for medical use of preparation
Active ingredient: Nimesulide;
1 tablet contains Nimesulide 100 mg.
Additional ingredients: Microcrystalline cellulose, Croscarmellose sodium, Magnesium stearate, Silica colloidal anhydrous.
Pharmaceutical Form: Tablets.
Nonsteroidal anti-inflammatory and anti-rheumatic medicines. Code АТС М01А Х17.
Treatment of acute pain. Symptomatic treatment of osteoartrosis with pain syndrome. Primary dismenorrhea.
Known hypersensitivity to Nimesulide or any preparation components. Hyperergic reactions in anamnesis (bronchospasm, rhinitis, urticaria) due to the use of acetylsalicinic acid or other non-steroidal anti-inflammatory drugs; hepatotoxic reaction to Nimesulide in anamnesis; acute gastric and duodenum peptic ulcer, recurrent GIT ulcers, cerebrovascular bleeding or other lesions associated with bleeding; severe disorders of blood coagulability; severe kidney or hepatic insufficiency; fever and flu-like symptoms, suspected acute surgical pathology. It is not concurrently used with other medicines, which may potentially cause hepatotoxic reactions. Alcoholism, drug dependence. III trimester of pregnancy or lactation period. Children age less 12 years old.
Administration and Dosage:
Nimid® is administered after a precise assessment of risk/benefit ratio. It is used the minimum effective dose for the shortest period. The maximum duration of the treatment with Nimid® is 15 days.
Adults and elderly patients: 1 tablet (100 mg) 2 times per day (daily dose is 200 mg).
Children older than 12 years: The dose adjustment is not required.
Patients with renal dysfunction: For patients with mild or moderate renal insufficiency (creatinine clearance is 30-80 ml/min), the dose adjustment is not necessary. The preparation is used per oral after a meal, taking enough water with one’s medicine.
The frequency of side effects is classified as follows: very common ( 1/10), common ( 1/100, 1/10), sometimes ( 1/1000, 1/100), rare ( 1/10 000, 1/1000), very rare ( 1/10 000), unknown (it is impossible to assess them as per available data).
Blood system: rare – anemia, eosinophilia; very rare – thrombocytopenia, pancytopenia, purpura.
Immune system: rare – hypersensitiveness reactions, very rare – anaphylaxis;
Metabolic disorders: rare – hyperkalemia.
Psychics: rare – feeling of fear, nervousness, nightmares.
Nervous system: sometimes – dizziness, very rare – headache, drowsiness and encephalopathy (Reye syndrome).
Organ of vision: rare – blurred vision.
Hearing organ: very rare – vertigo (dizziness).
Cardio-vascular system: rare – tachycardia, hemorrhage, lability of blood pressure, flushing, and sometimes – arterial hypertension.
Respiratory system: sometimes – shortness of breath, very rare – asthma, bronchospasm.
Gastrointestinal tract: common – diarrhea, nausea, vomiting and sometimes – constipation, meteorism, gastritis, very rare – abdominal pain, dyspepsia, stomatitis, black bowel movements, bleeding in digestive tract, ulcers and perforation of duodenum/stomach.
Hepatobiliary system: very rare – hepatitis, fatal fulminant hepatitis, including jaundice and cholestasis.
Skin: sometimes – itch, skin rash, increased sweating, rare – erythema, dermatitis, very rare – urticaria, angioedema, erythema multiforme, urticaria, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Urinary system: rare – dysuria, hematuria, urinary retention, very rare – renal failure, oliguria, interstitial nephritis.
General disorders: sometimes – edema, rare – malaise, asthenia, very rare – hypothermia.
Laboratory tests: common – increase in liver enzymes.
Symptoms of acute overdose with non-steroidal anti-inflammatory drugs (NSAIDs) are usually as follows: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible in supportive treatment. Gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression, coma are possible, however, such phenomena are rare. There have been reports about anaphylactoid reactions during the use of therapeutic doses of NSAIDs and their overdose. There is no specific antidote. The treatment of overdose is symptomatic and supportive one. There is no data concerning Nimesulide excretion via dialysis, but if the high degree of Nimesulide binding to plasma proteins (up to 97.5%) is taken into account, it is unlikely that dialysis will be effective. In case of symptoms of overdose or after the use of a large dose of the preparation within 4 hours after its intake the following measures may be administered to patients: artificial vomiting turn up and/or intake of activated charcoal (60–100 g for adults), and/or intake of osmotic laxative agent. Forced diuresis, increase of urine alkalinity, hemodialysis and hemoperfusion may be ineffective due to high degree of Nimesulide binding to plasma proteins. Renal and hepatic function should be monitored.
