Consumer medicine information

Aspalgin

Aspirin; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Aspalgin

Active ingredient

Aspirin; Codeine phosphate hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aspalgin.

SUMMARY CMI

ASPALGIN®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using ASPALGIN?

ASPALGIN contains the active ingredient aspirin and codeine phosphate hemihydrate. ASPALGIN is used for the temporary relief of acute moderate pain, inflammation and fever.

For more information, see Section 1. Why am I using ASPALGIN? in the full CMI.

2. What should I know before I use ASPALGIN?

Do not use if you have ever had an allergic reaction to aspirin and codeine phosphate hemihydrate or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use ASPALGIN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ASPALGIN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ASPALGIN?

  • Your doctor will decide what dose you should receive.
  • The usual dose for adults and children over 12 years of age is 2 tablets dissolved in water, every four hours or as directed.

More instructions can be found in Section 4. How do I use ASPALGIN? in the full CMI.

5. What should I know while using ASPALGIN?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ASPALGIN.
  • Tell your doctor immediately if you become pregnant or are breast-feeding while taking ASPALGIN.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking ASPALGIN.
Things you should not do
  • Do not take ASPALGIN to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
Driving or using machines
  • Be careful driving or operating machinery until you know how ASPALGIN affects you.
Drinking alcohol
  • You must not drink alcohol while using ASPALGIN.
Looking after your medicine
  • Keep the pack in a cool, dry place (below 25°C) in its original packaging.
  • Do not store ASPALGIN in the bathroom, near a sink, on a window sill or in the car.
  • Keep your tablets where children cannot reach it.

For more information, see Section 5. What should I know while using ASPALGIN? in the full CMI.

6. Are there any side effects?

Tell your doctor or pharmacist if you notice any of the following and they worry you: nausea (feeling sick), constipation, dizziness, lethargy, drowsiness, sweating, vomiting, skin rashes, runny nose, stomach pains, deafness, Reye's Syndrome.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING:

Limitations of Use

ASPALGIN should only be used when your doctor decides that other treatment options are not able to effectively manage your pain or you cannot tolerate them.

Hazardous and Harmful Use

ASPALGIN poses risks of abuse, misuse and addiction which can lead to overdose and death. Your doctor will monitor you regularly during treatment.

Life Threatening Respiratory Depression

ASPALGIN can cause life-threatening or fatal breathing problems (slow, shallow, unusual or no breathing), even when used as recommended. These problems can occur at any time during use, but the risk is higher when first starting ASPALGIN and after a dose increase, if you are older, or have an existing problem with your lungs. Your doctor will monitor you and change the dose as appropriate.

Use of Other Medicines While Using ASPALGIN

Using ASPALGIN with other medicines that can make you feel drowsy such as sleeping tablets (e.g. benzodiazepines), other pain relievers, antihistamines, antidepressants, antipsychotics, gabapentinoids (e.g. gabapentin and pregabalin), cannabis and alcohol may result in severe drowsiness, decreased awareness, breathing problems, coma and death. Your doctor will minimise the dose and duration of use; and monitor you for signs and symptoms of breathing difficulties and sedation. You must not drink alcohol while using ASPALGIN.



FULL CMI

ASPALGIN®

Active ingredient(s): aspirin and codeine phosphate hemihydrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using ASPALGIN. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ASPALGIN.

Where to find information in this leaflet:

1. Why am I using ASPALGIN?
2. What should I know before I use ASPALGIN?
3. What if I am taking other medicines?
4. How do I use ASPALGIN?
5. What should I know while using ASPALGIN?
6. Are there any side effects?
7. Product details

1. Why am I using ASPALGIN?

ASPALGIN contains the active ingredients aspirin and codeine phosphate hemihydrate. Aspirin belongs to a group of medicines called analgesics which are used to block pain. It is also an antipyretic. That means it helps reduce your body temperature if you have a fever. Codeine phosphate hemihydrate belongs to a group of medicines called opioid analgesics and it acts by blocking pain and your emotional response to pain.

ASPALGIN is used for the temporary relief of acute moderate pain, inflammation and fever.

Addiction

You can become addicted to ASPALGIN even if you take it exactly as prescribed. ASPALGIN may become habit forming causing mental and physical dependence. If abused it may become less able to reduce pain.

Dependence

As with all other opioid containing products, your body may become used to you taking ASPALGIN. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking ASPALGIN suddenly, so it is important to take it exactly as directed by your doctor.

Tolerance

Tolerance to ASPALGIN may develop, which means that the effect of the medicine may decrease. If this happens, more may be needed to maintain the same effect.

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

Your doctor may have prescribed it for another reason.

2. What should I know before I use ASPALGIN?

Warnings

Do not use ASPALGIN if:

  • you are allergic to aspirin, codeine phosphate hemihydrate or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include:
    - 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
Always check the ingredients to make sure you can use this medicine.
  • you have a stomach ulcer
Elderly patients are more likely to have less effective kidney or liver function due to age. This may increase the risk of side effects. You should discuss how much ASPALGIN to take with your doctor or pharmacist.
  • the expiry date (EXP) printed on the pack has passed or the packaging is torn or shows signs of tampering.
If it has expired or is damaged, return it to your pharmacist for disposal.
If you are not sure whether you should start taking this medicine, talk to your doctor.

Do not give this medicine to a child under the age of 12 years unless your doctor has prescribed it for them.

Do not give to children or teenagers suffering viral illness (such as influenza or chicken pox) or fever.

Do not give to children 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 and life-threatening adverse reactions.

Aspirin has been implicated in cases of Reye's Syndrome, a potentially fatal illness which results from brain inflammation.

Check with your doctor if you:

  • are allergic to any other medicines, foods, dyes or preservatives
  • have had any of the following medical conditions:
    - liver disease, hepatitis
    - kidney disease
    - peptic ulcer
    - disorders of the gastrointestinal tract
    - asthma
    - bleeding disorders
    - inflammatory bowel disease
  • you are a heavy drinker or use drugs
  • you are about to have surgery under a general anaesthetic
  • you have recently had gastrointestinal tract or urinary tract surgery
  • you have had a recent head injury

Ask your doctor if you have a deficiency of liver enzymes that metabolise codeine or if your liver enzymes metabolise codeine too rapidly.

If you have not told your doctor about any of the above, tell them before you start taking ASPALGIN.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Your doctor can discuss with you the risks and benefits involved.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Do not breast-feed if you are taking this medicine.

The active ingredients in ASPALGIN pass into the breast milk and there is a possibility that your baby may be affected.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and ASPALGIN may interfere with each other.

These include:

  • medicines used to treat inflammation such as aspirin
  • medicines used to treat epilepsy
  • medicines used to treat gout
  • diuretics
  • hypnotics, sedatives or phenothiazines

These medicines may be affected by ASPALGIN or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ASPALGIN.

4. How do I use ASPALGIN?

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Adults and children over 12 years of age:

  • 2 tablets dissolved in water, to be taken every four hours or as directed.

DO NOT take more than 8 tablets in one day.

DO NOT give to children under 12 years of age unless on medical advice.

How to take it

Dissolve the tablets in a glass of water and then swallow the entire contents of the glass.

When to take ASPALGIN

  • ASPALGIN should be taken at about the same time each day.
  • Taking it at the same time each day will have the best effect. It will also help you remember when to take it.
  • It does not matter if you take this medicine before or after food.

How long to take it

Withdrawal

Continue taking your medicine for as long as your doctor tells you. If you stop taking this medicine suddenly, your pain may worsen and you may experience some or all of the following withdrawal symptoms:

  • nervousness, restlessness, agitation, trouble sleeping or anxiety
  • body aches, weakness or stomach cramps
  • loss of appetite, nausea, vomiting or diarrhoea
  • increased heart rate, breathing rate or pupil size
  • watery eyes, runny nose, chills or yawning
  • increased sweating

ASPALGIN given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

If you forget to use ASPALGIN

ASPALGIN should be used regularly at the same time each day.

If it is less than 4 hours before your next dose, skip the dose you missed and take your next dose when you are meant to.

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 the dose that you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

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

If you use too much ASPALGIN

If you or someone else take too much (overdose), and experience one or more of the symptoms below, immediately call triple zero (000) for an ambulance. Keep the person awake by talking to them or gently shaking them every now and then. You should follow the above steps even if someone other than you has accidentally taken ASPALGIN that was prescribed for you. If someone takes an overdose they may experience one or more of the following symptoms:

  • slow, unusual or difficult breathing
  • drowsiness, dizziness or unconsciousness
  • slow or weak heartbeat
  • nausea or vomiting
  • convulsions or fits

If you think you or someone else may have taken too much ASPALGIN, you should immediately:

  • phone the Poisons Information Centre (Australia telephone 13 11 26) for advice, or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Depending on your body's individual ability to break down codeine, you may experience signs of overdose even when you take ASPALGIN as recommended by your doctor. If overdose symptoms occur, seek immediate medical advice.

When seeking medical attention, take this leaflet and remaining medicine with you to show the doctor. Also tell them about any other medicines or alcohol which have been taken.

5. What should I know while using ASPALGIN?

Things you should do

  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking ASPALGIN.
  • Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.
It may affect other medicines used during surgery.
  • If you become pregnant while taking this medicine, tell your doctor immediately.
  • Keep all of your doctor's appointments so that your progress can be checked.
Your doctor needs to check your progress and to determine whether you need to continue taking ASPALGIN.
  • Tell your doctor if you feel ASPALGIN is not helping your condition.

Things you should not do

  • Do not take ASPALGIN to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
If you stop taking it suddenly, your condition may worsen.

Driving or using machines

Be careful driving or operating machinery until you know how ASPALGIN affects you.

This medicine may cause nausea, vomiting, constipation, drowsiness, dizziness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, dizziness or light-headedness may be worse.

Looking after your medicine

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

If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C. Keep the tablets in a dry place.

Do not store ASPALGIN 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 it 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.

Getting rid of any unwanted medicine

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking ASPALGIN.

This medicine helps most people with the temporary relief of acute moderate pain, inflammation and fever, but it may have unwanted side effects in some people. All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

Common side effects

Common side effectsWhat to do
  • nausea (feeling sick)
  • constipation
  • dizziness
  • lethargy
  • drowsiness
  • sweating
  • vomiting
  • skin rashes
  • runny nose
  • stomach pains
  • deafness
  • Reye's Syndrome (refer to previous comments on use in children and teenagers)
Speak to your doctor if you have any of these side effects and they worry you.

The above list includes the more common side effects of your medicine.

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

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What ASPALGIN contains

Active ingredient
(main ingredient)		ASPALGIN contains 300 mg of aspirin and 8 mg of codeine phosphate hemihydrate
Other ingredients
(inactive ingredients)
  • calcium carbonate
  • citric acid
  • disodium edetate
  • purified talc
  • saccharin sodium
  • sodium lauryl sulfate
  • wheat starch
Potential allergensASPALGIN contains gluten and saccharin.

Do not take this medicine if you are allergic to any of these ingredients.

What ASPALGIN looks like

ASPALGIN tablets are round, white and flat with bevelled edges with one side plain and one side engraved FM having a diameter of 17/32. They are available in blister packs of 40. (AUST R 13431).

Who distributes ASPALGIN

Viatris Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in April 2022.

ASPALGIN® is a Viatris company trade mark

ASPALGIN_cmi\Apr22/00

Published by MIMS June 2022

BRAND INFORMATION

Brand name

Aspalgin

Active ingredient

Aspirin; Codeine phosphate hemihydrate

Schedule

S4

 

1 Name of Medicine

Aspirin and codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

Each Aspalgin dispersible tablet contains 300 mg aspirin and 8 mg codeine phosphate hemihydrate as the active ingredients.

Excipients of known effect.

Gluten, saccharin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Aspalgin dispersible tablets are round, white and flat with bevelled edges with one side plain and one side engraved FM having a diameter of 17/32".

4 Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of acute moderate pain, inflammation and fever.

4.2 Dose and Method of Administration

Aspalgin dispersible tablets should be dissolved in a little water before taking.

Adults and children 12 years and over.

2 tablets every four hours or as directed, to a maximum of 8 tablets per day.

Children.

Not for use in children as follows:
younger than 12 years (see Section 4.3 Contraindications);
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 and life-threatening adverse reactions (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
Aspalgin is not recommended for use in children and teenagers with chickenpox, influenza or fever.

4.3 Contraindications

Aspalgin is contraindicated in patients with known hypersensitivity to aspirin, salicylates, codeine or any of the excipients used in the product.
Due to codeine's structural similarity to morphine and oxycodone, patients experiencing systemic allergy (generalised rash, shortness of breath) to these drugs should not receive codeine.
Due to the codeine content, Aspalgin is contraindicated in the following conditions:
severe respiratory disease, acute respiratory disease and respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion, since codeine may exacerbate the condition;
bronchial asthma attack or in heart failure secondary to chronic lung disease;
after operations on the biliary tract as codeine may cause biliary contraction;
in the presence of acute alcohol intoxication, head injuries and conditions in which intracranial pressure is raised;
in patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such treatment;
in patients with diarrhoea caused by poisoning, until the toxic substance has been eliminated from the gastrointestinal tract, or diarrhoea associated with pseudomembranous colitis caused by antibiotic administration since codeine may slow the elimination of the toxic material or antibiotic.
Due to the aspirin content, Aspalgin is contraindicated in patients with: bleeding disorders, severe hepatic disease, kidney disease, uraemia, erosive gastritis, peptic ulcer, taking anticoagulant therapy.
Aspalgin is contraindicated for use in patients who are:
CYP2D6 ultra-rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
younger than 12 years (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
aged between 12 and 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 and life-threatening adverse reactions (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

Aspalgin contains the opioid codeine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed codeine 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 Aspalgin.
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 Aspalgin 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 Aspalgin 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 and in patients with existing impairment of hepatic, renal or 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 Aspalgin 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 Aspalgin 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 Aspalgin.

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 Aspalgin 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; see Section 4.2 Dose and Method of Administration).

Accidental ingestion/exposure.

Accidental ingestion or exposure of Aspalgin, especially by children, can result in a fatal overdose of codeine. Patients and their caregivers should be given information on safe storage and disposal of unused Aspalgin (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.
Concurrent use of alcohol and aspirin may increase gastric irritation and occult blood loss, which may lead to iron deficiency anaemia with prolonged use. Concurrent use of NSAIDs may increase the risk of gastric ulceration. Because of its anti-platelet effects, it may be advisable to withdraw aspirin prior to surgery.
Codeine should be used with caution in patients with head injuries (due to risk of respiratory depression), inflammatory bowel disease or recent gastrointestinal tract surgery.
Codeine should be given with caution or in reduced doses to patients with hypothyroidism, adrenocortical insufficiency or shock.
Codeine should be administered with caution in patients with prostatic hypertrophy, urethral stricture or recent urinary tract surgery since codeine may cause urinary retention.

CYP2D6 metabolism.

Aspalgin is 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 to infants of rapid metaboliser mothers who take codeine.
The prevalence of codeine ultra-rapid metabolism by CYP2D6 in children is not known, but 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% to 10% in Caucasians. The highest prevalence (16% to 28%) occurs in North African, Ethiopian and Arab populations.
See Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Use in hepatic impairment.

Codeine should be given with caution or in reduced doses to patients with impaired hepatic function.

Use in renal impairment.

Caution is necessary when renal function is impaired. Opioids and their metabolites are excreted primarily via the kidneys. Because of this there is an increased risk of adverse effects in patients with renal function impairment. Prolonged administration of large doses of aspirin has been associated with renal papillary necrosis.

Use in the elderly.

Codeine should be used with caution in elderly or debilitated patients because of the danger of respiratory or cardiac depression.
The elderly are more likely to have age-related renal impairment and may be more susceptible to the respiratory effects of opioid analgesics. Dose reduction may be required.

Paediatric use.

The use of aspirin in children and adolescents has been implicated in some cases of Reye's syndrome and paediatric use is not recommended, particularly during viral illness.
Aspalgin is contraindicated for use in children:
younger than 12 years;
aged between 12 to 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-rapid metabolisers of codeine due to a CYP2D6 polymorphism.
See Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism.

Effects on laboratory tests.

Plasma amylase and lipase activity.

Codeine may cause increased biliary tract pressure, thus increasing plasma amylase and/or lipase concentrations.

Gastric emptying studies.

Gastric emptying is delayed by codeine so gastric emptying studies will not be valid.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Food.

Food delays gastric emptying and hence the absorption of aspirin; nevertheless, it may be preferable to take aspirin with food in order to minimise gastric irritation.

Alcohol.

Concurrent ingestion of alcohol and aspirin may enhance gastric irritation. The CNS depressant effects of alcohol may be enhanced by codeine.

Anticoagulants.

Aspirin may affect the coagulation process and should be avoided in patients on anti-coagulants.

Diphenylhydantoin, sodium valproate, sulphonamides and methotrexate.

Aspirin can displace these drugs from protein binding sites thereby enhancing their effect. The activity of methotrexate may be markedly enhanced and its toxicity increased by administration with aspirin.

Probenecid.

Low dose aspirin reduce the actions of uricosuric agents such as probenecid.

Sulphonylureas.

High doses of aspirin enhance the hypoglycaemic effects of sulphonylureas.

Caffeine.

Caffeine increases aspirin absorption while urinary alkalinisers increase the rate of excretion.

Spironolactone.

Aspirin antagonises the diuretic effect of spironolactone.

General anaesthetics.

Codeine may potentiate the effects of general anaesthetics.

CNS depressants (such as anaesthetics, hypnotics, sedatives and phenothiazines).

Codeine may potentiate the depressant effects of CNS depressants such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics and other CNS depressants (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

Opioid analgesics.

Codeine may potentiate the effects of opioid agonists.

Antihistamines.

Concomitant use of codeine and antihistamines with anticholinergic effects may result in an increased risk of severe constipation and/or urinary retention. Codeine may potentiate the CNS depressant effects of certain antihistamines.

Monoamine oxidase inhibitors.

Serious and sometimes fatal reactions have occurred in patients concurrently administered MAO inhibitors and pethidine. Codeine should not be given to patients taking non-selective MAO inhibitors or within 14 days of stopping such treatment. Caution is advised with the combination of codeine and selective MAO inhibitors (reversible inhibitors of monoamine oxidase A).

Quinidine.

Quinidine interferes with the metabolism of codeine to morphine lowering the analgesic effect of codeine.

Cimetidine.

Cimetidine may reduce the metabolism of codeine, enhancing the possibility of codeine toxicity.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Aspirin inhibits prostaglandin synthesis. When given late in pregnancy, it may cause premature closure of the fetal ductus arteriosus, delay labour and birth. Aspirin increases the bleeding time both in the newborn infant and in the mother because of its antiplatelet effects. Products containing aspirin should be avoided in the last trimester.
Opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependence in the fetus, leading to withdrawal symptoms in the neonate.
 Aspirin is excreted in breast milk in low concentrations but since neonates excrete salicylates slowly and are sensitive to aspirin it should be avoided in nursing mothers, particularly in high doses.
Aspalgin is contraindicated during breastfeeding (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 breastfeeding mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultrarapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolised by cytochrome P4502D6 (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, Aspalgin is 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. Breastfeeding mothers should be told how to recognise 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

Patients should be warned that codeine might impair their ability to perform activities requiring mental alertness or physical coordination (e.g. operating machinery, driving a motor vehicle). This medication may cause drowsiness. If affected, patients should not drive a vehicle or operate machinery. Avoid alcohol.

4.8 Adverse Effects (Undesirable Effects)

See Table 1.

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

Overdosage with Aspalgin involves treatment of both aspirin and codeine poisoning.

Aspirin.

Symptoms.

Mild chronic salicylate intoxication usually occurs only after repeated administration of large doses. Symptoms include: dizziness, tinnitus, deafness, sweating, nausea and vomiting, headache and mental confusion, may be controlled by reducing the dose.
Symptoms of more severe intoxication or of acute poisoning following overdosage include: hyperventilation, fever, restlessness, ketosis, and respiratory alkalosis and metabolic acidosis. Depression of the central nervous system may lead to coma, cardiovascular collapse, and respiratory failure. In children, drowsiness and metabolic acidosis commonly occur, hypoglycaemia may be severe.

Treatment.

In acute salicylate overdosage, the stomach should be emptied by aspiration. Patients with mild intoxication should be encouraged to increase fluid intake. In patients with more severe intoxication, forced alkaline diuresis may be required. Plasma electrolytes, particularly potassium, and the acid-base balance should be monitored regularly. In the presence of cardiac or renal function impairment or in very severe intoxication, haemodialysis or haemoperfusion may need to be considered.

Codeine.

Symptoms.

Symptoms of codeine overdosage include vomiting, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma.

Treatment.

Support respiratory and cardiovascular function. Assisted ventilation may be necessary. Induction of emesis is not recommended because of the potential for CNS depression and seizures. Administer activated charcoal, taking care to protect the airway as necessary. If clinically significant respiratory or cardiac depression is present, give naloxone. The usual adult dose is 0.4 to 2.0 mg intravenously (or subcutaneously), repeated every 2 to 3 minutes if necessary up to 10 mg. The use of naloxone in physically dependent patients may precipitate withdrawal symptoms.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

It has been shown that the analgesic effects of aspirin and codeine are additive due to their different mechanisms of action.

Aspirin.

Aspirin is a potent inhibitor of prostaglandin synthesis through its irreversible blocking of the cyclooxygenase enzyme. This action on prostaglandins (including thromboxane A2) contributes to its antiplatelet activity and its anti-inflammatory, analgesic and antipyretic actions. The analgesic properties of aspirin are mainly peripheral through blocking of pain impulse generation, although a central action, possibly in the hypothalamus, is also likely. The anti-inflammatory action is also peripheral, due to inhibition of prostaglandin synthesis at the site of injury and a reduction in the prostaglandin mediated inflammatory response. The antipyretic effect may involve a central action of the hypothalamic heat-regulating centre to produce peripheral vasodilatation and subsequent heat loss. The anti-platelet effect is due to irreversible blockade of cyclooxygenase in platelets, necessary for the formation of the aggregating agent, thromboxane A2.

Codeine.

Codeine is an opioid analgesic which binds with stereospecific receptors at many sites within the CNS to alter processes affecting both the perception of pain and the emotional response to pain. There are multiple sub-types of opioid receptors, each mediating various therapeutic and/or side effects of drugs. Codeine has about one-sixth the analgesic activity of morphine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Aspirin.

After oral administration, aspirin is absorbed partly from the stomach but mainly from the upper part of the small intestine.

Codeine.

Codeine is absorbed from the gastrointestinal tract and peak plasma concentrations are reached 1 hour after oral administration.

Distribution.

Aspirin.

Salicylates are extensively bound to plasma proteins, particularly albumin (80% to 90%). Salicylates cross the placenta and are excreted in breast milk.

Metabolism.

Aspirin.

Aspirin is rapidly hydrolysed to the therapeutically important salicylate. This conversion occurs in many tissues, particularly the G.I. mucosa and the liver. With low doses of aspirin, the salicylate has a half-life of 2 to 3 hours. In the liver, salicylate is converted to salicyluric acid and glucuronide conjugates.

Codeine.

The plasma half-life is 3 to 4 hours, after oral or intramuscular administration. It is metabolised in the liver to morphine and norcodeine.

Excretion.

Aspirin.

Aspirin has a very short elimination half-life (30 minutes). Excretion occurs mainly by the kidney. The rate of excretion of aspirin varies with the pH of the urine, increasing as the pH rises.

Codeine.

Codeine and its metabolites are excreted almost entirely by the kidney within 24 hours, mainly as conjugates with glucuronic acid.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aspalgin contains the following excipients: calcium carbonate, citric acid, disodium edetate, purified talc, saccharin sodium, sodium lauryl sulfate and wheat starch.

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 25°C. Store in a dry place.

6.5 Nature and Contents of Container

Container type: blister pack (PA/Al/PVC/Al).
Pack sizes: 20, 40.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 13431 - Aspalgin aspirin 300 mg codeine phosphate hemihydrate 8 mg dispersible tablet blister pack.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Aspirin.

Aspirin exists as colourless or white crystals or white crystalline powder. It is odourless or almost odourless. It is slightly soluble in water, freely soluble in alcohol, soluble in chloroform and ether.
Chemical name: salicylic acid acetate.
Molecular formula: C9H8O4.
Molecular weight: 180.2.

Codeine phosphate hemihydrate.

Codeine phosphate hemihydrate is a small, colourless, odourless crystal or a white, odourless crystalline powder. Codeine phosphate is soluble in 4 parts of water, slightly soluble in ethanol (96%), practically insoluble in chloroform and ether.
Chemical name: (5R,6S)-7,8-didehydro-4,5-epoxy-3-methoxy-N-methylmorphinan-6-ol dihydrogen orthophosphate hemihydrate.
Molecular formula: C18H21NO3.H3PO4.1/2H2O.
Molecular weight: 406.4.

CAS number.

Aspirin: 50-78-2.
Codeine phosphate hemihydrate: 41444-62-6.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes