SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Tenoxicam 20mg Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20mg tenoxicam.

3 PHARMACEUTICAL FORM

Film-coated tablets

Round, yellowish, film-coated tablets.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

IV, IM tenoxicam is also available for these indications in those patients considered unable to take oral tenoxicam.

4.2. Posology and Method of Administration

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

Adults):

A single daily dose of 20 mg Tenoxicam Tablet should be taken orally, at the same time each day.

In acute musculoskeletal disorders treatment should not normally be required for more than 7 days, but in severe cases it may be continued up to a maximum of 14 days.

Children:

There are insufficient data to make a recommendation for administration of tenoxicam tablets to children.

There is insufficient information to make dosage recommendations for tenoxicam tablets in patients with pre-existing hepatic impairment.

Elderly:

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

Tenoxicam 20 mg Tablets are for oral administration with water or other fluid.

4.3. Contraindications

Hypersensitivity to tenoxicam or any of the other ingredients.

History of hypersensitivity to aspirin or any other NSAID including those in whom attacks of asthma, angioedema, urticaria or rhinitis have been precipitated by aspirin or any other NSAID.

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

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

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

Anti-coagulant therapy.

Thrombocytopenia.

Pregnancy and breastfeeding.

4.4. Special Warnings and Precautions for Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest possible duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

The use of tenoxicam with concomitant NSAIDs including cycloxygenase-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 - Posology and Method of Administration).

Respiratory disorders:

Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma 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, the elderly and those recovering from major surgery. Renal function should be monitored in these patients (Also see section 4.3 - Contraindications).

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 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).

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 gastrotoxicity or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5)

When GI bleeding or ulceration occurs in patients receiving tenoxicam, 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. Tenoxicam should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Renal:

In rare cases, non-steroidal anti-inflammatory drugs 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. In these patients, administration of a non-steroidal anti-inflammatory drug 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.

Hepatic:

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

Platelet Aggregation:

Tenoxicam Tablets reduce platelet aggregation and may prolong bleeding time. This should be considered in patients who undergo major surgery (e.g joint replacement) and when bleeding time needs to be determined.

Opthalmic:

Adverse eye findings have been reported with non-steroidal anti-inflammatory drugs, therefore it is recommended that patients who develop visual disturbances during treatment with Tenoxicam Tablets have ophthalmic evaluation.

Impaired Female fertility:

The use of tenoxicam 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 tenoxicam should be considered.

4.5. Interactions with other Medicaments and other forms of Interaction

Other analgesics (including cycloxygenase-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. The activity of diuretics may be inhibited by some NSAIDs. Increased serum potassium levels may result when tenoxicam is given concomitantly with potassium-sparing diuretics. Serum potassium levels should therefore be monitored.

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

Close monitoring of the effects of oral hypoglycaemic agents is advised, especially during the initial stages of treatment with Tenoxicam Tablets.

Lithium: Decreased elimination of lithium. Non-steroidal anti-inflammatory drugs have been reported to produce lithium retention. If tenoxicam is prescribed for a patient receiving lithium therapy, the frequency of lithium monitoring should be increased, the patient warned to maintain fluid intake and to be aware of symptoms of lithium intoxication.

Methotrexate: NSAIDs can reduce the tubular secretion of methotrexate thereby increasing the plasma concentrations of methotrexate. For this reason, for patients on high dosages of methotrexate (more than 15 mg/week), the concomitant use of NSAIDs is not recommended.

The risk of an interaction between NSAID preparations and methotrexate, should be considered also in patients on low dosage of methotrexate, especially in patients with impaired renal function. In case combination treatment is necessary blood cell count and the renal function should be monitored. Caution should be taken in case both NSAID and methotrexate are given within 3 days, in which case the plasma level of methotrexate may increase and cause increased toxicity.

Ciclosporin: Increased risk of nephrotoxicity as a result of the effect of NSAIDs on renal prostaglandins.

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 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).

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.

Antiplatelet 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.

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

4.6. Pregnancy and Lactation

The safety of Tenoxicam Tablets during pregnancy and lactation has not been established and the drug should therefore, not be given in these conditions.

Although animal studies have shown no teratogenic effects, tenoxicam, like other non-steroidal anti-inflammatory drugs, is associated with prolonged and delayed parturition and adverse influence on neonatal viability when administered to animals in late pregnancy. Non-steroidal anti-inflammatory agents are also known to induce closure of the ductus arteriosus in infants.

No information is available on penetration of tenoxicam into milk in humans, animal studies indicate that significant levels may be achieved.

4.7.    Effects on Ability to Drive and Use Machines

Dizziness, drowsiness, visual disturbances or headache are possible undesirable effects after taking NSAIDs, 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, (including gastric or duodenal ulcers) have been observed. Perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4 - Special Warnings and Precautions for Use). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, anorexia, 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. Pancreatitis has been reported very rarely.

Anorexia.

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).

Cardiovascular and Cerebrovascular: 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).

Vascular:

Vasculitis

Other adverse reactions reported less commonly include:

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

Hepatic: Hepatitis and jaundice. As with most other non-steroidal antiinflammatory drugs, changes in various liver function parameters have been observed. Reversible elevations of blood urea nitrogen have been reported. Some patients may develop raised serum transaminase levels during treatment. Although such reactions are rare, if abnormal liver function tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (eosinophilia, rash) Tenoxicam Tablets should be discontinued.

Neurological and special senses: Visual disturbances (including blurred vision), swollen eyes, eye irritation, optic nephritis, 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 - Special Warnings and Precautions for Use), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Other effects on the central nervous system include somnolence, insomnia, nervousness, mental confusion and dream abnormalities.

Haematological: Thrombocytopenia, non thrombocytopenic purpura, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. Leucopenia and eosinophilia have been reported. Epistaxis has been reported infrequently. Decreases in haemoglobin unrelated to gastrointestinal bleeding.

Dermatological: Bullous reactions including Stevens Johnson Syndrome,

Lyell Syndrome, and Toxic Epidermal Necrolysis (very rare). Photosensitivity. Nail disorders and alopecia.

Metabolic: Metabolic abnormalities, such as weight decrease or increase and hypercalcaemia, have occurred rarely.

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 measures

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.

No specific measures are available; administration of H₂-antagonist drugs may be of benefit. Gastric lavage should be carried out as soon as possible after drug ingestion and the patient should be closely observed and general supportive measures taken as necessary.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) which has a marked anti-inflammatory and analgesic activity and some anti-pyretic

activity. As with other non-steroidal anti-inflammatory drugs, the precise mode of action is unknown, though it is probably multi-factorial, involving inhibition of prostaglandin biosynthesis and reduction of leucocyte accumulation at the inflammatory site.

5.2. Pharmacokinetic Properties

After oral administration, tenoxicam is rapidly and completely absorbed as unchanged drug. Concomitant food reduces the rate, but not the extent, of absorption of tenoxicam. Tenoxicam penetrates well into synovial fluid to give concentrations approximately half those in plasma. The mean plasma elimination half-life is approximately 72 hours.

With the recommended dosage regimen of 20 mg once daily, steady-state plasma concentrations are reached within 10-15 days, with no unexpected accumulation.

Tenoxicam is strongly bound to plasma protein. It is cleared from the body almost exclusively by metabolism. Approximately, two-thirds of the administered dose is excreted in the urine, mainly as the pharmacologically inactive 5-hydroxypyridyl metabolite, and the remainder in the bile, much of it as glucuronide conjugate of hydroxy metabolites.

Tenoxicam does not undergo any pre-systemic metabolism. The bioavailability of the drug is essentially 100%.

No age specific changes in the pharmacokinetics of tenoxicam have been found although inter-individual variation tends to be higher in elderly persons.

5.3. Preclinical Safety Data

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

6. PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Lactose Maize starch Pregelatinized starch Talc

Colloidal silicon dioxide Magnesium stearate

Hypromellose Titanium dioxide(E171) Yellow iron oxide (E172)

6.2. Incompatibilities

None stated

6.3 Shelf life

48 Months

6.4. Special Precautions for Storage

Do not store above 25°C. Store in the original package.

6.5. Nature and Contents of Container

White, opaque PVC/PVdC aluminium blister packs. Pack size: 28 or 56 tablets.

6.6. Instruction for Use, Handling and Disposal

None stated.

7. MARKETING AUTHORISATION HOLDER

Waymade PLC t/a Sovereign Medical

Sovereign House

Miles Gray Road

Basildon

Essex

SS14 3FR

United Kingdom

MARKETING AUTHORISATION NUMBER(S)

PL 06464/1022

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16^th August 2001

10 DATE OF REVISION OF THE TEXT

05/03/2009