SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Cuprofen Ibuprofen Effervescent Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 200mg For excipients, see 6.1.

3    PHARMACEUTICAL FORM

Effervescent tablets

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the relief of rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.

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 and short-term use only.

Adults, the elderly and children over 12 years

The minimum effective dose should be used for the shortest time necessary to relieve symptoms.

If in children and adolescents, between the age of 12 and 18 years this medicinal product is required for more than 3 days, or if symptoms worsen, a doctor should be consulted.

For adults aged 18 years or older if the product is required for more than 10 days or if the symptoms worsen or persist, the patient should consult a pharmacist or a doctor.

Initial dose - One or two tablets to be taken. The initial dose may be followed by further doses of one or two tablets every four hours. Leave at least four hours between doses and do not take more than 1200mg (6 tablets) in any 24 hour period. To be taken preferably after food.

Children

Not suitable for children under 12 years.

Directions

The tablets must be dissolved in half a glass of water (100ml). The tablets dissolve more quickly in warm water, or if stirred.

4.3 Contraindications

Hypersensitivity to ibuprofen or any of the constituents in the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal antiinflammatory drugs.

Active or previous peptic ulcer.

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

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

Severe heart failure (NYHA Class IV)

Each tablet contains 661mg or 28.8 mmol 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

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

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

The elderly are at increased risk of the serious consequences of adverse reactions.

Systemic lupus erythematosus and mixed connective tissue disease increased risk of aseptic meningitis (see section 4.8 Undesirable effects).

Chronic inflammatory intestinal disease (ulcerative colitis, Crohn’s disease) - as these conditions may be exacerbated (See section 4.8 Undesirable effects).

Hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur.

Renal impairment as renal function may further deteriorate (See section 4.3 Contraindications and Section 4.8 Undesirable effects).

Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects).

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.

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime 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 ibuprofen, the treatment should be withdrawn.

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.

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

Cardiovascular and cerebrovascular effects

Clinical studies suggest that use of ibuprofen, particularly at high doses (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 (2400mg/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)

The label will include:

Read the enclosed leaflet before taking this product. Do not take if you -

•    have or have ever had 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 75mg.

•    are in the last 3 months of pregnancy.

Speak to a pharmacist or your doctor before taking this product if you

•    have asthma, liver, heart, kidney or bowel problems.

•    are in the first 6 months of pregnancy.

If symptoms persist or worsen, consult your dentist or doctor.

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 acid cannot be excluded.

No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1)

Other NSAIDs: As these may increase the risk of adverse effects (See section 4.3 Contraindications).

Ibuprofen should be used with caution in combination with: Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4).

Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Corticosteroids'. May increase the risk of adverse reactions in the adverse reactions in the gastrointestinal tract (See section 4.4 Special warnings).

Lithium: There is evidence for potential increases in plasma levels of lithium. Methotrexate: There is a potential for an increase in plasma methotrexate.

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 Cuprofen 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

None expected at recommended doses and duration of therapy.

4.8 Undesirable effects

Hypersensitivity reactions have been reported and these may consist of:

(a)    Non-specific allergic reactions and anaphylaxis.

(b)    Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, dyspnoea

(c)    Various skin reactions, e.g. pruritis, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses, for short-term use. In the treatment of chronic conditions, under longterm treatment, additional adverse effects may occur.

Hypersensitivity reactions: Uncommon: Hypersensitivity reactions with urticaria and pruritus.

Very rare: severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).

Exacerbation of asthma or bronchospasm.

Gastrointestinal: Uncommon: abdominal pain, nausea, and dyspepsia. Rare: diarrhoea, flatulence, constipation and vomiting.Very rare: peptic ulcer, perforation or gastrointestinal haemorrhage,sometimes fatal, particularly in the elderly.

Exacerbation of ulcerative colitis and Crohn’s disease (See section 4.4).

Nervous system:

Uncommon: Headache.

Renal: Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Hepatic: Very rare: liver disorders.

Haematological: Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Skin:

Uncommon: Various skin rashes.

Very rare: Severe forms of skin reactions such as erythema multiforme and epidermal necrolysis can occur.

Immune System: In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed (See section 4.4).

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

Clinical studies suggest that use of ibuprofen (particularly at high doses 2400mg/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

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamics studies show that when single doses of Ibuprofen 400 mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic acid dosing (81 mg) 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 cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5)

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food peak levels are observed after 1 to 2 hours. These times may vary with different dosage forms.

The half-life of ibuprofen is about 2 hours.

In limited studies, ibuprofen appears in the breast milk in very low concentrations.

5.3 Preclinical safety data

None stated.

6    PHARMACEUTICAL PARTICULARS

6.1    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 Mango flav-o-lok 610575E IMS

6.2    Incompatibilities

None stated.

6.3    Shelf life

24 months unopened.

6.4    Special precautions for storage

Store in a cool dry place.

6.5 Nature and contents of container

Strip pack using PPFM laminate, constructed of: 40gsm MGBK paper / 12gsm LDPE / 8p aluminium foil / 23gsm LDPE. Strips are packed into a carton containing either 10, 12, 16, 24, 30, 36, 50, 56, 100 or 112 tablets

6.6 Special precautions for disposal

None.

7    MARKETING AUTHORISATION HOLDER

Ayrton Saunders Limited,

North Way,

Walworth Industrial Estate,

Andover,

SP10 5AZ United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 16431/0056

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22/01/91 / 29/01/99

10 DATE OF REVISION OF THE TEXT

03/02/2016