Boldovera

Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see DOSAGE AND ADMINISTRATION, and risks relating 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 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 medicinal products should be avoided and alcohol consumption should be discouraged. 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 reported rarely, including very rare cases with a fatal outcome (see ADVERSE REACTIONS). Patients who develop symptoms suggestive of hepatic 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-administered nimesulide. Hepatic injury, in most cases reversible, has been reported after short-term exposure to the medicinal product. Patients receiving nimesulide who develop fever and/or influenza-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, have been reported at any time during treatment with all NSAIDs. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of ulcer disease, particularly when complicated by haemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. Such patients should commence treatment at the lowest possible dose. Combination therapy with protective agents, such as misoprostol or proton pump inhibitors, should be considered for these patients and for those who require concomitant use of low-dose acetylsalicylic acid or other medicinal products that increase the risk of gastrointestinal complications (see below and INTERACTIONS). Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially 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 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 medicinal products 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, or antiplatelet agents may cause exacerbation of Crohn's disease and other gastrointestinal disorders. Cardiovascular and cerebrovascular effects. 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 during 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 ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with nimesulide only after careful assessment. A similar assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus, or 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 in cardiovascular prophylaxis. Effects on the kidneys. Caution is required in patients with renal impairment or heart failure, 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 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 impairment of renal, cardiac, and hepatic function; appropriate clinical monitoring is therefore 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 NSAID use (see ADVERSE REACTIONS). Patients appear to be at highest risk for these reactions early in the course of treatment, with the majority of cases occurring within the first month of therapy. Nimesulide should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Cases of fixed drug eruption (FDE) have been reported with 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 in women planning to conceive. 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-foetal development. Data from epidemiological studies suggest that use of prostaglandin synthesis inhibitors during early pregnancy may increase the risk of miscarriage and of foetal cardiac malformations and gastroschisis. The absolute risk of cardiovascular anomaly increases from less than 1% to approximately 1.5%. The risk is considered 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-foetal mortality. Furthermore, in animals receiving prostaglandin synthesis inhibitors during the period of organogenesis, an increased incidence of various foetal malformations, including cardiovascular malformations, was reported. Use of nimesulide from the 20th week of pregnancy onwards may cause oligohydramnios as a result of foetal renal dysfunction. This may occur shortly after the start of treatment and is usually reversible upon discontinuation of the medicinal product. In addition, cases of constriction of the ductus arteriosus have been reported following use of the medicinal product during the second trimester of pregnancy, most of which resolved upon discontinuation of treatment. Therefore, nimesulide should not be taken during the first and second trimester of pregnancy unless strictly necessary. If nimesulide is used by women attempting to conceive or during the first and second trimester of pregnancy, 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 if nimesulide exposure occurs over several days from gestational week 20. Pregnant women should discontinue nimesulide if oligohydramnios or constriction of the ductus arteriosus is found. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may cause the foetus to develop: • pneumocardial toxic injury (premature constriction/closure of the ductus arteriosus and pulmonary hypertension); • renal dysfunction, which may progress to renal failure with the development of oligohydramnios (see above); In the mother at the end of pregnancy and in the neonate: • prolongation of bleeding time, an antiplatelet effect which may occur even at very low doses; • inhibition of uterine contractions, leading to delayed or prolonged labour. Breastfeeding. It is not known whether nimesulide is excreted into 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 PRECAUTIONS). Women who have difficulty conceiving or who are undergoing investigation for infertility should discontinue nimesulide. If pregnancy is confirmed during nimesulide use, the treating 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 medicinal products containing nimesulide on the ability to drive or operate machinery have been performed; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving or operating machinery.