SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Taylor's Ibuprofen Tablets BP 200 mg. Galpharm Ibuprofen Tablets BP 200 mg.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 200 mg Ibuprofen BP.

Excipient(s) with known effect:

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Pink, biconvex film coated tablets with APS on one side, plain on reverse; or plain unmarked tablets.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

POM

Rheumatoid arthritis including Still’s Disease, osteoarthritis and seronegative (nonrheumatoid) arthropathies, ankylosing spondylitis, non-articular rheumatic conditions, soft-tissue injuries, mild to moderate pain (such as dysmenorrhoea, dental and postoperative pain).

General sales list

Adults, older people and children over 12 years

Rheumatic and muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.

Children under 12 years

Rheumatic or muscular pain, headache, dental pain, feverishness, symptoms of colds and influenza.

4.2 Posology and method of administration

Posology

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control the symptoms (see section 4.4).

POM

Method of administration

For oral administration. To be taken preferably with or after food.

Adults (all indications)

Initially 1200 mg per day in divided doses.

In severe conditions up to 1800 mg per day may be given until the acute phase of the condition has been brought under control.

Some patients may be maintained on doses in the range of 600 - 1200 mg per day.

Under no circumstances should the dose of ibuprofen exceed 2400 mg in any 24 hours.

Paediatric population Children (all indications)

20 mg/kg of body weight given daily in divided doses.

The tablets are not suitable for children weighing less than 20 kg and no more than two 200 mg tablets should be given in 24 hours to those weighing less than 30 kg.

Older people

Older people are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest dose should be used and the patient should be monitored for GI bleeding for 4 weeks following initiation of NSAID therapy.

General sales list

For oral administration and short -term use only.

Adults, the elderly and children over 12 years:

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.

For immediate release preparations: 200mg -400mg, up to three times a day as required. For prolonged release preparations: 200 mg - 400mg up to twice a day is required.

Leave at least four hours between doses and do not take more than 1200 mg in any 24 hour period.

Do not give to children under 12 years except on the advice of a doctor.

• in children (age range: > 6 months to < 12 years) and/or in adolescents (age range: > 12 years to < 18 years):

If in children aged from 6 months and in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

4.3 Contraindications

Ibuprofen is contraindicated in patients with hypersensitivity to ibuprofen or to any of the excipients listed in section 6.1.

Ibuprofen should not be used in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

Ibuprofen is also contraindicated in patients with a history of upper gastrointestinal bleeding or perforation related to previous NSAID therapy. Ibuprofen should not be used in patients with active or history or recurrent peptic ulcer/ haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding.

Ibuprofen is contraindicated in patients with severe heart failure hepatic failure and renal failure (See section 4.4).

Ibuprofen is contraindicated during the last trimester of pregnancy (See section 4.6)

4.4 Special warnings and precautions for use

Paediatric population

There is a risk of renal impairment in dehydrated children and adolescents.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 and GI and cardiovascular risks below).

As with other NSAIDs, ibuprofen may mask the signs of infection

The use of Ibuprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the increased risk of ulceration or bleeding (see section 4.5).

Older people :

Older people have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).

Respiratory disorders:

Caution is required if administration to patients suffering from, or with a previous history of bronchial asthma since NSAIDs have been reported to precipitate bronchospasms in such patients.

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependant reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly.

Renal function should be monitored in these patients (see also section 4.3).

Ibuprofen should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with ibuprofen administration.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. < 1200mg daily) is associated with an increased risk of myocardial infarction.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Renal effects

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and older people. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or 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, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3) and in older people. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

Patients with a history of gastrointestinal toxicity, particularly when older, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

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).

When GI bleeding or ulceration occurs in patients receiving Ibuprofen Tablets, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated (see section 4.8).

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of the therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen should be discontinued at the first appearance of skin risk, mucosal lesions, or any other sign of hypersensitivity.

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.

Aseptic meningitis

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

Impaired female 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 fertility, withdrawal of ibuprofen should be considered.

GSL

The label will include:

Read the enclosed leaflet before taking this product.

Do not take if you:

•    Have (or have had two or more episodes of) a stomach ulcer, perforation or bleeding

•    Are allergic to ibuprofen or any other ingredient of the product, aspirin or other related painkillers

•    Are taking other NSAID painkillers, or aspirin with a daily dose above 75 mg

Speak to a pharmacist or your doctor before taking if you:

•    Have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems

•    Are a smoker

•    Are pregnant

If symptoms persist or worsen, consult your doctor.

4.5 Interaction with other medicinal products and other forms of interaction

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (See section 4.4).

Anti-hypertensives, beta-blockers and diuretics:

NSAID’s may reduce anti-hypertensive effect such as ACE inhibitors, beta-blockers and diuretics.

Diuretics:    Reduced diuretic effect. Diuretics can increase the risk of

nephrotoxicity of NSAIDs.

Cardiac glycosides:    NSAIDs may exacerbate cardiac failure, reduce GFR and

increase plasma glycoside levels.

Cholestyramine:

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

Decreased elimination of lithium.

NSAIDs may inhibit the tubular secretion of methotrexate and decreased elimination of methotrexate.

Increased risk of nephrotoxicity.

NSAIDs should not be used for 8 - 12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy.

Other analgesics and cyclooxygenase-2 selective inhibitors:

Avoid concomitant use of two or more NSAIDs including Cox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4).

Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.

Experimental data suggests that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex-vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen

use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Corticosteroids:    Increased risk of gastrointestinal ulceration or bleeding (see

section 4.4)

Anticoagulants:    NSAIDs may enhance the effects of anti-coagulants, such as

warfarin (See section 4.4).

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.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs); Increase risk of gastrointestinal bleeding (see section 4.4)

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

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

Aminoglycosides:

NSAIDs may decrease the excretion of aminoglycosides.

Herbal extracts:

Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

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.

General sales list

Ibuprofen should be avoided in combination with:

Aspirin: unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse effects (see section 4.4)

4.6 Fertility, pregnancy and breast-feeding

POM

Pregnancy:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss 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 and 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 oligo-hydroamniosis;

At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to the following:

•    possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

•    inhibition of uterine contractions, which may result in delayed or prolonged labour.

Consequently, Ibuprofen is contraindicated during the third trimester of pregnancy. Breast-feeding:

In limited studies so far available, ibuprofen can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breast feeding.

Fertility

See section 4.4 Special warnings and precautions for use, regarding female fertility. General sales list

Whilst no tetratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy should if possible be avoided. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (a closure of ductus arteriosus), use in late pregnancy should be avoided.

In the limited studies so far available, ibuprofen appears in the breast milk in very low concentrations and is unlikely to adversely affect the breast-fed infant.

See section 4.4 regarding female fertility.

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8 Undesirable effects

Gastrointestinal disorder: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation of GI bleeding, sometimes fatal, particularly in older people, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis exacerbation of colitis and Crohn’s disease (see section 4.4) have been reported following ibuprofen administration. Less frequently, gastritis has been observed. Gastrointestinal perforation has been rarely reported with ibuprofen use. Pancreatitis has been reported very rarely.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

Cardiac disorders: Oedema and cardiac failure have been reported in association with NSAID treatment.

Vascular disorder: Hypertension has been reported in association with NS AID treatment. Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (2400 mg daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Other adverse events reported less commonly and for which causality has not necessarily been established include:

Psychiatric disorders: Insomnia, anxiety, depression, confusional state, hallucination

Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4).

Renal and urinary disorders: Impaired renal failure and toxic nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure.

Hepatobiliary disorders: Abnormal liver function, hepatitis and jaundice.

Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or

disorientation (See section 4.4), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Blood and lymphatic system disorders: Leukopenia,, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Skin and subcutaneous tissue disorders: Bullous reactions including Steven Johnson Syndrome and toxic epidermal necrosis (very rare) and Photosensitivity.

General disorders and administration site conditions: Malaise, fatigue.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

POM

Paediatric population

In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop symptoms within 4 to 6 hours.

The most frequently reported symptoms of overdose include nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Management

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

General sale list

In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Management

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

5 PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

The active ingredient is a non-steroidal anti-inflammatory agent with analgesic and anti-pyretic activity. The analgesic activity of ibuprofen is thought to be due to inhibition of prostaglandin synthesis.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81 mg), a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

5.2    Pharmacokinetic Properties

Ibuprofen is well absorbed (>80%) from the gastro-intestinal tract. Peak plasma levels occur 1 to 2 hours after ingestion with a half life of 2 hours (+/-0.5 hours). It is extensively bound to plasma proteins (>99%). It is rapidly excreted in the urine mainly as metabolites and their conjugates.

5.3 Preclinical Safety Data

Preclinical information has not been included because the safety data of ibuprofen has been established after many years of clinical use. Please refer to Section 4.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

The tablet contains Starch Ph. Eur., Pregelled Starch BP, Colloidal Silicon Dioxide USNF, Sodium Starch Glycollate BP, Stearic Acid BP, hydroxypropyl methylcellulose, Talc Ph. Eur. The coating contains titanium dioxide E171, erythrosine aluminium lake E127 and hydroxypropyl methylcellulose E464.

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months

6.4 Special Precautions for Storage

Store in a dry place at or below 25°C. Protect from light.

6.5    Nature and contents of container

In polypropylene securitainers with polyethylene security closures or amber glass bottles with finoplas or plastissue as cushioning agent or HDPE containers with LDPE lids or child resistant caps, pack size 12, 100, 500.

250 pm PVC / 40 gsm PVdC with 20 pm hard tempered aluminium foil strip

Pack size 7, 10, 12, 14, 16, 21, 28, 30, 56, 60, 84, 90, 100, 110, 112, 120, 150, 160 and 168.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

MARKETING AUTHORISATION HOLDER

TEVA UK Limited Brampton Road Hampden Park Eastbourne East Sussex BN22 9AG

8.    MARKETING AUTHORISATION NUMBER

PL 00289/0062

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27.09.1983 / 12.03.2009

10    DATE OF REVISION OF THE TEXT

15/10/2014