Pharmacological properties

Pharmacodynamics. Nimesulide — npvp groups of metansulfonanilid which has the anti-inflammatory, anesthetizing and febrifugal effect. medical effect of Nimesulide is caused by the fact that it interacts with a cascade of arachidonic acid. Nimesulide selectively inhibits tsog tsog-2 synthesis of prostaglandins in the inflammation center.

Nimesulide inhibits myeloperoxidase enzyme release and also education of free radicals of oxygen oppresses, without influencing processes of phagocytosis and a chemotaxis, formation of a factor of necrosis of tumors and other mediators of inflammation oppresses.

Pharmacokinetics. After intake, Nimesulide is quickly soaked up in a GIT. The C _max in blood plasma is reached in 2–3 h. Up to 97.5% of Nimesulide contacts proteins of blood plasma.

in a liver with participation of CYP 2C9, P450 cytochrome enzyme. A key product of metabolism is hydroxynimesulide — pharmacological active agent. T _½ — from 3.2 to 6 h. Nimesulide is removed from an organism with urine — about 50% of the accepted dose. About 29% of the accepted dose are removed with a stake in a metabolizirovanny look. Only 1–3% are brought out of an organism in not changed look. The pharmacokinetic profile at elderly people does not change.

Indication

Elimination of an acute pain. treatment of primary dysmenorrhea.

Nimesulide should be applied only as medicine of the second line. The decision on prescribing of Nimesulide should be made on the basis of assessment of all risks for the specific patient.

Use

to minimize possible undesirable side effects, it is necessary to apply a minimal effective dose during the shortest time. the maximum duration of a course of treatment — 15 days.

Adult. On 1 tablet (100 mg) 2 times a day — in the morning and in the evening.

Elderly person. Dose adjustment is not required.

Children are aged more senior than 12 years. Dose adjustment is not required.

Patients with a renal failure. For patients with easy or moderate degree of a renal failure (clearance of creatinine of 30-80 ml/min.) of dose adjustment it is not required.

Drug is taken inside after a meal and washed down with enough liquid.

by the minimum term of the treatment necessary for control of symptoms.

Contraindication

Known hypersensitivity to Nimesulide or any component of medicine. the giperergichesky reactions arising in the past (bronchospasm, rhinitis, a small tortoiseshell) in connection with use of acetylsalicylic acid or others npvp. hepatotoxic reactions to Nimesulide which developed in the past. simultaneous use of other substances with potential hepatotoxicity. alcoholism and medicament addiction. suspicion of sharp surgical pathology. the gastrointestinal bleedings or perforation in the anamnesis connected with the previous application npvp. ulcer of stomach or duodenum in an aggravation phase, existence in the anamnesis of an ulcer, perforation or bleeding in a digestive tract. existence in the anamnesis of cerebrovascular bleedings or other hemorrhages and also diseases which are followed by bleeding. heavy violations of fibrillation. heavy heart failure. heavy renal failures. abnormal liver function. patients with the increased body temperature and/or grippopodobny symptoms. children aged up to 12 years. iii trimester of pregnancy and period of feeding by a breast.

Side effects

from the system of blood: anemia, eosinophilia, thrombocytopenia, pancytopenia, purple.

from the immune system: hypersensitivity reactions, anaphylaxis.

Metabolic violations: hyperpotassemia.

from mentality: feeling of alarm, nervousness, nightmares.

from nervous system: dizziness, headache, drowsiness, encephalopathy (syndrome to Reja).

from an organ of sight: illegibility of sight.

from an organ of hearing and a vestibular mechanism: vertigo (dizziness).

from a cardiovascular system: tachycardia, hemorrhage, lability of the ABP, inflows, AG.

from a respiratory system: short wind, OH, bronchospasm.

from digestive system: diarrhea, nausea, vomiting, a lock, a meteorism, gastritis, an abdominal pain, dyspepsia, stomatitis, kcal of black color, bleeding in a digestive tract, an ulcer and perforation of a duodenum or stomach.

from a gepatobiliarny system: hepatitis, instant (fulminantny) hepatitis with a lethal outcome, including jaundice, a cholestasia, increase in level of enzymes of a liver.

from skin: an itch, skin rashes, the increased sweating, an erythema, dermatitis, a small tortoiseshell, a Quincke's disease, a face edema, a poliformny erythema, Stephens's syndrome — Johnson, a toxic epidermal necrolysis.

from an urinary system: dysuria, hamaturia, urination delay, hypostases, renal failure, oliguria, interstitial nephrite.

General violations: hypostases, indisposition, adynamy, hypothermia.

Laboratory indicators: increase in level of liver enzymes.

Most often at application of NPVP are noted by side reactions from a digestive tract. Developing of round ulcers, perforation or bleedings in a digestive tract, sometimes life-threatening, especially at patients of advanced age is possible. There were messages about such side reactions after use of this group of medicines: nausea, vomiting, diarrhea, abdominal distension, lock, dyspepsia, abdominal pain, kcal of black color, hematemesis, stomacace, exacerbation of colitis and Crohn's disease, gastritises, developing of hypostasis, AG and heart failure; such skin reactions as formation of bubbles, Stephens's syndrome — Johnson and a toxic epidermal necrolysis.

