Instructions for Nimedar tablets 100 mg No. 30
Composition
active ingredient: nimesulide;
1 tablet contains nimesulide 100 mg;
excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, colloidal anhydrous silica, hydroxypropylcellulose, croscarmellose sodium, sodium lauryl sulfate, talc, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: light yellow, round tablets with a biconvex surface. Marbling is allowed on the surface of the tablets.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A X17.
Pharmacological properties
Pharmacodynamics
Nimesulide is a nonsteroidal anti-inflammatory drug of the methanesulfonanilide group, which exhibits anti-inflammatory, analgesic and antipyretic effects. The therapeutic effect of nimesulide is due to the fact that it interacts with the arachidonic acid cascade and reduces prostaglandin biosynthesis by inhibiting cyclooxygenase.
Pharmacokinetics
In humans, nimesulide is well absorbed after oral administration, reaching a maximum plasma concentration after 2–3 hours. Up to 97.5% of nimesulide is bound to plasma proteins. Nimesulide is actively metabolized in the liver with the participation of CYP2C9, an isoenzyme of cytochrome P450. The main metabolite is a parahydroxy derivative, which also has pharmacological activity. The half-life is from 3.2 to 6 hours. Nimesulide is excreted from the body with urine - about 50% of the dose taken. About 29% of the dose taken is excreted with feces in a metabolized form. Only 1–3% is excreted from the body unchanged. The pharmacokinetic profile in the elderly does not change.
Indication
Treatment of acute pain; primary dysmenorrhea.
Nimesulide should only be used as a second-line drug. The decision to prescribe the drug should be made based on an assessment of all the risks for the individual patient.
Contraindication
Hypersensitivity to nimesulide or to any component of the drug; previous hypersensitivity reactions (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs); previous hepatotoxic reactions to nimesulide; gastric and duodenal ulcers in the acute phase; recurrent ulcers or bleeding in the digestive tract; history of gastrointestinal bleeding associated with previous use of non-steroidal anti-inflammatory drugs; cerebrovascular bleeding; bleeding accompanying other diseases; severe blood clotting disorders; severe heart failure; severe renal failure (creatinine clearance < 30 ml/min); severe hepatic failure; elevated body temperature and/or flu-like symptoms; suspected acute surgical pathology. Alcoholism and drug addiction.
Do not use simultaneously with other drugs that can potentially cause hepatotoxic reactions.
Children under 12 years old.
Third trimester of pregnancy and breastfeeding.
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin or acetylsalicylic acid, so this combination is not recommended or contraindicated in patients with severe coagulation disorders. If such combination therapy cannot be avoided, careful monitoring of blood coagulation parameters should be carried out.
In healthy individuals, nimesulide rapidly reduces the sodium-excreting effect of furosemide and, to a lesser extent, the potassium-excreting effect, and also reduces the diuretic effect. Simultaneous use of nimesulide and furosemide leads to a decrease (by approximately 20%) in the area under the concentration-time curve (AUC) and a decrease in the cumulative excretion of furosemide without changes in the renal clearance of furosemide.
Pharmacokinetic interactions.
NSAIDs have been reported to reduce lithium clearance, leading to increased plasma lithium levels and lithium toxicity. When prescribing nimesulide to patients receiving lithium therapy, frequent monitoring of plasma lithium levels should be performed.
Tolbutamide, salicylic acid, valproic acid displace nimesulide from binding sites. However, despite the possible effect on the drug's plasma levels, these interactions are not considered clinically significant.
There is no clinically significant interaction with glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacids (aluminum and magnesium hydroxide combination).
Nimesulide inhibits the activity of the CYP2C9 enzyme. When drugs that are substrates of this enzyme are used simultaneously with nimesulide, their plasma concentrations may increase. Caution is required when nimesulide is administered less than 24 hours before or less than 24 hours after taking methotrexate, as it may increase the serum levels of the latter and increase its toxicity.
Due to the effect on renal prostaglandin synthetase inhibitors, to which nimesulide belongs, it is possible to increase the nephrotoxicity of cyclosporines.
The effect of other drugs on nimesulide.
In vitro studies have shown that nimesulide is displaced from binding sites by tolbutamide, salicylic acid and valproic acid. Although these interactions have been identified in plasma, these effects have not been observed during clinical use of the drug.
Application features
Nimesulide should only be used as a second-line drug. The decision to prescribe it should be based on an assessment of all the risks for the individual patient.
Undesirable side effects can be minimized by taking the lowest effective dose for the shortest period necessary to control the symptoms of the disease. In the absence of treatment effectiveness (alleviation of symptoms of the disease), drug therapy should be discontinued.
Severe hepatic reactions, including fatal cases, have been reported with the use of the drug. Patients who experience symptoms suggestive of liver damage (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) and patients with abnormal liver function tests should discontinue the drug. Re-administration of nimesulide to such patients is contraindicated. Reversible liver damage was observed in most cases after short-term use of the drug.
Gastrointestinal bleeding or ulceration/perforation may occur at any time during treatment with or without warning symptoms, with or without a history of gastrointestinal disease. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued.
Ulceration, bleeding or perforation in the digestive tract can be life-threatening, especially if there is a history of similar events in the patient when using any other NSAIDs (without a prescription). The risk of such events increases with increasing NSAID dose in patients with a history of gastrointestinal ulcer, especially complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be started with the lowest possible effective dose.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially possible bleeding and perforations in the digestive tract, which can be fatal for the patient.
Patients with toxic lesions of the digestive tract, especially the elderly, should report any unusual symptoms that occur in the digestive tract, especially bleeding. This is especially important in the initial stages of treatment.
Patients taking concomitant medications that increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed of the need to exercise caution when using nimesulide. For these patients, as well as for those taking concomitant low-dose acetylsalicylic acid or other medications that increase the risk of gastrointestinal complications, combination therapy with drugs such as misoprostol or proton pump inhibitors should be considered.
NSAIDs should be prescribed with caution to patients with Crohn's disease or ulcerative colitis in history, as nimesulide may exacerbate them. Patients with arterial hypertension and patients with a history of heart failure, as well as patients with fluid retention and edema due to the use of NSAIDs, require appropriate monitoring and consultation with a doctor. Clinical studies and epidemiological data suggest that some NSAIDs, especially in high doses and with prolonged use, may lead to arterial thrombotic episodes, such as myocardial infarction and stroke. There is insufficient data to exclude the risk of such events with the use of nimesulide.
Patients with uncontrolled hypertension, acute heart failure, ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be prescribed nimesulide after careful assessment. Patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, should also be carefully assessed before prescribing the drug.
The drug should be prescribed with caution to patients with renal or heart failure due to possible deterioration of renal function. In case of deterioration of the condition, treatment should be discontinued.
Elderly patients require careful clinical monitoring due to the possibility of developing bleeding and perforation of the digestive tract, impaired renal, hepatic or cardiac function.
Since nimesulide may affect platelet function, it should be used with caution and under constant supervision in patients with hemorrhagic diathesis.
Nimesulide does not replace acetylsalicylic acid in the prevention of cardiovascular diseases.
There have been rare reports of severe skin reactions with NSAIDs, some of which may be fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Patients are at very high risk of such reactions if they have previously experienced a reaction during the first month of treatment. Nimesulide should be discontinued at the first signs of skin rash, mucosal lesions or other signs of an allergic reaction.
The use of nonsteroidal anti-inflammatory drugs may mask fever associated with an underlying bacterial infection. In the event of fever or flu-like symptoms in patients taking nimesulide, the drug should be discontinued.
Nimesulide may impair female fertility and is not recommended for use in women attempting to conceive. Nimesulide is not recommended for use in women who are unable to conceive or are undergoing investigation for infertility.
The medicinal product contains lactose, therefore patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome should not take the medicinal product.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect of nimesulide on the ability to drive and perform work requiring increased attention has not been studied. However, patients who experience dizziness or drowsiness after taking nimesulide should refrain from driving or operating other mechanisms.
Use during pregnancy or breastfeeding
Fertility. Nimesulide may impair female fertility and is not recommended for use in women attempting to conceive. Nimesulide is not recommended for women who have difficulty conceiving or who are undergoing investigation for infertility. If pregnancy occurs while taking nimesulide, the doctor should be informed.
Pregnancy. The drug is not recommended for use in the first and second trimesters of pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or foetal development. Epidemiological data suggest that use of prostaglandin synthesis inhibitors in early pregnancy increases the risk of spontaneous abortion, foetal heart defects and gastroschisis. The absolute risk of cardiovascular malformation has been reported to increase from less than 1% to approximately 1.5%. The risk appears to increase with dose and duration of exposure.
Nimesulide should not be taken in the first and second trimesters of pregnancy unless clearly necessary. If the drug is necessary for 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.
In addition, an increased incidence of various malformations, including those of the cardiovascular system, was recorded in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can lead to the development of the following in the fetus:
pneumocardiac toxic lesion (with premature closure of the ductus arteriosus and hypertension in the pulmonary artery system); renal dysfunction, which may progress to renal failure with the development of oligohydramnios.
In the mother and fetus at the end of pregnancy, it is possible:
increased bleeding time, anti-aggregation effect, which may occur even when using very low doses of the drug; inhibition of uterine contractile activity, which may lead to a delay or prolongation of the period of labor.
Therefore, nimesulide is contraindicated in the third trimester of pregnancy.
Like other NSAIDs that inhibit prostaglandin synthesis, nimesulide may cause premature closure of the botal duct, pulmonary hypertension, oliguria, oligohydramnios. The risk of bleeding, labor weakness and peripheral edema increases. There are isolated reports of renal failure in newborns born to women who used nimesulide late in pregnancy.
Breastfeeding. Since it is not known whether nimesulide is excreted in breast milk, its use is contraindicated during breastfeeding.
Method of administration and doses
The drug should be prescribed after a careful assessment of the benefit/risk ratio. Use the minimum effective dose for the shortest possible time. The maximum duration of treatment with nimesulide is 15 days.
Adults and children over 12 years of age: take 1 tablet (100 mg) 2 times a day (daily dose – 200 mg).
Elderly patients: no dose adjustment is required.
Patients with renal impairment: For patients with mild or moderate renal insufficiency (creatinine clearance 30–80 ml/min), no dose adjustment is required. The drug should be taken orally after meals and washed down with sufficient fluid. In severe renal insufficiency (creatinine clearance < 30 ml/min), the drug is contraindicated.
Patients with impaired liver function. The use of nimesulide for the treatment of patients with impaired liver function is contraindicated (see section "Contraindications").
Children
The drug is contraindicated in children under 12 years of age. The dosage for children over 12 years of age is the same as for adults.
Overdose
Symptoms of acute overdose with nonsteroidal anti-inflammatory drugs (NSAIDs) are usually limited to the following manifestations: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with supportive therapy. Gastrointestinal bleeding, arterial hypertension, acute renal failure, respiratory depression, coma may occur, but such phenomena are rare. There have been reports of anaphylactoid reactions with the use of therapeutic doses of NSAIDs and with their overdose.
Treatment is symptomatic and supportive. There is no data on the removal of nimesulide by hemodialysis, but taking into account the high degree of binding of nimesulide to plasma proteins (up to 97.5%), dialysis is unlikely to be effective. In the presence of symptoms of overdose or after the use of a large dose of the drug within 4 hours after its administration, patients may be prescribed: artificial induction of vomiting and/or administration of activated charcoal (60–100 g for adults) and/or administration of an osmotic laxative. Forced diuresis, increased urine alkalinity, hemodialysis and hemoperfusion may be ineffective due to the high degree of binding of nimesulide to plasma proteins. Kidney and liver function should be monitored.
There is no specific antidote.
Adverse reactions
The following classification is used to assess the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10,000 and < 1/1000), very rare (< 1/10,000), including isolated cases.
On the part of the organs of vision: rarely - blurred vision; very rarely - visual impairment.
From the side of the organs of hearing and vestibular apparatus: very rarely - vertigo (dizziness).
From the respiratory system, thoracic and mediastinal organs: infrequently - shortness of breath; very rarely - asthma, bronchospasm.
From the gastrointestinal tract: often - diarrhea, nausea, vomiting; infrequently - constipation, flatulence, gastritis, bleeding in the digestive tract, ulcer and perforation of the duodenum or stomach; very rarely - gastritis, abdominal pain, dyspepsia, stomatitis, black stools.
From the liver and biliary tract: often - increased liver enzymes; very rarely - hepatitis, fulminant hepatitis with fatal outcome, jaundice, cholestasis.
From the kidneys and urinary system: rarely - dysuria, hematuria; very rarely - urinary retention, renal failure, oliguria, interstitial nephritis.
From the side of metabolism: rarely - hyperkalemia.
From the nervous system: infrequently - dizziness; very rarely - headache, drowsiness, encephalopathy (Reye's syndrome).
From the cardiovascular system: rarely - tachycardia; infrequently - arterial hypertension; rarely - hemorrhage, blood pressure fluctuations, hot flashes.
From the blood and lymphatic system: rarely - anemia, eosinophilia; very rarely - thrombocytopenia, pancytopenia, purpura.
On the part of the immune system: rarely - hypersensitivity reactions; very rarely - anaphylaxis.
Skin and subcutaneous tissue disorders: common: itching, skin rash, increased sweating; rare: erythema, dermatitis; very rare: urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
General disorders: infrequently - edema; rarely - malaise, asthenia; very rarely - hypothermia, hyperthermia.
Laboratory indicators: often - increased liver enzymes.
The most common adverse reactions observed with nonsteroidal anti-inflammatory drugs (NSAIDs) are gastrointestinal. Peptic ulcers, perforations or bleeding in the digestive tract may occur, which are sometimes life-threatening, especially in elderly patients. The following adverse reactions have been reported with this group of drugs: nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, black stools, bloody vomiting, ulcerative stomatitis, exacerbation of colitis and Crohn's disease. Gastritis has been observed less frequently. There have been reports of edema, hypertension and heart failure as reactions to the use of NSAIDs. Very rarely, skin reactions such as blistering, Stevens-Johnson syndrome and toxic epidermal necrolysis may occur with the use of NSAIDs. There is evidence that some NSAIDs, especially at high doses and with long-term use, slightly increase the risk of arterial thrombotic complications, such as myocardial infarction or stroke.
Expiration date
3 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 tablets in a contour blister pack, 3 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
