Consumer medicine information

Trust Ibuprofen Plus Codeine

Ibuprofen; Codeine phosphate hemihydrate

BRAND INFORMATION

Brand name

Trust Ibuprofen Plus Codeine

Active ingredient

Ibuprofen; Codeine phosphate hemihydrate

Schedule

What is in this Leaflet?

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

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

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Trust Ibuprofen Plus Codeine 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 Trust Ibuprofen Plus Codeine is used for

Trust Ibuprofen Plus Codeine tablets contain the active ingredients Ibuprofen and Codeine phosphate. Ibuprofen belongs to a family of medicines called non-steroidal anti-inflammatory drugs (NSAIDS). These medicines work by relieving pain and/or inflammation (swelling, redness, soreness) and fever. Codeine is an opioid analgesic that works in the brain and spinal cord to relieve pain.

Trust Ibuprofen Plus Codeine 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 Trust Ibuprofen Plus Codeine 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 Trust Ibuprofen Plus Codeine

When you must not take it

Do not take Trust Ibuprofen Plus Codeine if

you have an allergy to:

Ibuprofen, codeine or other opioids, or any of the ingredients listed at the end of this leaflet.
any medicine containing ibuprofen, aspirin 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 which may cause difficulty in swallowing or breathing.
- hives, itching or skin rash.
- fainting.
If you are allergic to aspirin or NSAIDs and take Trust Ibuprofen Plus Codeine these symptoms may be severe.

you are in the last three months of pregnancy or are breastfeeding

Trust 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.

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.

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

Do not take Trust 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 Trust Ibuprofen Plus Codeine, contact your pharmacist or doctor.

Do not give Trust 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 doctor if

you have allergies to:

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

you are pregnant or intend to become pregnant

Trust Ibuprofen Plus Codeine is not recommended during the last 3 months of pregnancy. Your doctor will decide if you should take Trust Ibuprofen Plus Codeine during the first 6 months of pregnancy.

you are breast-feeding or plan to breast-feed

Trust 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 Trust Ibuprofen Plus Codeine while you are breast-feeding, your pharmacist or doctor will discuss with you the benefits and risks of using it.

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 intracranial 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 Nurofen Plus.

Taking other medicines

Tell your pharmacist or 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 Nurofen Plus.

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 prevent blood clots.
medicines that are used to treat high blood pressure including diuretics (fluid tablets)
methotrexate.
zidovudine.
lithium
mifeprisone, 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 - medicines used to treat gout
phenytoin - medicine used to treat epilepsy
other opioid pain killers.

These medicines may be affected by Trust 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 pharmacist and doctor have more information on medicines to avoid or be careful with while taking Trust Ibuprofen Plus Codeine.

How to Take Trust Ibuprofen Plus Codeine

Follow all directions given to you by your pharmacist or doctor carefully. They may differ from the information contained in this leaflet.

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

How much to take

The usual dose of Trust Ibuprofen Plus Codeine is 2 tablets then, if necessary 1 or 2 tablets every 4 to 6 hours. Do not take more than six tablets in 24 hours.

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

How to take it

Take Trust Ibuprofen Plus Codeine by mouth with fluid. It may also be taken with or immediately after food.

How long to take it

You should not take Trust 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 Trust 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/or gastric irritation, drowsiness, dizziness and/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 Trust Ibuprofen Plus Codeine

Things you must do

If you become pregnant while taking Trust Ibuprofen Plus Codeine tell your doctor immediately.

If you are about to be started on any new medicine tell your doctor and pharmacist that you are taking Trust Ibuprofen Plus Codeine.

Tell all of the doctors, dentists and pharmacists that are treating you that you are taking Trust Ibuprofen Plus Codeine.

If you are going to have surgery, tell your doctor you are taking Trust 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.

Things you must not do

Do not give Trust Ibuprofen Plus Codeine to anyone else, even if they have the same condition as you.

Do not use Trust Ibuprofen Plus Codeine to treat any other complaints unless your doctor tells you to.

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

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 Trust Ibuprofen Plus Codeine affects you. Trust 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, light-headedness and/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 Trust 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, Trust Ibuprofen Plus Codeine can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

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

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

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

stomach upset including nausea (feeling sick), vomiting.
heartburn, indigestion.
loss of appetite
sleeplessness, nightmares
change in mood for example depression, restlessness, irritability
sore or dry mouth or tongue
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 Trust 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 sensation
severe or persistent headache
tingling or numbness of the 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 the 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 or 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 Trust 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

The above list includes 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 Trust Ibuprofen Plus Codeine. 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 Trust Ibuprofen Plus Codeine

Storage

Keep the tablets in the original 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 Trust Ibuprofen Plus Codeine tablets 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 is a good place to store medicines.

Disposal

When you stop taking Trust 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 Trust Ibuprofen Plus Codeine tablets, your doctor or pharmacist can best assist you.

Product Description

What it looks like

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

Ingredients

Trust Ibuprofen Plus Codeine contains 200mg Ibuprofen and 12.8mg Codeine phosphate hemihydrate as the active ingredients.

The other ingredients in Trust Ibuprofen Plus Codeine are:

starch – pregelatinised maize
cellulose microcrystalline
croscarmellose sodium
silica colloidal anhydrous
water purified
opadry white colouring

Trust Ibuprofen Plus Codeine tablets do not contain gluten, lactose or preservatives.

Presentation:

Trust Ibuprofen Plus Codeine tablets are available in Australia in blister packs of 10, 12, 15, 18, 20, 24, and 30 tablets*.

*Not all pack sizes are marketed in Australia.

Distributor:

Pharmacor Pty Ltd
Suite 803, Tower A, The Zenith,
821 Pacific Highway,
Chatswood NSW 2067
Australia

Web: www.pharmacor.com.au
Phone: 1300 138 805

AUST R 175264

This leaflet was prepared in October 2020.

Published by MIMS February 2021

BRAND INFORMATION

Brand name

Trust Ibuprofen Plus Codeine

Active ingredient

Ibuprofen; Codeine phosphate hemihydrate

Schedule

1 Name of Medicine

Ibuprofen and codeine phosphate hemihydrate.

2 Qualitative and Quantitative Composition

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

3 Pharmaceutical Form

Trust Ibuprofen Plus Codeine tablets: white to off-white capsule-shaped, biconvex film-coated tablets.

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).

4.2 Dose and Method of Administration

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 6 tablets in a 24 hour period.
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

Pregnancy.

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

Children.

Do not give to children under 12 years.
Trust 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 (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.3 Contraindications

Known hypersensitivity or idiosyncratic reaction to ibuprofen, codeine or other opioid analgesics, or any other ingredients in the product listed, 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.
Active, or history of recurrent peptic ulcer/haemorrhage.
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).
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).
Use with concomitant NSAIDs, including cyclo-oxygenase-2 specific inhibitors - increased risk of adverse reactions 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).
During the last 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.
Use of codeine containing products is contraindicated in women during breast feeding (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
In patients who are CYP2D6 ultra rapid metabolisers (see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
In 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 and 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).
Severe respiratory disease, acute respiratory disease and respiratory depression.

4.4 Special Warnings and Precautions for Use

Trust Ibuprofen Plus Codeine tablets should be administered with caution and at lowest effective dose in elderly patients.

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.
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).
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.

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 Trust 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 Trust Ibuprofen Plus Codeine, the treatment should be withdrawn.

Respiratory depression.

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

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.

As with other NSAIDs, elevations of one or more liver function tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may resolve with continued therapy. Meaningful elevations (three times the upper limit of normal) of ALT or AST occurred in controlled clinical trials in less than 1% of patients.
Trust Ibuprofen Plus Codeine tablets should be administered with caution and at lowest effective dose in patients with hepatic impairment (see Section 4.3 Contraindications for severe 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.

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.
Trust Ibuprofen Plus Codeine tablets should be administered with caution and used at the lowest effective dose in patients with hypertension or fluid retention (see Section 4.3 Contraindications).

Skin and subcutaneous tissue disorders.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, drug reaction with eosinophilia with systemic symptoms (see 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)). 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. Trust Ibuprofen Plus Codeine use should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Trust Ibuprofen Plus Codeine tablets should be administered with caution and 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;
who are taking other respiratory depressants or sedatives including alcohol.

Severe skin reactions.

Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) have 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 Trust Ibuprofen Plus Codeine should be discontinued and appropriate measures taken if needed.

Drug reaction with eosinophilia with systemic symptoms (DRESS).

DRESS has been reported in patients using 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.

CYP2D6 metabolism.

Trust 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. Estimates of prevalence of ultra-rapid metabolizers in different populations are summarised in Table 1.

Also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Paediatric use.

Trust Ibuprofen Plus Codeine is 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-rapid metabolisers of codeine due to a 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). 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.

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.

Hazardous and harmful use.

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

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 Trust 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 Trust 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 Trust 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 nonpharmacological 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 Trust 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 Trust Ibuprofen Plus Codeine, especially by children, can result in a fatal overdose of codeine. Patients and their caregivers should be given information on safe storage and disposal of unused Trust 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.

Masking of symptoms of underlying infections.

Trust 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 Trust 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.

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. Trust Ibuprofen Plus Codeine tablets should therefore be administered with caution in such situations.
Trust Ibuprofen Plus Codeine should be administered with caution in patients who have recently had gastrointestinal surgery, paralytic ileus, as codeine may reduce gastrointestinal motility.
Trust Ibuprofen Plus Codeine tablets should be administered with caution and at lowest effective dose in patients with hypotension and/or hypothyroidism.
The tablets should be used with caution and at lowest effective dose in patients with raised intracranial pressure or head injury.
Trust Ibuprofen Plus Codeine tablets should be administered with caution and at the lowest effective dose in patients with prostatic hypertrophy since codeine may cause urinary retention.
Care is advised in the administration of Trust Ibuprofen Plus Codeine tablets to patients with adrenocortical insufficiency and also in patients with a history of drug abuse.

Use in renal impairment.

In patients with renal impairment, renal function should be monitored since it 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)).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Trust Ibuprofen Plus Codeine tablets 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. 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.
Concurrent use of ibuprofen with aspirin or other NSAIDs can lead to increased gastrointestinal adverse effects.
Trust Ibuprofen Plus Codeine tablets should be used with caution in combination with:

Abiraterone.

Abiraterone might reduce analgesic effect of codeine by CYP2D6 inhibition.

Anticholinergics.

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

Anticoagulants.

Ibuprofen interferes with the stability of INR and may increase the risk of severe bleeding and sometimes-fatal haemorrhage, especially from the gastrointestinal tract. Ibuprofen should only be used in patients taking anticoagulants if absolutely necessary. Patients taking this combination must be closely monitored.
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.

Antidiarrhoeals and antiperistaltic agents.

Concurrent use of codeine with antidiarrhoeal and antiperistaltic agents such as loperamide and kaolin may increase the risk of severe constipation.

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.

ACE inhibitors, diuretics and other antihypertensives.

Ibuprofen, like other NSAIDs can reduce the antihypertensive effect of ACE inhibitors and beta-blockers with possible loss of blood pressure control and can attenuate the natriuretic effects of diuretics. And diuretics may cause 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 antiinflammatory 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.

Antiperistaltic antidiarrhoeals (including kaolin, pectin, loperamide).

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

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRls).

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 including alcohols.

Codeine may potentiate the effects of CNS depressants. Concomitant use of codeine with central nervous system depressants (e.g. barbiturates, chloral hydrate, sedatives, benzodiazepines, gabapentinoids, cannabis, tricyclic antidepressants, antihistamines, antipsychotics, tranquillisers, hypnotics, centrally-acting anti-emetics and centrally acting muscle relaxants), including alcohol, can cause addictive CNS depression and may result in sedation, respiratory depression, coma and death (see Section 4.4, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

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 ulceration or bleeding may occur with corticosteroids (see Section 4.4 Special Warnings and Precautions for Use).

Drugs 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.

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 has been shown to 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.

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.

Mexiletine.

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

Mifepristone.

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

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 analgesics. Naltrexone also blocks the therapeutic effect of opioids.

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 (see Section 4.4, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

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.

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.

Tacrolimus.

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

Tranquillizers, sedatives and hypnotics.

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

Zidovudine.

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

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.
(Category C)
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 should be used at the lowest effective dose.
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), 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, inhibition of platelet aggregation and inhibition of uterine contractions, which may result in delayed or prolonged labour and birth.
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.
Trust 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 neonatal 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.
Trust Ibuprofen Plus Codeine is 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 breastfeeding mothers taking codeine may have an increased risk of morphine overdose if the mother is an ultra-rapid metaboliser of codeine. Codeine is excreted into human breast milk. Codeine is partially metabolised by cytochrome P450 2D6 (CYP2D6) into morphine, which is excreted into breast milk. If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. This may result in symptoms of opioid toxicity in both mother and the breastfed infant. Life-threatening adverse events or neonatal death may occur even at therapeutic doses (also see Section 4.4 Special Warnings and Precautions for Use, CYP2D6 metabolism).
Therefore Trust 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 recognise signs of high morphine levels in themselves and their babies. For example, in a mother, symptoms include extreme sleepiness, and trouble caring for the baby. In the baby, symptoms include signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Medical advice should be sought immediately.

4.7 Effects on Ability to Drive and Use Machines

Codeine may cause drowsiness.
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, 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 below, 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 2.

Other adverse effects.

Gastro-intestinal.

Heartburn, loss of appetite, stomach pain.

Renal.

Papillary necrosis, which can lead to renal failure.

Cardiovascular.

Fluid retention and in some cases oedema occur rarely.

Other.

Hepatic dysfunction.

Euphoria and dysphoria.

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 http://www.tga.gov.au/reporting-problems.

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.

Ibuprofen.

The 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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 (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 protein bound 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 is 2 to 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

It also contains cellulose-microcrystalline, starch - pregelatinised maize, croscarmellose sodium, silica-colloidal anhydrous, and Opadry complete film coating system OY-58900 white.
Trust 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.

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

Available in the following pack sizes: 10s, 12s, 15s, 18s, 20s, 24s and 30s.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Ibuprofen.

Chemical name: 2-(4-isobutylphenyl) propionic acid.
Molecular formula: C₁₃H₁₈O₂.
MW: 206.3.
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.

Codeine phosphate hemihydrate.

Chemical name: (5R, 6S)-7, 8-didehydro-4,5-epoxy-3-methoxy-N-methylmorphinan-6-ol dihydrogen orthophosphate hemihydrate.
Molecular formula: C₁₈H₂₁NO₃.H₃PO₄.½H₂O.
MW: 406.4.
It is a small, colourless, odourless crystal or a white, odourless crystalline powder. Codeine phosphate hemihydrate is soluble in four parts water, slightly soluble in ethanol (96%), practically insoluble in chloroform and ether.

CAS number.

Ibuprofen.

15687-27-1.

Codeine phosphate hemihydrate.

41444-62-6.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

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Trust Ibuprofen Plus Codeine

Ibuprofen; Codeine phosphate hemihydrate

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Trust Ibuprofen Plus Codeine Tablets