Consumer medicine information

Brufen

Ibuprofen

BRAND INFORMATION

Brand name

Brufen

Active ingredient

Ibuprofen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Brufen.

What is in this leaflet

This leaflet answers some common questions about BRUFEN. 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 BRUFEN against the benefits they expect it will have for you.

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

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

What BRUFEN is used for

BRUFEN relieves pain and reduces inflammation (swelling, redness or soreness) that may occur:

  • in different types of arthritis including rheumatoid arthritis, osteoarthritis and juvenile rheumatoid arthritis
  • in muscle and bone injuries such as sprains, strains, lower back pain (lumbago), rheumatism, and tendonitis, such as tennis elbow
  • from swelling and pain after setting broken or dislocated bones
  • menstrual cramps (period pain)
  • following surgery
  • due to dental pain

BRUFEN also relieves fever (high temperature).

Although BRUFEN can relieve the symptoms of pain and inflammation, it will not cure your condition.

BRUFEN belongs to a group of medicines called non-steroidal anti-inflammatory drugs (or NSAIDs).

Ask your doctor if you have any questions about why BRUFEN has been prescribed for you. Your doctor may have prescribed BRUFEN for another reason.

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

BRUFEN is not addictive.

Before you take BRUFEN

When you must not take it

Do not take BRUFEN if you have an allergy to:

  • any product containing ibuprofen
  • any of the ingredients listed at the end of this leaflet
  • aspirin or any other NSAID medicine

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • hives, itching or skin rash
  • stomach ache, fever, chills, nausea and vomiting.
  • fainting

Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAID medicines. If you are not sure if you are taking any of these medicines, ask your doctor or pharmacist.

If you are allergic to aspirin or any other NSAID medicines and take BRUFEN, these symptoms may be severe.

Do not take BRUFEN if:

  1. you are pregnant or intend to become pregnant.
BRUFEN may affect your developing baby if you take it during pregnancy.
  1. you are breast-feeding or intend to breast-feed.
BRUFEN passes into breast milk and may affect your baby.
  1. you have (or have previously) vomited blood or material that looks like coffee grounds.
  2. you are (or have previously) bleeding from the rectum (back passage), have black sticky bowel motions (stools) or bloody diarrhoea.
  3. you have a condition resulting in an increased tendency to bleed.
  4. you have a peptic ulcer (i.e. stomach or duodenal ulcer), a recent history of one, or have had peptic ulcers before.
  5. you have, or have a history of, Ulcerative Colitis or Crohn's Disease
  6. you have severe heart failure
  7. you have severe liver disease
  8. you have severe kidney disease

Do not take this medicine/it after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if:

  1. you have any allergies to:
  • any other substances, such as medicines, foods, preservatives or dyes
  1. you are pregnant or intend to become pregnant.
Like most NSAID medicines, BRUFEN is not recommended to be used during pregnancy.
It may also impair female fertility.
  1. you are breast-feeding or plan to breast-feed.
Like most NSAID medicines, BRUFEN is not recommended while you are breast-feeding.
  1. you have or have had any medical conditions, especially the following:
  • heart disease or high blood pressure
  • heartburn, indigestion, stomach ulcer or any other stomach problems
  • vomiting blood or bleeding from the back passage
  • severe skin reactions such as Stevens-Johnson syndrome
  • asthma
  • vision problems
  • liver or kidney disease
  • tendency to bleed or other blood problems
  • bowel or intestinal problems such as ulcerative colitis or Crohn's Disease
  • heart failure
  • swelling of the ankles or feet
  • diarrhoea
  1. you currently have an infection
If you take BRUFEN while you have an infection, it may hide some of the signs and symptoms of an infection. This may make you think, mistakenly, that you are better or that it is not serious.
  1. you plan to have surgery

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

Taking other medicines

Tell your doctor or pharmacist 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 and BRUFEN may interfere with each other. These include:

