Instructions for Nise tablets 100 mg No. 20
Composition
active ingredient: nimesulide;
1 tablet contains nimesulide 100 mg;
excipients: calcium hydrogen phosphate, microcrystalline cellulose, corn starch, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, talc, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round, smooth, biconvex tablets from almost white to yellow.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX 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. Nimesulide selectively inhibits COX II (cyclooxygenase II) and suppresses the synthesis of prostaglandins in the focus of inflammation.
Nimesulide inhibits the release of the enzyme myeloperoxidase, and also inhibits the formation of free oxygen radicals, without affecting the processes of phagocytosis and chemotaxis, and inhibits the formation of tumor necrosis factor and other inflammatory mediators.
Pharmacokinetics
After oral administration, nimesulide is rapidly absorbed from the gastrointestinal tract. The maximum concentration in blood plasma is reached after 2–3 hours. Up to 97.5% of nimesulide binds to blood plasma proteins.
The drug is actively metabolized in the liver with the participation of CYP2C9, a cytochrome P450 isoenzyme. The main product of metabolism is hydroxynimesulide - a pharmacologically active substance. 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. Treatment of 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 component of the drug. Hyperergic reactions that occurred in the past (bronchospasm, rhinitis, urticaria) in connection with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
Hepatotoxic reactions to nimesulide that have occurred in the past.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
Suspicion of acute surgical pathology.
History of gastrointestinal bleeding or perforation associated with previous use of nonsteroidal anti-inflammatory drugs.
Gastric or duodenal ulcer in the acute phase, history of ulcer, perforation or bleeding in the digestive tract.
History of cerebrovascular bleeding or other hemorrhages, as well as diseases accompanied by bleeding.
Severe blood clotting disorders.
Severe heart failure.
Severe renal dysfunction.
Liver dysfunction.
Elevated body temperature and/or flu-like symptoms.
The patient's age is up to 12 years.
Third trimester of pregnancy and breastfeeding period.
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 ulceration or bleeding.
Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients), the concomitant use of ACE inhibitors, angiotensin II antagonists or agents that inhibit the cyclooxygenase system may lead to further deterioration of renal function and the development of acute renal failure, which is usually reversible. These interactions should be taken into account when the patient is taking nimesulide concomitantly with ACE inhibitors or angiotensin II antagonists. Extreme caution should be exercised when using this combination, especially in elderly patients. Patients should be adequately hydrated and renal function should be closely monitored after initiation of this combination. Nimesulide temporarily weakens the effect of furosemide on sodium excretion and, to a lesser extent, potassium excretion, and also reduces the diuretic effect. The combined use of furosemide and nimesulide in patients with impaired renal or cardiac function requires caution.
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.
Other NSAIDs: The concomitant use of nimesulide-containing medicinal products (see section 4.1) 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.
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.
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 used simultaneously with nimesulide, drugs that are substrates of this enzyme may increase their concentration in the blood plasma.
Caution is required if nimesulide is to be 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.
Effects of other drugs on nimesulide.
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.
Application features
Nimesulide should only be used as a second-line drug. The decision to prescribe nimesulide should be based on an assessment of all the risks for the individual patient.
To reduce the risk of side effects, it is necessary to use the minimum effective dose with the shortest duration of treatment. In the absence of treatment effectiveness (reduction of symptoms of the disease), therapy with the drug should be discontinued.
There have been reports of severe hepatic reactions, including fatal ones, with the use of nimesulide. If liver enzyme levels increase or signs of liver damage occur (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) or if laboratory liver function tests are abnormal, the drug should be discontinued. Re-administration of nimesulide in such patients is contraindicated.
During treatment with nimesulide, it is recommended to avoid the simultaneous use of hepatotoxic drugs, analgesics, other non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, and to refrain from drinking alcohol.
Patients with toxic lesions of the digestive tract, especially the elderly, should be informed of 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 may increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed of the need to exercise caution when using nimesulide.
If a patient receiving nimesulide experiences bleeding or ulcers in the digestive tract, treatment with the drug should be discontinued.
NSAIDs should be prescribed with caution to patients with Crohn's disease or a history of nonspecific ulcerative colitis, as nimesulide may lead to their exacerbation.
Concomitant 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.
Patients with arterial hypertension and/or a history of heart failure, as well as patients with fluid retention and edema due to the use of NSAIDs, require appropriate monitoring of the condition and consultation with a doctor.
Clinical trials and epidemiological data suggest that some NSAIDs, especially at high doses and with long-term use, may be associated with a small risk of arterial thrombotic events, such as myocardial infarction and stroke. There is insufficient data to exclude a risk of such events with nimesulide. Patients with uncontrolled hypertension, acute heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with nimesulide only after careful assessment. Patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, should also be carefully assessed before starting nimesulide.
Patients with renal or heart failure should be prescribed the drug with caution due to possible deterioration of renal function. In case of deterioration of the condition, treatment should be discontinued. Elderly patients should be carefully monitored clinically due to the possibility of bleeding and perforation of the gastrointestinal tract, deterioration of renal, hepatic or cardiac function. Since nimesulide may affect platelet function, it should be prescribed with caution to patients with hemorrhagic diathesis. However, nimesulide does not replace acetylsalicylic acid in the prevention of cardiovascular diseases.
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.
Skin reactions
Cases of fixed drug eruption have been reported with nimesulide. Nimesulide should not be re-administered to patients who have had a history of fixed drug eruption associated with nimesulide (see section 4.8).
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, with a previously prescribed course of treatment, the reaction in most cases occurred within the first month of treatment. Nimesulide should be discontinued at the first signs of skin rash, mucosal lesions or other allergic manifestations.
