Xten

Xten is indicated for the symptomatic treatment of the following painful inflammatory and degenerative disorders of the musculoskeletal system:

Rheumatoid arthritis.

Osteoarthritis.

Arthrosis.

Ankylosing spondylitis.

Extra-articular disorders, e.g. tendinitis, bursitis, periarthritis of the shoulders (shoulder-hand syndrome) or hips, strains, and sprains.

Acute gout.

Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties and it also inhibits platelet aggregation. Tenoxicam inhibits prostaglandin biosynthesis. In-vitro tests of leukocyte peroxidase suggest that tenoxicam may act as a scavenger for active oxygen at the site of inflammation. Tenoxicam is a potent in-vitro inhibitor of human metalloproteinases (stromelysin and collagenase), which induce cartilage breakdown. These pharmacological effects explain, at least in part, the therapeutic benefit of Tenoxicam in the treatment of painful inflammatory and degenerative disorders of the musculoskeletal system. Tenoxicam showed no mutagenic, carcinogenic or teratogenic effects in animals. As with other prostaglandin inhibitors, renal and gastrointestinal effects, increased incidence of dystocia and delayed parturition were observed in animal safety studies.

Standard dosage : For all indications except acute gout, a daily dosage of 20 mg should be given at the same time of day. In acute attacks of gout : The recommended dose for acute attacks of gout is 40 mg once daily for two days followed by 20 mg once daily for a further five days. In the treatment of chronic disorders : The therapeutic effect of tenoxicam is evident early in treatment but there is a progressive increase in response over time. In chronic disorders, daily doses higher than 20 mg should be avoided since this would increase the frequency and intensity of unwanted reactions without significantly increasing efficacy. For patients needing long-term treatment, a reduction to a daily oral dose of 10 mg may be tried for maintenance. Special dosage instructions : In principle, the above dosage recommendations also apply to elderly patients and to patients suffering from kidney or liver disease. Because of lack of clinical experience, no dosage recommendations have so far been established for children and adolescents.

As in the case of other NSAIDs, salicylate displaces Xten from protein-binding sites and increases clearance and volume of distribution of Xten. Concurrent treatment with salicylate or other NSAIDs should be avoided because of increased risk of gastrointestinal undesirable reactions. The co-administration of some NSAIDs and methotrexate has been associated with reduced renal tubular secretion of methotrexate, higher plasma concentrations of methotrexate, and severe methotrexate toxicity. Therefore, caution should be exercised when Xten is administered concurrently with methotrexate. No clinically relevant interaction was found in the small number of patients receiving concomitant treatment with gold, penicillamine or probenecid. As Xten may decrease the renal clearance of lithium, their concomitant administration may lead to increased plasma levels and toxicity of lithium. The plasma levels of lithium should be closely monitored. As with NSAIDs in general, Xten should not be administered concurrently with K-sparing diuretics. There is a known interaction between these two classes of compounds, which may cause hyperkalemia and renal failure. No clinically significant interaction between Xten and furosemide was noted, but Xten attenuates the blood pressure-lowering effect of hydrochlorothiazide. As known from other NSAIDs, Xten might attenuate the antihypertensive effects of alpha-adrenergic blockers and ACE-inhibitors. No interactions have been reported between NSAIDs and centrally-acting alpha agonists or calcium channel blockers. There was no clinically relevant interaction when Xten was administered together with atenolol. During clinical trials no interaction was reported for patients treated concomitantly with digitalis products. Thus concurrent dosing of Xten and digoxin appears to be without major risk. No interaction has been found with concomitantly administered antacids, cimetidine, warfarin and phenprocoumon at the recommended dosages. The clinical effect of oral antidiabetic drugs (glibornuride, glibenclamide, tolbutamide) was likewise not modified by Xten. Nevertheless, careful monitoring is recommended when patients concomitantly receive anticoagulants or oral antidiabetic drugs. No clinically relevant interaction has been found between Xten and low molecular weight heparin.

Tenoxicam must not be administered to patients:

known to be hypersensitive to the drug;

in whom salicylates or other non-steroidal anti-inflammatory drugs (NSAIDs) induce symptoms of asthma, rhinitis, or urticaria;

suffering or having suffered from the disease of the upper gastrointestinal tract, such as gastritis, gastric and duodenal ulcer.

Based on clinical trials including large numbers of patients, Xten proved to be well tolerated in the recommended dose. Usually, the undesirable effects reported were mild and transient. In a small proportion of patients, the interruption of treatment due to undesirable effects was necessary. Local tolerance of Xten given parenterally was good. The following undesirable effects have been reported: Frequency is greater than 1%-

Gastrointestinal tract: gastric, epigastric and abdominal discomfort, dyspepsia, heartburn, nausea.

Central nervous system: dizziness, headache.

Frequency less than 1%-

Gastrointestinal tract: constipation, diarrhea, stomatitis, gastritis, vomiting, ulcers, Gl-bleeding including hematemesis and melena.

Central nervous system: fatigue, sleep disturbances, appetite loss, dry mouth, vertigo.

Skin: itching (also in the anal region after rectal administration), erythema, exanthema, rash, urticaria.

Urinary tract and kidneys: increase in BUN or creatinine, edema.

Liver and biliary tract: increased liver enzyme activity.

Cardiovascular system: palpitations.

Isolated cases (frequency less than 0.01%)-

Gastrointestinal tract: Gl-perforation.

Central nervous system: visual disturbances.

Skin: Stevens-Johnson and Lyell's syndrome, photosensitivity reaction, vasculitis.

Blood: anemia, agranulocytosis, leukopenia, thrombocytopenia.

Hypersensitivity reactions: dyspnea, asthma, anaphylaxis, angioedema.

Cardiovascular system: elevated blood pressure, mainly in patients treated with cardiovascular drugs.

Liver/Biliary tract: hepatitis.

NSAIDs have an inhibitory effect on prostaglandin synthesis and, when given during late pregnancy, may cause the closure of the fetal ductus arteriosus, prolong labor and delay parturition. Treatment during the third trimester of pregnancy should be avoided. Based on findings from single-dose administration, a very small amount (approximately 0.2%) of tenoxicam passes into breast milk. There is no evidence of adverse reactions in breast-fed infants of mothers taking Tenoxicam. Nevertheless, infants should be weaned or the drug discontinued.

NSAIDs inhibit renal prostaglandin synthesis and consequently may have an undesirable effect on renal hemodynamics and on salt and water balance. It is necessary to adequately monitor the patient with a special emphasis on cardiac and renal function (BUN, creatinine, development of edema, weight gain, etc.) when giving Xten to patients with conditions that could increase their risk of developing renal failure, such as pre-existing renal disease, impaired renal function in diabetics, hepatic cirrhosis, congestive heart failure, volume depletion or concomitant treatment with potentially nephrotoxic drugs, diuretics and corticosteroids. Xten inhibits platelet aggregation and may affect hemostasis. Xten has no significant influence on blood coagulation factors, coagulation time, prothrombin time or activated thromboplastin time. Patients having coagulation disorders or receiving drug therapy that interferes with hemostasis should, however, be carefully observed when Xten is administered. Any patient being treated with Xten who presents with symptoms of gastrointestinal disease should be closely monitored. If peptic ulceration or gastrointestinal bleeding occurs, Xten should be immediately withdrawn. If severe skin reactions (e.g. Lyell's or Stevens-Johnson syndrome) occur, the treatment should be discontinued immediately. Adverse eye findings have been reported with Xten. Thus ophthalmic evaluation is recommended for patients who develop visual disturbances. Because of the high plasma protein binding of Xten, caution is required when plasma albumin levels are markedly reduced. In common with anti-inflammatory drugs, Xten may mask the usual signs of infection. Xten Tablets should not be given to patients who either dislike or do not tolerate milk products.

Although there is no experience of acute overdosage with Xten, it may be expected that the signs and symptoms mentioned under Undesirable effects would be more pronounced. Overdose should be countered by conventional measures to reduce absorption (e.g. gastrolavage and charcoal) and speed up elimination (e.g. cholestyramine).

Do not store above 30°C, protect from light & moisture. Keep out of the reach of children.