  • aspirin, salicylates or other NSAID medicines
  • warfarin, medicines used to stop blood clots
  • lithium, a medicine used to treat some types of depression
  • SSRIs such as sertraline, medicines used to treat depression
  • various medicines used to treat high blood pressure or other heart conditions
  • medicines used to treat heart failure such as digoxin
  • diuretics, also called fluid tablets
  • methotrexate, a medicine used to treat arthritis and some types of cancer
  • corticosteroids, such as prednisone, cortisone
  • ciclosporin or tacrolimus, medicines used to treat certain problems with the immune system or to help prevent organ transplant rejection
  • aminoglycosides, medicines used to treat certain infections
  • Gingko biloba, an herbal medicine used to thin the blood
  • quinolone antibiotics, medicines used to treat certain infections
  • zidovudine, a medicine used to treat HIV
  • colestyramine, a medicine used to treat high cholesterol
  • sulfonylureas, medicines to treat diabetes
  • voriconazole or fluconazole, medicines to treat certain fungal infections
  • mifepristone (RU-486), a medicine used to end a pregnancy

These medicines may be affected by BRUFEN 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 or pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take BRUFEN

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

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

How much to take

Your doctor will tell you how many BRUFEN tablets to take each day and when to take them.

Take the exact amount your doctor tells you to, no more or less.

Adults and Children Over 12 Years of Age

The usual daily dose of BRUFEN is one tablet taken three or four times a day.

In acute conditions, your doctor may prescribe two tablets three times a day.

Do not take more than six tablets in one day.

It is usual for elderly patients to be prescribed a smaller dose of BRUFEN.

Period Pain

The usual dose of BRUFEN is one to two tablets at the first sign of pain or menstrual bleeding. Then take one tablet every 4 to 6 hours as necessary.

Do not take more than four tablets in one day.

How to take it

Take BRUFEN with or straight after food with a full glass of water. This may help reduce the possibility of an upset stomach.

How long to take it

Do not take BRUFEN for longer than your doctor tells you to. Depending on your condition, you may need BRUFEN for a few days, a few weeks or for longer periods.

As with other NSAID medicines, if you are taking BRUFEN for arthritis, it will not cure your condition, but it should help to control pain, swelling and stiffness.

BRUFEN usually begins to work within a few hours but several weeks may pass before you feel the full effects of the medicine.

If you have arthritis, BRUFEN should be taken every day for as long as your doctor prescribes.

For period pain, BRUFEN should be taken for a few days until the pain goes away.

If you are not sure how long to take BRUFEN for, talk to your doctor or pharmacist.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

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

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

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much BRUFEN. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much BRUFEN you may experience the following:

  • feel sick or vomit
  • have stomach pain
  • have convulsions
  • feel tired, drowsy or lack energy
  • feel dizzy or even become unconscious
  • have a headache or ringing in the ears
  • unusual eye movements, shivering, confusion, interrupted or breathing difficulties
  • low blood pressure, low or rapid heart beat

While you are using BRUFEN

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking BRUFEN.

Tell any other doctors, dentists and pharmacists that are treating you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. NSAID medicines can slow down blood clotting.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you get an infection while taking this medicine, tell your doctor. BRUFEN may hide some of the signs of an infection and may make you think mistakenly, that you are better or that it is not serious. Signs of an infection may include fever, pain, swelling and redness.

Tell your doctor if you get any visual disturbances such as blurred vision. You may need to have an eye examination to make sure BRUFEN is not causing any side effects.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed. Otherwise your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel the medicine is not helping your condition. This will help your doctor to determine the best treatment for you.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may want to take some blood tests from time to time. This helps to prevent unwanted side effects.

Things you must not do

Do not take any other medicines to relieve pain and reduce inflammation while you are taking BRUFEN without first telling your doctor.

This includes:

  • aspirin (also called acetylsalicylic acid)
  • other medicines containing ibuprofen, the active ingredient in BRUFEN
  • any other NSAID medicine

Do not take BRUFEN to treat any other complaints unless your doctor tells you to.

Do not give BRUFEN to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of:

Be careful driving or operating machinery until you know how BRUFEN affects you. As with other NSAID medicines, BRUFEN may cause dizziness or light-headedness, drowsiness or blurred vision in some people.

