Consumer medicine information

Sandoz Ibuprofen Plus Codeine

Ibuprofen; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Sandoz 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 Sandoz Ibuprofen Plus Codeine.

What is in this Leaflet?

This leaflet answers some common questions about Sandoz Ibuprofen Plus Codeine tablets. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Sandoz Ibuprofen Plus Codeine tablets against the benefits this medicine is expected to have for you.

If you have any concerns about taking this medicine, ask your pharmacist or doctor.

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

What Sandoz Ibuprofen Plus Codeine is used for

Sandoz Ibuprofen Plus Codeine tablets contain two active ingredients:

Ibuprofen and Codeine phosphate hemihydrate.

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 is an opioid analgesic that works in the brain and spinal cord to relieve pain.

Sandoz Ibuprofen Plus Codeine tablets provides temporary relief of acute moderate pain and inflammation in patients over the age of 12 years.

After taking codeine, the body changes codeine into the active morphine by a special liver enzyme. However, about 8% of people may experience less pain relief compared to others, as their bodies do not change codeine to morphine as well as others.

Do not give Sandoz Ibuprofen Plus Codeine tablets to children under the age of 12 years.

Ask your doctor if you have any questions about this medicine.

Your doctor may have given it for another reason.

Before You Take Sandoz Ibuprofen Plus Codeine

When you must not take it

Do not take Sandoz Ibuprofen Plus Codeine tablets if

  1. you have an allergy to:
  • Ibuprofen, codeine or other opioids, or any of the ingredients of Sandoz Ibuprofen Plus Codeine tablets, listed at the end of this leaflet
  • any medicine containing aspirin, ibuprofen or other NSAIDs.

Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAID. 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; this may affect swallowing or breathing
  • hives, itching or skin rash
  • fainting.

If you are allergic to Aspirin or NSAID group of medicines and take Sandoz Ibuprofen Plus Codeine tablets, these symptoms may be severe.

  1. you are in the last three months of pregnancy or are breastfeeding
    Sandoz Ibuprofen Plus Codeine should not be taken during pregnancy except during the first 6 months of pregnancy. All NSAIDs should not be taken during the last three months of pregnancy.
  2. you are vomiting blood or material that looks like coffee grounds
  3. you are bleeding from the rectum (back passage), have black sticky bowel motions (stool) or bloddy diarrhoea
  4. you have peptic ulcer (ie. Stomach or duodenal ulcer), or have had one before
  5. you are using other NSAIDs
  6. you have chronic constipation or shallow breathing, or severe diarrhoea
  7. you consume regular and heavy amounts of alcohol
  8. you are a CYP2D6 ultra-rapid metaboliser

Do not take Sandoz Ibuprofen Plus Codeine if the packaging is torn or shows signs of tampering

Do not take Sandoz Ibuprofen Plus Codeine if the expiry date (EXP) printed on the pack has passed.

If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should start taking Sandoz Ibuprofen Plus Codeine, contact your doctor.

Do not give Sandoz Ibuprofen Plus Codeine to children under 12 years or to those aged 12-18 years in whom respiratory function may be compromised.

Before you start to take it

Tell your pharmacist or doctor if:

  1. you have allergies to any other medicines including aspirin, or other NSAID medicines
  2. you are pregnant or intend to become pregnant
    Sandoz Ibuprofen Plus Codeine is not recommended during the last 3 months of pregnancy. Your doctor should decide if you should take Sandoz Ibuprofen Plus Codeine during the first 6 months of pregnancy.
  3. you are breast-feeding or plan to breast-feed
    Sandoz Ibuprofen Plus Codeine should not be taken while breastfeeding except on your doctor's advice.
    Codeine passes into the breast milk.
    If there is a need to consider Sandoz Ibuprofen Plus Codeine while you are breast-feeding, your pharmacist or doctor will discuss with you the benefits and risks of using it.
  4. you have or have had any of the following medical conditions:
    - 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
    - thyroid problems or low blood pressure
    - a head injury or intercranial pressure
    - prostatic problems
    - stomach problems or recent stomach surgery.