Special instructions

Nimesulide should be applied only as medicine of the second line. the decision on prescribing of Nimesulide needs to be made on the basis of assessment of all risks for the certain patient.

needs to apply a minimal effective dose To reduction of risk of development of side effects with the smallest duration of a course of treatment. In case of lack of efficiency of treatment (reduction of expressiveness of symptomatology of a disease) the therapy should be stopped.

. In case of increase in level of liver enzymes or identification of signs of injury of a liver (for example anorexia, nausea, vomiting, an abdominal pain, feeling of fatigue, urine of dark color) or at a rejection of these laboratory analyses of function of a liver from norm medicine needs to be cancelled. Repeated prescribing of Nimesulide is contraindicated to such patients.

during treatment by Nimesulide is recommended to avoid simultaneous use of hepatotoxic medicines, analgetics, other NPVP, including selection TsOG-2 inhibitors and also to abstain from alcohol intake. At patients of advanced age side effects owing to administration of drug, including gastrointestinal bleedings, perforation, dysfunction of heart, kidneys and a liver which can be lethal for the patient most often develop. Therefore regular clinical control of a condition of the patient is recommended.

Ulcer, bleeding or perforation of a GIT can threaten the patient's life, especially if in the anamnesis there are data that the similar phenomena arose at the patient at application of any other NPVP (without limitation period). The risk of the similar phenomena increases together with increase in a dose of NPVP at the patients having in the anamnesis the ulcer in a digestive tract which is especially complicated by bleeding or perforation and also at patients of advanced age. Such patients should begin treatment with the minimum possible effective dose. For these patients and also for those which accept at the same time in low doses the acetylsalicylic acid or other medicines increasing risk of emergence of complications from a digestive tract it is necessary to consider the possibility of application of combination therapy with intake of such medicines as mizoprostol or inhibitors of a proton pomp. To patients with toxic damage of a digestive tract, especially to elderly people, it is necessary to report about any unusual symptoms arising in a digestive tract, especially about bleeding. It is especially important at initial stages of treatment. The patients taking the accompanying medicaments which can increase risk of developing of an ulcer or bleeding such as GKS, anticoagulants, selective serotonin reuptake inhibitors, antithrombocytic means (acetylsalicylic acid) need to be informed on need to be careful at use of Nimesulide. In case of emergence at the patients receiving Nimesulide, bleedings or ulcers of a digestive tract the medicament treatment should be stopped. Patients should appoint NPVP with care with Crohn's disease or with nonspecific ulcer colitis in the anamnesis as Nimesulide can lead to aggravation. Patients with AG and/or heart failure in the anamnesis and also with a liquid delay in an organism and hypostases owing to application of NPVP demand the corresponding control of a state and consultation of the doctor. Clinical trials and epidemiological data allow to draw a conclusion that some NPVP, especially in high doses and at prolonged use, can result in insignificant risk of emergence of arterial trombotichesky episodes, for example a myocardial infarction and a stroke. For an exception of risk of emergence of such phenomena at use of Nimesulide of data it is not enough. Patients with uncontrollable AG, the acute heart failure established to an ischemic heart disease, diseases of peripheral arteries and/or cerebrovascular diseases should appoint Nimesulide after careful assessment of a state. Also it is necessary to estimate carefully a condition of patients with risk factors of developing cardiovascular diseases, for example at AG, a lipidemia, diabetes, smoking, before prescribing of medicine. Patients with renal or heart failure should appoint medicine with care owing to possible deterioration in kidney function. In case of aggravation of symptoms the treatment should be stopped. For elderly people it is necessary to carry out careful clinical control because of a possibility of development of bleeding and perforation of a GIT, a renal failure, a liver or heart. As Nimesulide can influence function of platelets, it is necessary to appoint it with care the patient with hemorrhagic diathesis. However Nimesulide does not replace acetylsalicylic acid at prevention of cardiovascular diseases.

Use of NPVP can mask the fervescence connected with a background bacterial infection. In case of fervescence or emergence of grippopodobny symptoms in the patients accepting Nimesulide, administration of medicament should be cancelled.

, some of them can be deadly, for example exfoliative dermatitis, Stephens's syndrome — Johnson, a toxic epidermal necrolysis. Patients have very high risk of such reactions if at earlier appointed reaction course of treatment in most cases developed within the first month of treatment. Nimesulide needs to be cancelled at emergence of the first symptoms of skin rash, damage of mucous membranes and other allergic manifestations.

Drug contains lactose therefore it should not be applied to patients with rare hereditary forms of intolerance of a galactose, insufficiency of Lappa lactase or a syndrome of glyukozo-galaktozny malabsorption.

If at you established intolerance of some sugars, consult with the doctor before intake of this medicine.

Ability to influence speed of response at control of vehicles or other mechanisms. Influence of Nimesulide on ability to drive the car and to perform the works requiring special attention was not studied. However patients who after use of Nimesulide test dizziness or drowsiness should refrain from driving and performance of the work requiring special attention.

Use during pregnancy and feeding by a breast. Pregnancy. Use of Nimesulide is contraindicated in the last trimester of pregnancy. As well as other NPVP suppressing synthesis of prostaglandins, Nimesulide can cause premature closing of an arterial channel, pulmonary hypertensia, an oliguria, an oligoamnios. Risk of developing bleeding, weakness of patrimonial activity and peripheral hypostasis increases. There are separate messages about a renal failure at newborns whose mothers accepted Nimesulide at the end of pregnancy.

Considering also lack of data on use of medicine for pregnant women, it is not recommended to appoint Nimesulide in I and II trimester of pregnancy.

Feeding by a breast. As it is unknown whether Nimesulide gets into breast milk, use of medicine is contraindicated during feeding by a breast. Nimesulide can worsen fertile function at women therefore it is not recommended to be applied at women who try to become pregnant. At women who cannot become pregnant or the women undergoing inspection regarding infertility it is necessary to consider a question of a possibility of cancellation of Nimesulide. If pregnancy is established at use of Nimesulide, then the doctor has to be informed on it.

Children. Drug is contraindicated to children aged up to 12 years.

Interaction

Pharmakodinamichesky interactions.

GKS: the risk of developing of an ulcer of a digestive tract or bleeding increases.

Antithrombocytic means and selection inhibitors of repeated serotonin reuptake: the risk of developing of bleedings in a digestive tract increases.

Anticoagulants: NPVP can strengthen effect of anticoagulants, such as warfarin or acetylsalicylic acid therefore such combination is not recommended or is contraindicated to patients with heavy disorders of coagulation. If such combination therapy cannot be avoided, it is necessary to carry out careful control of indicators of fibrillation.

Diuretic means, APF inhibitors and antagonists of angiotensin II: NPVP can reduce effect of diuretics and other antihypertensive medicines. At some patients with a renal failure (for example with dehydration or elderly people) the general use of the APF inhibitors, antagonists of angiotensin II or substances suppressing the COG system, perhaps further deterioration in function of kidneys and emergence of OPN which, as a rule, is reversible. These interactions should be considered when the patient accepts Nimesulide combined with APF inhibitors or antagonists of angiotensin II. It is necessary to be very careful, applying such combination, especially to elderly people. Patients have to receive enough liquid, and function of kidneys needs to be controlled carefully after the beginning of application of such combination. Nimesulide temporarily reduces influence of furosemide on sodium removal, to a lesser extent — on removal of potassium and reduces diuretic effect. Simultaneous use of furosemide and Nimesulide demands care from patients with violation of kidney or warm function.

At healthy faces Nimesulide quickly reduces the effect of furosemide directed to sodium removal and to a lesser extent — on potassium removal and also reduces diuretic action. Simultaneous use of Nimesulide and furosemide leads to reduction (approximately for 20%) to AUC and decrease in cumulative excretion of furosemide without changes of kidney clearance of furosemide.

Pharmacokinetic interactions with other medicines. There were messages that NPVP reduce clearance of lithium that leads to increase in level of lithium in blood plasma and toxicity of lithium. When prescribing Nimesulide the patients receiving therapy by lithium medicines should control often lithium level in blood plasma.

clinically significant interaction with glibenclamide, theophylline, warfarin, digoxin, Cimetidinum and antiacid medicines (combination of aluminum and magnesium of hydroxide). Nimesulide suppresses activity of CYP enzyme 2C9. At simultaneous application with Nimesulide of the medicines which are substrates of this enzyme, their concentration in blood plasma can increase.

in case Nimesulide is applied less than for 24 h to or in 24 h after reception of a methotrexate as increase in level of the last in blood plasma and increase in its toxicity is possible.

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Influence of other medicines on Nimesulide. The researches in vitro showed that Nimesulide is forced out from places of binding by tolbutamide, salicylic acid and valproic acid. In spite of the fact that these interactions are defined in blood plasma, the specified effects are noted in the course of clinical use of medicine.

Incompatibility. It is unknown.

Overdose

Symptoms of sharp overdose npvp are usually limited to such manifestations: apathy, drowsiness, nausea, vomiting, pain in epigastric area. these symptoms, as a rule, are reversible at maintenance therapy. developing of gastrointestinal bleeding, ag, opn, respiratory depressions, a coma is possible, however such phenomena are noted seldom. there were messages about anaphylactoid reactions at application of therapeutic doses npvp and at their overdose. there is no specific antidote. overdose treatment — symptomatic and supporting. there are no data on removal of Nimesulide by means of a hemodialysis, but if to take into account high extent of linking of Nimesulide with proteins of plasma (to 97.5%), then it is improbable that dialysis will be effective. in the presence of symptoms of overdose or after use of medicine in a high dose during 4 h after reception to patients can be appointed: artificial calling of vomiting and/or intake of activated carbon (60–100 g for adults) and/or intake of osmotic depletive. the artificial diuresis, increase in alkalinity of urine, a hemodialysis and hemoperfusion can be inefficient owing to high extent of linking of Nimesulide with proteins of blood plasma. it is necessary to control functions of kidneys and a liver.

Storage conditions

At a temperature not above 25 °C in original packing.