If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking BRUFEN. This medicine helps most people, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

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

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

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

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

  • nausea or vomiting
  • loss of appetite
  • heartburn or pain in the upper part of your stomach
  • cramps, wind, constipation or diarrhoea
  • headache
  • sleepiness
  • dizziness
  • buzzing or ringing in the ears or other trouble hearing
  • sleeplessness
  • changes in mood, for example feeling anxious, depression, confusion, nervousness

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • severe pain or tenderness in the stomach
  • eye problems such as blurred vision, sore red eyes, itching
  • 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, headaches, being short of breath, and looking pale
  • yellowing of the skin and/or eyes, also called jaundice
  • unusual weight gain, swelling of ankles or legs
  • tingling of the hands and feet
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal
  • severe or persistent headache
  • fast or irregular heartbeats, also called palpitations

These may be serious side effects of BRUFEN. You may need urgent medical attention. Serious side effects are rare.

If any of the following happen, stop taking BRUFEN and tell your doctor immediately or go to Accident and Emergency 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
  • sudden or severe itching, skin rash, hives
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals (Stevens Johnson Syndrome)
  • fever, generally feeling unwell, nausea, stomach ache, headache and stiff neck
  • hearing difficulties, ringing in the ears

BRUFEN may be associated with a small increased risk of heart attack (myocardial infarction).

Blood disorders and kidney problems may occur with BRUFEN.

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

Tell your doctor if you notice anything that is making your feel unwell. Other side effects not listed above may occur in some patients.

After using BRUFEN

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack, they may not keep well.

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

Do not store BRUFEN or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

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

Disposal

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

Product description

What BRUFEN looks like

BRUFEN tablets are white, pillow shaped film-coated tablets.

The tablets are available in a blister pack containing 30 tablets.

Ingredients

BRUFEN contains 400 mg of ibuprofen as the active ingredient.

The inactive ingredients are:

  • microcrystalline cellulose
  • croscarmellose sodium
  • lactose monohydrate
  • colloidal anhydrous silica
  • sodium lauryl sulfate
  • magnesium stearate
  • hypromellose
  • purified talc
  • titanium dioxide

BRUFEN does not contain gluten, tartrazine or any other azo dyes.

Supplier

BRUFEN is supplied in Australia by:

Mylan Health Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point, NSW 2000
www.mylan.com.au
For Medical Information Phone: 1800 314 527

AUST R 80659

Things that would be helpful for your arthritis

Some self-help measures suggested below may help your condition.

Talk to your doctor, physiotherapist, or pharmacist about these measures and for more information.

Weight

Your doctor may suggest losing some weight to reduce the stress on your joints.

Exercise

May be recommended by your doctor or physiotherapist to help keep or improve movement and strengthen muscles.

Ask a physiotherapist for an exercise plan suited to your condition.

As a general rule if any exercise hurts then do not do it.

Rest

Is important and is usually balanced with exercise and activity. Rest is needed when joints are hot, swollen or painful.

Heat

Hot showers or baths may help to ease the pain and relax the muscles that can become tense with arthritis. Your physiotherapist or doctor can prescribe other forms of heat treatment.

Physical Aids

Are available to help with daily household tasks. For example, there are gadgets and aids to help turn on taps, remove screw tops, pick up objects and handles that can be fitted in bathrooms. Ask your doctor for more information.

This leaflet was prepared in February 2020.

Published by MIMS April 2020

BRAND INFORMATION

Brand name

Brufen

Active ingredient

Ibuprofen

Schedule

S4

 

1 Name of Medicine

Ibuprofen.

6.7 Physicochemical Properties

Chemical structure.

The structural formula for ibuprofen is:
Ibuprofen is a (±)-2-(p-isobutylphenyl) propionic acid. Ibuprofen is a white crystalline solid with a melting point of 74-77°C and is practically insoluble in water (< 0.1 mg/mL) and readily soluble in organic solvents such as ethanol and acetone.

CAS number.

15687-27-1.

2 Qualitative and Quantitative Composition

Each tablet contains 400 mg of ibuprofen as the active ingredient.
Excipients with known effect: Brufen tablets contain sugars (as lactose monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White, pillow-shaped, film-coated tablet.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ibuprofen is a nonsteroidal anti-inflammatory agent that possesses analgesic and antipyretic activities. Its mode of action, like that of other nonsteroidal anti-inflammatory agents, is not completely understood, but may be related to prostaglandin synthetase inhibition.
Ibuprofen has shown anti-inflammatory, analgesic and antipyretic activity in both animal and human studies. These properties provide symptomatic relief of inflammation and pain in rheumatoid arthritis, osteoarthritis and allied conditions.

