1. Name Of The Medicinal Product
Naproxen Tablets BP 500mg.
2. Qualitative And Quantitative Composition
Each tablet contains 500mg Naproxen BP.
3. Pharmaceutical Form
Tablets.
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.
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. To be taken preferably with or after food.
In rheumatic disorders the usual initial dose of naproxen is 250 mg, twice daily, adjusted to 500 mg to 1g 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.
A dose of 10 mg per body weight daily, in two divided doses has been used in children over 5 years of age with juvenile rheumatoid arthritis.
The elderly are at increased risk of the serious consequences of adverse reactions. If 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.
4.3 Contraindications
1) Hypersensitivity to Naproxen sodium or to any of the constituents of naproxen tablets.
2) Naproxen is 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/analgesic drugs.
3) Severe hepatic, renal and cardiac failure (See section 4.4 – special warnings and precautions for use).
4) During the last trimester of pregnancy (see section 4.6 – Pregnancy and lactation).
5) Active or previous acute peptic ulcer.
6) History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
7) Use with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors (See section 4.5 Interactions).
8) Severe heart failure.
4.4 Special Warnings And Precautions For Use
In 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 administration)
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, 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 also be monitored in these patients (See section 4.3 – Contraindications)
Use in patients with impaired renal function:
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 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 the 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.
Use in patients with cardiovascular impairment:
Caution should be exercised 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. 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 with naproxen therapy.
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
Naproxen should be given under close supervision 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).
Naproxen decreases platelet aggression and prolongs bleeding time.
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.
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).
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 Contradindications).
Anti-hypertensives:
Reduced anti-hypertensive effect.
Naproxen can reduce the anti-hypertensive effect of propanolol and other beta blocking agents.
Diuretics:
Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
The natriuretic effect of frusemide has been reported to be inhibited by some drugs of this class.
Probenecid:
Probenecid given concurrently increases naproxen plasma levels and extends its plasma half life considerably.
Cardiac glycosides:
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Lithium:
Decreased elimination of lithium.
Inhibition of renal lithium clearance leading to increase in plasma lithium concentration has been reported.
Methotrexate:
Decreased elimination of 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:
Increased risk of nephrotoxicity.
Mifepristone:
NSAIDs should not be used for 8-12 days after mifepristone admininstration 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). Due to the plasma protein binding of naproxen, patients simultaneously receiving anticoagulants should be observed for signs of overdosage of these drugs.
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 with tacrolimus.
Sulphonamides and hydantoins:
Due to the plasma protein binding of naproxen, patients simultaneously receiving hydantoins or a highly protein bound sulphonamide should be observed for signs of overdosage of these drugs.
4.6 Pregnancy And Lactation
Pregnancy:
Congenital abnormalities have been reported in associated with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. 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 be delayed and the duration increased with an increased bleeding tendency in both mother and child by naproxen (See section 4.3 Contraindications). Therefore, naproxen should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.
Lactation:
In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. The use of naproxen should be avoided in patients who are breastfeeding.
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 naproxen. 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, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, abdominal discomfort, epigastric distress, 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, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Anaphylactic reactions may occur due to naproxen.
Cardiovascular: Mild peripheral oedema has been observed. Sodium retention may occur in patients with questionable or compromised cardiac function when taking naproxen. Occasional angio-oedema has been reported.
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
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 events reported less commonly include:
Renal: Nephropathy and nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
Hepatic: Abnormal liver function, fatal hepatitis and jaundice.
Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, 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, hallucination, tinnitus, hearing impairment, vertigo, dizziness, malaise, fatigue, drowsiness, inability to concentrate, insomnia and cognitive dysfunction.
Haematological: Granulocytopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Dermatological: Photosensitivity. Occasional skin rashes have been reported.
4.9 Overdose
a) Symptoms
Symptoms include headache, nausea, vomiting, indigestion, epigastic pain, gastrointestinal bleeding, rarely diarrhoea, heartburn, 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. Should a patient ingest a large amount of naproxen, the stomach may be emptied and usual supportive measures employed (it is not known what dose of drug would be life threatening).
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
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 giucuronide.
5.3 Preclinical Safety Data
Not applicable.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose, starch (maize), polyvinyl pyrrolidone, magnesium stearate, sodium starch glycollate and quinoline yellow (E104).
6.2 Incompatibilities
Not known
6.3 Shelf Life
36 months.
6.4 Special Precautions For Storage
Store in a dry place below 25°C. Protect from light. Keep container tightly closed.
6.5 Nature And Contents Of Container
Tamper evident container comprised of polyethylene and polypropylene.
Pack sizes: 28, 30, 56, 60, 84, 100, 250, 500 and 1000 tablets.
Blister pack: 60 GSM PVDC coated 250 microns, white opaque PVC film and 25 microns aluminium foil.
Pack sizes: 28, 30, 56, 60, 84 and 100 tablets.
No Data Held
7. Marketing Authorisation Holder
Aurobindo Pharma Limited
Ares,
Odyssey Business Park,
West End Road,
South Ruislip HA4 6QD,
United Kingdom
8. Marketing Authorisation Number(S)
PL 20532/0028
9. Date Of First Authorisation/Renewal Of The Authorisation
27/06/2011
10. Date Of Revision Of The Text
27/06/2011
No comments:
Post a Comment