Cepastil

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 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 product. During treatment with nimesulide, concomitant use of hepatotoxic drugs should be avoided and alcohol consumption should be refrained from. The use of NSAIDs may mask fever associated with 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 suggestive of liver injury during nimesulide therapy, such as anorexia, nausea, vomiting, abdominal pain, fatigue, or dark urine, or patients whose liver function laboratory test results deviate from normal values, should discontinue therapy. Nimesulide should not be re-administered to such patients. Liver injury, mostly reversible, has been reported after short-term exposure to the medicinal product. Patients receiving 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), which may be fatal, has 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, especially when complicated by hemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. These patients should initiate treatment with the lowest possible dose. For these patients, as well as those requiring concomitant low-dose acetylsalicylic acid or other drugs 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 WITH OTHER MEDICINAL PRODUCTS). Patients with a history of GI toxicity, particularly the elderly, 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 a history of GI events. If gastrointestinal bleeding or ulceration occurs, nimesulide should be discontinued. Nimesulide should be used with caution in patients with gastrointestinal disorders, including peptic ulcer, gastrointestinal bleeding, ulcerative colitis, or Crohn's disease in their medical history (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 for 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, or 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 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 for nimesulide. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with nimesulide after careful assessment. A similar assessment should be carried out 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 replace acetylsalicylic acid for 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 WITH OTHER MEDICINAL PRODUCTS). Elderly patients. Elderly patients may have an increased incidence of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which in some cases may be fatal (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 them 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 highest risk for these 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 nimesulide use. Nimesulide should not be re-administered to patients with a history of nimesulide-related FDE (see ADVERSE REACTIONS). Effects on fertility. Use of Nimesil may impair female fertility and is not recommended for women planning pregnancy. Women who have difficulty conceiving or who are undergoing fertility investigation 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. Epidemiological data suggest that use of prostaglandin synthesis inhibitors in early pregnancy may increase the risk of miscarriage and fetal cardiac malformations and gastroschisis. 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. Additionally, increased incidence of various fetal malformations, including cardiovascular malformations, was reported in animals receiving prostaglandin synthesis inhibitors during organogenesis. Use of nimesulide from the 20th week of pregnancy onward may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. In addition, cases of fetal ductus arteriosus constriction have been reported following use during the second trimester of pregnancy, most of which resolved after discontinuation of treatment. Therefore, nimesulide should not be used during the first and second trimesters of pregnancy unless clearly necessary. If nimesulide is used by women attempting to conceive or during the first or second trimester of pregnancy, the lowest possible dose and shortest possible duration of treatment should be used. Antenatal monitoring for oligohydramnios and fetal ductus arteriosus constriction should be considered following nimesulide exposure for several days from gestational week 20 onward. Nimesulide should be discontinued if oligohydramnios or fetal ductus arteriosus 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 oligohydramnios (see above); In the mother at the end of pregnancy and in the newborn: • prolonged 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, medicinal products containing nimesulide are not recommended for women attempting to conceive (see SPECIAL PRECAUTIONS). Women who have difficulty conceiving or who are undergoing fertility investigation should discontinue nimesulide use. If pregnancy is confirmed 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 medicinal products containing nimesulide on the ability to drive or operate machinery have been conducted; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving or operating machinery.