Clinical Trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Ibuprofen is well absorbed after oral administration. Single doses of 200 mg taken on an empty stomach by volunteers produced peak serum levels after approximately 45 minutes. When taken after food, absorption was slower, peak levels appearing at 1.5 to 3 hours.
The bioavailability of ibuprofen from one Brufen 400 mg tablet is equivalent to that from two Brufen 200 mg tablets.

Distribution.

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 the drug enters the CSF or is excreted in breast milk.
99% of ibuprofen is protein bound. The high protein binding of the drug should be borne in mind when prescribing ibuprofen together with other protein bound drugs which bind to the same site on human serum albumin.

Metabolism.

About 90% of ibuprofen is metabolised to two major metabolites (A and B) and these are as follows.
Metabolite A: (+) 2-4'-(2-hydroxy-2-methylpropylphenyl) propionic acid.
Metabolite B: (+) 2-4'-(2-carboxypropylphenyl) propionic acid.
Both metabolites are dextrorotatory and are devoid of anti-inflammatory and analgesic activity.
Normal volunteers and patients with rheumatoid arthritis were given 800 mg ibuprofen as a single dose. After 14-24 hours the plasma levels of drug and metabolites were less than 0.25 microgram/mL.

Excretion.

The kidney is the major route of excretion. 95% of the drug was excreted in the urine within 24 hours of a single dose of 500 mg, 35% as metabolite A (15% free, 20% conjugated); 51% as metabolite B (42% free, 9% conjugated); ibuprofen 9% (1% free, 8% conjugated).
Plasma half-life of ibuprofen is in the range 1.9 to 2.2 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Rheumatoid arthritis; osteoarthritis; juvenile rheumatoid arthritis; primary dysmenorrhoea; pyrexia.
Brufen is also indicated for the relief of acute and/or chronic pain states in which there is an inflammatory component.

4.3 Contraindications

Known hypersensitivity to ibuprofen or any of the inactive ingredients.
Hypersensitivity (e.g. asthma, rhinitis or urticaria) to aspirin or other nonsteroidal anti-inflammatory drugs.
History or active gastrointestinal bleeding or perforation related to previous NSAID therapy.
History or active, ulcerative colitis, Crohn's disease, recurrent peptic ulceration or gastrointestinal haemorrhage (defined as two or more distinct episodes of proven ulceration or bleeding).
Severe heart failure (NYHA IV).
Patients with severe hepatic impairment.
Treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).
Severe renal failure (glomerular filtration below 30 mL/min).
Conditions involving an increased tendency or active bleeding.
During the third trimester of pregnancy.
Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in Pregnancy).
Lactation (see Section 4.6 Fertility, Pregnancy and Lactation, Use in Pregnancy).

4.4 Special Warnings and Precautions for Use

General precautions.

Prolonged use of any painkillers may induce headaches, which must not be treated with increased doses of the painkillers, including ibuprofen.
Through concomitant consumption of alcohol, NSAID related undesirable effects, particularly those that concern the gastrointestinal tract or the central nervous system, may be increased on use of NSAIDs.

Cardiovascular thrombotic events.

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) or increased duration of use, may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk. Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.
Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
To minimize the potential risk of an adverse cardiovascular event in patients taking an NSAID, especially in those with cardiovascular risk factors, the lowest effective dose should be used for the shortest possible duration (see Section 4.2 Dose and Method of Administration.)
Physicians and patients should remain alert for such CV events, even in the absence of previous CV symptoms. Patients should be informed about signs and/or symptoms of serious CV toxicity and the steps to take if they occur.
There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.

Hypertension.

NSAIDs may lead to onset of new hypertension or worsening of pre-existing hypertension and patients taking antihypertensives with NSAIDs may have an impaired antihypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.

Heart failure.

Fluid retention and oedema have been observed in some patients taking NSAIDs, therefore, caution is advised in patients with fluid retention or heart failure.

Gastrointestinal events.

