Biostymina

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see DOSAGE AND ADMINISTRATION and the risks related to the GI tract and cardiovascular system below). If treatment proves ineffective, therapy should be discontinued. Concomitant use of nimesulide with other NSAIDs, including selective COX-2 inhibitors, should be avoided. During treatment with Nimesil, patients should be advised to refrain from using other analgesics. Nimesil contains sucrose. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicinal product. During treatment with nimesulide, concomitant use of hepatotoxic drugs should be avoided and alcohol consumption should be avoided. The use of NSAIDs may mask fever associated with an underlying bacterial infection. Effects on the liver. Serious hepatic reactions associated with the use of nimesulide have been rarely reported, including very rarely fatal cases (see ADVERSE REACTIONS). Patients who develop symptoms suggestive of liver injury during nimesulide therapy, such as anorexia, nausea, vomiting, abdominal pain, fatigue, or dark urine, or patients whose liver function laboratory tests deviate from normal values, should discontinue therapy. Such patients should not be re-administered nimesulide. Hepatic injury, in most cases reversible, has been reported after short-term exposure to the medicinal product. Patients taking nimesulide who develop fever and/or flu-like symptoms should discontinue treatment. Effects on the GI tract. Gastrointestinal bleeding, ulceration, or perforation (with or without warning symptoms or a history of serious GI events) have been reported with all NSAIDs and may be fatal, occurring at any time during treatment. The risk of gastrointestinal bleeding, ulceration, or perforation increases with increasing NSAID doses, in patients with a history of ulcer, particularly when complicated by hemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. Treatment should be initiated at the lowest possible dose in such patients. Combination therapy with protective agents such as misoprostol or proton pump inhibitors should be considered for these patients and for those requiring concomitant use of low-dose acetylsalicylic acid or other medications that increase the risk of GI complications (see below and INTERACTIONS). Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly during the early stages of treatment. GI bleeding, ulceration, or perforation may occur at any time during treatment with or without warning symptoms or a history of GI events. If GI bleeding or ulceration occurs, nimesulide should be discontinued. Nimesulide should be used with caution in patients with GI disorders, including a history of peptic ulcer, gastrointestinal bleeding, ulcerative colitis, or Crohn's disease (see ADVERSE REACTIONS). Patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents such as acetylsalicylic acid, should be informed of the need to exercise caution. If GI bleeding or ulceration occurs in patients receiving nimesulide, treatment should be discontinued. NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as exacerbation may occur (see ADVERSE REACTIONS). Concomitant use of nimesulide with other medicinal products such as oral contraceptives, anticoagulants, and antiplatelet agents may cause exacerbation of Crohn's disease and other gastrointestinal disorders. Effects on the cardiovascular and cerebrovascular systems. Patients with a history of hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and medical advice, as fluid retention and edema have been reported in association with NSAID therapy. Clinical studies and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and with long-term treatment, may be associated with a small increase in the risk of arterial thrombotic events, such as myocardial infarction or stroke. There are insufficient data to exclude such a risk for nimesulide. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with nimesulide only after careful assessment. A similar assessment should be conducted before initiating long-term treatment in patients with cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, and smoking. Since nimesulide may affect platelet function, it should be used with caution in patients with hemorrhagic diathesis (see also CONTRAINDICATIONS). However, Nimesil cannot substitute for acetylsalicylic acid in the prevention of cardiovascular disease. Effects on the kidneys. Patients with renal impairment or heart failure should exercise caution, as the use of nimesulide may lead to deterioration of renal function. In such cases, treatment should be discontinued (see also INTERACTIONS). Elderly patients. Elderly patients may experience an increased frequency of adverse reactions to NSAIDs, particularly GI bleeding and perforation, which in some cases may be fatal (see ADVERSE REACTIONS), as well as impaired renal, cardiac, and hepatic function; therefore, appropriate clinical monitoring is recommended. Skin reactions. Very rarely, serious skin reactions, some of which are life-threatening, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs (see ADVERSE REACTIONS). Patients appear to be at highest risk for these reactions early in the course of therapy, with the majority of cases occurring within the first month of treatment. Nimesulide should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity. Fixed drug eruption (FDE) has been reported with the use of nimesulide. Nimesulide should not be re-administered to patients with a history of nimesulide-associated FDE (see ADVERSE REACTIONS). Effects on fertility. The use of Nimesil may impair female fertility and is not recommended for women planning pregnancy. Women who have difficulty conceiving or who are undergoing investigation for infertility should consider discontinuation of Nimesil (see Use during pregnancy or breastfeeding). Use during pregnancy or breastfeeding Pregnancy. The use of nimesulide is contraindicated during the third trimester of pregnancy (see CONTRAINDICATIONS). Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Data from epidemiological studies suggest that in early pregnancy, the use of prostaglandin synthesis inhibitors may increase the risk of miscarriage and cardiac malformations and gastroschisis in the fetus. The absolute risk of cardiovascular malformation increases from less than 1% to approximately 1.5%. The risk is believed to increase with higher doses and longer duration of therapy. In animals, administration of prostaglandin synthesis inhibitors resulted in increased pre- and post-implantation losses and increased embryo/fetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, was reported in animals receiving prostaglandin synthesis inhibitors during the period of organogenesis. The use of nimesulide from gestational week 20 may cause oligohydramnios due to fetal renal dysfunction. This may be observed shortly after treatment initiation and is usually reversible upon discontinuation. In addition, cases of constriction of the ductus arteriosus in the fetus have been reported following administration during the second trimester, most of which resolved after treatment discontinuation. Therefore, nimesulide should not be used during the first and second trimesters unless strictly necessary. If nimesulide is used by women attempting to conceive, or during the first and second trimesters, the lowest possible dose and shortest possible duration of treatment should be used. Antenatal monitoring for oligohydramnios and constriction of the ductus arteriosus should be considered following nimesulide exposure for several days from gestational week 20 onward. Nimesulide should be discontinued in pregnant women if oligohydramnios or constriction of the ductus arteriosus is detected. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to: • pneumocardial toxic effects (premature constriction/closure of the ductus arteriosus and pulmonary hypertension); • renal dysfunction, which may progress to renal failure with development of oligohydramnios (see above); The mother at the end of pregnancy and the neonate may experience: • prolongation of bleeding time, an antiplatelet effect that may occur even at very low doses; • inhibition of uterine contractions, resulting in delayed or prolonged labor. Breastfeeding. It is not known whether nimesulide is excreted in human breast milk. Nimesulide is contraindicated during breastfeeding (see CONTRAINDICATIONS and Preclinical safety data). Fertility. As with other NSAIDs, nimesulide-containing medicinal products are not recommended for women attempting to conceive (see SPECIAL WARNINGS AND PRECAUTIONS). Women who have difficulty conceiving or who are undergoing investigation for infertility should discontinue nimesulide. If pregnancy is established during nimesulide use, the physician should be informed. Children. Nimesil is contraindicated in children under 12 years of age. Ability to drive and use machines. No studies on the effects of nimesulide-containing medicinal products on the ability to drive vehicles or operate machinery have been conducted; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving vehicles or operating machinery.