SUMMARY OF PRODUCT CHARACTERISTICS

1.    NAME OF THE MEDICINAL PRODUCT

Ibuprofen Film Coated Tablets 600 mg

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 600 mg

For a full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Pink capsule shaped, biconvex 22 x 10 mm, film coated tablets marked with “LPC I 600” on one side and decorative scoreline on the other.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic indications

Ibuprofen is indicated for its analgesic and anti-inflammatory effect in rheumatoid arthritis (including juvenile rheumatoid arthritis or Still’s disease) ankylosing spondylitis, osteoarthritis and other non-rheumatoid arthropathies.

In non-articular rheumatoid conditions, ibuprofen is indicated in periarticular conditions e.g. frozen shoulder, bursitis, tendinitis, tenosynovitis and low back pain. Ibuprofen can be used in soft-tissue injuries, e.g. sprains and strains. It is also indicated for the relief of mild to moderate pain, e.g. dental and postoperative pain and dysmenorrhoea.

It is also indicated for the relief of migraine.

4.2.    Posology and method of administration

Posology:

Adults:

Initial dosage is 1800 mg daily in divided doses. Some patients can be maintained on 600 -1800 mg daily. In severe or acute conditions it may be advantageous to increase the dosage provided that the total daily dosage does not exceed 2400 mg in divided doses.

Elderly:

The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Children:

Ibuprofen BP 600 mg tablets are not suitable for children.

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

Do not break the tablet in half.

For infants aged 3 - 5 months medical advice should be sought if symptoms worsen or not later than 24 hours if symptoms persist.

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

Method of administration:

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

4.3.    Contraindications

Hypersensitivity to any of the constituents.

NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other NSAIDs.

Severe hepatic, renal and cardiac failure (See section 4.4 Special warnings and precautions for use).

Last trimester of pregnancy (see section 4.6 Pregnancy and lactation).

Active or previous peptic ulcer /haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (See section 4.5 Interactions).

Severe heart failure.

4.4.    Special warnings and precautions for use

All patients:

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).

Elderly

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2 Posology and method of administration).

Other NSAIDs:

The use of Ibuprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

SLE and mixed connective tissue disease:

Systemic lupus erythematosus as well as those with mixed connective tissue disease -increased risk of aseptic meningitis (see section 4.8)

Respiratory disorders:

Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients. The possibility of cross-sensitivity with aspirin and other NSAIDs should be borne in mind.

Cardiovascular, renal and hepatic impairment:

The administration of an NSAID may cause a dose dependent 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). There is a risk of renal impairment in dehydrated children and adolescents.

For POM:

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 a 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). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. . </= 1200 mg daily) is associated with an increased risk of myocardial infarction.

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. 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) , particularly if high doses of ibuprofen (2400 mg/day) are required.

For OTC:

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Cardiovascular and cerebrovascular effects:

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (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). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. “1200 mg daily) is associated with an increased risk of myocardial infarction.

Impaired female fertility:

There is limited evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.

Gastrointestinal:

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).

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 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 the elderly. These patients should commence treatment on the lowest dose available. Patients with a history of GI toxicity, particularly the elderly, should report

any unusual abdominal symptoms (especially GI 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).

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

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 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 rash, mucosal lesions, or any other sign of hypersensitivity.

4.5.    Interaction with other medicinal products and other forms of interaction

Other analgesics: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.3 Contraindications)

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long term use of ibuprofen may reduce the cardioprotective effect of low dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Antihypertensives: Reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs. NSAIDs may increase risk of hyperkalaemia with potassium-sparing diuretics and may also antagonise thiazides, and reduce anti-hypertensive effect of furosemide.

Cardiac Glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Lithium: Decreased elimination of lithium.

Methotrexate: Decreased elimination of methotrexate.

Cyclosporin: Increased risk of nephrotoxicity.

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

Corticosteroids: Increased risk of GI bleeding (see section 4.4 Special warnings and precautions for use).

Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4 Special warnings and precautions for use).

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

Increased risk of gastrointestinal bleeding (see section 4.4).

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

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

Phenytoin Sodium: Phenytoin concentration and toxicity have been increased by Ibuprofen. Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

4.6.    Fertility, Pregnancy and lactation

Pregnancy:

Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernable pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3 Contraindications). NSAIDs should not be used in the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

During the third trimester of pregnancy, 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 oligohydroamniosis; The mother and the neonate, at the end of the pregnancy, to:

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

-    inhibition of uterine contractions resulting in delayed or prolonged labour.

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

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

Fertility:

See section 4.4 Special warnings and precautions for use regarding female fertility.

4.7.    Effects on ability to drive and use machines

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

System Organ Class	Frequency	Adverse Event
Gastrointestinal	Uncommon	Abdominal pain, nausea, dyspepsia
	Rare	Diarrhoea, flatulence, constipation and vomiting
	Very rare	Peptic and duodenal ulcers, perforation or GI bleeding, melaena, haematemesis.Ulcerative stomatitis, gastritis, sometimes fatal, particularly in the elderly may occur (see section 4.4 Special warnings and precautions for use).
	Not Known	Exacerbation of colitis and Crohn’s disease (see section 4.4) have been reported following administration.
Cardiac Disorders	Not Known	Oedema has been reported in association

		with NSAID treatment. Fluid retention may rarely precipitate congestive heart failure in elderly patients.
Vascular Disorders	Not Known	Hypertension
Renal and Urinary Disorders	Very rare	Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. Haematuria.
	Not Known	Renal insufficiency
Hepatobiliary Disorders	Very rare	Abnormal liver function, hepatitis and jaundice.
Nervous System Disorders	Very rare	Visual disturbances, optic neuritis, parasthesia, rarely reports of aseptic meningitis (especially in patients with existing auto-immune 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, nervousness, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, insomnia, fatigue and drowsiness. Toxic amblyopia may occurred; on cessation of treatment recovery
	Uncommon	Headache
Blood and Lymphatic System Disorders	Very rare	Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
Skin and Subcutaneous Tissue Disorders	Uncommon	Various skin rashes
	Very rare	Photosensitivity. Severe forms of skin reactions such as bullous reactions including Stevens- Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur.
Investigations	Very rare	Decreased haemoglobin levels
Immune system	Hypersensitivity reactions consisting of1:
	Uncommon	Urticaria and pruritus

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

c)    Assorted skin reactions, including rashes of various types, pruritis, urticaria, purpurea, angiodema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme).

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). 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

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

Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products, nonsteroids, propionic acid derivatives. ATC code: MO1AE01 Ibuprofen is a phenylpropionic acid derivative which has analgesic, anti inflammatory and anti-pyretic actions.

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. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long term use of ibuprofen may reduce the cardioprotective effect of low dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use.

5.2.    Pharmacokinetic properties

Ibuprofen is absorbed from the gastro-intestinal tract and peak plasma concentrations occur about 1 to 2 hours after ingestion. Ibuprofen is extensively bound to plasma proteins and has a half-life of about 2 hours. The excretion of Ibuprofen is rapid and complete via the kidneys.

5.3.    Preclinical safety data

Ibuprofen has been used in general medicine over a long period exceeding 20 years.

6. PHARMACEUTICAL PARTICULARS

6.1.    List of excipients

Cores:

Pregelatinised starch Maize starch

Maize starch as a 22% paste Aerosil

Magnesium stearate Coating:

Hypromellose Macrogol 6000

Erythrosine lake FD&C Red no. 3 ( E127)

Titanium dioxide ( E171)

Dioctyl sodium sulphosuccinate.

6.2.    Incompatibilities

Not applicable.

6.3.    Shelf life

Three years when packed in tablets containers.

Two years when packed in blister packs.

6.4.    Special precautions for storage

Do not store above 25°C. Store in the original container/outer carton

6.5.    Nature and contents of container

Tablet container:

Pack sizes: 12, 21, 24, 28, 48, 56, 84, 96, 100, 250, 500 and 1000 Packaging composition: high density polyethylene.

Blister packs

Pack sizes: 12, 21, 24, 28, 48, 56,84, 96, 100

Packaging composition: rigid white PVC and 20Dm aluminium foil.

Not all pack sizes may be marketed.

6.6.    Special precautions for disposal

N/A

7.    MARKETING AUTHORISATION HOLDER

Special Concept Development (UK) Limited,

Unit 1-7 Colonial Way,

Watford, Hertfordshire,

WD24 4YR United Kingdom.

8.    MARKETING AUTHORISATION NUMBER(S)

PL 36722/0028

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

24/06/2014

10. DATE OF REVISION OF THE TEXT

22/06/2016