Bronchisan fix

Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see DOSAGE AND ADMINISTRATION and gastrointestinal and cardiovascular risks 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 medicinal products should be avoided and alcohol consumption should be refrained from. The use of NSAIDs 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 fatal outcome (see ADVERSE REACTIONS). Patients who develop symptoms consistent with liver injury during treatment with nimesulide, 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-exposed to nimesulide. Hepatic injury, in most cases reversible, has been reported following short-term exposure to the medicinal product. Patients using 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), which may be fatal, has been reported during treatment with any NSAID and may occur 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 if complicated by haemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. Such patients should commence treatment at the lowest possible dose. For these patients, as well as those requiring concomitant low-dose acetylsalicylic acid or other medicinal products 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 the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during the initial stages of treatment. Gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, with or without warning symptoms or a 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 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 advised to exercise caution. If gastrointestinal bleeding or ulceration occurs in patients receiving nimesulide, treatment should be discontinued. NSAIDs should be prescribed with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as exacerbation of these conditions 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 oedema 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 for nimesulide. Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with nimesulide after careful assessment. Similar assessment should be conducted before initiating long-term treatment of patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidaemia, diabetes mellitus, and smoking. As nimesulide may affect platelet function, it should be used with caution in patients with haemorrhagic diathesis (see also CONTRAINDICATIONS). However, Nimesil cannot replace acetylsalicylic acid for cardiovascular prophylaxis. Effects on the kidneys. Caution is required in patients with renal impairment or heart failure, 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 have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal in some cases (see ADVERSE REACTIONS), as well as renal, cardiac, and hepatic impairment; therefore, appropriate clinical monitoring is recommended. Skin reactions. Very rarely, serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with NSAID use (see ADVERSE REACTIONS). Patients appear to be at the highest risk of 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. Cases of fixed drug eruption (FDE) have been reported with the use of nimesulide. Nimesulide should not be re-administered 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/foetal development. Data from epidemiological studies suggest that the use of prostaglandin synthesis inhibitors in early pregnancy may increase the risk of miscarriage and of cardiac malformations and gastroschisis in the foetus. The absolute risk of cardiovascular malformation increases from less than 1% to approximately 1.5%. The risk is believed to increase with increasing dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor resulted in increased pre- and post-implantation losses and increased embryo/foetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, was reported in animals receiving a prostaglandin synthesis inhibitor during the period of organogenesis. The use of nimesulide from week 20 of pregnancy onward may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. In addition, cases of ductal constriction have been reported following administration in the second trimester of pregnancy, most of which resolved upon treatment discontinuation. Therefore, nimesulide should not be taken during the first and second trimesters of pregnancy unless strictly necessary. If nimesulide is used by women attempting to conceive, or during the first and second trimesters of pregnancy, the lowest possible dose and the shortest possible duration of treatment should be used. Antenatal monitoring for oligohydramnios and ductal constriction should be considered following exposure to nimesulide for several days from gestational week 20 onward. Pregnant women should discontinue nimesulide if oligohydramnios or ductal constriction is detected. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: • cardiopulmonary toxicity (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: • prolonged bleeding time, an antiplatelet effect that may occur even at very low doses; • inhibition of uterine contractions, resulting in delayed or prolonged labour. 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, medicinal products containing nimesulide 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. Effects on ability to drive and use machines. No studies on the effects of medicinal products containing nimesulide on the ability to drive or use machines have been performed; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving or operating machinery.