Pregnancy and lactation:
Nimesulide administration can disturb women fertility and is not recommended for women planning to become pregnant.
It is not recommended to administer Nimid® to women who have problems with becoming pregnant or if they are on the examination because of infertility.
Nimid® administration is contraindicated in III trimester of pregnancy.
Like other non-steroidal anti-inflammatory drugs Nimid® is not recommended to administer to women who are planning to become pregnant.
Like other non-steroidal anti-inflammatory drugs, which inhibit prostaglandinsynthesis, Nimesulide may bring to premature arterial (Botallo's) duct closure, pulmonary hypertension, oliguria, oligohydramnios. There is an increased risk of bleeding, uterine insufficiency and peripheral oedema. There are single reports on renal failure in infants born by women who have used Nimesulide in late pregnancy.
This preparation is not used in I and II trimesters of pregnancy.
Since it is not known whether Nimesulide is excreted in breast milk it is not recommended to use Nimid® during lactation period.
Nimesulide is not used in children under 12 years old.
Peculiarities in usage:
Nimesulide should be used only as a second line. Decision on Nimesulide administration should be based on the assessment of risks for individual patients.
Unwanted side effects can be minimized by taking the least effective dose for the shortest period of administration required for symptoms control. In case of treatment ineffectiveness (reduction of disease symptoms), this preparation therapy should be discontinued. There were reports on cases of liver severe reactions, including fatal ones, during Nimesulide use. Patients with symptoms similar to symptoms of liver lesion during Nimid® treatment, such as anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine, or patients, which laboratory parameters of liver function are abnormal, should stop this preparation usage. Re-administration of Nimesulide to such patients is contraindicated. It is necessary to avoid other analgesics use during Nimid® treatment. It is necessary to avoid concomitant use of other NSAIDs, including selective cyclooxygenase-2. Patients who used Nimesulide and who have symptoms similar to flu or colds should discontinue its use. There are increased incidences of adverse reactions associated with NSAIDs, especially possible bleeding and perforation in the digestive tract that may be dangerous for a patient, in elderly patients. Ulcer bleeding or perforation of the digestive tract may threaten the life of a patient, especially if there is an evidence of such phenomena in anamnesis in patients during usage of any other NSAIDs (without limitation period). The risk of such events is increased together with NSAID dose increasing in patients with GIT ulcers in anamnesis, especially complicated by bleeding or perforation, as well as in elderly patients. The treatment in such patients should be started with the least effective dose. For these patients, as well as for those who use concurrently low-dose of acetylsalicinic acid or other medicines that increase the risk of complications in the digestive tract, it should be considered the possibility of combination therapy with such medicines as misoprostol or proton pump inhibitors. Patients with toxic lesion of the digestive tract, especially elderly ones, should inform about any unusual symptoms that occur in the digestive tract, especially about bleeding. Patients who use concomitant medications that may increase the risk of ulcers or bleeding, such as corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed about the need of caution during the use of Nimesulide. In case of bleeding or GIT ulcers in patients who use Nimid® this preparation treatment should be discontinued. It is necessary to administer NSAIDs with caution to patients with Crohn's disease or ulcerative colitis in anamnesis, since Nimesulide may aggravate them. Patients with hypertension and/or heart failure in anamnesis, as well as those with water retention and edema due to the use of NSAIDs, require an appropriate state monitoring and a doctor’s advice. Clinical studies and epidemiological data suggest that some NSAIDs, especially in high doses and in long-term use, can lead to insignificant risk of arterial thrombotic episodes, for example, myocardial infarction and stroke. There is no sufficient data concerning exclusion of the risk of such events occurrence during Nimesulide use. Nimesulide should be administered to patients with uncontrolled arterial hypertension, acute cardiac insufficiency, known coronary heart disease, peripheral arterial disease and/or cerebrovascular disease only after a precise assessment of their states. It is also necessary to carefully assess the states of patients with risk factors of cardiovascular diseases, such as hypertension, hyperlipidemia, diabetes and smoking, before this preparation administration. It should be administered to patients with renal or heart failure with caution due to possible worsening of renal function. In case of recrudescence the treatment should be stopped. It is necessary a thorough clinical control under elderly patients due to possible development of bleeding and perforation of the digestive tract, renal liver or heart impairment. Since Nimesulide may affect platelet function, it should be administered with caution in patients with hemorrhagic diathesis. However, Nimesulide does not substitute acetylsalicylic acid in cardiovascular disease prevention. Nimid® should be withdrawn when the first signs of skin rash, mucous membranes lesions and other phenomena of allergic reaction occur.
