SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Soluble Cufen Ef, Ibuprofen Effervescent Tablets 400mg.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 400mg/tablet.

For excipients, see 6.1.

3 PHARMACEUTICAL FORM

Effervescent tablets

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Ibuprofen is a non steroidal anti-inflammatory and analgesic drug that is used in the treatment of Rheumatoid Arthritis (including juvenile Rheumatoid Arthritis or Still’s Disease), osteoarthritis, ankylosing spondylitis and other non-Rheumatoid Arthropathies and in the treatment of non-articular rheumatic conditions.

It is also indicated in periarticular disorders such as bursitis, frozen shoulder, tendinitis, tensosynivitis and low back pain. It may also be used in soft tissue injuries such as sprains and strains.

It may be used for the relief of mild to moderate pain such as period pains, dental and post-operative pain and in the relief of migraine.

4.2 Posology and method of administration

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

For oral administration.

Adults and children aged over 12 years

The recommended dose is one tablet to be taken three or four times daily. Some patients can be maintained on one tablet two or three times daily.

In severe or acute conditions it can be advantageous to increase the dose until the acute phase is brought under control provided the daily dose does not exceed six tablets per day in divided doses.

Children

Not suitable for children under 12 years.

The 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.

Directions The tablets must be dissolved in half a glass of water (100ml). The tablets dissolve more quickly in warm water, or if stirred. 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 non-steroidal anti-inflammatory drugs.

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

During the last trimester of pregnancy (See section 4.6 - Pregnancy and lactation). Active or previous peptic ulcer.

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

Use with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors (See section 4.5 Interactions).

Severe heart failure (NHYA Class IV)

Each tablet contains 995mg or 43.3 mmols of Na+. This should be taken into account when prescribing for patients on a sodium restricted diet.

4.4 Special warnings and precautions for use

In all patients:

Undesirable effects may be minimised by using the maximum effective dose for the shortest possible duration.

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 administration).

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.

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 - Contraindications).

Caution in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

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.

Patients with a history of GI toxicity, particularly when 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 gastrotoxicity or bleeding, such as corticosteroids, or anticoagulants such as warfarin or anti-platelet agents such as aspirin (see section 4.5 - Interactions).

When GI bleeding or ulceration occurs in patients receiving Soluble Cufen EF Ibuprofen Effervescent Tablets 400mg, 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 - Undesirable effects).

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 -Undesirable effects).

Female fertility:

The use of Soluble Cufen EF Ibuprofen Effervescent Tablets 400mg 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 Soluble Cufen EF Ibuprofen Effervescent Tablets 400mg should be considered.

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).

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 studies suggest that use of ibuprofen, particularly at a high dose (2400mg/day) 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/day) is associated with an increased risk of arterial thrombotic events.

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.

There is a risk of renal impairment in dehydrated adolescents (age range: > 12 years to < 18 years)

4.5 Interaction with other medicinal products and other forms of interaction

Acetylsalicylic acid

Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects

Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, See section 4.3 Contraindications

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid 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 cannot be excluded.No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

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).

Anti-hypertensives: Reduced anti-hypertensive effect.

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.

Lithium: Decreased elimination of lithium.

Methotrexate: Decreased elimination of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity.

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

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

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4 - Special warnings and precautions for use).

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.

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

Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 Pregnancy and lactation

Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Soluble Cufen Ef Ibuprofen Effervescent Tablets should, if possible, be avoided during the first 6 months of pregnancy.

During the 3^rd trimester, ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistant pulmonary hypertension. 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).

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

See section 4.4 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

Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforations or GI bleeding, sometimes fatal, particularly in the elderly, 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 Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed.

Hypersensitivity: 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 of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular: Oedema has been reported in association with NSAID treatment. Other adverse events reported less commonly include:

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephritic syndrome and renal failure.

Hepatic: 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.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: photosensitivity.

Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.

Clinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg /day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

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: Ibuprofen, ATC code: M01AE01. Analgesic/anti-inflammatory.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly.Some pharmacodynamic studies show that when a single doses of ibuprofen 400mg were taken within 8 hours before or within 30 minutes after immediate release acetylsalicylic acid dosing (81mg), a decreased effect of acetylsalicylic acid 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 (see section 4.5)

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

None stated.

6 PHARMACEUTICAL PARTICULARS

List of excipients

Sodium bicarbonate

Sodium carbonate (anhydrous)

Sodium cyclamate

Sodium saccharin

Citric acid anhydrous

Docusate sodium

Polyethylene glycol powder 6000

Povidone

Orange mint flavour 611160E IMS

6.2 Incompatibilities

None stated.

6.3 Shelf life

36 months unopened.

6.4 Special precautions for storage

Store in a cool dry place.

6.5 Nature and contents of container

Strip pack using PPFP laminate, constructed of: 40gsm MGBK paper/l2gsm LDPE/8p aluminium foil/23gsm LDPE. Strips are packed into a carton containing either 12, 24, 48, 96, 112 or 144 tablets

6.6 Special precautions for disposal

None.

MARKETING AUTHORISATION HOLDER

Ayrton Saunders Limited, North Way,

Walworth Industrial Estate, Andover,

SP10 5AZ United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 16431/0092

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27 June 1991 / 09 December 1998

10    DATE OF REVISION OF THE TEXT

03/02/2016