Alax

Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see DOSAGE AND ADMINISTRATION and information on gastrointestinal and cardiovascular risks below). If treatment is ineffective, therapy should be discontinued. Concomitant use of nimesulide with 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 underlying bacterial infection. Effects on the liver. Serious hepatic reactions related to nimesulide have been reported rarely, including very rare cases with fatal outcome (see ADVERSE REACTIONS). Patients who develop symptoms suggestive of 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-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 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 during treatment with all NSAIDs at any time. 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 haemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. These patients should start treatment with the lowest possible dose. For these patients, as well as for those requiring concomitant use of 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 initial stages of treatment. The occurrence of gastrointestinal bleeding, ulceration, or perforation is possible 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 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 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 consultation, 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, especially 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 ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with nimesulide only after careful evaluation. Similar evaluation should be performed before initiating long-term treatment in patients with cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus, and smoking. Since 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 disease prophylaxis. Effects on the kidneys. Caution is required in patients with renal impairment or heart failure, as 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, especially 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, 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 treatment; in the majority of cases, reactions occur within the first month of therapy. 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 in 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/foetal 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 foetus. The absolute risk of cardiovascular malformation increased from less than 1% to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors resulted in increased pre- and post-implantation losses and increased embryo/foetal mortality. In addition, increased incidences of various malformations, including cardiovascular, were reported in animals that received prostaglandin synthesis inhibitors during the period of organogenesis. Use of nimesulide from the 20th week of pregnancy onwards may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, cases of constriction of the ductus arteriosus in the foetus have been reported following administration during the second trimester of pregnancy, most of which resolved upon discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, nimesulide should not be taken 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 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 onwards. 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 following in the foetus: • 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); The following effects are possible 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, leading to 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 in women who are attempting to conceive (see SPECIAL WARNINGS AND PRECAUTIONS). Women who have difficulty conceiving or who are being investigated for infertility should consider discontinuing nimesulide. If pregnancy is established during the use of nimesulide, 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 medicinal products containing nimesulide 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.