Naproxen Tablets Bp 250mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Naproxen Tablets BP 250 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Naproxen 250 mg
Also contains lactose. See section 6.1 for excipients.
3 PHARMACEUTICAL FORM
Tablets (uncoated)
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Naproxen is used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhoea, and acute gout. Naproxen is effective in the treatment of juvenile rheumatoid arthritis in children over 5 years of age.
4.2 Posology and method of administration
Administered orally with or after food.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Adults:
In rheumatoid disorders the usual initial dose of Naproxen is 250 mg twice daily, adjusted from 500 mg to 1 g daily in two divided doses.
In acute gout, an initial dose of 750 mg followed by 250 mg every 8 hours has been suggested while in dysmenorrhoea 500 mg may be given initially followed by 250 mg every 6 to 8 hours.
Acute musculoskeletal disorders: The recommended dose is 500 mg initially followed by 250 mg at 6-8 hour intervals as needed, with a maximum daily dose after the first day of 1250 mg.
Children:
A dose of 10 mg per kg body weight daily in two divided doses has been used in children over 5 years of age with juvenile rheumatoid arthritis.
Naproxen is not recommended for use in any other indication in children under 16 years of age.
Elderly:
The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest recommended dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
A reduction in dosage may be necessary if there is impaired renal function.
4.3 Contraindications
NSAIDs are contraindicated in patients who have:
• Active or history of recurrent peptic ulceration / haemorrhage (two or more distinct episodes of proven ulceration or bleeding),
• Hypersensitivity to Naproxen, Naproxen sodium formulations or to any of the other constituents,
• 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 and cardiac failure (See section 4.4 - Special warnings and precautions for use),
• A history of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
• During the last trimester of pregnancy (See section 4.6 - Pregnancy and lactation)
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).
The use of Naproxen with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors should be avoided (See section 4.5 Interactions).
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:
Bronchospasm may be precipitated in patients suffering from or with a history of bronchial asthma or allergic disease.
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 naproxen 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).
Naproxen decreases platelet aggregation and prolongs bleeding time. Patients receiving anti-coagulant therapy and patients who have coagulation disorders should be carefully monitored if prescribed Naproxen Tablets BP 250 mg.
Use in patients with impaired renal function:
Naproxen is eliminated to a large extent (95%) by urinary excretion via glomerular filtration, it should be used with great caution in patients with significantly impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. Naproxen should not be used chronically in patients having baseline creatinine clearance less than 20ml/minute. Certain patients, specifically those where 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 Naproxen therapy. Some elderly patients, in whom impaired renal function may be expected, could also fall within this category. A reduction in the daily dosage should be considered to avoid the possibility of excessive accumulation of Naproxen metabolites in these patients.
Use in patients with impaired liver function.
Chronic alcoholic liver disease and probably other forms of cirrhosis reduce the total plasma concentration of Naproxen but the plasma concentration of unbound Naproxen is increased, so caution is advised when high doses are required.
Gastrointestinal bleeding, ulceration and perforation:
Although Naproxen has been found to be well tolerated by patients exhibiting dyspepsia with other similar agents, none the less, episodes of gastro intestinal bleeding have been reported in patients on Naproxen therapy. Naproxen should be given under close supervision to patients with a history of gastro intestinal disease. It should also be used with caution in patients with a history of peptic ulceration. 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).
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).
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 Naproxen, the treatment should be withdrawn.
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 naproxen 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 naproxen should be considered.
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.
Naproxen should be discontinued at the first appearance of skin rash, mucosal leisions or any other sign of hypersensitivity.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Other analgesic including cyclooxygenase-2 selective inhibitors: Due to increased risk of adverse reactions, avoid concomitant administration of two or more NSAIDs, including aspirin (See section 4.3 Contraindications).
Antihypertensives: Naproxen can reduce the anti hypertensive effect of Propranolol and other beta blocking agents. ACE inhibitors and other antihypertensive drugs will have decreased hypotensive effects, and may cause renal failure and increased risk of hyperkalaemia, when used in conjunction with NSAIDs.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs. The natriuretic effect of Furosemide has been reported to be inhibited by some drugs of this class. There is a risk of nephrotoxicity when Naproxen is used with diuretics and there is an increased risk of hyperkalaemia with potassium-sparing diuretics.
Cardiac glycosides (e.g. digoxin): NSAIDs used with cardiac glycosides may exacerbate heart failure, reduce glomerular filteration rate, and increase plasma-cardiac glycoside concentration.
Lithium: Inhibition of renal lithium clearance leading to increase in plasma lithium concentration has also been reported.
Methotrexate: Caution is advised when Methotrexate is administered concurrently because of possible enhancement of its toxicity since Naproxen has been reported to reduce the tubular secretion of Methotrexate in the animal model.
Ciclosporin: Ciclosporin used together with Naproxen will increase the risk of nephrotoxicity.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. NSAIDs have a possible risk of convulsions when used together with 4-quinolone antibiotics such as norfloxacin and ciprofloxacin.
Mifepristone: The manufacturer of Mifepristone recommends avoiding NSAIDs until 8-12 days after administration as NSAIDs can reduce the effect of mifepristone.
Corticosteroids: Use of Naproxen with corticosteroids will increase the risk of gastrointestinal bleeding and ulceration. (See section 4.4 - Special warnings and precautions for use).
Anti-coagulants: Patients receiving anti-coagulant therapy and patients who have coagulation disorders should be carefully monitored if prescribed Naproxen Tablets BP 250 mg. NSAIDs may enhance the effects of anti-coagulants, such as warfarin. Due to the high plasma protein binding of Naproxen, patients simultaneously receiving anti coagulants or a highly protein bound sulphonamide should be observed for signs of overdosage of these drugs. (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).
Antiepileptics: Effects of phenytoin or hydantoin is enhanced by azapropazone and possibly other NSAIDs, like naproxen.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Probenecid given concurrently increases Naproxen plasma levels and extends its plasma half-life considerably.
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.
Naproxen may interfere with some tests for 17-ketogenic steroids or assays for urinary 5-hydroxyindoleacetic acid.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are in low frequency and do not appear to follow any discernible 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). Good medical practice indicates minimal drug usage in pregnancy and the use of this class of therapeutic agent requires cautious balancing of possible benefit against potential risk to mother and foetus, especially in the first two trimesters of pregnancy.
Lactation
In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. The use of Naproxen should, if possible, be avoided in patients who are breast-feeding.
See section 4.4 Special warnings and precautions for use, regarding female fertility.
4.7 Effects on ability to drive and use machines
If undesirable effects such as headache, dizziness, drowsiness, fatigue, visual disturbances and insomnia should occur, patients should not drive or operate machinery because Naproxen may cause difficulty in concentration.
4.8 Undesirable effects
Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers (sometimes with haemorrhage and perforation) or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, anorexia, vomiting, epigastric distress, abdominal pain, constipation, dyspepsia, melaena, haematemesis, flatulence, ulcerative stomatitis, diarrhoea, non peptic gastro-intestinal ulceration, 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. Pancreatitis has been reported very rarely.
Hypersensitivity: Hypersensitivty reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylactic reactions to naproxen and naproxen sodium formulations in patients with, or without, a history of previous hypersensitivity reactions to NSAIDs (eosinophilic pneumonia may occur rarely) (b) respiratory tract reactivity comprising asthma, aggravated asthma, alveolitis, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angio-oedema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme), alopecia and Stevens Johnson syndrome.
Cardiovascular: 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). Sodium retention may occur in patients with questionable or compromised cardiac function when taking naproxen.
Other adverse events reported less commonly include:
Renal: Nephrotoxicity in various forms, including glomerular nephritis, interstitial nephritis, nephrotic syndrome, haematuria, renal papillary necrosis, rarely hyperkalaemia and renal failure.
Hepatic: Abnormal liver function, rarely hepatitis and jaundice.
Neurological and special senses: Visual disturbances, convulsions, insomnia, inability to concentrate, cognitive dysfunction, optic neuritis, paraesthesia, headaches or hearing impairment. Reports of induction or exacerbation of colitis and 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, malaise, fatigue dizziness, nervousness, and drowsiness.
Haematological: Thrombocytopenia, neutropenia, vasculitis, granulocytopenia including agranulocytosis, aplastic anaemia and haemolytic anaemia may occur rarely.
Dermatological: Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely Photosensitivity reactions (including cases in which the skin resembles porphyria cutanea tarda, ‘pseudoporphyria’).
4.9 Overdose
Symptoms
Significant overdosage may be characterised by:
Headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, dizziness, tinnitus, fainting, occasionally convulsions, drowsiness, heartburn, indigestion. In cases of significant poisoning acute renal failure and liver damage are possible.
Therapeutic measures
Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount, activated charcoal may be given. 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. In renal failure haemodialysis may be appropriate. 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.
It is not known what dose of naproxen will be life threatening.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Naproxen has analgesic, anti-inflammatory and anti pyretic actions.
5.2 Pharmacokinetic properties
Naproxen is readily absorbed from the gastro intestinal tract. It is extensively bound to plasma proteins and has a half-life of about 14 hours. About half of the dose is excreted in the urine in 24 hours and about 94% in 5 days largely as the glucuronide.
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 SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Starch (Maize)
Polyvinylpyrrolidone Sodium Starch Glycollate Magnesium Stearate Quinoline Yellow E104 Isopropyl Alcohol
6.2 Incompatibilities
None stated
6.3 Shelf life
Containers - 36 months. Blister packs - 24 months.
6.4 Special precautions for storage
Keep the tablets in the original container tightly closed, or in the same outer carton, in a dry place. Do not store above 25°C. Protect from light.
6.5 Nature and contents of container
Securitainer or securitainers type containers (i.e. polypropylene/polythene containers opaque to light with tamper evident lid).
Pack sizes: 1000, 500, 250, 100, 84, 70, 56, 42, 28, 21, 15, 14
Blister pack strips composed of aluminium foil and PVC film.
Pack sizes: 84, 70, 56, 42, 28, 21, 15, 14
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Chatfield Pharmaceutical Ltd T/A Chatfield Laboratories Kramer Mews London SW5 9JL United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 02142/0020
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
21/11/2008
10 DATE OF REVISION OF THE TEXT
July 2008