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

If you have not told your doctor about any of the above, tell him/her before you start taking Sandoz Ibuprofen Plus Codeine.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines may interfere with Sandoz Ibuprofen Plus Codeine. These include:

  • medicines used to help you relax, sleep or relieve anxiety, such as barbiturates and sedatives.
  • aspirin, salicylates or other NSAID medicines
  • warfarin or other medicines used to stop blood clots or thin the blood
  • medicines that are used to treat high blood pressure eg diuretics (fluid tablets)
  • methotrexate
  • zidovudine
  • lithium
  • mifepristone, quinolone antibiotics
  • medicines used to relieve stomach cramps, prevent travel sickness and to treat Parkinson's disease
  • medicines used to treat diarrhoea (eg. kaolin, pectin, loperamide)
  • metoclopramide, a medicine used to treat nausea and vomiting
  • Selective Serotonin Reuptake Inhibitors (SSRIs), and Monoamine Oxidase Inhibitors (MAOIs), medicines used to treat some types of depression
  • Quinidine, a medicine used to treat abnormal or irregular heart beat
  • Phenothiazines and antipsychotic agents, medicines used to treat mental disorders
  • medicines such as cyclosporin, tacrolimus, prednisone, prednisolone and cortisone, which reduce the activity of your immune system
  • Probenecid - medicine used to treat gout
  • Phenytoin - medicine used to treat epilepsy
  • other opioids pain killers

These medicines may be affected by Sandoz 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.

Your doctor has more information on medicines to avoid or be careful with while taking Sandoz Ibuprofen Plus Codeine tablets.

How to Take Sandoz Ibuprofen Plus Codeine

How much to take

The usual dose of Sandoz 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 to 6 hours.

Do not take more than 6 tablets in 24 hours.

Sandoz Ibuprofen Plus Codeine is not recommended for children under 12 years of age. If you do not understand the instructions on the pack, ask your doctor for help.

How to take it

Take Sandoz Ibuprofen Plus Codeine by mouth with fluid. It may also be taken before, or after food.

How long to take it

You should not take Sandoz Ibuprofen Plus Codeine for more than a few days.

If your symptoms persist, worsen or new symptoms develop, talk to your doctor.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (in Australia 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital if you think you or anyone else may have taken too much Sandoz Ibuprofen Plus Codeine. Do this even if there are no signs of discomfort or poisoning.

If you take too much of this medicine you may experience nausea or upset stomach, vomiting and gastric irritation, drowsiness, dizziness or very slow, laboured breathing. You may also experience blurred vision, ringing in the ears, or rapid uncontrollable movements of the eyes. Excitability, convulsions and unconsciousness may be experienced in rare cases.

While You Are Using Sandoz Ibuprofen Plus Codeine

Things you must do

  • If you become pregnant while taking Sandoz Ibuprofen Plus Codeine tablets stop taking and talk to your doctor.
  • If you are about to be started on any new medicine tell your doctor that you are taking Sandoz Ibuprofen Plus Codeine tablets.
  • Tell all of the doctors, dentists and pharmacists that are treating you that you are taking Sandoz Ibuprofen Plus Codeine tablets.
  • If you are going to have surgery, tell your doctor you are taking Sandoz Ibuprofen Plus Codeine tablets.
  • Talk to your doctor or pharmacist if your symptoms do not improve.
  • Your doctor will assess your condition and decide if you should continue to take the medicine

Things you must not do

  • Do not give Sandoz Ibuprofen Plus Codeine tablets to anyone else, even if they have the same condition as you
  • Do not use Sandoz Ibuprofen Plus Codeine tablets to treat any other complaints
  • Do not take more than the recommended dose unless your doctor tells you
  • Excessive use can be harmful and increase the risk of heart attack, stroke or liver damage.

Things to be careful of

  • Be careful driving or operating machinery until you know how Sandoz Ibuprofen Plus Codeine tablets affects you.
  • Sandoz Ibuprofen Plus Codeine tablets may cause dizziness, light-headedness or drowsiness in some people. If this occurs, do not drive or operate machinery. If you drink alcohol, dizziness, light-headedness or drowsiness may be worse.
  • 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.

Side Effects

Check with your doctor as soon as possible if you have any problems while taking Sandoz Ibuprofen Plus Codeine, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, Sandoz Ibuprofen Plus Codeine can cause some side effects in some people. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Ask your doctor to answer any questions you may have.