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 are undergoing investigation for infertility.
Use during pregnancy or breastfeeding
From the 20th week of pregnancy, the use of NSAIDs may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus in the fetus after treatment with NSAIDs in the second trimester of pregnancy, which in most cases disappeared after discontinuation of treatment. Therefore, 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 chosen.
It may be appropriate to monitor antenatally for oligohydramnios and ductus arteriosus after exposure to the drug for several days, starting from the 20th week of gestation. The drug should be discontinued if oligohydramnios or ductus arteriosus is detected.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can lead to the development of the following in the fetus:
pneumocardial toxic lesion (with premature narrowing/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 at the end of pregnancy and the fetus, it is possible:
increased bleeding time, anti-aggregation effect, which can occur even when using very low doses of the drug;
suppression of uterine contractile activity, which can lead to a delay or prolongation of the period of labor.
Therefore, nimesulide is contraindicated in the third trimester of pregnancy.
The use of nimesulide may impair fertility in women, so the drug is not recommended for women trying to conceive. For women who experience difficulty conceiving or are undergoing infertility studies, nimesulide should be discontinued. If pregnancy is established during the use of nimesulide, the doctor should be informed.
As an NSAID that inhibits prostaglandin synthesis, nimesulide can cause premature closure of the ductus arteriosus, pulmonary hypertension, oliguria, oligohydramnios. The risk of bleeding, labor weakness, and peripheral edema increases. There are isolated reports of renal failure in infants whose mothers used nimesulide late in pregnancy. Animal studies have shown atypical reproductive toxicity, but there are no reliable data on the use of nimesulide in pregnant women.
Since it is not known whether nimesulide passes into breast milk, its use is contraindicated during breastfeeding.
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, vertigo or drowsiness after taking nimesulide should refrain from driving or operating other mechanisms.
Method of administration and doses
To minimize possible unwanted side effects, the minimum effective dose should be used for the shortest possible time.
The maximum duration of the treatment course is 15 days.
Adults: 1 tablet (100 mg) 2 times a day – morning and evening.
Elderly: No dose adjustment is required.
Children over 12 years of age: No dose adjustment is required.
Patients with renal impairment: No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 30–80 mL/min), while severe renal impairment (creatinine clearance < 30 mL/min) is a contraindication.
The drug should be taken orally after meals and washed down with sufficient fluid.
Undesirable effects can be minimized by using the shortest duration of treatment necessary to control symptoms.
Children
The medicine is contraindicated in children under 12 years of age.
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 are possible, but such phenomena are rare. There have been reports of anaphylactoid reactions when using therapeutic doses of NSAIDs and in case of their overdose. There is no specific antidote. Treatment of overdose is symptomatic and supportive. There is no data on the removal of nimesulide by hemodialysis, but if we take into account the high degree of binding of nimesulide to blood 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 blood plasma proteins. Kidney and liver function should be monitored.
Adverse reactions
From the blood system: anemia, eosinophilia, thrombocytopenia, pancytopenia, purpura.
Immune system disorders: hypersensitivity reactions, anaphylaxis.
Metabolic disorders: hyperkalemia.
On the part of the psyche: feelings of anxiety, nervousness, night terrors.
From the nervous system: dizziness, headache, drowsiness, encephalopathy (Reye's syndrome).
From the organs of vision: blurred vision, visual disturbances.
From the side of the organs of hearing and vestibular apparatus: vertigo (dizziness).
Cardiovascular system: tachycardia, hemorrhage, blood pressure lability, hot flashes, arterial hypertension.
From the respiratory system: shortness of breath, asthma, bronchospasm.
On the part of the digestive tract: diarrhea, nausea, vomiting, constipation, flatulence, gastritis, abdominal pain, dyspepsia, stomatitis, black stools, bleeding in the digestive tract, ulcer and perforation of the duodenum or stomach.
From the hepatobiliary system: hepatitis, fulminant hepatitis with fatal outcome, including jaundice, cholestasis, increased liver enzymes.
Skin and subcutaneous tissue disorders: itching, skin rashes, fixed drug rash (see section "Special warnings and precautions for use"), increased sweating, erythema, dermatitis, urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the urinary system: dysuria, hematuria, urinary retention, edema, renal failure, oliguria, interstitial nephritis.
General disorders: edema, malaise, asthenia, hypothermia.
Laboratory indicators: 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, which are sometimes life-threatening, especially in elderly patients, may occur. 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, vomiting with blood, ulcerative stomatitis, exacerbation of colitis and Crohn's disease, gastritis, edema, hypertension and heart failure, skin reactions such as blistering, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Clinical and epidemiological studies suggest that some NSAIDs, especially at high doses and with long-term use, may lead to a small increased risk of arterial thrombotic complications, such as myocardial infarction or stroke.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Manufacturer 1.
Dr. Reddy's Laboratories Ltd., FTO – II
Location of the manufacturer and its business address
Station No. 42r, 43, 44r, 45r, 46r, 53, 54, 83, Bachupali Village, Bachupali Mandal, Medchal Malkaigiri District – 500090, Telangana State, India
Manufacturer 2.
Dr. Reddy's Laboratories Limited
Location of the manufacturer and its business address
Production site - VI Village Khol, Nalagar Road, Baddi, Solan District, Himachal Pradesh, 173205, India
You can report an adverse reaction or lack of effectiveness when using a medicine by calling:
+380 44 207 51 97 or +380 50 414 39 39; and also by email: DrugSafetyUa@drreddys.com (24/7).
