||Hypersensitivity to the active substance or to any of the excipients
* History of gastrointestinal ulceration, bleeding, perforation.
* Patient history of gastrointestinal disorders that predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancers or diverticulitis.
Patients with gastritis, dyspepsia, severe blood changes or hemorrhagic diathesis. Concomitant use of other NSAID´s, including COX-2 selective inhibitors and acetylsalicylic acid at analgesic doses.
Concomitant use of anticoagulant. History of serious allergic drug reactions of any type, especially skin reactions such as erythema multiform, Stevens Johnson syndrome, toxic epidermal necrolysis. Porphyria, severe heart failure. Previous skin reactions (regardless of severity) to piroxicam, other NSAID's and other medications. Known or suspected pregnancy, during lactation and in children. There is a potential for cross-sensitivity with acetylsalicylic acid and other NSAID’s. The product should not be given to patients in whom acetylsalicylic acid and other NSAID's have induced symptoms of asthma, rhinitis, nasal polyposis, angioedema, urticaria. The sachet dosage form contains aspartame as sweetener and therefore their use is contraindicated in cases of phenyl ketonuria.
||Gastrointestinal (GI) effects, risk of GI ulceration, bleeding and perforation:
NSAID´s including piroxicam can cause serious gastrointestinal events including bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAID´s.
NSAID exposure of both short and long duration carries an increased risk of serious GI events. Evidence from observational studies suggests that, compared to other NSAIDs, piroxicam may be associated with a high risk of serious gastrointestinal toxicity. Patients with significant risk factors for serious GI events should be treated with piroxicam only after careful consideration.
Serious GI Complications: Identification of at-risk subjects :
The risk for developing serious GI complications increases with age. Being aged over 70 years is associated with a high risk of complications. Administration to patients older than 80 years should be avoided. Patients taking concomitant oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs), anticoagulants such as warfarin or anti-platelet agents such as low-dose acetylsalicylic acid are at increased risk of serious GI complications. As with other NSAIDs, the use of piroxicam in combination with gastro-protective agents (e.g. misoprostol or proton pump inhibitors) must be considered for these at-risk patients.
Patients and physicians should be alert for signs and symptoms of GI ulceration and or bleeding during piroxicam treatment. Patients should be asked to report any new or unusual abdominal symptom during treatment. If a gastrointestinal complication is suspected during treatment, piroxicam should be discontinued immediately and additional clinical. Evaluation and alternative treatment should be considered.
Cardiovascular and cerebrovascular effects :
Suitable monitoring and instructions are necessary in patients with positive anamnesis for hypertension and congestive heart failure, as water retention and edema have been reported in association with NSAID treatment .Clinical studies and epidemiological data indicate that the use of some NSAlDs (especially at high doses and for long-term treatment) may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are not enough data to exclude such a risk for piroxicam. Patients with uncontrolled hypertension, congestive heart failure. Established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with piroxicam only after careful evaluation. Similar considerations should be made before starting long term treatment in patients with risk factors for cardiovascular diseases (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking). Piroxicam reduces platelet aggregation and prolongs bleeding time; this characteristic must be taken into account when blood tests are performed and when the patient is concomitantly treated with other platelet aggregation inhibitors. Patients with impaired renal function should be periodically monitored, as in such patients the inhibition of prostaglandin synthesis caused by piroxicam may result in a severe decrease in renal perfusion that may lead to acute renal failure. In this regard, elderly patients and patients treated with diuretics should be considered as at risk. Caution should also be paid in patients with impaired hepatic function. It is advisable to monitor their clinical and laboratory parameters especially in case of prolonged treatment. Due to its interactions metabolism, the drug may induce bronchospasms and possibly shock and other allergic phenomena in asthmatic and predisposed patients.
As some ocular changes have been observed during therapy with NSAIDs, periodic ophthalmological examinations are advised during prolonged treatment. It is also advisable to frequently check blood glucose levels in diabetic patients and prothrombin time in patients concomitantly receiving anticoagulant treatment with dicoumarol derivatives.
