Name of the medicinal product :
Brexin 20 mg Tablets and Sachets
Oualitative and quantitative composition :
Each tablet. sachet contains: Piroxicam beta cyclodextrin 191.2 mg,(equivalent to piroxicam 20 mg).
Clinical particulars :
Therapeutic Indications :
Piroxicam is indicated for sympcomatic relief of osteoarthritis, rheumatoid arthritis, or ankylosing spondilytitis. Due to its safety profile, piroxicam is not. first line option should an NSAIOs be indicated. The decision to prescribe piroxicam should be based on
an assessment of the individual patient’s overall risks
Posolgy and method administration :
The prescnption of piroxicam should be initiated by physicians with experience in the diagnostic evaluation and treatment of patients with inflammatory or degenerative rheumatic diseases The maximwn recommended daily dose is 20 mg Undesirable effects may be minimized by using the minimum effective dose for the shortest duration necessary to control symptoms. The benefit and tolerability of treatment should be reviewed within 14 days. If connnued treatment is considered necessary, this should be accompanied by frequent review. Given that piroxicam has been shown to be associated with an increased risk of gastrointestinal complications the possible need for combination therapy with gastro-protective agents (e.g.miscprostot or proton pump inhibitors) should be carefully considered, in particular for
elderly patients. Dosage and indications in children have not been established yet, In elderly patients, posology must be carefully established by ibe physiCians who have 10 consider a possible reduction of the dosage indicated above. Tablets and sachets: I tablet or I full· dose sachet (:ID mg) per day.
Hyperseasmvity to the active substance or to any of the excipients History of pstrointestinal ulceration, bleeding, perforatioa.
Patient history of gastrointestmal disorden that predispose to bleeding disorders such as ulcerative colitis, Crohn’s disease,
g&StrointesllnaJ canccn or diverticulius. Patients with gastritis., dyspepsia. severe blood changes or bemonhagic diatbc:sis. Coocomitaot use of other NSAlDs, including COX-2 selective
inhibiton and acetybalicylic: acid It analgesic doses. Coocomitant use of anticoagulanl HislOl’y of serious allergic drug reactions of any type, es:pc:cially skin reactJons such as erythema multiform, Stcveas-Johnsoo syndrome, toxic epidennal necrotysis ,porphyria, severe heart failure. Previous Wo reactions to piroxicam, other NSAlDs and Olber medications.
Known or suspected pregnancy, during lactation and in children. lbc:re is I potmtill for cross-sensitivity with acetylsalicylic acid and other NSAlDs. The product should not be given to patients in whom acetylsalicylic acid and other NSAIDs blve induced symptoms of ISthmI. rhinitis, nasal polyposis, angioedema. urticaria. The sachet dosage form contains aspartame as sweetener and therefore !be use is contrauldicated in cases of phenylketonuria.
Special warnings and precautions for use :
Undesirable effects may be minimized by using the lowest effective dose for the shonest duration necessary 10 coeeot symploms.
The clinical benefit and tolerability of the treatment should be re-evaluated periodically and treatment should be immediately discontinued at the first appearance of skin reactions or significant gastrointcstinal events.
Gastrointestinal GI effects risk of GI ulceration bleeding and perforation :
NSAlDs 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 It any time, with or without warning symptoms. in patients treated with NSAIOs. NSAID exposureofbo(h sbort and long duration carries an increased risk of serious GI events. Evidence from observational studies suggests that. compared 10 other NSAIDs, piroxicam may be associated wnb a bigh risk of serious gastrointestinal toxicity. Patients with significant risk factors for serious Gl events should be treated with piroxicam only after careful consideration
Serious GI Campligtions: Identification of risk subjects :
The risk for developing serious GI complications increases with age. Bemg aged over 70yeats is associated with a high risk of complications Admtnistration to patients older than 80 years should be avoided Patients taking ooncomill.nt oral corticosteroids,
sdttth~ tm)(Onin reuptake inhibitors (SSRls). 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 NSAIOs., the use of pinuicam in combinatioo the gastro-protective agents (e.g. misoprostol or proton pump inhibitors ) must be considmd for these at risk patients. Patients and physicians should be alert for signs and symptoms of GI ukcration andIor bleeding during puoxicam treatment Patients should be asked to report any new or unusual abdominal symptom during treatment. If a gastrointestinal complication is suspected dunng treatment, piroxicam should be discontinued unmediately and additional clinieaI evaluation and treatment should be coosidend.
Cardiovascular and cerebrovascular effects :
Suitable monitoring and instructions are necessary in patumts with positive anamnesis for hypertension and congestive bean 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 NSAIDs (especially 11 high doses and for long-term treabnent) may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are not enough data 10 exclude such a risk for piroxK:aro. Patients with uncontrolled hypertension, congestive bean
failure. Established ischemic heart disease, peripheral arterial disease andIor cerebrovascular disease should be treated with piroxicam only after careful evaluation. Similar considerations should be made before starting longterm 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 thc 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 10 acute renal failure. In this regard, elder1y 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 10 its interactions metabolism,
the drug may induct bronchospasms and possibly shock and other allergic phenomm! in asthmatic and prechsposed patients. some ocular changes have been observed dunng therapy with NSAIDs., periodic opbtbalmological examinabons arc advised during prolonged treatmenl is also advisable to frequently ched blood glucose levels in diabetic patients and prothrou:!bin time in receivina anticoagulant trutment with dicoumarol denvanves.
Serious skin reactions, some of tbem fatal, including exroliate dermatitis, Stevens-Jobnson syndrome, and toxic epidermal oecrotysis., have been reponed very rarely in association with the use of NSAlDs. Evidence from olwcrvational studies sugsests that piroxicam may be associated with higher risk of serious skin than other nonoxicam. NSAlDs Pahenls 10 be at highest risk of these reactioos early iD the course of therapy, siece most cases occur witbm the first month oftreatmcol Pvoxicam lreItrnenI should be discontinued at the first appearvtce ofskin rash, mucosal lesions, or any other sign of bypersensitiveThe use or pironcam as of any other prostaglanden inhibitor and synthesis, is not recommennded in women planning 10 start a pregnancy. The administration of piroxicam should be discontinued in women with fertility problems or undergoing fertility investigations. The tablets dosage form contatn lactose: patlenlS With rare hereditary problems of galactose mtoleranoe,lapp lactase deficiency or galactose-lactose malabsorption should not take utis drug. The sachct dosage fonn contains sorbitol: patients with rare hereditary problems of galactose intolerance lapp lactase deficiency or galactose lactose malabsorption should not take this drug.
Interactions with other medicaments and other forms of interaction :
Acetylsgljcylic acid or other NSAIDS as with other NSAIDs the use or piroxicam together with acetylsalicylic acid or concomitant use with other NSAIDs, including other piroxicam fonnulations, must be avoided, since data arc 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 ofpiroxicam and acetylsalicylic acid reduces the plasma piroxicem concennaticn to about 80 % of the usual value. Piroxicam interacts with acetylsalicylic acid, with other oon-stcroidal anti- inflammatory drugs and with platelet aggregation inhibitors.
Cortcostreoids :increased risk ofgastromtcsllnal ulceratiee or bleeding. ~NSAIDs, including piroxicam, may enhance the effects of
anticoagulants sucb as warfarin. Therefore, the use of piroxicam with anticoagulants such as warfarin should be avoided
Anti platelet agents and selective serotonin reuptake inhibitors : increased risk of gastrointestinal bleeding
Diuretics ace inhibitors and angiotensin II antagonists : NSAIDs may reduce the efficacy of diuretics and other antihypertensive drugs 10 some patiants with impaired renal
function (e.g. debydrated patients or elderly patients with impaired renal function) the coadmtnistntion of an ACE inhibitors and angiotensin antagonists and agents that inhibit the funherdeerior!tc renal function,with possible acute renal failure. which is
generally revenible. These interactions should be taken into consideration in patiants taking piroxicam togetber with ACE-inhibitors and angiotensin
displacemenl of other protem bound drugs can be expected. Patients receiving piroxicam with other-highly protein bound drugs must be closely monitored by the doctor, in order 10 adjust dosage if necessary. Piroxicam absoIption was slightly increased after cimetidine administration. However, use increase did not prove to be chlically significant.therapy ofpiroxicam with digoxin or digitoxin affect the plasma levels of either drug.s phenytoin. PatiCllts must be
monitored closely for change in dosage requirements when gIving Bream to pauents already receiving other highly protein bound drugs. intrauterine devices. Amjno glyco.tjdq·reduction in renal function in susttptible individuals decreased elimination or aminoglycosides and increased plasma concentrations have been reponed. ~reduction in metabolism and elimination ofNSAID and metabolites occurs with probenicid. Oral hypgglycemk gerntr’inhibition of metabolism of sulfonylurea drugs., prolonged hllf-Iife and increased risk: ofhypoglycemia is known to occur with oral hypoglycemic agents.
Pregnancy and lactation :
Piroxicam is contraindicated during ascertained or suspected pregnancy and during breast feeding. Pregnancy: inhibition of prosuglandio synthesis can adversely affect pregnancy and /or embryo/foetal development Results from epidemiological studies suggest ID increased risk of miscarriage, cardiac malfonnation and gastroschi.sis Ifter use of a prostaglandin synthesis inhibttor dunn& early pregnmcy nevertheless the absolute risk of cardiac malformations increased &om less than 1 % up to approximately 1.5 %. It was considered that the risk is dose-retaled and also increases with duration of therapy. In animals, the adnumstration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation losses and in embryolfoetal mortality. Moreover, an increased incidence of Various malformations, lDCludingcardiovascular malfonnatioa, was reported in animals given prostaglandin synthesis inhibitors during organogeocsis During the third trimester of pregnancy, all prostaglandin syntbesis inhibiton can expose fetuses to cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension Renal dysfunction, that
can lead to renal failure with oligo-hydroamniosis, both mother and baby, It the end of pregnancy to: Possible prolongalion of bleeding time and anti aggergating effect that can even occur with very low doses. Inhibition of uterine contractions resulting In delayed or prolonged labour.
produced by :
El nile co for pharmaceuticals and chemical industries cairo a.r.e