Ibuprofen should be used with extreme caution and at the lowest effective dose in patients with a history of peptic ulceration and other gastrointestinal disease since their condition may be exacerbated.
All NSAIDs can cause gastrointestinal discomfort and serious, potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation, which may increase with dose or duration of use, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest dose available. These adverse events can occur at any time without warning or a previous history of serious gastrointestinal events. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, as well as patients requiring concomitant low dose aspirin, or for other drugs likely to increase gastrointestinal risk (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The concomitant administration of ibuprofen and other NSAIDs, including cyclooxygenase-2 (COX-2) selective inhibitors, should be avoided due to the increased risk of ulceration or bleeding (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Caution is advised in patients with risk factors for gastrointestinal events who may be at greater risk of developing serious gastrointestinal events, e.g. the elderly, those with a history of serious gastrointestinal events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patients about signs and symptoms of serious gastrointestinal toxicity.
Caution should be exercised in patients receiving concomitant medication which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet drugs such as aspirin (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.

Severe skin reactions.

NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash or any other sign of hypersensitivity.
Severe skin infections and soft tissue complications may occur in patients with a varicella infection. The role of NSAIDs in the worsening of these infections is uncertain, therefore it is advisable to avoid the use of ibuprofen in known or suspected cases of varicella.

Infections and infestations.

Exacerbation of infection related inflammations (e.g. development of necrotising fasciitis) coinciding with the use of NSAIDs has been described. If signs of an infection occur or get worse during use of ibuprofen the patient is therefore recommended to go to a doctor without delay.

Respiratory disorders.

Caution is required if ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma, chronic rhinitis or allergic diseases since ibuprofen has been reported to cause bronchospasm, urticarial or angioedema in such patients.

Ophthalmological effects.

Adverse ophthalmological effects have been observed with NSAIDs; accordingly, patients who develop visual disturbances during treatment with ibuprofen should have an ophthalmological examination.

Impaired liver function or a history of liver disease.

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.
Physicians and patients should remain alert for hepatotoxicity. Patients should 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. Patients with impaired liver function or a history of liver disease who are on long-term ibuprofen therapy should have hepatic function monitored at regular intervals. Ibuprofen has been reported to have a minor and transient effect on liver enzymes.
Severe hepatic reactions, including jaundice and cases of fatal hepatitis, though rare, have been reported with ibuprofen as with other NSAIDs. If abnormal liver tests persist or worsen, or if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), ibuprofen should be discontinued.

Impaired renal function.

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration. There is a risk of renal impairment especially in dehydrated children, adolescents and in the elderly.
The two major metabolites of ibuprofen are excreted mainly in the urine and impairment of renal function may result in their accumulation. The significance of this is unknown. NSAIDs have been reported to cause nephrotoxicity in various forms; interstitial nephritis, nephrotic syndrome and renal failure. In patients with renal, cardiac or hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly, caution is required since the use of NSAIDs may result in deterioration of renal function. The long-term concomitant intake of similar analgesics further increases the risk. For patients with renal, hepatic or cardiac impairment, use the lowest effective dose, for the shortest possible duration and monitor renal function especially in long-term treated patients.

Combination use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics.

The use of an ACE inhibiting drug (ACE inhibitor or angiotensin receptor antagonist), an anti-inflammatory drug (NSAID or COX-2 inhibitor) and thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Aseptic meningitis.

Aseptic meningitis has been reported only rarely, usually but not always in patients with systemic lupus erythematosus (SLE) or other connective tissue disorders.

Haematological monitoring.

Blood dyscrasias have been rarely reported. Patients on long-term therapy with ibuprofen should have regular haematological monitoring.

Coagulation defects.

Like other NSAIDs, ibuprofen can inhibit platelet aggregation. Ibuprofen has been shown to prolong bleeding time (but within the normal range), in normal subjects. Because this prolonged bleeding effect may be exaggerated in patients with underlying haemostatic defects, ibuprofen should be used with caution in persons with intrinsic coagulation defects and those on anticoagulant therapy.

Masking signs of infection.

As with other drugs of this class, ibuprofen may mask the usual signs of infection.

Special precautions.

In order to avoid exacerbation of disease or adrenal insufficiency, patients who have been on prolonged corticosteroid therapy should have their therapy tapered slowly rather than discontinued abruptly when ibuprofen is added to the treatment program.

Lactose monohydrate.

This medicine contains lactose monohydrate. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome should not take this medicine.

Use in the elderly.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Care should be taken in patients treated with anti-coagulants, such as warfarin, due to an enhanced effect of anti-coagulants.
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.
Brufen should only be used in patients taking warfarin if absolutely necessary. Patients taking this combination must be closely monitored.

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

Increased risk of gastrointestinal bleeding.

Aminoglycosides.

NSAIDs may decrease the excretion of aminoglycosides.
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.
Ibuprofen like other NSAIDs can reduce the antihypertensive effect of ACE inhibitors, angiotensin II receptor antagonists and beta-blockers with possible loss of blood pressure control, and can attenuate the natriuretic effects of diuretics. Diuretics can also 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 COX-2 inhibitor) all at the same time increases the risk of renal impairment (see Section 4.4 Special Warnings and Precautions for Use).
NSAIDs may exacerbate cardiac failure, reduce glomerular filtration rate and increase plasma cardiac glycoside levels. Care should, therefore, be taken in patients treated with cardiac glycosides.

Colestyramine.

The concomitant administration of ibuprofen and colestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.

Corticosteroids.

Increased risk of gastrointestinal ulceration or bleeding.

Herbal extracts.

Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

Other analgesics.

Avoid concomitant use of two or more NSAIDs, including aspirin and cyclooxygenase 2 (COX-2) selective inhibitors, because of the potential of increased adverse effects. Ibuprofen antagonizes the irreversible inhibition of platelet COX-1 induced by low dose aspirin. To reduce this effect, ibuprofen should be administered at least 8 hours before or 30 minutes after taking low dose aspirin.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic studies show that when a single daily dose of ibuprofen 400 mg was given within 8 hours before or within 30 minutes after immediate release aspirin (81 mg), and when multiple daily doses of ibuprofen 400 mg are given with aspirin, a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. Although there are uncertainties regarding extrapolation of this data to the clinical situation the possibility that regular, long-term use of ibuprofen may reduce the cardio-protective effect of aspirin cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use.

Ciclosporin or tacrolimus.

Increased risk of nephrotoxicity when used with NSAIDs.

Mifepristone.

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

Quinolone antibiotics.

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

Sulfonylureas.

NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.

Zidovudine.

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of hemarthroses and hematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
NSAIDs inhibit tubular secretion of methotrexate in animals. As a result, reduction of clearance of methotrexate may occur. Use of high doses of methotrexate concomitant with NSAIDs should be avoided. At low doses of methotrexate caution should be used if ibuprofen is administered concomitantly.

CYP2C9 inhibitors.

Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), an increased S(+)-ibuprofen exposure by approximately 80 to 100% has been shown. Reduction of the ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high dose ibuprofen is administered with either voriconazole or fluconazole.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The use of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ibuprofen should be considered.
(Category C)
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/ foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, the administration of a prostaglandin synthesis inhibitor has been shown to result in increased preimplantation and postimplantation losses and embryo/ foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.
During the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to the following: 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 the following: possible prolongation of bleeding time;
inhibition of uterine contractions, which may result in delayed or prolonged labour.
Consequently, ibuprofen is contraindicated during the third trimester of pregnancy.

Use in labour and delivery.

Administration of ibuprofen is not recommended during labour and delivery. The onset of labour may be delayed and the duration increased with a greater bleeding tendency in both mother and child.
Ibuprofen is not recommended for use in nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

The following adverse reactions possibly related to ibuprofen displayed by MedDRA frequency convention and system organ classification. Frequency groupings are classified according to the subsequent conventions: very common (≥ 10%), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000) and Not known (cannot be estimated from the available data). See Table 1.

Precise incidence unknown (but greater than 1%) causal relationship unknown.

Gastrointestinal.

Epigastric pain, heartburn, abdominal distress, abdominal cramps and bloating.

Auditory and vestibular.

Tinnitus, hearing impaired.

Cardiovascular.

Oedema, fluid retention. Fluid retention generally responds promptly to discontinuation of the drug.

Central nervous system.

Nervousness.

Dermatological.

Pruritus.

General.

Decreased appetite.

Precise incidence unknown (but less than 1%) causal relationship unknown.

Central nervous system.

Emotional lability, somnolence, hallucinations and dream abnormalities.

Dermatological.

Alopecia.

Gastrointestinal.

Abnormal liver function tests.

Haematological.

Eosinophilia and decrease in haemoglobin and haematocrit.

Ocular.

Amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision) have occurred but is usually reversed after cessation of therapy. Any patient with eye complaints should have an ophthalmological examination which includes central vision fields (see Section 4.4 Special Warnings and Precautions for Use). Visual impairment and toxic neuropathy have also been reported.

Allergic.

Serum sickness, lupus erythematosus syndrome, Henoch-Schonlein vasculitis and chills.

Special senses.

Conjunctivitis, diplopia and cataracts.

Haematological.

Bleeding episodes (e.g. epistaxis, menorrhagia).

Metabolic/ endocrine.

Gynaecomastia, hypoglycaemic reaction, acidosis.

Cardiovascular.

Arrhythmias (sinus tachycardia, sinus bradycardia).

Additional postmarketing adverse reactions.

Adverse reactions have been reported during postapproval use of Brufen. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Brufen exposure.

Gastrointestinal.

Exacerbation of colitis and Crohn's disease (see Section 4.3 Contraindications). Pancreatitis has been reported very rarely.

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

After assessing risk/ benefit ratio in each individual patient, the lowest effective dose for the shortest duration should be used.

Adults and children 12 years and over.

The recommended initial dose of ibuprofen is 400 mg three to four times daily (1,200-1,600 mg per day) with food or fluids. The dose may be taken on an empty stomach. It is recommended that patients with sensitive stomachs take ibuprofen with food.
For acute exacerbations of rheumatoid arthritis and osteoarthritis in patients already on treatment with ibuprofen, a maximum daily dosage of 2,400 mg (800 mg three times daily) may be prescribed, reverting to a maximum of 1,600 mg (400 mg four times daily) daily once the patient is stabilised.

Primary dysmenorrhoea.

The initial dose is 400-800 mg at the first sign of pain or menstrual bleeding, then 400 mg 4-6 hourly with a maximum total daily dose of 1,600 mg.

Maintenance dose.

In all indications the dose should be adjusted for each patient and the smallest dose that results in acceptable control of the symptoms employed. In general, patients with rheumatoid arthritis and osteoarthritis tend to require higher doses than patients with other conditions.

Elderly population.

In elderly patients receiving 600-1,200 mg daily, ibuprofen appeared to be well tolerated. However, since elderly patients may have a degree of impaired liver or renal function, the adult dosage should be used with caution.

Tablet formulation.

Take ibuprofen tablets with plenty of fluid. Ibuprofen tablets should be swallowed whole and not chewed, broken, crushed or sucked on to avoid oral discomfort and throat irritation.

Impaired liver function.

Ibuprofen should be used with caution in patients with impaired liver function (see Section 4.4 Special Warnings and Precautions for Use).

Impaired renal function.

Ibuprofen should be used with caution in patients with impaired renal function (see Section 4.4 Special Warnings and Precautions for Use).

Cardiovascular.

Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.

4.7 Effects on Ability to Drive and Use Machines

Following treatment with ibuprofen, the reaction time of patients may be affected. This should be taken into account where increased vigilance is required, e.g. when driving a car or operating machinery.

4.9 Overdose

Most patients who have ingested significant amounts of ibuprofen will manifest symptoms within 4 to 6 hours.
The most frequently reported symptoms of overdose include nausea, abdominal pain, vomiting, lethargy and drowsiness. Central nervous system (CNS) effects including headache, tinnitus, dizziness, convulsion and loss of consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea and depression of the CNS and respiratory system have also been rarely reported. Cardiovascular toxicity, including hypotension, bradycardia and tachycardia, has been reported. In cases of significant overdose, renal failure and liver damage are possible. Large overdoses are generally well tolerated when no other drugs are being taken.
There is no specific antidote to ibuprofen. Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. If necessary, serum electrolyte balance should be corrected.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, croscarmellose sodium, lactose monohydrate, colloidal anhydrous silica, sodium lauryl sulfate, magnesium stearate, hypromellose, purified talc and titanium dioxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C. Protect from moisture.

6.5 Nature and Contents of Container

Available in PVC/PVDC/Al or PVC/Al blister packs containing 10, 30, 40, or 60 tablets.
Some pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes