Instructions for Nimid tablets 100 mg No. 100
Composition
active ingredient: nimesulide;
1 tablet contains nimesulide 100 mg;
Excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Pills.
Main physicochemical properties: round tablets of light yellow color, smooth on both sides.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A X17.
Pharmacological properties
Pharmacodynamics
Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) 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
Absorption.
Nimesulide is well absorbed after oral administration. After a single dose of 100 mg of nimesulide, the maximum plasma concentration (3–4 mg/l) is reached in adults in 2–3 hours.
The area under the concentration-time curve (AUC) is 20–35 mg×h/l. There was no statistically significant difference between these results and those observed after administration of 100 mg nimesulide twice daily for 7 days. Up to 97.5% of nimesulide is bound to plasma proteins.
Metabolism.
Nimesulide is actively metabolized in the liver by several metabolic pathways, including the cytochrome P450 isoenzyme CYP2C9. Therefore, there is a possibility of drug interactions when used simultaneously with drugs metabolized by CYP2C9 (see section "Interaction with other medicinal products and other types of interactions"). The main metabolite is the parahydroxy derivative, which also has pharmacological activity. The time to detection of this metabolite in the blood is short (about 0.8 hours), but the reaction constant of its formation is low and significantly less than the absorption coefficient of nimesulide. Hydroxynimesulide is the only metabolite detected in blood plasma, which is almost completely bound. The half-life is from 3.2 to 6 hours.
Breeding.
Nimesulide is excreted from the body with urine - about 50% of the dose taken. Only 1-3% is excreted unchanged. Hydroxynimesulide is the main metabolite, found only in the form of glucuronate. About 29% of the dose taken is excreted with feces in a metabolized form. The pharmacokinetic profile of nimesulide in the elderly does not change with a single or repeated dose.
Preclinical safety data.
Preclinical data obtained in standard studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential revealed no special hazard for humans. In repeated dose toxicity studies, nimesulide showed gastrointestinal, renal and hepatic toxicity. In reproductive toxicity studies, when the drug was administered to female animals at doses that did not cause toxicity, embryotoxic and teratogenic effects (skeletal malformations, dilatation of the cerebral ventricles) were observed in rabbits, but not in rats. In rats, increased mortality of offspring in the early postnatal period and impaired fertility were observed.
Indication
Treatment of acute pain, primary dysmenorrhea.
Nimesulide should only be used as a second-line drug.
The decision to prescribe nimesulide should be made based on an assessment of all risks for the individual patient.
Contraindication
Hypersensitivity to nimesulide, to any other NSAID or to any of the excipients of the medicinal product.
History of hyperergic reactions (e.g. bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs.
History of hepatotoxic reactions to nimesulide.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
Gastric or duodenal ulcer in the acute phase or history of ulcer, perforation or bleeding in the digestive tract.
Cerebrovascular bleeding or other hemorrhages, as well as diseases accompanied by bleeding.
Severe blood clotting disorders.
Severe heart failure.
Severe renal impairment.
Liver dysfunction.
Suspicion of acute surgical pathology.
Fever and/or flu-like symptoms.
Children under 12 years old.
Third trimester of pregnancy and breastfeeding (see sections “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions.
Corticosteroids.
The risk of gastrointestinal ulceration or bleeding increases (see section "Special warnings and precautions for use").
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs).
The risk of bleeding in the digestive tract increases (see section "Special instructions").
NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use"). In the case of treatment with nimesulide in patients taking warfarin or similar anticoagulants or acetylsalicylic acid, there is an increased risk of bleeding complications. Therefore, this combination is not recommended (see section "Special precautions for use") and is contraindicated in patients with severe coagulation disorders (see section "Contraindications"). If combination therapy cannot be avoided, careful monitoring of blood coagulation parameters is necessary.
Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II antagonists (AIII).
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with reduced renal function (e.g. dehydrated patients or elderly patients with impaired renal function), the combined use of ACE inhibitors and cyclooxygenase inhibitors may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. The possibility of such interactions should be considered in patients who need to use nimesulide-containing drugs together with ACE inhibitors or AIIRAs. Therefore, such a combination of drugs should be prescribed with caution, especially in elderly patients. Patients should receive adequate fluid intake. The need for monitoring renal function after starting concomitant treatment and periodic monitoring after its discontinuation should be analyzed.
Other nonsteroidal anti-inflammatory drugs (NSAIDs).
The concomitant use of medicinal products containing nimesulide (see section "Special warnings and precautions for use") with other NSAIDs, including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g as a single dose or ≥ 3 g per day), is not recommended.
Pharmacokinetic interactions with other drugs: the effect of nimesulide on the pharmacokinetics of other drugs.
Furosemide.
In healthy volunteers, nimesulide temporarily weakens the effect of furosemide on sodium excretion and, to a lesser extent, on potassium excretion, 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 cumulative excretion of furosemide without changing its renal clearance. The combined use of furosemide and drugs containing nimesulide in patients with impaired renal or cardiac function requires caution (see section "Special instructions").
Lithium.
There have been reports that NSAIDs reduce lithium clearance, leading to increased plasma lithium levels and lithium toxicity. When nimesulide is prescribed to a patient receiving lithium therapy, careful monitoring of plasma lithium levels is recommended.
Pharmacokinetic interactions: the effect of other drugs on the pharmacokinetics of nimesulide.
In vitro studies have shown that nimesulide is displaced from its binding sites by tolbutamide, salicylic acid and valproic acid. However, despite the possible effect on its plasma concentration, such interactions are not clinically significant.
Other interactions.
Possible pharmacokinetic interactions with glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacids (namely a combination of aluminium and magnesium hydroxide) have also been studied in vivo. No clinically significant interactions were observed. Nimesulide inhibits the activity of the CYP2C9 enzyme. Plasma concentrations of medicinal products that are substrates of this enzyme may increase when administered concomitantly with nimesulide. Caution should be exercised when nimesulide is administered less than 24 hours before or less than 24 hours after administration of methotrexate, as an increase in the serum levels of the latter and an increase in its toxicity may occur.
Due to their effects on renal prostaglandins, prostaglandin synthetase inhibitors such as nimesulide may increase the nephrotoxicity of cyclosporines.
Application features
Adverse reactions can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms of the disease (see section “Method of administration and dosage” and on gastrointestinal and cardiovascular risks below).
If treatment is ineffective, drug therapy should be discontinued.
Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. During therapy with Nimid, the patient should refrain from using other analgesics.
During treatment with nimesulide, it is recommended to avoid the simultaneous use of hepatotoxic drugs and to refrain from drinking alcohol.
The use of NSAIDs may mask fever associated with an underlying bacterial infection. Patients taking nimesulide who develop fever and/or flu-like symptoms should discontinue treatment.
Serious hepatic reactions have been reported rarely with nimesulide, including very rare fatal cases (see also section "Adverse reactions"). Patients who develop symptoms suggestive of liver damage during nimesulide treatment, such as anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine, or patients whose liver function tests are abnormal should discontinue therapy. Nimesulide should not be re-administered to such patients.
Liver damage, most of which was reversible, has been reported after short-term exposure to the drug.
Effect on the gastrointestinal tract.
Gastrointestinal bleeding or ulceration/perforation (with or without warning symptoms or a history of serious gastrointestinal complications) has been reported, which can be fatal and can occur at any time during treatment with all NSAIDs. The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID doses in patients with a history of ulcer, especially if complicated by bleeding or perforation (see section 4.3), and in the elderly. In such patients, treatment should be started at the lowest possible dose. For these patients, as well as for 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 section 4.5).
Patients with a history of toxic gastrointestinal lesions, especially elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially in the initial stages of treatment.
Gastrointestinal bleeding or ulceration/perforation may occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal complications. 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 section "Adverse reactions").
Patients taking concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid, should be advised to exercise caution when using nimesulide (see section 4.5). 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 its exacerbation is possible (see section "Adverse reactions"). Simultaneous use of nimesulide with other drugs, such as oral contraceptives, anticoagulants, antiplatelet agents, may cause exacerbation of Crohn's disease and other diseases of the digestive tract.
Effects on the cardiovascular and cerebrovascular systems.
Patients with a history of hypertension and/or mild to moderate heart failure require appropriate monitoring and medical advice, as fluid retention and edema have been reported with NSAIDs.
Clinical trials and epidemiological data suggest that the use of some NSAIDs, especially at high doses and in long-term treatment, slightly increases the risk of arterial thrombotic complications, 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 carried out before starting long-term treatment in patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, smoking.
Since nimesulide may affect platelet function, it should be used with caution in patients with hemorrhagic diathesis (see also section "Contraindications"). However, nimesulide cannot replace acetylsalicylic acid in the prevention of cardiovascular diseases.
Effect on the kidneys.
Caution should be exercised in patients with impaired renal function or heart failure, as the use of nimesulide may lead to deterioration of renal function. In case of deterioration, treatment should be discontinued (see also section "Interaction with other medicinal products and other forms of interaction").
Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, in some cases even fatal (see section "Adverse reactions"), as well as impaired renal, cardiac and hepatic function, therefore appropriate clinical monitoring is recommended.
Skin reactions.
Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). The greatest risk of such reactions is evident at the beginning of 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.
Impact on fertility.
Nimesulide may impair female fertility and is not recommended in women attempting to conceive. If a woman has difficulty conceiving or is undergoing investigation for infertility, discontinuation of nimesulide should be considered (see section 4.6).
Use during pregnancy or breastfeeding
Pregnancy.
The use of nimesulide is contraindicated in the third trimester of pregnancy (see section "Contraindications").
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data suggest that use of prostaglandin synthesis inhibitors in early pregnancy increases the risk of miscarriage and of fetal heart defects and gastroschisis. The absolute risk of developing cardiovascular anomalies increases from less than 1% to approximately 1.5%. The risk is believed to increase with increasing dose and duration of nimesulide therapy.
In animals, the use of prostaglandin synthesis inhibitors has resulted in increased pre- and post-implantation losses and increased embryo and/or fetal mortality. In addition, it has been reported that animals treated with prostaglandin synthesis inhibitors during organogenesis have an increased incidence of various fetal malformations, including cardiovascular malformations.
Since there are no reliable data on the use of nimesulide in pregnant women and the potential risk to humans has not been determined, nimesulide should not be taken during the first and second trimesters of pregnancy unless clearly necessary. If the drug is prescribed to 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 chosen.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors may lead to the development of the following in the fetus:
• pneumocardial toxic lesion (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with the development of oligohydramnios.
In the mother at the end of pregnancy and the newborn, it is possible:
• increased bleeding time, anti-aggregation effect, which may occur even when using very low doses;
• suppression of uterine contractile activity, leading to delayed or prolonged labor.
Breast-feeding.
It is not known whether nimesulide is excreted in human milk. Nimesulide is contraindicated during breastfeeding (see section "Contraindications").
Fertility.
As with other NSAIDs, nimesulide-containing products are not recommended in women attempting to conceive (see section 4.4). Women who have difficulty conceiving or are undergoing investigation of infertility should discontinue nimesulide.
If pregnancy is established while using nimesulide, the doctor should be informed.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of medicines containing nimesulide on the ability to drive or use machines have not been conducted, however, patients who experience dizziness, vertigo or drowsiness after taking nimesulide should refrain from driving or using machines.
Method of administration and doses
In order to reduce the frequency of adverse reactions, the minimum effective dose should be used for the shortest possible time (see section "Special instructions for use"). The maximum duration of treatment with nimesulide is 15 days.
Adults: 1 tablet (100 mg nimesulide) 2 times a day after meals.
Elderly patients.
Elderly patients do not require a reduction in the daily dose (see section "Pharmacokinetics").
Children.
Nimesulide-containing medicinal products are contraindicated in children under 12 years of age (see also section "Contraindications"). Given the pharmacokinetic profile in adults and the pharmacodynamic characteristics of nimesulide, no dose adjustment is required for children aged 12 to 18 years.
Considering pharmacokinetics, no dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance 30–80 ml/min), while in severe renal impairment (creatinine clearance < 30 ml/min) nimesulide is contraindicated (see sections “Contraindications” and “Pharmacokinetics”).
Liver dysfunction.
Nimesulide is contraindicated in patients with impaired liver function (see section 5.2). The likelihood of adverse reactions can be minimized by using the drug for the shortest period of time necessary to control symptoms (see section 4.4).
Children.
The drug Nimid is contraindicated in children under 12 years of age.
Overdose
Symptoms of acute NSAID overdose are usually limited to: apathy, drowsiness, nausea, vomiting and epigastric pain, which are usually reversible with supportive therapy. Gastrointestinal bleeding may occur. Rarely, arterial hypertension, acute renal failure, respiratory depression and coma may occur. Anaphylactoid reactions have been reported with therapeutic doses of NSAIDs, which may occur with overdose. In case of NSAID overdose, patients should be provided with symptomatic and supportive treatment. There are no specific antidotes. There is no information on the removal of nimesulide by hemodialysis, but taking into account its high degree of binding to plasma proteins (up to 97.5%), dialysis is unlikely to be effective in overdose. If symptoms are present or in the event of a severe overdose within 4 hours of ingestion, patients may be given emesis and/or activated charcoal (60–100 g for adults) and/or an osmotic laxative. Forced diuresis, urine alkalinization, hemodialysis or hemoperfusion may be ineffective due to the high degree of protein binding. Renal and hepatic function should be monitored.
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.
From the blood and lymphatic system:
Rare: anemia, eosinophilia.
Very rare: thrombocytopenia, pancytopenia, purpura.
On the part of the immune system:
Rare: hypersensitivity.
Very rare: anaphylaxis.
Metabolic disorders:
Rare: hyperkalemia.
From the psyche:
Rare: feeling of fear, nervousness, night terrors.
From the nervous system:
Uncommon: dizziness.
Very rare: headache, drowsiness, encephalopathy (Reye's syndrome).
On the part of the organs of vision:
Rare: blurred vision.
Very rare: visual disturbances.
On the part of the organs of hearing and balance:
Very rare: vertigo (dizziness).
From the cardiovascular system:
Uncommon: hypertension.
Rare: tachycardia, hemorrhage, blood pressure lability, hot flashes.
On the part of the respiratory system:
Uncommon: dyspnoea.
Very rare: asthma, bronchospasm.
From the digestive tract:
Common: diarrhea, nausea, vomiting.
Uncommon: constipation, flatulence, gastrointestinal bleeding, duodenal/gastric ulcer and perforation.
Very rare: gastritis, abdominal pain, dyspepsia, stomatitis, black stools (melena).
From the hepatobiliary system (see section "Special instructions for use"):
Common: increased liver enzymes.
Rare: hepatitis, fulminant hepatitis (including fatal), jaundice, cholestasis.
Skin and subcutaneous tissue disorders:
Uncommon: itching, skin rash, increased sweating.
Rare: erythema, dermatitis.
Very rare: urticaria, angioedema, facial oedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the kidneys and urinary system:
Rare: dysuria, hematuria;
Very rare: urinary retention, renal failure, oliguria, interstitial nephritis.
General violations:
Uncommon: edema.
Rare: malaise, asthenia.
Very rare: hypothermia.
The most common adverse reactions observed with NSAIDs are gastrointestinal. Peptic ulcers, perforations or bleeding in the digestive tract, which are sometimes life-threatening, may occur, especially in elderly patients. The following adverse reactions have been reported after the use of 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.
Reporting of suspected adverse reactions after the registration of a medicinal product plays an important role. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.
Expiration date
4 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister, 1 blister in a cardboard box No. 10 (10×1).
10 tablets in a blister, 1 blister in a cardboard box, 10 packs in box No. 100 (10×1×10).
Vacation category
According to the recipe.
Producer
KUSUM HEALTHCARE PVT LTD/
KUSUM HEALTHCARE PVT LTD.
Location of the manufacturer and its business address.
SP-289 (A), RIICO Industrial Area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India/
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