Tell your doctor if you notice any of the following symptoms that worry you:

  • stomach upset including nausea (feeling sick), vomiting
  • heartburn, indigestion
  • loss of appetite
  • sleeplessness, nightmares
  • change in mood for example depression, restlessness, irritability
  • diarrhoea, pain in the stomach
  • dizziness, light-headedness, drowsiness
  • constipation
  • shallow breathing
  • cough suppression
  • headache
  • hearing disturbance.

These are the more common side effects of Sandoz Ibuprofen Plus Codeine and are usually mild and short lived.

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

  • shallow breathing or shortness of breath
  • unusual or extreme mood swings
  • dizziness, light-headedness
  • flushing of the face
  • fast heart beat
  • severe pain or tenderness in the stomach
  • eye problems such as blurred vision, sore red eyes, itching
  • severe dizziness, spinning sensations
  • severe or persistent headache
  • tingling or numbness of hands or feet
  • difficulty hearing, deafness
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • 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
  • a change in the colour of urine passed, blood in urine
  • a change in the amount or frequency of urine passed, burning feeling when passing urine
  • yellowing of the skin and eyes, also called jaundice
  • unusual weight gain, swelling of ankles and legs
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal

The above side effect may be serious and may require urgent medical attention.

Serious side effects are rare for low doses of this medicine and when used for a short period of time.

If any of the following happen, stop taking Sandoz Ibuprofen Plus Codeine and tell your doctor immediately or go to casualty at your nearest hospital:

  • vomiting blood or material that looks like coffee grounds
  • bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
  • 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
  • sudden or severe itching, skin rash, hives, skin peeling
  • easy bruising

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

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

Some people may get other side effects while taking Sandoz Ibuprofen Plus Codeine tablets. Tell your doctor or pharmacist if you notice anything else that worries you.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After Using Sandoz Ibuprofen Plus Codeine

Storage

Keep the tablets in the pack until it is time to take the dose. If you take them out they will not keep well.

Keep the tablets in a cool dry place where the temperature stays below 30°C.

Do not store Sandoz Ibuprofen Plus Codeine or any other medicine in the bathroom or near a sink.

Do not leave the tablets in the car or on windowsills. Heat and dampness can destroy some medicines.

Keep the tablets where children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground are a good place to store medicines.

Disposal

When you stop taking Sandoz Ibuprofen Plus Codeine or it has passed its expiry date, ask your pharmacist what to do with any tablets that are left over.

More Information

If you have any further questions or if you are not sure about anything relating to the use of Sandoz Ibuprofen Plus Codeine tablets, your doctor or pharmacist can best assist you.

Product Description

What it looks like?

Sandoz Ibuprofen Plus Codeine is white to off-white capsule-shaped, biconvex, film-coated tablet.

Ingredients

Sandoz Ibuprofen Plus Codeine tablets contains 200mg ibuprofen and 12.8mg codeine phosphate as the active ingredients.

The other ingredients in Sandoz Ibuprofen Plus Codeine tablets are:

  • pregelatinised maize starch
  • microcrystalline cellulose
  • croscarmellose sodium
  • colloidal anhydrous silica
  • Opadry complete film coating system OY-58900 white

Sandoz Ibuprofen Plus Codeine does not contain gluten or preservatives.

Presentation:

Sandoz Ibuprofen Plus Codeine tablets are available in Australia in blister packs of 30 tablets.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park NSW 2113
Australia
Tel: 1800 726 369

This leaflet was revised in June 2019

Australian Register Number:

200mg/12.8mg Tablets: AUST R 211512

Published by MIMS August 2019

BRAND INFORMATION

Brand name

Sandoz Ibuprofen Plus Codeine

Active ingredient

Ibuprofen; Codeine phosphate hemihydrate

Schedule

S4

 

1 Name of Medicine

Ibuprofen and codeine phosphate hemihydrate.

6.7 Physicochemical Properties

Ibuprofen is a white or almost white crystalline powder 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.
Codeine phosphate hemihydrate 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.

Ibuprofen.

Chemical name: (2RS)-2-[4-(2-methylpropyl)phenyl]propanoic acid.
Molecular formula: C13H18O2.
Molecular weight: 206.3.

Codeine phosphate hemihydrate.

Chemical name: 4,5α-epoxy-3-methoxy-17-methyl-7,8-didehydromorphinan-6α-ol phosphate hemihydrate.
Molecular formula: C18H21NO3.H3PO4.½ H2O.
Molecular weight: 406.4.

Chemical structure.


CAS number.

Ibuprofen.

15687-27-1.

Codeine phosphate hemihydrate.

41444-62-6.

2 Qualitative and Quantitative Composition

Each Sandoz Ibuprofen Plus Codeine film coated tablet contains 200 mg ibuprofen and 12.8 mg codeine phosphate hemihydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Sandoz Ibuprofen Plus Codeine tablets are white to off-white capsule-shaped, biconvex film-coated tablets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ibuprofen possesses analgesic, antipyretic and anti-inflammatory properties, similar to other nonsteroidal 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 on opiate receptors. Its analgesic effect 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

Absorption.

Ibuprofen.

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

Codeine.

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.

Ibuprofen.

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.

Protein binding.

It 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.

Codeine.

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.

Ibuprofen.

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

Codeine.

Codeine is metabolised by O- and N-demethylation in the liver (by CYP2D6 and CYP3A4 respectively) 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. About 8% of the general Australian 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.

Ibuprofen.

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.

Half-life.

The elimination half-life of ibuprofen is in the range of 1.9 to 2.2 hours.

Codeine.

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.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.3 Contraindications

Sandoz Ibuprofen Plus Codeine tablet is contraindicated for use in:
known hypersensitivity or idiosyncratic reaction to ibuprofen, codeine or other opioid analgesics, or any of the excipients (see Section 6.1 List of Excipients);
patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, bronchospasm or urticaria) in response to ibuprofen, acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs);
active gastrointestinal bleeding or in the presence of peptic ulceration;
respiratory depression, chronic constipation and active alcoholism;
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 or renal problems (see Section 4.4 Special Warnings and Precautions for Use);
severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use);
during the last trimester of pregnancy, including the last few days before expected birth (see Section 4.4 Special Warnings and Precautions for Use);
during labour when delivery of a premature infant is anticipated as it may produce codeine withdrawal symptoms in the neonate;
taking other products containing ibuprofen, aspirin, salicylates or with other anti-inflammatory medicines (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions);
concomitant treatment with Monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment;
use of codeine containing products is contraindicated in women during breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation);
patients for whom it is known they are CYP2D6 ultra rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism);
patients younger than 12 years (See Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
in patients aged between 12-18 years in whom respiratory function might be compromised, including post tonsillectomy, and/or adenoidectomy for obstructive sleep apnoea due to an increased risk of developing serious life threatening adverse reactions (See Section 4.4 Special Warnings and Precautions for Use, Paediatric use);
treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).

4.4 Special Warnings and Precautions for Use

Sandoz Ibuprofen Plus Codeine tablets should be administered with caution and at lowest effective dose in patients:
with decreased respiratory reserve, e.g. asthma or COPD or pre-existing respiratory depression;
with asthma, especially those patients who have not taken an NSAID. Sandoz Ibuprofen Plus Codeine tablets are contraindicated for use in patients with acute respiratory depression (see Section 4.3 Contraindications);
who are taking other respiratory depressants or sedatives, including alcohol;
with hepatic impairment;
with previous history of gastrointestinal haemorrhage or ulcers;
who have had recent gastrointestinal tract surgery;
who are pregnant (see Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation).

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 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. Codeine may also obscure the diagnosis or the course of gastrointestinal diseases.
Care is advised in the administration of Sandoz 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 Sandoz 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.

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.
Sandoz Ibuprofen Plus Codeine tablets should be administered with caution in patients with hypertension or fluid retention (see Section 4.3 Contraindications, Heart failure).

Dermatological.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see Section 4.8 Adverse Effects (Undesirable Effects)). Sandoz Ibuprofen Plus Codeine use should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

CYP2D6 metabolism.

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

Other.

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. Sandoz Ibuprofen Plus Codeine should therefore be administered with caution in such situations.
Sandoz Ibuprofen Plus Codeine should be administered with caution and at lowest effective dose in patients who have recently had gastrointestinal surgery, as codeine may reduce gastrointestinal motility.
Sandoz Ibuprofen Plus Codeine should be administered with caution and at lowest effective dose in those with hypotension and/or hypothyroidism. The tablets should be used with caution and at the lowest effective dose in patients with raised intracranial pressure or head injury.
Physical and/or psychological dependence may occur following prolonged administration of codeine. Tolerance may also develop following prolonged administration and irritability and restlessness may be experienced when the tablets are stopped.
Sandoz Ibuprofen Plus Codeine should be administered with caution and at lowest effective dose in patients with prostatic hypertrophy since codeine may cause urinary retention.
Care is advised in the administration of Sandoz Ibuprofen Plus Codeine to patients with adrenocortical insufficiency and also in patients with a history of drug abuse.

Use in hepatic impairment.

Sandoz Ibuprofen Plus Codeine tablets should be administered with caution and at lowest effective dose 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.

In patients with renal impairment, renal function may deteriorate following the use of any NSAID, especially in dehydrated paediatric patients (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)).

Use in the elderly.

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.
Adverse effects may have more serious consequences in the elderly, and they may be more susceptible to the CNS depressant effects of opioids.
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 above).
The elderly are also more likely to have age related renal impairment and may be more susceptible to the respiratory depressant effects of codeine.

Paediatric use.

Sandoz Ibuprofen Plus Codeine tablets are contraindicated for use in children:
younger than 12 years;
aged between 12-18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea. Respiratory depression and death have occurred in some children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-metabolisers of codeine due to CYP2D6 polymorphism.

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).

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.

Opioid analgesics interfere with a number of laboratory tests including plasma amylase, lipase, bilirubin, alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. Opioids may also interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Sandoz Ibuprofen Plus Codeine should be avoided in combination with:

Aspirin.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly.

Other NSAIDs.

Including cyclooxygenase-2-selective inhibitors.
Sandoz Ibuprofen Plus Codeine should be used with caution in combination with:

Anticholinergics.

Concurrent use of codeine and anticholinergic agents may increase the risk of severe constipation and/or urinary retention.

Anticoagulant, including warfarin.

Concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal haemorrhage. 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. Sandoz Ibuprofen Plus Codeine should only be used in patients taking warfarin if absolutely necessary. Patients taking this combination must be closely monitored.
Ibuprofen interferes with the stability of INR and may increase the risk of severe bleeding.

Antihypertensives.

Ibuprofen, like other NSAIDs can reduce the antihypertensive effect of ACE inhibitors and beta-blockers and diuretics and may cause natriuresis and hyperkalemia in patients under these treatments.
Hypotensive effects of antihypertensive agents may be potentiated when used simultaneously with codeine and lead to orthostatic hypotension. NSAIDs may diminish the effects of antihypertensives and diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs. The combined use of the three classes of drugs, diuretics, an ACE inhibiting drug (ACE inhibitor or angiotensin receptor antagonist) and an anti-inflammatory drug (NSAID or cyclooxygenase-2 (COX-2) inhibitor) all at the same time increases the risk of renal impairment. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Anti-muscarinics.

Concomitant use of anti-muscarinics 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.

Antiperistaltic antidiarrhoeals (including kaolin, pectin, loperamide).

Concurrent use of these agents with codeine may increase the risk of severe constipation.

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

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

Cardiac glycosides.

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

Central nervous system depressants.

Concomitant use of codeine with central nervous system depressants (e.g. barbiturates, chloral hydrate, sedatives, alcohol and centrally acting muscle relaxants) can cause additive CNS depression.

Ciclosporin.

An increased risk of nephrotoxicity.

Cimetidine.

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

Corticosteroids.

An increased risk of gastrointestinal bleeding may occur with corticosteroids (see Section 4.4 Special Warnings and Precautions for Use).

Drugs that inhibit CYP2D6.

Quinidine, phenothiazines and antipsychotic agents can interfere with the metabolism of codeine to morphine, reducing the analgesic effect of codeine.

Hydroxyzine.

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

Lithium.

Ibuprofen may decrease the renal clearance and increase plasma concentrations of lithium. Lithium plasma concentrations should be monitored in patients on concurrent ibuprofen therapy.

Metoclopramide, cisapride and domperidone.

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

Methotrexate.

Ibuprofen reduces methotrexate clearance. Use of high doses of methotrexate concomitantly with NSAIDs should be avoided and caution should be used if low doses of methotrexate are administered concomitantly with ibuprofen.

Mexiletine.

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

Moclobemide.

Risk of hypertensive crisis.

Monoamine oxidase inhibitors (MAOIs).

Concurrent administration or use within 14 days of ceasing monoamine oxidase inhibitors 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, or within two weeks of stopping treatment with them.

Naloxone.

Naloxone antagonises the analgesic, CNS and respiratory depressant effects of opioid analgesic. 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.

Opioid analgesics.

Concurrent use of codeine and other opioid receptor agonists is usually inappropriate as additive CNS depression, respiratory depression and hypotensive effects may occur.

Probenecid and phenytoin.

Interactions may also occur with probenecid, antidiabetic medications and phenytoin.

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.

Quinidine.

Quinidine can inhibit the analgesic effect of codeine.

Tacrolimus.

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

Tranquillizers, sedatives and hypnotics.

Codeine may potentiate the effects of these preparations.

Zidovudine.

Concurrent administration with ibuprofen may prolong bleeding time in patients. There is evidence of an increased risk of hamemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
NSAIDs inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the foetal ductus arteriosus, foetal renal impairment, inhibition of platelet aggregation, and delay labour and birth. Use of ibuprofen is thus contraindicated during the third trimester of pregnancy, including the last few days before expected birth.
Further, there is insufficient experience with the safety of use of ibuprofen in humans during pregnancy. Ibuprofen 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. The use of codeine may prolong labour. Administration of codeine during labour may cause respiratory depression in the newborn infant. Sandoz Ibuprofen Plus Codeine is contraindicated for use during the last trimester of pregnancy (see Section 4.3 Contraindications).
Based on animal studies and limited clinical experience there is no evidence to suggest foetal abnormalities associated with the use of codeine. However, ibuprofen 200 mg/codeine phosphate 12.8 mg tablets should be avoided during pregnancy.
Ibuprofen appears in breast milk in very low concentrations. Sandoz Ibuprofen Plus Codeine tablets are contraindicated during breastfeeding (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism) due to risk of respiratory depression in the infant. Analgesic doses excreted in breast milk are generally low. However, infants of breast feeding mothers taking codeine may have increased risk of morphine overdose if the mother is an ultra-rapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine partially metabolised by cytochrome P450 2D6 (CYP2D6) into morphine, which is excreted into breast milk. If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses.
Therefore Sandoz Ibuprofen Plus Codeine tablets are contraindicated for use during breastfeeding. However, in circumstances where a breastfeeding mother requires codeine therapy, breastfeeding should be suspended and alternative arrangements should be made for feeding the infant for any period during codeine treatment. Breast feeding mothers should be told how to recognize signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness, and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Medical advice should be sought immediately.

4.8 Adverse Effects (Undesirable Effects)

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.
Adverse effects with short-term use of ibuprofen and codeine phosphate may include:

Gastrointestinal.

Heartburn, loss of appetite, stomach pain.

Skin.

Rarely exfoliative dermatitis has been reported with ibuprofen. Unknown frequency of drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Renal.

Papillary necrosis, which can lead to renal failure.

Cardiovascular.

Fluid retention and in some cases oedema occur rarely.

Other.

Euphoria, and dysphoria. Rarely, allergic reactions such as swelling of the face, or breathing difficulties and rarely thrombocytopenia.
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.

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.

4.2 Dose and Method of Administration

Dosage.

Adults and children 12 years and over.

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.

Children.

Do not give to children under 12 years.
Sandoz Ibuprofen Plus Codeine is contraindicated for use in patients who are:
younger than 12 years;
aged between 12-18 years in whom respiratory function might be compromised, including post tonsillectomy and/or adenoidectomy for obstructive sleep apnoea (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.7 Effects on Ability to Drive and Use Machines

Physical and/or psychological dependence, including drug tolerance, may occur following prolonged administration of codeine. Codeine may cause drowsiness; those affected should not drive or operate machinery.
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.

4.9 Overdose

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 of overdose with ibuprofen include nausea, vomiting, abdominal pain, 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.
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. The pupils may be pinpoint in size. Hypotension and tachycardia are possible.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, pregelatinised maize starch, croscarmellose sodium, colloidal anhydrous silica, Opadry complete film coating system OY-58900 white.
Sandoz Ibuprofen Plus Codeine tablets do not contain gluten or preservatives.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Sandoz Ibuprofen Plus Codeine is available in blister pack of 30 tablets.

6.6 Special Precautions for Disposal

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

Summary Table of Changes