SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Stirlescent 250 mg Effervescent Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 250 mg Naproxen.

This medicinal product contains 341.89 mg sodium per effervescent tablet.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Effervescent tablets.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Stirlescent is used in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute musculoskeletal disorders, dysmenorrhoea and acute gout in adults.

4.2    Posology and method of administration

Posology

Use of the lowest effective dose for the shortest duration necessary to control symptoms is recommended, in order to minimise undesirable effects (see section 4.4).

Rheumatoid arthritis, osteoarthritis and ankylosing spondylitis

Start at 250 mg, twice daily. Adjust to 500 mg to 1000 mg daily in two divided doses.

Acute gout

Start at 750 mg, followed by 250 mg every 8 hours.

Acute musculoskeletal disorders and dvsmenorrhoea Start at 500 mg, followed by 250 mg every 6 to 8 hours.

Paediatric population

Stirlescent should not be used in the paediatric population because the correct dose cannot be administered using this formulation.

Elderly

Reduced elimination in the elderly (see section 4.4). Increased risk of serious consequences of adverse reactions. If NSAID use is considered necessary, the lowest effective dose should be used for the shortest possible duration. Monitor regularly for GI bleeding during treatment. Review treatment at regular intervals and discontinue if no benefit is seen, or if intolerance occurs.

Renal/hepatic impairment

Consider a lower dose in patients with renal or hepatic impairment. Contraindicated in patients with baseline creatinine clearance less than 30 ml/minute due to potential accumulation of naproxen metabolites (see section 4.3).

Method of administration Oral.

Doses of 1 to 2 tablets must be dissolved in at least 150 ml (a glass) of water, doses of 3 tablets must be dissolved in 300 ml. The glass should be rinsed with a small amount of water (10 ml) and the contents drunk.

To be taken preferably with or after food.

Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

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

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

Severe hepatic, renal and cardiac failure (see section 4.4).

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

4.4 Special warnings and precautions for use

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). Patients treated with NSAIDs long-term should undergo regular medical supervision to monitor for adverse events.

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

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). Prolonged use of NSAIDs in these patients is not recommended. Where prolonged therapy is required, patients should be reviewed regularly.

Respiratory disorders:

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

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 and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Although data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Stirlescent 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).

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 the elderly. 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 dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

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 ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving Stirlescent, 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 therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Stirlescent should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Renal:

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, angiotensin converting enzyme inhibitors, angiotensin-II receptor antagonists and the elderly. Renal function should be monitored in these patients (see also Section 4.3).

As naproxen is eliminated to a large extent (95%) by urinary excretion via glomerular filtration, it should be used with great caution in patients with impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised and patients should be adequately hydrated. Stirlescent is contraindicated in patients having a baseline creatinine clearance of less than 30ml/minute.

Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding.

Certain patients, specifically those whose renal blood flow is compromised, such as in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease, should have renal function assessed before and during Stirlescent therapy. Some elderly patients in whom impaired renal function may be expected, as well as patients using diuretics, may also fall within this category. A reduction in daily dosage should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients.

Hepatic:

As with other non-steroidal anti-inflammatory drugs, elevations of one or more liver function tests may occur. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. Severe hepatic reactions, including jaundice and hepatitis (some cases of hepatitis have been fatal) have been reported with this drug as with other non-steroidal anti-inflammatory drugs. Cross reactivity has been reported.

Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for Stirlescent dosing is unknown but it is prudent to use the lowest effective dose.

Anaphylactic reactions:

Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin, other non-steroidal antiinflammatory drugs or naproxen-containing products. They may also occur in individuals with a history of angio-oedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps.

Haematological:

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.

Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis should be carefully observed if naproxen-containing products are administered.

Patients at high risk of bleeding or those on full anti-coagulation therapy (e.g. dicoumarol derivatives) may be at increased risk of bleeding if given naproxen-containing products concurrently.

Ocular effects:

Studies have not shown changes in the eye attributable to naproxen administration. In rare cases, adverse ocular disorders including papillitis, retrobulbar optic neuritis and papilloedema, have been reported in users of NSAIDs including naproxen, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with naproxen-containing products should have an ophthalmological examination

Impaired female fertility:

The use of Stirlescent 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 Stirlescent should be considered.

General

The antipyretic and anti-inflammatory activities of Stirlescent may reduce fever and inflammation, thereby diminishing their utility as diagnostic signs.

Sodium

This medicinal product contains 341.89 mg sodium per effervescent tablet. To be taken into consideration by patients on a controlled sodium diet.

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: 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.

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

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anti-coagulants: 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.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4).

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

Zidovudine: 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.

Due to the high plasma protein binding of naproxen, patients simultaneously receiving hydantoins, anticoagulants, other NSAIDs, aspirin or a highly protein-bound sulphonamide should be observed for signs of overdosage of these drugs. Patients simultaneously receiving Stirlescent and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required. No interactions have been observed in clinical studies with naproxen and anticoagulants or sulphonylureas, but caution is nevertheless advised since interaction has been seen with other non-steroidal agents of this class.

It is suggested that Stirlescent therapy be temporarily discontinued 48 hours before adrenal function tests are performed, because naproxen may artifactually interfere with some tests for 17-ketogenic steroids. Similarly, naproxen may interfere with some assays of urinary 5-hydroxyindoleacetic acid.

4.6 Fertility, pregnancy and lactation

Pregnancy

Congenital abnormalities in man have been reported; these are low in frequency and no discernible pattern is apparent. In view of the known effects of naproxen on the human foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may also be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). Do not use during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

NSAIDs can appear in breast milk in very low concentrations. Do not use in patients who are breastfeeding.

Fertility

Naproxen may impair female fertility. Not recommended in women attempting to conceive. Consider withdrawal of treatment in women who have difficulties conceiving or who are undergoing investigation of infertility.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Gastrointestinal disorders:

The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation 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, obstruction, oesophagitis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease (see section 4.4) have been reported following administration.

Less frequently, gastritis has been observed. 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, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiac disorders:

Oedema, palpitations, cardiac failure and congestive heart failure have been reported.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses 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 reactions reported less commonly include:

Renal and urinary disorders:

Nephrotoxicity in various forms, including glomerulonephritis, haematuria, raised serum creatinine, renal papillary necrosis, interstitial nephritis, nephrotic syndrome and renal failure.

Hepatobiliary disorders:

Abnormal liver function, hepatitis (including fatal hepatitis) and jaundice. Nervous system disorders:

Visual disturbances, optic neuritis, headaches, paraesthesia, convulsions, cognitive dysfunction, inability to concentrate, 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, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Blood and lymphatic system disorders:

Thrombocytopenia, neutropenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Skin and subcutaneous tissue disorders:

Skin rashes including fixed drug eruption, itching (pruritus), urticaria, ecchymoses, purpura, sweating. Alopecia, erythema multiforme, Stevens Johnson syndrome, erythema nodosum, lichen planus, pustular reaction, SLE, epidermal necrolysis, very rarely toxic epidermal necrolysis, photosensitivity reactions (including cases in which skin resembles porphyria cutanea tarda “pseudoporphyria”) or epidermolysis bullosalike reactions which may occur rarely.

If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.

Musculoskeletal and connective tissue disorders: Myalgia and muscle weakness.

Reproductive system and breast disorders: Female infertility.

General disorders and administration site conditions: Thirst, pyrexia, fatigue and malaise.

Respiratory, thoracic and mediastinal disorders:

Dyspnoea, asthma, eosinophilic pneumonitis and pulmonary oedema.

Vascular disorders: Hypertension, vasculitis.

Eye Disorders:

Visual disturbances, comeal opacity, papillitis and papilloedema.

Ear and Labyrinth disorders:

Tinnitus, hearing disturbances including impairment and vertigo.

Metabolic and nutrition disorders:

Hyperkalaemia.

Psychiatric disorders:

Insomnia, dream abnormalities, depression, confusion and hallucinations.

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard

4.9 Overdose

a)    Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions. In cases of significant poisoning acute renal failure and liver damage are possible.

b)    Therapeutic measure

Patients should be treated symptomatically as required.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, nonsteroids, propionic acid derivatives, ATC code: M01AE02

Naproxen is a non-steroidal anti-inflammatory analgesic agent.

Antipyretic properties have been demonstrated in classical animal test systems.

Naproxen exhibits its anti-inflammatory effect even in adrenalectomised animals, indicating that its action is not mediated through the pituitary-adrenal axis. Like other NSAIDs, naproxen inhibits prostaglandin synthetase. However, the exact mechanism of its anti-inflammatory action is not known.

5.2    Pharmacokinetic properties

Naproxen is completely absorbed from the gastro-intestinal tract, and peak plasma levels are reached in 2 to 4 hours. Naproxen is present in the blood mainly as unchanged drug, extensively bound to plasma proteins. The plasma half-life is between 12 and 15 hours, enabling a steady state to be achieved within 3 days of initiation of therapy on a twice daily dose regimen. The degree of absorption is not significantly affected by either foods or most antacids. Excretion is almost entirely via the urine, mainly as conjugated naproxen, with some unchanged drug. Metabolism in children is similar to that in adults. Chronic alcoholic liver disease reduces the total plasma concentration of naproxen but the concentration of unbound naproxen increases. In the elderly, the unbound plasma concentration of naproxen is increased although total plasma concentration is unchanged.

5.3    Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Citric acid

Sodium hydrogen carbonate Sodium carbonate Sodium cyclamate Saccharin sodium Sodium citrate Povidone

Macrogol 6000 Mannitol (E421) Simeticone Docusate sodium Blackcurrant Flavour

6.2    Incompatibilities

Not known.

6.3    Shelf life

36 months.

6.4    Special precautions    for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

Polypropylene tube with polyethylene desiccant stopper or laminated aluminium paper foil

Pack sizes: 10, 12, 15, 20, 24 and 30 effervescent tablets.

Not all pack sizes may be marketed.

6.6    Special precautions    for disposal

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

7    MARKETING AUTHORISATION HOLDER

Stirling Anglian Pharmaceuticals Ltd.

Hillington Park Innovation Centre,

1 Ainslie Road, Hillington Park,

Glasgow G52 4RU,

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 42582/0009

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/12/2015

10    DATE OF REVISION OF THE TEXT

03/12/2015