In case of body temperature increase or flu-like symptoms occurrence in patients using Nimesulide, the preparation should be withdrawn.
Influence on reaction rate while driving a motor transport and operating other machines:
Nimid® influence on ability to drive a car and perform a work requiring a high attention has not been studied. However, patients who have dizziness or drowsiness during Nimesulide use should avoid driving a car and work requiring a high attention.
Drug interactions and other types of interaction:
Corticosteroids: increased risk of ulcers or gastrointestinal bleeding.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding in the digestive tract.
Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin or acetylsalicinic acid, therefore, this combination is not recommended to or contraindicated in patients with severely impaired coagulation. If such combination therapy cannot be avoided, it is required a careful monitoring of blood coagulation parameters.
Diuretic agents, ACE inhibitors and angiotensin-II antagonists: NSAIDs can reduce the effect of diuretics and other antihypertensive drugs. Some patients with renal dysfunction (e.g., in patients with dehydration or elderly ones) the simultaneous use of ACE inhibitors, angiotensin-II antagonists or substances that inhibit cyclooxygenase system may have further impairment of renal function and occurrence of acute renal failure, which is generally reversible. These interactions should be taken into account when the patient concurrently uses Nimid® and ACE inhibitors or angiotensin-II antagonists. Patients, especially elderly, should be very careful when using such a combination. Patients should take plenty of fluid and kidney function should be carefully monitored after the start of such combination use. Nimesulide temporarily reduces the effect of Furosemide on sodium excretion, to a lesser extent – on potassium excretion, and reduces diuretic effect. Simultaneous use of Furosemide and Nimid® requires for a caution in patients with renal or cardiac dysfunction.
There have been reports that NSAIDs decrease lithium clearance that leads to an increase in plasma lithium level and lithium toxicity. In Nimid® administration to patients who receive lithium therapy a frequent monitoring of plasma lithium levels should be carried out.
There was not clinically significant interaction in concomitant usage of Nimesulide with Glibenclamid, Theophyllin, Warfarin, Digoxin, Cimetidine and antacids (combination of aluminium and magnesium hydroxide).
Nimesulide inhibits CYP2C9 enzyme action. Therefore, concentration of agents, which are substrates of this enzyme, may be increased in their concurrent usage with Nimid®. It is necessary to be careful if Nimesulide is used less than 24 hours before or after the use of Methotrexate because of possible increasing of Methotrexate concentration in plasma and its toxicity.
Pharmacodynamics: Nimesulide is a non-steroidal anti-inflammatory drug of methanesulfonamide group, which has anti-inflammatory, analgesic and antipyretic actions. Medicinal effect of Nimid® is caused by it interaction with a cascade of arachidonic acid and reduces the biosynthesis of prostaglandins via cyclooxygenase inhibiting.
Pharmacokinetics: Nimesulide is well absorbed in a human organism in per oral use, reaching the maximal plasma concentration in 2–3 hours. About 97.5% of Nimesulide are bound to plasma proteins. Nimesulide is actively metabolized in liver via CYP2C9 isoenzyme of P450 cytochrome. The main metabolism product is para hydroxy derivative, which has a pharmacological activity. Half-life period is 3.2 to 6 hours. Nimesulide is excreted from the organism with the urine – approximately 50% of the used dose. Approximately 29% of the used dose are excreted with faeces in a metabolised form. Only 1–3% are excreted from the organism as unchanged ones. Pharmacokinetic profile in elderly patients is not changed.
General physic-chemical properties:pale yellow, round, plain on both sides tablets.
Store at a temperature not more 25°C in a dry, protected from light place.
Keep it out of reach of children.
There are 10 tablets in a blister, there is 1 blister in a carton package; there are 10 packages in a carton box.
Conditions of supply:
KUSUM HEALTHCARE PVT. LTD.
SP 289 (A), RIICO Indl.Area, Chopanki, Bhiwadi (Raj.), India.