain on one side and with a break line on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of acute moderate pain in patients over the age of 12 years (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.2 Dose and Method of Administration

Adults and children over 12 years: 2 tablets four times a day if required (maximum 8 tablets in 24 hours).
Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are contraindicated for use in patients who are:
younger than 12 years;
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.3 Contraindications

Hypersensitivity to paracetamol or codeine or other ingredients (see Section 2 Qualitative and Quantitative Composition).
Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are also contraindicated for use in patients:
with severe respiratory disease, acute respiratory disease, and respiratory depression;
with chronic constipation;
during labour when delivery of a premature infant is anticipated as it may produce codeine withdrawal symptoms in the neonate;
with active alcoholism;
with diarrhoea caused by pseudomembranous colitis or poisoning (until the causative organism or toxin has been eliminated from the gastrointestinal tract, since codeine may slow down the elimination, thereby prolonging the diarrhoea);
who are CYP2D6 ultra rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
younger than 12 years of age (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy, and/or adenoidectomy for obstructive sleep apnoea due to an increased risk of developing serious life threatening adverse reactions (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
who are breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets contain the opioid codeine phosphate and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets at recommended doses.
The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Patients should be advised not to share Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets with anyone else.

Respiratory depression.

Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets, but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients, in patients with renal and hepatic impairment, and in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma). Opioids should be used with caution and with close monitoring in these patients (see Section 4.2 Dose and Method of Administration). The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations, (see Section 4.2 Dose and Method of Administration), together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response.

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while taking Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets.

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

Opioid analgesics have an established role in the treatment of acute pain, cancer pain and palliative and end-of-life care. Current evidence does not generally support opioid analgesics in improving pain and function for most patients with chronic non-cancer pain. The development of tolerance and physical dependence and risks of adverse effects, including hazardous and harmful use, increase with the length of time a patient takes an opioid. The use of opioids for long-term treatment of CNCP is not recommended.
The use of an opioid to treat CNCP should only be considered after maximised non-pharmacological and non-opioid treatments have been tried and found ineffective, not tolerated or otherwise inadequate to provide sufficient management of pain. Opioids should only be prescribed as a component of comprehensive multidisciplinary and multimodal pain management.
Opioid therapy for CNCP should be initiated as a trial in accordance with clinical guidelines and after a comprehensive biopsychosocial assessment has established a cause for the pain and the appropriateness of opioid therapy for the patient (see Hazardous and harmful use, above). The expected outcome of therapy (pain reduction rather than complete abolition of pain, improved function and quality of life) should be discussed with the patient before commencing opioid treatment, with agreement to discontinue treatment if these objectives are not met.
Owing to the varied response to opioids between individuals, it is recommended that all patients be started at the lowest appropriate dose and titrated to achieve an adequate level of analgesia and functional improvement with minimum adverse reactions. Immediate-release products should not be used to treat chronic pain, but may be used for a short period in opioid-naïve patients to develop a level of tolerance before switching to a modified-release formulation. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment. Discontinue opioid therapy if there is no improvement of pain and/or function during the trial period or if there is any evidence of misuse or abuse. Treatment should only continue if the trial has demonstrated that the pain is opioid responsive and there has been functional improvement. The patient's condition should be reviewed regularly, and the dose tapered off slowly if opioid treatment is no longer appropriate (see Ceasing opioids).

Tolerance, dependence and withdrawal.

Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid. Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced. Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
When discontinuing Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Ceasing opioids; Section 4.2 Dose and Method of Administration).

Accidental ingestion/exposure.

Accidental ingestion or exposure of Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets, especially by children, can result in a fatal overdose of codeine phosphate. Patients and their caregivers should be given information on safe storage and disposal of unused Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Hyperalgesia.

Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance, dependence and withdrawal). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.

Ceasing opioids.

Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance, dependence and withdrawal). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been taking, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.

Other precautions.

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets should be administered with caution to patients with hepatic or renal dysfunction.
It should be used with caution in patients who:
have raised intracranial pressure or head injury;
have prostatic hypertrophy;
have hypotension;
have hypothyroidism;
have had recent gastrointestinal tract surgery.
Codeine may obscure the diagnosis or the course of gastrointestinal diseases.
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.

CYP2D6 metabolism.

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are contraindicated for use in patients who are CYP2D6 ultra-rapid metabolisers.
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels. General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases, this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. Children are particularly susceptible due to their immature airway anatomy. Deaths have been reported in children with rapid metabolism who were given codeine for analgesia post adenotonsillectomy. Morphine can also be ingested by infants through breast milk, causing risk of respiratory depression in infants of rapid metaboliser mothers who take codeine.
The prevalence of codeine ultra-rapid metabolism by CYP2D6 in children is not known, but it is assumed to be similar to that reported in adults. The prevalence of ultra-rapid metabolisers is estimated to be 1% in those of Chinese, Japanese and Hispanic descent, 3% in African Americans and 1%-10% in Caucasians. The highest prevalence (16%-28%) occurs in North African, Ethiopian and Arab populations. Also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Use in the elderly.

The elderly are more likely to have age related renal impairment and may be more susceptible to the respiratory depressant effects of codeine.

Paediatric use.

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are contraindicated for use in children:
younger than 12 years;
aged between 12 - 18 years in whom respiratory function might be compromised, including post tonsillectomy and /or adenoidectomy for obstructive sleep apnoea. Respiratory depression and death have occurred in some children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-metabolisers of codeine due to CYP2D6 polymorphism. Also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism.
Due to the preparations sedative action, impairment of the mental and/or physical abilities required for the performance of potentially hazardous activities may occur. Hence, children engaging in bike riding and other hazardous activities should be supervised to avoid potential harm.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticoagulant drugs (warfarin) - dosage may require reduction if this medication and anticoagulants are taken for a prolonged period of time.
Paracetamol absorption is increased by drugs which increase gastric emptying, e.g. metoclopramide, and decreased by drugs which decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties and narcotic analgesics.
Paracetamol may increase chloramphenicol concentrations.
The likelihood of paracetamol toxicity may be increased by the concomitant use of other hepatotoxic drugs or liver microsomal enzyme inducing agents, such as alcohol or antiepileptic drugs.
Paracetamol excretion may be affected and plasma concentrations altered when given with probenecid.
Cholestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol.
CNS depressants, including alcohol - concomitant use of codeine with central nervous system (CNS) depressants (e.g. other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, and other CNS depressants) can cause additive CNS depression and may result in sedation, respiratory depression, coma and death. See Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.
Anticholinergics - concurrent use of codeine with anticholinergic agents may increase the risk of severe constipation and/or urinary retention.
Antihypertensives - hypotensive effects may be potentiated when used concurrently with codeine and lead to orthostatic hypotension.
Antiperistaltic antidiarrhoeals (e.g. kaolin, pectin and loperamide) - concurrent use with codeine may increase the risk of severe constipation.
Monoamine oxidase inhibitors (MAOIs) - concurrent administration or use within 14 days of ceasing MAOIs may enhance the potential respiratory depressant effects of codeine.
Opioid analgesics - concurrent use of codeine and other opioid receptor antagonists is usually inappropriate as additive CNS depression, respiratory depression and hypotensive effects may occur. See Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.
It is possible that interactions could occur between drugs that can inhibit CYP2D6 (such as quinidine, phenothiazines and antipsychotic agents) and codeine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category A)
Category A: Both paracetamol and codeine have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
Opioid analgesics may cause respiratory depression in the newborn infant. Prolonged high-dose use of codeine prior to delivery may produce codeine withdrawal symptoms in the neonate.
Use of codeine during labour when delivery of a premature infant is anticipated is contraindicated as it may produce codeine withdrawal symptoms in the neonate.
 Paracetamol and codeine both appear in breast milk in low concentrations. Maternal ingestion of paracetamol in recommended doses does not appear to present a risk to breastfed infants. However, codeine may cause respiratory depression in newborn infants.
Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are contraindicated during breastfeeding (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant.
Analgesic doses excreted in breast milk are generally low. However, infants of breast feeding mothers taking codeine may have increased risk of morphine overdose if the mother is an ultra-rapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolised by cytochrome P450 2D6 (CYP2D6) into morphine, which is excreted into breast milk. If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore, Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are contraindicated for use during breastfeeding. However, in circumstances where a breastfeeding mother requires codeine therapy, breastfeeding should be suspended, and alternative arrangements should be made for feeding the infant for any period during codeine treatment.
Breast feeding mothers should be told how to recognize signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness, and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Medical advice should be sought immediately.

4.7 Effects on Ability to Drive and Use Machines

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets may cause drowsiness and may increase the effects of alcohol. Therefore, patients should be cautioned about operating vehicles or machinery, or engaging in activities that require them to be fully alert. Alcohol should be avoided.
Due to the preparation's sedative action, impairment of the mental and/or physical abilities required for the performance of potentially hazardous activities may occur. Hence, children engaging in bike riding and other hazardous activities should be supervised to avoid potential harm.

4.8 Adverse Effects (Undesirable Effects)

Paracetamol.

Reports of adverse reactions are rare. Although the following reactions have been reported, a causal relationship to the administration of paracetamol has been neither confirmed nor refuted: dyspepsia, nausea, allergic and hematological reactions.

Codeine.

Nausea and vomiting, constipation, dizziness and drowsiness have been reported at therapeutic doses of codeine. Other adverse effects include: cough suppression, respiratory depression, euphoria, dysphoria, histamine release (hypotension, flushing of the face, tachycardia, breathlessness) and other allergic reactions. Very rarely, skin rashes may occur in patients hypersensitive to codeine. Prolonged use of large doses of codeine may result in physiological dependence.

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.

4.9 Overdose

Symptoms.

Toxic symptoms include vomiting, abdominal pain, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma. The most serious adverse effect of acute overdosage of paracetamol is a dose dependent, potentially fatal hepatic necrosis.
In adults, hepatotoxicity may occur after ingestion of a single dose of paracetamol 10 to 15 g (30 tablets); a dose of 25 g (50 tablets) or more is potentially fatal.
Symptoms during the first two days of acute poisoning by paracetamol do not reflect the potential seriousness of the intoxication. Major manifestations of liver failure, such as jaundice, hypoglycemia and metabolic acidosis, may take at least three days to develop.

Treatment.

For information on the management of overdose, contact the Poisons Information Centre Australia (131 126).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Paracetamol's analgesic mechanism of action has not been fully elucidated, but may involve blocking impulse generation at the bradykinin sensitive chemoreceptors that evoke pain.
The antipyretic effect of paracetamol rises from its ability to block the action of prostaglandin synthetase and so prevent the synthesis of prostaglandins in response to the pyrogen stimulus in the region of the anterior hypothalamus.
Codeine acts centrally. It produces analgesia by dulling the response to painful stimuli at several loci in the central nervous system. This causes an alteration in the sensation and affective response of pain.
There is evidence to suggest that a combination of paracetamol with codeine is superior in analgesic action to either drug administered alone.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Paracetamol.

Absorption.

After oral administration, paracetamol is absorbed rapidly and completely from the small intestine; peak plasma levels occur 30 to 120 minutes after administration. Food intake delays paracetamol absorption. Paracetamol is uniformly distributed throughout most body fluids; the apparent volume of distribution is 1 to 1.2 L/kg.
Paracetamol can cross the placenta and is excreted in milk. Plasma protein binding is negligible at usual therapeutic concentrations, but increases with increasing concentrations.

Metabolism.

Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults, at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). A minor proportion (less than 20%) is metabolised to catechol derivatives and mercapturic acid compounds via oxidation. Paracetamol is metabolised differently by infants and children compared to adults, the sulfate conjugate being predominant.

Excretion.

Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol, with 85 to 90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from one to four hours.

Codeine.

Absorption.

Codeine has about one-sixth of morphine's analgesic activity. It is well absorbed from the gastrointestinal tract and does not interfere with paracetamol absorption.

Metabolism.

It is metabolised in the liver to morphine and norcodeine which, with codeine, are excreted in the urine, partly as conjugates with glucuronic acid.

Excretion.

Excretion is almost complete within 24 hours. Patients who metabolise drugs poorly via CYP2D6 are likely to obtain reduced benefit from codeine due to reduced formation of the active metabolite. This may be the case in about 8% of patients.

5.3 Preclinical Safety Data

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Amcal Strong Pain Relief Extra paracetamol 500 mg and codeine phosphate hemihydrate 15 mg tablets are white to off white capsule shaped uncoated tablets, plain on one side and with a break line on the other side. The product is available in PVC/PVDC/Al blister packs of 20 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Codeine phosphate hemihydrate is a white or almost white, crystalline powder or small, colourless crystals. It is freely soluble in water, slightly soluble or very slightly soluble in ethanol (96%). Codeine phosphate is an analgesic.
Paracetamol is a white or almost white crystalline powder. It is sparingly soluble in water, freely soluble in alcohol, very slightly soluble in methylene chloride. Paracetamol is an analgesic and antipyretic.

Paracetamol.

N-(4-hydroxyphenyl)acetamide.

Chemical structure.


Molecular formula: C8H9NO2.
Relative molecular mass: 151.2.

CAS number.

103-90-2.

Codeine phosphate hemihydrate.

(5R,6S)-7,8-didehydro-4,5-epoxy-3-methoxy-N-methylmorphinan-6-ol dihydrogen orthophosphate hemihydrate.

Chemical structure.


Molecular formula: C18H24NO7P,½H2O.
Molecular weight: 406.4.

CAS number.

41444-62-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes