Consumer medicine information

Amcal Ibuprofen Plus Codeine

Ibuprofen; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Amcal Ibuprofen Plus Codeine

Active ingredient

Ibuprofen; Codeine phosphate hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amcal Ibuprofen Plus Codeine.

SUMMARY CMI

AMCAL IBUPROFEN PLUS CODEINE

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 AMCAL IBUPROFEN PLUS CODEINE?

AMCAL IBUPROFEN PLUS CODEINE contains the active ingredients Ibuprofen and Codeine phosphate. AMCAL IBUPROFEN PLUS CODEINE is used to relieve pain, inflammation (swelling, redness, soreness) and fever when other analgesics have proven not to be effective.

For more information, see Section 1. Why am I using AMCAL IBUPROFEN PLUS CODEINE? in the full CMI.

2. What should I know before I use AMCAL IBUPROFEN PLUS CODEINE?

Do not use if you have ever had an allergic reaction to AMCAL IBUPROFEN PLUS CODEINE 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. Do not use at all during the last three months of pregnancy.

For more information, see Section 2. What should I know before I use AMCAL IBUPROFEN PLUS CODEINE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with AMCAL IBUPROFEN PLUS CODEINE 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 AMCAL IBUPROFEN PLUS CODEINE?

The usual dose of AMCAL IBUPROFEN PLUS CODEINE for adults and children over 12 years of age is 2 tablets followed by, if necessary 1 or 2 tablets every 4 hours. Do not take more AMCAL IBUPROFEN PLUS CODEINE than 6 tablets in 24 hours. More instructions can be found in Section 4. How do I use AMCAL IBUPROFEN PLUS CODEINE? in the full CMI.

5. What should I know while using AMCAL IBUPROFEN PLUS CODEINE?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using AMCAL IBUPROFEN PLUS CODEINE.
  • Tell your doctor immediate if you become pregnant, have surgery including dental.
Things you should not do
  • Do not give AMCAL IBUPROFEN PLUS CODEINE to anyone else, even if they have the same condition as you or treat any other complaints.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how AMCAL IBUPROFEN PLUS CODEINE affects you.
  • AMCAL IBUPROFEN PLUS CODEINE may cause dizziness, lightheadedness or drowsiness in some people. If this occurs, do not drive or operate machinery.
Drinking alcohol
  • If you drink alcohol, dizziness, lightheadedness or drowsiness may be worse.
Looking after your medicine
  • Keep the tablets in a cool dry place where the temperature stays below 25°C
  • Do not store the medicine in the bathroom or near a sink

For more information, see Section 5. What should I know while using AMCAL IBUPROFEN PLUS CODEINE? in the full CMI.

6. Are there any side effects?

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of the following side effects; asthma, wheezing or shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, hives, itching or skin rash, fainting. These may be the sign of an allergic reaction. Speak to your doctor if you have any of the following common side effects and they worry you: nausea or vomiting, constipation or dizziness, light-headedness, drowsiness.

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

AMCAL IBUPROFEN PLUS CODEINE 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

AMCAL IBUPROFEN PLUS CODEINE 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

AMCAL IBUPROFEN PLUS CODEINE 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 AMCAL IBUPROFEN PLUS CODEINE 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 AMCAL IBUPROFEN PLUS CODEINE

Using AMCAL IBUPROFEN PLUS CODEINE 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 AMCAL IBUPROFEN PLUS CODEINE.



FULL CMI

AMCAL IBUPROFEN PLUS CODEINE

Active ingredients: Ibuprofen and Codeine phosphate

Consumer Medicine Information (CMI)

This leaflet provides important information about using AMCAL IBUPROFEN PLUS CODEINE. 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 AMCAL IBUPROFEN PLUS CODEINE.

Where to find information in this leaflet:

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

1. Why am I using AMCAL IBUPROFEN PLUS CODEINE?

AMCAL IBUPROFEN PLUS CODEINE contains the active ingredient Ibuprofen and Codeine phosphate. AMCAL IBUPROFEN PLUS CODEINE is a pain reliever. Ibuprofen belongs to a family of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). This group of medicines work by relieving pain, inflammation (swelling, redness, soreness) and fever. Codeine phosphate is an opioid analgesic that works in the brain and spinal cord to relieve pain.

AMCAL IBUPROFEN PLUS CODEINE is used to relieve inflammation and strong pain associated with migraine headache, tension headache, headache, period pain, dental pain, back pain, neuralgia, rheumatic pain, arthritic pain and muscular pain when other analgesics have proven not to be effective.

AMCAL IBUPROFEN PLUS CODEINE is not recommended for children under 12 years of age.

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

2. What should I know before I use AMCAL IBUPROFEN PLUS CODEINE?

Warnings

Do not use AMCAL IBUPROFEN PLUS CODEINE if:

  • you are allergic to ibuprofen, codeine or other opioid analgesics such as morphine or pethidine or, aspirin, any other NSAID medicine or other anti-inflammatory medicines, or any of the ingredients listed at the end of this leaflet.
    Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAIDs. If you are not sure if you are taking any of these medicines, ask your pharmacist.
    Symptoms of an allergic reaction to these medicines may include:
    - asthma, wheezing or shortness of breath.
    - swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing.
    - hives, itching or skin rash.
    - fainting.
    Always check the ingredients to make sure you can use this medicine.
    If you are allergic to aspirin or NSAIDs and take AMCAL IBUPROFEN PLUS CODEINE these symptoms may be severe.
  • you are in the third trimester of pregnancy (see Pregnancy and breastfeeding).
  • you are vomiting blood or material that looks like coffee grounds
  • you are bleeding from the rectum (back passage), have black sticky bowel motions (stool) or bloody diarrhoea
  • you have peptic ulcer (i.e. stomach or duodenal ulcer) or have had one before.
  • you are using other NSAIDS
  • you have chronic constipation or shallow breathing, or severe diarrhoea.
  • you consume regular and heavy amounts of alcohol.
  • you are a CYP2D6 ultra-rapid metaboliser.
  • you have severe liver impairment
  • you have heart or kidney problems
  • you are currently taking a Monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with a MAOI.

Do not take AMCAL IBUPROFEN PLUS CODEINE if the packaging is torn or shows signs of tampering.

Do not give AMCAL IBUPROFEN PLUS CODEINE to children under 12 years or to those aged 12 -18 years in whom respiratory function may be compromised.

Check with your doctor if you:

  • difficulty breathing, wheezing, chronic cough, allergies, asthma or other breathing conditions
  • a history of drug dependence, including alcohol dependence
  • skin rash (dermatitis)
  • skin irritation
  • a history of stomach ulcer.
  • liver disease.
  • kidney disease.
  • heart problems/failure, including. swelling of ankles or feet.
  • have thyroid problems or low blood pressure.
  • a head injury or intracranial pressure.
  • have prostatic problems.
  • have stomach problems or recent stomach surgery.

Tell your doctor if you take sedatives (medicines used to help you relax or sleep).

Tell your doctor if you have allergies to:

  • any other medicines including aspirin, or other NSAID medicines.
  • any other substances, such as foods, preservatives or dyes.

Not recommended for use in children under 12 years of age.

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.

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

Do not take AMCAL IBUPROFEN PLUS CODEINE at all during the last three months (third trimester) of pregnancy. Your doctor will decide if you should take AMCAL IBUPROFEN PLUS CODEINE during the first 6 months of pregnancy.

Tell your doctor if you are breast-feeding or plan to breast-feed.

Small amounts of ibuprofen and codeine pass into the breast milk.

Codeine may also cause breathing problems in newborn infants.

AMCAL IBUPROFEN PLUS CODEINE is contraindicated during breastfeeding due to risk of respiratory depression in the infant.

Addiction

You can become addicted to AMCAL IBUPROFEN PLUS CODEINE even if you take it exactly as prescribed. AMCAL IBUPROFEN PLUS CODEINE 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 AMCAL IBUPROFEN PLUS CODEINE. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking AMCAL IBUPROFEN PLUS CODEINE suddenly, so it is important to take it exactly as directed by your doctor.

Tolerance

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

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 may interfere with AMCAL IBUPROFEN PLUS CODEINE and affect how it works.

  • warfarin or other medicines used to prevent blood clots
  • lithium, a medicine used to treat mood swings and some types of depression
  • selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), medicines used to treat depression, if taken within the last 14 days
  • medicines used to treat high blood pressure including diuretics (fluid tablets)
  • methotrexate, a medicine used to treat arthritis and some types of cancer
  • medicines such as ciclosporin, tacrolimus, prednisone, prednisolone and cortisone, which reduce the activity of your immune system
  • zidovudine, a medicine used to treat HIV infection
  • medicines used to help you relax, sleep or relieve anxiety, such as barbiturates and sedatives
  • medicines used to relieve stomach cramps, prevent travel sickness and to treat Parkinson's disease
  • medicines for diarrhoea, such as kaolin, pectin and loperamide
  • metoclopramide, a medicine used to treat nausea and vomiting
  • Medicines that affect serotonin levels (serotonergic medicines)
  • aspirin, salicylates and other non-steroidal anti-inflammatory drugs (NSAIDs)
  • quinidine, a medicine used to treat abnormal or irregular heart beat
  • phenothiazines and antipsychotic agents, medicines used to treat mental disorders
  • mifeprisone, quinolone antibiotics
  • probenecid-medicines used to treat gout
  • phenytoin – medicine used to treat epilepsy
  • other opioid pain killers.

These medicines may be affected by AMCAL IBUPROFEN PLUS CODEINE or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

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

4. How do I use AMCAL IBUPROFEN PLUS CODEINE?

How much to take

  • The usual dose of AMCAL IBUPROFEN PLUS CODEINE for adults and children over 12 years of age is 2 tablets followed by, if necessary 1 or 2 tablets every 4 hours. Do not take more than 6 tablets in 24 hours.
  • AMCAL IBUPROFEN PLUS CODEINE is not recommended for children under 12 years of age.
  • Also, contraindicated in 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.
  • Follow the instructions provided and use AMCAL IBUPROFEN PLUS CODEINE until your doctor tells you to stop.

When to take AMCAL IBUPROFEN PLUS CODEINE

  • AMCAL IBUPROFEN PLUS CODEINE should be used for not more than 3 days. If your symptoms persist, worsen or new symptoms develop, talk to your doctor.

How to take AMCAL IBUPROFEN PLUS CODEINE

Take AMCAL IBUPROFEN PLUS CODEINE by mouth with fluid. It may also be taken before, or after food.

If you forget to use AMCAL IBUPROFEN PLUS CODEINE

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 you missed.

If you use too much AMCAL IBUPROFEN PLUS CODEINE

If you think that you or someone else have used too much AMCAL IBUPROFEN PLUS CODEINE, you may need urgent medical attention. 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 have accidentally used AMCAL IBUPROFEN PLUS CODEINE that was prescribed for you. If someone takes an overdose they may experience one or more of the following symptoms:

  • nausea or upset stomach, vomiting and/or gastric irritation,
  • drowsiness, dizziness or very slow,
  • slow, unusual or difficult breathing.
  • blurred vision, ringing in the ears, or rapid uncontrollable movements of the eyes.
  • excitability,
  • convulsions, fits or unconsciousness may be experienced in rare cases.

If you think you or someone else may have used too much AMCAL IBUPROFEN PLUS CODEINE, you should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), 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.

5. What should I know while using AMCAL IBUPROFEN PLUS CODEINE?

Things you should do

Tell your doctor immediately:

  • If you are about to be started on any new medicine tell your doctor and pharmacist that you are taking AMCAL IBUPROFEN PLUS CODEINE.
  • if you become pregnant
  • if you are about to be started on any new medicine that you are taking AMCAL IBUPROFEN PLUS CODEINE
  • If you are going to have surgery, including dental, tell your service provider (doctor or dentist) that you are taking AMCAL IBUPROFEN PLUS CODEINE.

Talk to doctor if your symptoms do not improve.

Your doctor will assess your condition and decide if you should continue to take the medicine.

Call your doctor straight away if you:

Become pregnant while taking AMCAL IBUPROFEN PLUS CODEINE

Remind any doctor, dentist or pharmacist you visit that you are using AMCAL IBUPROFEN PLUS CODEINE.

Things you should not do

  • Do not take high doses of the medicine for long periods of time unless your doctor tells you to. Products containing codeine should not be taken for prolonged periods. Codeine may be habit forming.
  • Do not give AMCAL IBUPROFEN PLUS CODEINE to anyone else, even if they have the same condition as you
  • Do not use AMCAL IBUPROFEN PLUS CODEINE to treat any other complaints unless your doctor tells you to.
  • Do not exceed the recommended dose unless your doctor tells you to.
  • Excessive use of ibuprofen can be harmful and increase the risk of heart attack, stroke or liver damage.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how AMCAL IBUPROFEN PLUS CODEINE affects you.

AMCAL IBUPROFEN PLUS CODEINE may cause dizziness, light-headedness or drowsiness in some people If this occurs, do not drive or operate machinery. If you drink alcohol, dizziness, lightheadedness and/or drowsiness may be worse.

Drinking alcohol

Tell your doctor if you drink alcohol.

Using AMCAL IBUPROFEN PLUS CODEINE with alcohol may result in severe breathing difficulties, decreased awareness, drowsiness, coma and death.

Withdrawal

Continue taking your medicine for as long as your doctor tells you. If you stop having 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.

AMCAL IBUPROFEN PLUS CODEINE given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

Looking after your medicine

  • Keep the tablets in the pack until it is time to take the dose.
  • If you take them out they will not keep well.
  • Store where the temperature stays below 25°C.
  • A locked cupboard at least one-and-a-half metres above the ground are a good place to store medicines.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

When you stop taking AMCAL IBUPROFEN PLUS CODEINE or it has passed its expiry date, ask your pharmacist what to do with any tablets that are left over.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

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.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Gastrointestinal related:
  • stomach upset including nausea, (feeling sick), heartburn, stomach pain or vomiting
  • loss of appetite
  • indigestion
  • diarrhoea or constipation
Head and neurology related:
  • sleeplessness, nightmares
  • change in mood e.g. depression, restlessness, irritability
  • sore or dry mouth or tongue
  • dizziness, light-headedness, drowsiness
  • headache
  • hearing disturbance
  • central sleep apnoea
Respiratory related:
  • shallow breathing
  • cough suppression
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Gastrointestinal related:
  • severe pain or tenderness in the stomach
  • vomiting blood or material that looks like coffee grounds.
  • bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea.
Allergy related:
  • shallow breathing or shortness of breath
  • flushing of the face
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing.
  • asthma, wheezing, shortness of breath, pain or tightness in the chest
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal
Heart related:
  • fast heart beat
Skin related
  • yellowing of the skin and eyes, also called jaundice
  • sudden or severe itching, skin rash, hives, skin peeling
  • swollen lymph glands
Urinary related
  • a change in the amount or frequency of urine passed, burning feeling when passing urine
  • unusual weight gain, swelling of ankles or legs
Infection related:
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
Bleeding related:
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • signs of anaemia, such as tiredness, being short of breath, and looking pale
Head and neurology related:
  • unusual or extreme mood swings
  • dizziness, light-headedness
  • severe dizziness, spinning sensation
  • severe or persistent headache
  • difficulty hearing, deafness
  • tingling or numbness of the hands or feet
Eyes related:
  • eye problems such as blurred vision, sore red eyes, itching
Pregnancy related
  • not enough amniotic fluid in the womb during pregnancy
  • newborns with kidney failure
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

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 AMCAL IBUPROFEN PLUS CODEINE contains

Active ingredient
(main ingredient)
  • Ibuprofen
  • Codeine phosphate
Other ingredients
(inactive ingredients)
  • Lactose monohydrate
  • Maize starch
  • Glyceryl behenate
  • Colloidal anhydrous silica
  • magnesium stearate
  • opadry white complete film coating system Y-1-7000

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

What AMCAL IBUPROFEN PLUS CODEINE looks like

AMCAL IBUPROFEN PLUS CODEINE is white to off-white capsule-shaped, biconvex, film-coated tablet. (Aust R 227475).

Who distributes AMCAL IBUPROFEN PLUS CODEINE

Cipla Australia Pty Ltd
Level 1, 132-136 Albert Road
South Melbourne, VIC 3205
[email protected]
Phone: 1800-569-074

This leaflet was prepared in November 2022

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Amcal Ibuprofen Plus Codeine

Active ingredient

Ibuprofen; Codeine phosphate hemihydrate

Schedule

S4

 

1 Name of Medicine

Ibuprofen and codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

Each tablet contains ibuprofen 200 mg, codeine phosphate 12.8 mg.
Amcal Ibuprofen Plus Codeine tablets do not contain gluten or preservatives.

Excipients with known effect.

Contains sugars (as lactose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White-off white capsule-shaped biconvex film-coated tablets with a central breakline on one side and plain on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Amcal Ibuprofen Plus Codeine is used for temporary relief of acute moderate pain and inflammation in patients over the age of 12 years.

4.2 Dose and Method of Administration

Adults and children over 12 years of age.

Initial dose two tablets taken with fluid, then one or two tablets every 4 hours when necessary. Maximum dose is 6 tablets in a 24 hour period.
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.
Amcal Ibuprofen Plus Codeine is contraindicated for use in patients who are:
aged below 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 (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

Pregnancy.

See Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation.

4.3 Contraindications

Known hypersensitivity or idiosyncratic reaction to ibuprofen, codeine or other opioid analgesics, or any of the excipients.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, broncho-spasm or urticaria) in response to ibuprofen, acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs).
Active, or a history of recurrent peptic ulcer/haemorrhage. As with other non-steroidal anti-inflammatory agents, ibuprofen should not be used in active gastrointestinal bleeding or in the presence of peptic ulceration.
Severe respiratory disease, acute respiratory disease and respiratory depression.
Chronic constipation and active alcoholism.
During labour when delivery of a premature infant is anticipated as it may produce codeine withdrawal symptoms in the neonate.
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).
Use with concomitant NSAIDs, including cyclo-oxygenase-2 specific inhibitors - increased risk of adverse reactions.
Heart (see Section 4.4 Special Warnings and Precautions for Use, Cardiovascular and cerebrovascular effects) or renal problems (see Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment).
Severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment).
Use of ibuprofen is contraindicated during the third trimester of pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Concomitant treatment with Monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment.
Treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).
Use of codeine containing products is contraindicated in women during breast feeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
Amcal Ibuprofen Plus Codeine is also contraindicated for use in patients who are:
aged below 12 years (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 and life-threatening adverse reactions (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
CYP2D6 ultra-rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).

4.4 Special Warnings and Precautions for Use

Gastrointestinal.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated (see Section 4.8 Adverse Effects (Undesirable Effects)).
Gastrointestinal bleeding, ulceration and perforation which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses and patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see Section 4.3 Contraindications) and in the elderly. These patients should commence treatment on the lowest dose available.
Patients with a history of GI toxicity, particularly the elderly, patients with a history of gastrointestinal bleeding or perforation or peptic ulcer haemorrhage related to previous NSAID therapy should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Care is advised in the administration of Amcal Ibuprofen Plus Codeine to patients with obstructive bowel disorders, recent gastrointestinal surgery, gallstones, myasthenia gravis, a history of peptic ulcer or convulsions.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see Section 4.5 Interactions with Other Medicines and other Forms of Interactions).
When GI bleeding or ulceration occurs in patients receiving Amcal Ibuprofen Plus Codeine, the treatment should be withdrawn.

Respiratory.

Bronchospasm may be precipitated in patients suffering from, or with a history of bronchial asthma or allergic disease.

SLE and mixed connective tissue disease.

Use of ibuprofen in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease can increase the risk of aseptic meningitis.

Use in hepatic impairment.

Amcal Ibuprofen Plus Codeine should be administered with caution in patients with hepatic impairment. Patients should be advised to remain alert for hepatotoxicity and be informed about the signs and/or symptoms of hepatotoxicity (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and "flu-like" symptoms) and the steps to take should these signs and/or symptoms occur.

Use in renal impairment.

Renal impairment as renal function may deteriorate, especially in dehydrated paediatric patients (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)).

Cardiovascular and cerebrovascular effects.

Observational studies have indicated that NSAIDs may be associated with an increased risk of serious cardiovascular events, including myocardial infarction and stroke, which may increase with dose or duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk.
Patients should be advised to remain alert for such cardiovascular events, even in the absence of previous cardiovascular symptoms. Patients should be informed about signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur.
Fluid retention, hypertension and oedema have been reported in association with NSAID therapy. Patients taking antihypertensives with NSAIDs may have an impaired antihypertensive response.
Amcal Ibuprofen Plus Codeine should be administered with caution in patients with hypertension or fluid retention (see Section 4.3 Contraindications, Heart).

Other precautions.

As with other drugs of this class, ibuprofen may mask the usual signs of infection.
Codeine may also obscure the diagnosis or the course of gastrointestinal diseases. Amcal Ibuprofen Plus Codeine should therefore be administered with caution in such situations.
Amcal Ibuprofen Plus Codeine should be administered with caution in patients who have recently had gastrointestinal surgery, paralytic ileus, as codeine may reduce gastrointestinal motility.
Amcal Ibuprofen Plus Codeine should be administered with caution in those with hypotension and/or hypothyroidism. The tablets should be used with caution in patients with raised intracranial pressure or head injury.
Amcal Ibuprofen Plus Codeine should be administered with caution in patients with prostatic hypertrophy since codeine may cause urinary retention.
Care is advised in the administration of Amcal Ibuprofen Plus Codeine to patients with adrenocortical insufficiency.

Hazardous and harmful use.

Amcal Ibuprofen Plus Codeine contains the opioid (codeine phosphate hemihydrate) and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Amcal Ibuprofen Plus 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 Amcal Ibuprofen Plus Codeine.
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 Ibuprofen Plus Codeine with anyone else.

Severe skin reactions.

Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. The acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localised on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of Amcal Ibuprofen Plus Codeine should be discontinued and appropriate measures taken if needed.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS) (see Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS)) and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see Section 4.8 Adverse Effects (Undesirable Effects)). These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of skin rash, mucosal legion or any other sign of hypersensitivity, and the NSAID use be discontinued.

Masking of symptoms of underlying infections.

Amcal Ibuprofen Plus Codeine can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Amcal Ibuprofen Plus Codeine is administered for fever or pain relief in relation to infection, monitoring infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

Drug reaction with eosinophilia with systemic symptoms (DRESS).

DRESS has been reported in patients taking NSAIDs. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.

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 Ibuprofen Plus Codeine 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 Ibuprofen Plus Codeine 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 Ibuprofen Plus Codeine 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 Ibuprofen Plus Codeine.

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 Ibuprofen Plus Codeine 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 Amcal Ibuprofen Plus Codeine, especially by children, can result in a fatal overdose of opioid. Patients and their caregivers should be given information on safe storage and disposal of unused Amcal Ibuprofen Plus Codeine (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Central sleep apnoea.

Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

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.

CYP2D6 metabolism.

Amcal Ibuprofen Plus Codeine 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%-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.

Adverse effects may have more serious consequences in the elderly, and they may be more susceptible to the CNS depressant effects of opioids.
Ibuprofen should not be taken by adults over the age of 65 without careful consideration of co-morbidities and co-medications because of an increased risk of adverse effects, in particular heart failure, gastro-intestinal ulceration and renal impairment.
The elderly are also more likely to have age related renal impairment and may be more susceptible to the respiratory depressant effects of codeine.
Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms. The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see below).

Paediatric use.

Amcal Ibuprofen Plus Codeine is contraindicated for use in children:
aged below 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.
(Also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).

Post-operative use in children.

There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see Section 4.3 Contraindications). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

Children with compromised respiratory function.

Codeine is contraindicated for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Amcal Ibuprofen Plus Codeine should be avoided in combination with:

Aspirin.

Ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Other NSAIDs: including cyclooxygenase-2-selective inhibitors.

Avoid the use of two or more NSAIDs as this may increase the risk of adverse effects.
The following interactions have been noted:

Abiraterone.

Abiraterone might reduce analgesic effect of codeine by CYP2D6 inhibition.

Anticoagulants, including warfarin.

Ibuprofen interferes with the stability of INR and may increase risk of severe bleeding and sometimes fatal haemorrhage, especially from the gastrointestinal tract. The mechanism of this interaction is not known but may involve increased bleeding from NSAID-induced gastrointestinal ulceration or an additive effect of NSAID inhibition of platelet function with the anticoagulant effect of warfarin. Ibuprofen should only be used in patients taking warfarin if absolutely necessary and they must be closely monitored.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs).

Increased risk of gastrointestinal bleeding (see Section 4.4 Special Warnings and Precautions for Use).

Lithium.

Ibuprofen may decrease renal clearance and increase plasma concentration of lithium. Lithium plasma concentrations should be monitored in patients on concurrent ibuprofen therapy.
Ibuprofen may reduce the anti-hypertensive effect of ACE inhibitors and beta-blockers with possible loss of blood pressure control and can attenuate the natriuretic effects of diuretics. Hypotensive effects of antihypertensive agents may be potentiated when used concurrently with codeine and lead to orthostatic hypotension. NSAIDs may diminish the effects of antihypertensives and diuretics. The use of an ACE inhibiting drug (ACE-inhibitor or angiotensin receptor agonist), an anti-inflammatory drug (NSAID or COX-2) inhibitor and thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed combination medicines containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

Methotrexate.

NSAIDs inhibit tubular secretion of methotrexate in animals. As a result, reduction in the clearance of methotrexate may occur. Use of high doses of methotrexate concomitantly with NSAIDs should be avoided. At low doses of methotrexate, caution should be used if ibuprofen is administered concomitantly.

Cardiac glycosides.

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma levels of glycosides. Care should therefore be taken in patients treated with cardiac glycosides.

Corticosteroids.

Ibuprofen may increase the risk of gastrointestinal ulceration or bleeding especially if taken with corticosteroids (see Section 4.4 Special Warnings and Precautions for Use).

Zidovudine.

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen. Ibuprofen may prolong bleeding time in patients treated with zidovudine.

Probenecid and phenytoin.

Ibuprofen may also interact with probenecid, antidiabetic medicines and phenytoin.

CNS depressants including alcohol.

Codeine may potentiate the effects of CNS depressants, including alcohol and may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of Amcal Ibuprofen Plus Codeine with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tranquilisers, barbiturates, chloral hydrate, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, centrally acting muscle relaxants and other CNS depressants, should be reserved for patients for whom other treatment options are not possible (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.

Metoclopramide, cisapride and domperidone.

Codeine may antagonise the gastrointestinal effects of metoclopramide, cisapride and domperidone.

Monoamine oxidase inhibitors (MAOIs).

Concurrent administration or use within 14 days of ceasing MAOIs may enhance the potential respiratory depressant effects of codeine. CNS depression or excitation may occur if codeine is given to patients receiving monoamine oxidase inhibitors.

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).
Substances that inhibit CYP2D6 such as quinidine, phenothiazines and antipsychotic agents can interfere with the metabolism of codeine to morphine, reducing the analgesic effect of codeine.

Antimuscarinics.

Concomitant use of antimuscarinics or medications with muscarinic action, e.g. atropine and some antidepressants may result in increased risk of severe constipation which may lead to paralytic ileus and/or urinary retention.

Ciclosporin.

An increased risk of nephrotoxicity.

Cimetidine.

Cimetidine inhibits the metabolism of opioid analgesics resulting in increased plasma concentrations.

Hydroxyzine.

Concurrent use of hydroxyzine (anxiolytics) with codeine may result in increased analgesia as well as increased CNS depressant, sedative and hypotensive effects.

Mexiletine.

Codeine may delay the absorption of mexiletine and thus reduce the antiarrhythmic effect of the latter.

Mifepristone.

NSAIDs should not be used after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Moclobemide.

Risk of hypertensive crisis.

Naloxone.

Naloxone antagonises the analgesic, CNS and respiratory depressant effects of opioid analgesics. Naltrexone also blocks the therapeutic effect of opioids.

NSAIDs and aspirin.

Concurrent use of ibuprofen with aspirin or other NSAIDs can lead to increased gastrointestinal adverse effects.

Neuromuscular blocking agents.

The respiratory depressant effect caused by neuromuscular blocking agents may be additive to the central respiratory depressant effects of opioid analgesics.

Quinolone antibiotics.

Animal data indicate that NSAIDs can increase the risk of convulsions associated with Quinolone antibiotics. Patients taking NSAIDs and Quinolone may have an increased risk of developing convulsions.

Tacrolimus.

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Quinidine.

Quinidine can inhibit the analgesic effect of codeine.

Serotonergic drugs.

Serotonin syndrome has been reported during concomitant use of serotonergic drugs including triptans, selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), and tricyclic antidepressants, with opioids at recommended dosages.

Tranquilizers, sedatives and hypnotics.

Codeine may potentiate the effects of these drugs (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

Incompatibilities.

Codeine has been reported to be incompatible with phenobarbitone sodium forming a codeine phenobarbitone complex, and with potassium-iodide, forming crystals of codeine periodide. Acetylation of codeine phosphate by acetylsalicylic acid (aspirin) has occurred in solid dosage forms containing the two drugs, even at low moisture levels.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There is limited evidence that drugs which inhibit cyclo-oxygenase prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.
(Category C)
Pregnancy Category C - Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying text above should be consulted for further details.
Inhibition of prostaglandin synthesis by ibuprofen may adversely affect pregnancy and/or the embryo/foetal development. During the first and second trimester of pregnancy, this product should not be given unless clearly necessary, and is contraindicated in the third trimester.
During the third trimester, all prostaglandin synthesis inhibitors may expose the foetus to cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and renal dysfunction, which may progress to renal failure with oligohydramnios. At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to possible prolongation of bleeding time and inhibition of uterine contractions, which may result in delayed or prolonged labour. 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 this medicine is thus contraindicated during the third trimester of pregnancy (see Section 4.3 Contraindications), including the last few days before the expected birth.
Further, there is insufficient experience with the safety of use of ibuprofen in humans during pregnancy. Amcal Ibuprofen Plus Codeine should therefore not be used during the first 6 months of pregnancy unless the potential benefits to the patient outweigh the possible risk to the foetus.
Opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. Amcal Ibuprofen Plus Codeine is contraindicated for use during the last trimester of pregnancy (see Section 4.3 Contraindications).

Oligohydramnios and neonatal renal impairment.

Use of NSAIDs from about 20 weeks gestation may cause foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If, after careful consideration of alternative treatment options for pain management, NSAID treatment is necessary from about 20 weeks, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours. Discontinue treatment with NSAIDs if oligohydramnios occurs.
 Ibuprofen and codeine both appear in breast milk in low concentrations. Codeine may cause respiratory depressions in newborn infants.
Amcal Ibuprofen Plus Codeine is contraindicated during breastfeeding (also see Section 4.4 Special Warning 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 (also see Section 4.4 Special Warning and Precautions for Use, CYP2D6 metabolism).
Therefore, Amcal Ibuprofen Plus Codeine 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 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

This medication may cause drowsiness and may increase the effects of alcohol.
Opioid analgesics can impair mental function and cause blurred vision and dizziness. Rare side effects may include convulsions, hallucinations, blurred or double vision and orthostatic hypotension. Patients should be advised not to drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

The most commonly observed adverse events are gastrointestinal in nature. Adverse events are mostly dose-dependent, in particular the risk of occurrence of gastrointestinal bleeding which is dependent on the dosage range and duration of treatment.
Side effects from codeine are theoretical warnings based on drug class. No clinical data is available to determine frequency.
Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is then stopped.
Prolonged use of a painkiller for headache can make them worse.
The list of the following adverse events relates to those experienced with ibuprofen and codeine (maximum of 1200 mg ibuprofen per day), for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.
Adverse events which have been associated with ibuprofen and codeine are given in Table 1, tabulated by System Organ Class (SOC) and frequency.
The frequencies of adverse effects are defined as follows: very common: ≥ 1/10; common: ≥ 1/100, < 1/10; uncommon: ≥ 1/1,000, < 1/100; rare: ≥ 1/10,000, < 1/1,000; very rare: < 1/10,000, including isolated reports; not known: cannot be estimated from the available data.
Within each frequency grouping, adverse events are presented in order of decreased seriousness. See Table 1.

Gastrointestinal.

Dyspepsia, heartburn, nausea, loss of appetite, stomach pain, diarrhoea.
Other side effects include: cough suppression, respiratory depression, euphoria, dysphoria, skin rashes, histamine release (hypotension, flushing of the face, tachycardia, breathlessness) and other allergic reactions.

Post-marketing experience.

Skin and subcutaneous tissue disorders.

Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS).

Pregnancy, puerperium and perinatal conditions.

Oligohydramnios, neonatal renal impairment.

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

For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).
Overuse of this product, defined as consumption of quantities in excess of the recommended dose, or consumption for a prolonged period, may lead to physical or psychological dependency. Symptoms of restlessness and irritability may result when treatment is stopped.

Symptoms.

Ibuprofen.

Symptoms of overdose with ibuprofen include nausea, vomiting, abdominal pain, diarrhoea (rarely), headache, dizziness, drowsiness, nystagmus, vertigo, blurred vision, tinnitus and rarely, hypertension, metabolic acidosis convulsions, excitation, disorientation, coma, renal failure, liver damage, hypotension, respiratory depression, cyanosis and loss of consciousness. Exacerbation of asthma is possible in asthmatics.

Codeine.

Nausea and vomiting are prominent features of codeine overdose. Respiratory depression, excitability, convulsions, hypotension and loss of consciousness may occur with large codeine overdose. Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pinpoint in size. Hypotension and tachycardia are possible.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ibuprofen possesses analgesic, antipyretic and anti-inflammatory properties, similar to other non-steroidal anti-inflammatory drugs (NSAIDs). Its mechanism of action is unknown, but is thought to be through peripheral inhibition of cyclooxygenases and subsequent prostaglandin synthetase inhibition.
Codeine acts centrally. It has an analgesic effect, which is thought to be due mainly to its partial metabolic conversion to morphine. Codeine has about one-sixth the analgesic activity of morphine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Ibuprofen.

Absorption.

It is well absorbed after from the gastrointestinal tract after oral administration with peak serum levels occurring after 1-2 hours.

Distribution.

Apparent volume of distribution is 0.14 L/kg. Ibuprofen and its metabolites readily cross the placental barrier in pregnant animals (rabbits and rats). It is not known if ibuprofen enters the cerebrospinal fluid.
Ibuprofen is highly bound (90-99%) to plasma proteins and consequently, this characteristic of the drug should be considered when prescribing ibuprofen together with other drugs that bind to the same site on human serum albumin.

Metabolism.

90% of ibuprofen is extensively metabolised to inactive compounds in the liver, mainly by glucuronidation, to produce two metabolites - a hydroxylated compound and a carboxylated compound.

Excretion.

Both the inactive metabolites and a small amount of unchanged ibuprofen are excreted rapidly and completely by the kidney, with 95% of the administered dose eliminated in the urine within four hours of ingestion. The elimination half-life of ibuprofen is in the range of 1.9 to 2.2 hours.

Codeine.

Absorption.

Codeine and its salts are well absorbed from the gastrointestinal tract: peak plasma-codeine concentrations occur at about one hour after ingestion of codeine phosphate. Analgesic action occurs in 15 to 30 minutes and analgesia is maintained up to 4-6 hours.

Distribution.

After ingestion codeine is rapidly distributed to skeletal muscles, kidneys, liver, gastrointestinal tract, lungs, spleen and brain. It crosses the placenta and is distributed in low levels in breast milk.

Metabolism.

Codeine is metabolised by O- and N-demethylation in the liver (via the cytochrome P450 system) to morphine (about ten percent of a codeine dose is demethylated to morphine), norcodeine and other metabolites including normorphine and hydrocodone. The major metabolic pathway involves glucuronidation of codeine to codeine-6-glucuronide. Codeine can also undergo O- and N-demethylation catalysed by CYP2D6 and CYP3A4 respectively. About 8% of the general population cannot convert codeine to its active metabolite morphine as they are deficient in the CYP2D6 enzyme. These persons are likely to obtain reduced pain relief from codeine.

Excretion.

Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. Of the excreted material in the urine 40-70% is free or conjugated codeine, 5-15% is free or conjugated morphine, and 10-20% is free or conjugated norcodeine. Excretion is almost complete within 24 hours. The plasma half-life of codeine has been reported to be between 2 and 4 hours after oral administration. Only traces of codeine and its metabolites are found in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, maize starch, glyceryl behenate, magnesium stearate, colloidal anhydrous silica, Opadry white complete film coating system 04F58804 white.

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.

6.5 Nature and Contents of Container

Amcal Ibuprofen Plus Codeine is available in PVC/PE/PVDC blister packs of 30 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Ibuprofen.

Description.

Ibuprofen: It is a white or almost white powder or crystals with a characteristic odour. Practically insoluble in water, soluble 1 in 1.5 of alcohol, 1 in 1 of chloroform, 1 in 2 of ether and 1 in 1.5 of acetone; soluble in aqueous solutions of alkali hydroxides and carbonates.

Chemical name.

2-(4-Isobutylphenyl) propionic acid.

Molecular formula.

C13H18O2.

Molecular weight.

206.3.

Chemical structure.


CAS number.

15687-27-1.

Codeine phosphate.

Description.

Codeine: is a small, colourless, odourless crystal or a white, odourless crystalline powder. Codeine phosphate is soluble in four parts water, slightly soluble in ethanol (96%), practically insoluble in chloroform and ether.

Chemical name.

4,5α-Epoxy-3-methoxy-17-methyl-7,8-didehydromorphinan-6α-ol phosphate hemihydrate.

Molecular formula.

C18H24NO7P.½H2O.

Molecular weight.

406.4.

Chemical structure.


CAS number.

41444-62-6

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes