Boldaloin

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see DOSAGE AND ADMINISTRATION, and risks related to the gastrointestinal and cardiovascular systems 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 therapy 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 agents should be avoided and alcohol consumption should be avoided. NSAID use may mask fever associated with an underlying bacterial infection. Effects on the liver. Serious hepatic reactions associated with nimesulide use have been reported rarely, including very rare cases with a fatal outcome (see ADVERSE REACTIONS). Patients who develop symptoms suggestive of liver injury during nimesulide treatment, such as anorexia, nausea, vomiting, abdominal pain, fatigue, or dark urine, or patients whose liver function test results deviate from normal values, should discontinue therapy. Such patients should not be re-prescribed nimesulide. Liver injury, in most cases reversible, has been reported following short-term exposure to the medicinal product. Patients taking nimesulide who develop fever and/or flu-like symptoms should discontinue treatment. Effects on the gastrointestinal tract. Gastrointestinal bleeding, ulceration, or perforation (with or without warning symptoms or a history of serious gastrointestinal events) have been reported and may be fatal, occurring at any time during treatment with any NSAID. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of ulcer disease, especially when complicated by hemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. Such patients should initiate treatment at the lowest possible dose. For these patients, as well as those requiring concomitant low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, combination therapy with protective agents such as misoprostol or proton pump inhibitors should be considered (see below and INTERACTIONS). Patients with a history of gastrointestinal toxicity, particularly elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during the early stages of treatment. Gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without warning symptoms or prior history of gastrointestinal events. If gastrointestinal bleeding or ulceration occurs, nimesulide should be discontinued. Nimesulide should be used with caution in patients with gastrointestinal disorders, including a history of peptic ulcer, gastrointestinal bleeding, ulcerative colitis, or Crohn's disease (see ADVERSE REACTIONS). Patients receiving 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 advised to exercise caution. If gastrointestinal bleeding or ulceration occurs in patients receiving nimesulide, treatment should be discontinued. NSAIDs should be prescribed with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as exacerbation is possible (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 consultation, 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 increased risk of arterial thrombotic events such as myocardial infarction or stroke. There are insufficient data to exclude such a risk with 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. Similar assessment should be conducted before initiating long-term treatment in patients with cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, or 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 acetylsalicylic acid in the prevention of cardiovascular disease. Effects on the kidneys. Patients with renal impairment or heart failure should exercise caution, as nimesulide use 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 gastrointestinal bleeding and perforation, which in some cases may be fatal (see ADVERSE REACTIONS), as well as impairment of renal, cardiac, and hepatic function; therefore, appropriate clinical monitoring is recommended. Skin reactions. Very rarely, serious skin reactions, some of which are life-threatening, have been reported, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, associated with the use of NSAIDs (see ADVERSE REACTIONS). Patients appear to be at highest risk for such reactions early in the course of therapy, with most 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. Cases of fixed drug eruption (FDE) have been reported with the use of nimesulide. Nimesulide should not be re-prescribed to patients with a history of nimesulide-related 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 discontinuing 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 early in pregnancy, the use of prostaglandin synthesis inhibitors may increase the risk of miscarriage and of 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 led to increased pre- and post-implantation losses and increased embryo/fetal mortality. In addition, increased incidences of various malformations, including cardiovascular, were reported in animals receiving prostaglandin synthesis inhibitors during the period of organogenesis. Use of nimesulide from the 20th week of pregnancy may cause oligohydramnios resulting from fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. In addition, cases of fetal ductal constriction have been reported following use during the second trimester of pregnancy, most of which resolved after cessation of treatment. Therefore, nimesulide should not be taken during the first and second trimesters of pregnancy unless clearly necessary. If nimesulide is used by women attempting to conceive, or during the first and second trimesters of pregnancy, the lowest possible dose and shortest possible duration of treatment should be used. Antenatal monitoring for oligohydramnios and fetal ductal constriction should be considered when exposure to nimesulide occurs for several days from the 20th gestational week onward. Pregnant women should discontinue nimesulide if oligohydramnios or fetal ductal constriction is detected. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may cause the following in the fetus: • pneumocardiac 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); In the mother at the end of pregnancy and in the neonate: • 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 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 performed; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving vehicles or operating machinery.