Տենոկսին (Տենոկսիկամ)

Anti-inflammatory and antirheumatic products, non-steroids. Oxicams. Tenoxicam. ATC code: M01AC02 Mechanism of action The active substance of Tenoxin, tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, antipyretic properties, which also inhibits platelet aggregation. Tenoxicam reduces the biosynthesis of prostaglandins by inhibiting cyclooxygenase-1 (COX-1) and 2 (COX-2), both in vitro (sheep semen) and in vivo (protection against arachidonic acid-induced muscle toxicity). In vitro investigation of cyclooxygenase isoenzymes derived from human COS-7 cells has shown that tenoxicam inhibited COX-1 and COX-2 isoenzymes to approximately the same degree, i.e. the COX2 / COX-1 ratio is equal to 1.34. In vitro leukocyte peroxidase tests show that tenoxicam may neutralize active oxygen in the area of inflammation.  Tenoxin is a potent in vitro inhibitor of human metalloproteinases (stromelysin and collagenase) that cause cartilage cleavage. A further possible mechanism of action is the reduction of nitrite levels suggesting a change in the nitric oxide (NO) pathway. These pharmacological actions explain, at least in part, the therapeutic benefit of tenoxicam in the treatment of painful inflammatory and degenerative diseases of the musculoskeletal system. Clinical efficacy and safety The clinical efficacy of tenoxicam has been demonstrated in clinical trials for: − Rheumatoid arthritis: a dose of 20 or 40 mg once daily has been shown to be effective and the effect is maintained for up to two years. − Osteoarthritis: Tenoxicam is effective in treating osteoarthritis. The anti-inflammatory and analgesic effects are maintained for up to three years. − Ankylosing spondylitis: Clinical studies have shown that tenoxicam is effective in relieving pain and inflammation comparable to piroxicam. − Extra-articular syndromes: Tenoxicam (20mg once daily) was at least as effective as piroxicam (20mg daily) and diclofenac (75mg daily). Tenoxicam was better tolerated than diclofenac. − Acute gout: Although the database is small, all available studies suggest that tenoxicam is effective in treating acute gout, reducing pain and inflammation. The effect is at least partially dose dependent. − Postoperative pain: In placebo-controlled studies, tenoxicam treatment has been shown to be effective. − Primary dysmenorrhea: controlled clinical trials have shown that tenoxicam is effective in relieving the pain of dysmenorrhea. The effect increased over time. Tenoxicam was at least as effective as ibuprofen, a common drug used to treat primary dysmenorrhea.

Each vial contains 20mg tenoxicam as lyophilized sterile powder for reconstitution. Each ampoule of solvent contains 2 ml of water for injection. Excipients with known effect: each vial contains 2 mg of sodium metabisulfite.

Tenoxin is indicated for the symptomatic treatment of the following painful inflammatory and degenerative disorders of the musculoskeletal system: - rheumatoid arthritis - osteoarthritis - ankylosing spondylitis, other seronegative vertebral diseases - painful extra-articular syndromes, such as tendonitis, bursitis, periarthritis of the shoulder (arm syndrome) - acute gout - postoperative pain - primary dysmenorrhea

Tenoxin is contraindicated in patients: - with hypersensitivity to tenoxicam - in which salicylic or alkaline NSAIDs cause symptoms of asthma, rhinitis or urticaria - with active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding), ulcerative colitis, Crohn’s disease, severe gastritis, or history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. - who are going to undergo anesthesia or surgery in the next 48 hours. - with severe heart failure, hepatic failure and renal failure. - in the last trimester of pregnancy

During clinical trials involving a large number of patients, the product proved to be well recovered at the recommended dose. The side effects reported were usually mild and transient. In a small percentage of patients discontinuation of treatment was necessary due to adverse reactions. The most commonly observed NSAID-related adverse events are of a gastrointestinal nature. Peptic ulcers, perforation or gastrointestinal bleeding may occur, sometimes fatal, especially in elderly patients. Nausea, vomiting, diarrhea, flatulence, constipation, indigestion, blackheads, hematemesis, ulcerative stomatitis, worsening of colitis and Chron's disease have been reported after NSAID administration. Gastritis is less common. The adverse reactions listed below are defined using the following MedDRA convention and system organ class database: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1.000 to < 1/100); rare (≥ 1/10.000 to < 1/1.000); very rare (< 1/10.000), not known (cannot be estimated from the available data).  Description of selected adverse reactions Vascular disorders Clinical trials and epidemiological data suggest that use of selective cyclooxygenase-2 inhibitors   (COX2 inhibitors) 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). Also, tenoxicam has not shown to increase thrombotic events such as myocardial infarction, there are insufficient data to exclude such a risk with tenoxicam. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization 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 the national reporting system.

Alcohol: There is no significant pharmacodynamic interaction between Tenoxin and alcohol. Anticoagulants: Tenoxicam is highly bound to serum albumin, and can, as with all NSAIDs, enhance the effects of anticoagulants such as warfarin. Close monitoring of the effects of anticoagulants and oral glycaemic agents is advised, especially during the initial stages of treatment with Tenoxin. No interaction with digoxin has been observed. In healthy subjects no clinically relevant interaction between Tenoxin and low molecular weight heparin has been observed. Αntacids and H2-receptor antagonists: No clinically significant interaction has been observed with co-administration of antacids and cimetidine at the recommended dosages. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding. Antihypertensives: Tenoxicam and other NSAIDs can reduce the effects of anti-hypertensive drugs.  Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides. Cholestyramine: Cholestyramine may increase clearance and reduce the half-life of tenoxicam. Ciclosporin: As with all NSAIDs caution is advised when ciclosporin is coadministered because of the increased risk of nephrotoxicity. Cimetidine: No interaction has been found with concomitantly administered cimetidine. Corticosteroids: As with all NSAIDs, caution should be taken when co-administering corticosteroids because of the increased risk of GI ulceration or bleeding . Dextromethorphan: Co-administration of tenoxicam and dextromethorphan may increase the analgesic effect compared to monotherapy. Diuretics: Reduced diuretic effect. Non-steroidal anti-inflammatory drugs 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. These properties 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. Food: The degree of absorption of tenoxicam is not affected by food but the rate of absorption (Cmax) may be slower in the fasting state. Lithium: Non-steroidal anti-inflammatory drugs have been reported to decrease elimination of lithium. 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: Caution is advised where methotrexate is given concurrently because of possible enhancement of its toxicity, since NSAIDs have been reported to decrease elimination of methotrexate. Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone. NSAIDs, cyclooxygenase-2 selective inhibitors, salicylates: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects. Salicylates can displace tenoxicam from protein-binding sites and so increase the clearance and volume of distribution of Tenoxin. Concurrent treatment with salicylates or other non-steroidal antiinflammatory drugs should therefore be avoided because of the increased risk of adverse reactions (particularly gastro-intestinal). Oral antidiabetics: The clinical effect of the oral antidiabetic drugs glivornuride, glivenclamide, tolbutamide was not altered by the product. However, as with other NSAIDs, careful monitoring of patients receiving concomitant oral antidiabetic drugs is recommended. Penicillamine and parenteral gold: No clinically relevant interaction was found in small numbers of patients receiving treatment with penicillamine or parenteral gold. Pentoxyphylline: Co-administered with tenoxicam and dextromethorphan may increase analgesic effect compared with monotherapy. Probenecid: Co-administration of probenecid and tenoxicam may increase plasma concentrations of tenoxicam. The clinical significance of this observation has not been determined. Quinolones: 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. 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 positive haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Patients with NSAID overdose are generally asymptomatic. Overdose with NSAIDs causes only mild disorders of the central nervous and gastrointestinal systems, such as nausea and vomiting, epigastric pain, rarely diarrhea, gastrointestinal bleeding, tinnitus. headache, drowsiness, blurred vision and dizziness. Worsening of asthma is likely to occur. There have been isolated reports of more severe toxicity after ingestion of significant amounts. This included convulsions, coma and kidney failure. Cardiorespiratory arrest may also occur. Hepatic impairment, hypothrombinemia, and metabolic acidosis have also been reported. In case of overdose, appropriate supportive treatment is indicated and discontinuation of the drug, antacids and proton pump inhibition may also be indicated. There is no specific antidote. Dialysis does not significantly eliminate NSAIDs from the bloodstream.

Posology Adults For all indications, apart from primary dysmenorrhea, postoperative pain and acute gout, a single daily dose of 20mg should be administered at the same time each day. The recommended dose for primary dysmenorrhea is 20 to 40 mg once daily. For postoperative pain, the recommended daily dose is 40mg once daily. The administration period must not exceed five days. For acute gout, the recommended dose is 40mg once daily for two days, followed by 20mg once daily for the next five days. Where required, treatment may be initiated by intravenous or intramuscular administration once every one or two days and continued orally. In the treatment of chronic conditions, the therapeutic effect of tenoxicam is evident from the beginning of treatment and there is a progressive increase in response over time. In chronic conditions, daily doses greater than 20 mg are not recommended, as this would increase the frequency and severity of side effects without significantly increasing effectiveness. For patients in need of long-term treatment, a reduction in the daily oral dose to 10 mg may be tried for maintenance. Side effects can be minimized by using the lowest effective dose for the shortest duration of treatment required to control symptoms. Special population Patients with mild to moderate renal/hepatic impairment Side effects can be minimized by using the lowest effective dose for the shortest duration of treatment required to control symptoms. Elderly  The elderly are at increased risk of side effects with serious consequences. If the use of NSAIDs is considered necessary, the lowest effective dose should be given for the shortest possible duration. During NSAID treatment, the patient should be monitored regularly for possible gastrointestinal bleeding. Children There are insufficient data to make a recommendation for administration of Tenoxin to children. Method of administration The lyophilized powder in the vials should be dissolved in the solvent in the package (2ml distilled water for injection). The reconstituted solution should be administered immediately intravenously or intramuscularly.

Store at temperature below 25˚C. Protect from light