Cepasmel

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 the treatment is not effective, 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 drugs and consumption of alcohol should be avoided. 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 a fatal outcome (see ADVERSE REACTIONS). Patients who develop symptoms consistent with liver injury during nimesulide treatment, such as anorexia, nausea, vomiting, abdominal pain, fatigue, or dark urine, or patients whose liver function laboratory tests deviate from normal values, should discontinue therapy. Such patients should not be re-prescribed nimesulide. Liver injury, mostly 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 GI tract. Gastrointestinal bleeding or ulceration/perforation (with or without warning symptoms or a history of serious GI events), which could be fatal and may occur at any time during treatment with all NSAIDs, has been reported. The risk of gastrointestinal bleeding, ulceration, or perforation increases with increasing NSAID doses, in patients with a history of ulcers, particularly when complicated by hemorrhage or perforation (see CONTRAINDICATIONS), and in elderly patients. Such 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 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, especially elderly patients, should report any unusual abdominal symptoms (particularly GI bleeding), especially during the early stages of treatment. Gastrointestinal bleeding or ulceration/perforation may occur at any time during treatment, with or without warning symptoms or a prior history of GI events. If GI 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 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, and antiplatelet agents may exacerbate Crohn's disease and other gastrointestinal disorders. Effects on the cardiovascular and cerebrovascular systems. Patients with hypertension and/or mild to moderate congestive heart failure in their medical history 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 increase in the 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. A similar assessment should be performed before initiating long-term treatment of patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, and 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 disease prophylaxis. 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 WITH OTHER MEDICINAL PRODUCTS). 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 impaired renal, cardiac, and hepatic function; therefore, appropriate clinical monitoring is recommended. Skin reactions. Very rarely, serious skin reactions, some of which are life-threatening, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, associated with NSAID use have been reported (see ADVERSE REACTIONS). Patients appear to be at the highest risk for these reactions early in treatment; in most 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 nimesulide use. Nimesulide should not be re-prescribed 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 investigations 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/fetal development. Epidemiological data suggest that early in pregnancy, the use of prostaglandin synthesis inhibitors may increase the risk of miscarriage and cardiac malformations and gastroschisis in the fetus. 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/fetal mortality. Additionally, increased incidence of various malformations, including cardiovascular, was reported in animals receiving prostaglandin synthesis inhibitors during the period of organogenesis. Use of nimesulide from the 20th week of pregnancy 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 ductal constriction have been reported following use 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 absolutely 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. Prenatal monitoring for oligohydramnios and fetal ductal constriction should be considered if nimesulide exposure has occurred for several days from the 20th gestational week onward. Pregnant women should discontinue nimesulide if oligohydramnios or fetal ductal constriction is found. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may cause the following effects 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); 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 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 WARNINGS AND PRECAUTIONS). Women who have difficulty conceiving or who are undergoing fertility investigations 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 the ability to drive vehicles and operate machinery. No studies on the effects of medicinal products containing nimesulide on the ability to drive vehicles or operate machinery have been conducted; however, patients who experience dizziness, vertigo, or drowsiness after taking nimesulide should refrain from driving vehicles or operating machinery.