Skin reactions: 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. Evidence from observational studies suggests that piroxicam may be associated with a higher risk of serious skin reactions than other nonoxicam NSAIDs .Patients appear to be at highest risk of these reactions early in the course of therapy, since most cases occur within the first month of treatment. Piroxicam treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
The use of piroxicam, as of any other prostaglandin synthesis and cyclo-oxygenase inhibitor, is not recommended in women planning to start a pregnancy.The administration of piroxicam should be discontinued in women with fertility problems or undergoing fertility investigations. The tablet and sachets dosage forms contain lactose: patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.The sachet dosage form contains sorbitol: patients with rare hereditary problems fructose intolerance should not take this drug .
Interactions with other medicaments and other forms of interaction:
Acetylsalicylic acid or other NSAIDs. As with other NSAIDs. The use of piroxicam together with acetylsalicylic acid or concomitant use with other NSAIDs, including other piroxicam formulations, must be avoided, since data are inadequate to show that such combinations produce greater improvement than that achieved with piroxicam alone; moreover. The potential for adverse reactions is increased. Human studies have shown that concomitant use of piroxicam and acetylsalicylic acid reduces the plasma piroxicam concentration to about 80 % of the usual value. Piroxicam interacts with acetylsalicylic acid, with other non-steroidal anti-inflammatory drugs and with platelet aggregation inhibitors. Corticosteroids: increased risk of gastrointestinal ulceration or bleeding. Anticoagulants: NSAIDs, including piroxicam, may enhance the effects of anticoagulants such as warfarin. Therefore, the use of piroxicam with anticoagulants such as warfarin should be avoided Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding. Diuretics, ACE-inhibitors and angiotensin II antagonists: NSAIDs may reduce the efficacy of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function, the co administration of an ACE-inhibitors and angiotensin II antagonists and agents that inhibit the cyclo-oxygenase system, may further deteriorate renal function, with possible acute renal failure, which is generally reversible. These interactions should be taken into consideration in patients taking piroxicam together with ACE-inhibitors and angiotensin II antagonists. The combination should therefore be administered with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitoring should be considered after starting concomitant therapy. In case of concomitant intake of potassium-containing drugs, or diuretics that cause potassium retention, there is an additional risk of a rise in serum potassium concentration (hyperkalemia). Lithium: Concomitant administration of lithium and NSAIDs causes an increase in plasma lithium levels. Piroxicam is highly protein bound and therefore displacement of other protein bound drugs can be expected. Patients receiving piroxicam with other-highly protein bound drugs must be closely monitored by the doctor, in order to adjust dosage if necessary. Piroxicam absorption was slightly increased after cimetidine administration. However, this increase did not prove to be clinically significant .Alcohol intake should be avoided. Cardiac glycoside: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycosides levels; concomitant administration of antacids had no effect on piroxicam with digoxin or digitoxin affects the plasma levels or either drug. Sulphonamides and hydantoins : piroxicam is highly protein bound drugs e.g.anticoagulants,sulphonamides,and hydantoins such as phenytoin. Patients must be monitored closely for change in dosage requirements when giving Brexin to patients already receiving other highly protein bound drugs. Quinolone antibiotics: animal data indicate NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions. Mifepristone : in common with other NSAIDs, piroxicam should be avoided for at least 8 to 12 following mifepristone administration as NSAIDs can reduce the effect of mifepristone. Methotrexate : there is decreased elimination of methotrexate with NSAIDs . Ciclosporin : may increase ciclosporin nephrotoxicity as a result of their effect on renal prostaglandins. Piroxicam may reduce the efficacy of intrauterine devices. Concomitant use of NSAIDs and quinolone drugs are not recommended. Amino glycosides: reduction in renal function in susceptible individuals decreased elimination of aminoglycosides and increased and plasma concentrations have been reported. Probenicid: reduction in metabolism and elimination of NSAID and metabolites occurs with probenicid. Oral hypoglycemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia is known to occur with oral hypoglycemic agents.