Tenoxicam 20mg Tablets

Each film-coated tablet contains 20mg Tenoxicam

For excipients, see 6.1.

Film-coated tablet.

Round, yellowish film-coated tablet.

Tenoxicam tablets are for the treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis. It is also indicated for short term treatment of acute musculoskeletal disorders including strains, sprains and other soft-tissue injuries.

The tablets are for oral use and should be taken with water or other fluid, preferably with or after food.

Adults: The recommended dosage is a single daily dose of 20mg taken at the same time each day.

As there is no significantly greater therapeutic effect at higher doses, and higher doses may result in an increase of adverse events, oral doses greater than recommended should be avoided.

Tenoxicam 20 mg Tablets should only be used for up to a maximum of 2 weeks in cases of severe acute musculoskeletal disorders. Usually treatment of up to 7 days is sufficient.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest dose should be used and the patient should be monitored for GI bleeding for 4 weeks following initiation of therapy.

Children: Tenoxicam 20mg Tablets should not be used in children until sufficient data become available.

Use in renal and hepatic insufficiency:

In renal impairment, the normal dosage with careful monitoring is recommended for patients with a creatinine clearance of greater than 25ml/min (see 4.4 Special warnings and special precautions for use). There are insufficient data to make dosage recommendations for patients with a creatinine clearance of less than 25ml/min .

There are insufficient data to make dosage recommendations for Tenoxicam in patients with pre-existing hepatic impairment. (see 4.4 Special warnings and special precautions for use).

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

Tenoxicam 20 mg Tablets is contra-indicated in:-

• Severe heart failure

• Active peptic ulceration.

• A previous history of peptic ulceration, severe gastritis, or gastrointestinal bleeding.

• Patients with a known hypersensitivity to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs (symptoms of asthma, rhinitis, angioedema or urticaria).

• Previous known hypersensitivity to tenoxicam or any of the excipients contained in Tenoxicam 20 mg Tablets

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).

NSAIDs should only be given with care to patients with a history of gastrointestinal disease.

Patients showing signs of gastrointestinal disease during treatment with Tenoxicam, should be carefully monitored and if peptic ulceration or gastrointestinal bleeding occurs, the drug should be withdrawn immediately.

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 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). There are insufficient data to exclude such a risk for Tenoxicam.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Tenoxicam after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, papillary necrosis and the nephrotic syndrome. Such agents inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. Administration of a NSAID in these patients may precipitate overt renal decompensation, which returns to the pre-treatment state upon withdrawal of the drug. Patients at greatest risk of such a reaction are those with pre-existing renal disease (including diabetics with impaired renal function), nephrotic syndrome, volume depletion, hepatic disease, congestive cardiac failure and those patients receiving concomitant therapy with diuretics or potentially nephrotoxic drugs. Such patients should have their renal, hepatic and cardiac functions carefully monitored, and the dose should be kept as low as possible in patients with renal, hepatic or cardiac impairment. NSAIDs should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with NSAID administration.

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

Occasional elevations of serum transaminases or other indicators of liver function have been reported. The reports in most cases, have been small and transient increases above the normal range. If the abnormality is significant or persistent, Tenoxicam should be stopped and follow-up tests carried out. Particular care is required in patients with pre-existing hepatic disease.

Tenoxicam reduces platelet aggregation and may prolong bleeding time. Care is therefore required in patients undergoing major surgery and in patients whose bleeding time needs to be determined.

The elderly are at increased risk of the serious consequences of adverse reactions. Care should be taken to regularly monitor the patients to detect possible interactions with concomitant therapy and to review renal, hepatic and cardiovascular function which may be potentially influenced by NSAIDs.

Minor and serious ocular effects have been reported rarely in patients taking NSAIDs; ophthalmic evaluation is recommended for patients who develop visual disturbances during treatment with Tenoxicam.

Antacids may reduce the rate, but not the extent, of absorption of tenoxicam. The differences are not likely to be of clinical significance.

No interaction has been found with concomitantly administered cimetidine.

No clinically relevant interaction between tenoxicam and low molecular weight heparin has been observed in healthy subjects.

Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.

Anti-hypertensives: reduces anti-hypertensive effect.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Diuretics: NSAIDs may cause sodium, potassium and fluid retention and may interfere with the natriuretic action of diuretic agents, which can increase the risk of nephrotoxicity of NSAIDs. This should be kept in mind when treating patients with compromised cardiac function or hypertension since they may be responsible for a worsening of those conditions.

Lithium: More frequent monitoring is recommended. Lithium toxicity may result due to decreased elimination of lithium.

Methotrexate: Methotrexate toxicity due to decreased elimination of methotrexate.

Cyclosporin: 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.

Other analgesics: Avoid concomitant use of two or more NSAIDs due to increased risk of gastrointestinal irritation, ulcer formation and bleeding.

Salicylates: Salicylates can displace tenoxicam from protein-binding sites and so increase the clearance and volume of distribution of tenoxicam. Concomitant treatment should therefore be avoided because of the increased risk of adverse reactions (particularly gastro-intestinal).

Corticosteroids: Increased risk of GI bleeding.

Anticoagulants (excluding heparin): As tenoxicam is highly bound to serum albumin it can enhance the anticoagulant effect of warfarin and other anticoagulants. Close monitoring of the effects of anticoagulants and oral hypoglycaemic agents is advised, especially during the initial stages of treatment with tenoxicam.

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.

The safety of Tenoxicam during pregnancy and lactation has not been established and should not be given in these conditions.

Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of NSAIDs during pregnancy should if possible be avoided.

Congenital abnormalities have been reported in association 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 NSAIDs on the foetal cardiovascular system (a closure of the ductus arteriosus), use in late pregnancy should be avoided.

In the limited studies so far available, NSAIDs can appear in breast milk in very low concentrations and are unlikely to affect the breast-fed infant.

Dizziness, drowsiness, visual disturbances or headaches are possible undesirable effects after taking NSAIDs, if affected, patients should not drive or operate machinery.

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. They include nausea, vomiting, diarrhoea, constipation, flatulence, dyspepsia, abdominal pain, melaena, epigastric distress, haematemesis, ulcerative stomatitis and gastrointestinal haemorrhage. As with other NSAIDs, there is a risk of peptic ulceration or gastro-intestinal bleeding. Should either be reported during treatment, Tenoxicam should be stopped immediately and appropriate treatment instituted.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of non-specific allergic reactions and anaphylaxis, respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or assorted skin disorders, including rashes of various types, pruritis, urticaria, angioedema and, less commonly, bullous dermatoses (including epidermal necrolysis, erythema multiforme and exfoliative dermatitis). Photosensitivity reactions have also been reported rarely.

Cardiovascular: Oedema has been reported in association with NSAID treatment. Caution is advised in elderly patients with compromised cardiac function as an increase in oedema may result in congestive cardiac failure. Palpitations and dyspnoea have been reported rarely.

Other adverse events reported less commonly include:

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

Hepatic: Abnormal liver function, hepatitis and jaundice.

Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, depression, nervousness, confusion, hallucinations, dream abnormalities, insomnia, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

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

Metabolic effects: There have been rare occurrences of hyperglycaemia or weight increase or decrease.

Ophthalmological effects: Swollen eyes, blurred vision and eye irritation have been reported. No evidence of ocular changes have been revealed by ophthalmoscopy and slit-lamp examination.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

There are no reports of serious overdosage with tenoxicam. In general, symptoms of NSAID overdosage are mild, and usually include nausea and vomiting, headache, drowsiness, blurred vision, and dizziness. There have been isolated reports of more serious toxicity after ingestion of substantial quantities; they include seizures, hypotension, apnoea, coma, and renal failure. In the case of overdosage, gastric lavage, discontinuation of the drug, and the administration of activated charcoal, antacids and proton-pump inhibitors may be indicated.

Tenoxicam is a non-steroidal anti-inflammatory drug. It has anti-inflammatory, analgesics, and antipyretic effects. Its primary mode of action is the inhibition of the cyclooxygenases which are involved in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid.

Following oral administration, tenoxicam is rapidly and completely absorbed from the gastrointestinal tract. Concurrent administration of food reduces the rate but not the extent of absorption of tenoxicam. Tenoxicam does not undergo any pre-systemic metabolism. The bioavailability of the drug is essentially 100%.

Tenoxicam is distributed rapidly throughout the body. It is highly bound to plasma proteins, primarily to albumin. Peak concentrations of tenoxicam in synovial fluid are approximately half those in plasma.

Tenoxicam is eliminated slowly from the plasma, the mean plasma elimination half-life in healthy volunteers is approximately 67 hours and 40-52 hours in rheumatic patients. Elimination is almost entirely by metabolism in the liver. The majority of an oral dose (67%) is excreted in the urine mainly as the pharmacologically inactive metabolite, 5-hydroxytenoxicam, and the remainder in the bile much of it as glucuronide conjugates of hydroxy-metabolites.

The absorption, distribution, and elimination kinetics of tenoxicam are independent of dose. Steady state therapeutic plasma concentrations are achieved after 10-15 days of daily administration of 20 mg tenoxicam.

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

Lactose

Maize starch

Pregelatinised starch

Magnesium stearate

Talc

Colloidal silicon dioxide

Hypromellose

Titanium dioxide (E171)

Iron oxide yellow (E172)

Not applicable.

60 months.

Do not store above 25°C.

PVC/PvdC / Al/PVdC blisters in carton boxes of 28.

Not applicable.

Sandoz Ltd

Woolmer Way

Bordon

Hampshire GU35 9QE

PL: 4416/0397

03/03/2009

03/03/2009