Нимесил®

General characteristics. Structure:

Active ingredient: Nimesulide of 100 mg;

Excipients: ketomacrogoal 1000, sucrose, maltodextrin, citric acid anhydrous, orange fragrance.

Pharmacological properties:

Pharmacodynamics. Nimesulide is non-steroidal anti-inflammatory drug (NPVP) from a class of sulfonamides. Has the antiinflammatory, anesthetizing and febrifugal effect. Nimesulide works as inhibitor of the enzyme of cyclooxygenase which is responsible for synthesis of prostaglandins and inhibits, mainly, cyclooxygenase 2.

Pharmacokinetics. After intake drug is well soaked up from digestive tract, reaching the maximum concentration in a blood plasma in 2-3 hours; communication with proteins of plasma – 97,5%; the elimination half-life makes 3,2-6 hours. Easily gets through gistogematichesky barriers.

It is metabolized in a liver by means of an isoenzyme of P450 (CYP) cytochrome 2C9. The main metabolite is pharmacological active parahydroxyderivative Nimesulide – hydroxynimesulide. Gidroksinimesulid is brought with bile in a metabolizirovanny look (it is found only in the form of a glyukuronat - about 29%).

Nimesulide is removed from an organism, generally by kidneys (about 50% of the accepted dose). The pharmacokinetic profile of Nimesulide at elderly people does not change at purpose of single and repeated/repeated doses.

According to pilot study, carried out with participation of patients with easy and moderate degree of a renal failure (clearance of creatinine of 30-80 ml/min.) and healthy volunteers, the maximum concentration of Nimesulide and its metabolite in plasma of patients did not exceed concentration of Nimesulide at healthy volunteers. The area under a curve "concentration time" (AUC) and an elimination half-life at patients with a renal failure were 50% higher, but within pharmacokinetic values. At repeated administration of drug of cumulation it is not observed.

Indications to use:

• Treatment of acute pains (dorsodynia, waist; a pain syndrome in a musculoskeletal system, including injuries, sprains and dislocations of joints; tendinites, bursitis; dentagra);
• A symptomatic treatment of an osteoarthrosis with a pain syndrome;
• Algodismenorey.

Drug is intended for symptomatic therapy, reduction of pain and an inflammation at the time of use.

Route of administration and doses:

Нимесил® accept inside, on 1 bag (100 mg of Nimesulide) twice a day. Drug is recommended to be accepted after food. Contents of a bag are poured out in a glass and dissolved approximately in 100 ml of water. The prepared solution is not subject to storage.

Нимесил® it is applied only to treatment of patients 12 years are more senior.

Teenagers (from 12 to 18 years): on the basis of a pharmacokinetic profile and pharmakodinamichesky characteristics of Nimesulide of need for correction of a dose at teenagers is not present.

Patients with an impaired renal function: on the basis of pharmacokinetic data of need for correction of a dose at patients with the easy and moderated forms of a renal failure (clearance of creatinine of 30-80 ml/min.) is not present.

Patients of advanced age: at treatment of elderly patients need of correction of a daily dose decides by the doctor proceeding from a possibility of interaction on other medicines.

The maximum duration of treatment by Nimesulide makes 15 days.

For reduction of risk of emergence of undesirable side effects it is necessary to use a minimal effective dose minimum short course.

Features of use:

Undesirable side effects can be minimized when using a minimal effective dose of drug minimum possible short course.

Нимесил® it is necessary to apply with care at patients with gastrointestinal diseases in the anamnesis (ulcer colitis, a disease Krone) as the exacerbation of these diseases is possible.

The risk of developing of gastrointestinal bleeding, ulcer or perforation of the ulcer increases with increase in a dose of NPVP at patients with existence of the ulcer in the anamnesis which is especially complicated by bleeding or a perforation, and also at elderly patients therefore treatment should be begun with the smallest possible dose. At the patients receiving the medicines reducing coagulability of blood or suppressing aggregation of thrombocytes also the risk of developing of gastrointestinal bleeding increases. In case of developing of gastrointestinal bleeding or an ulcer at the patients accepting Nimesil®, treatment by drug it is necessary to cancel.

As Nimesil® is partially removed by kidneys, the dosage it for patients with renal failures should be reduced, depending on urination level.

There are data on emergence of exceptional cases of reactions from a liver. At emergence of signs of damage of a liver (a skin itch, yellowing of integuments, nausea, vomiting, the abdominal pain, urine darkening, increase in activity of "hepatic" transaminases) should stop administration of drug and to see the attending physician.

Despite a rarity of emergence of vision disorders at the patients accepting Nimesulide along with other NPVP, treatment has to be immediately stopped. If there is any vision disorder, the doctor-oculist has to inspect the patient.

Drug can cause a liquid delay in fabrics therefore patients with high arterial pressure and with disturbances of cordial activity of Nimesil® should apply with extra care.

At patients with renal or heart failure it is necessary to use the drug Nimesil® with care as deterioration in function of kidneys is possible. In case of an aggravation of symptoms, treatment by the drug Nimesil® needs to be stopped.

Clinical trials and epidemiological data allow to draw a conclusion that NPVP, especially in high doses and at prolonged use, can result in insignificant risk of developing of a myocardial infarction or stroke. For an exception of risk of emergence of such events at use of Nimesulide of data it is not enough.

Sucrose is a part of drug, it should be considered to the patients suffering from a diabetes mellitus (0,15-0,18 XE on 100 mg of drug) and to the persons keeping to a low-calorie diet. Нимесил® patients are not recommended to appoint with rare hereditary diseases of intolerance of fructose, malabsorption of glucose galactose or insufficiency of sucrose-isomaltose.

At emergence of symptoms of "cold" or acute respiratory and viral infection in the course of treatment by the drug Nimesil® administration of drug has to be stopped.

It is not necessary to apply Nimesil® along with other NPVP.

Nimesulide can change properties of thrombocytes therefore it is necessary to be careful at use of drug for persons with hemorrhagic diathesis, however drug does not replace preventive effect of acetylsalicylic acid at cardiovascular diseases.

Elderly patients are especially subject to adverse reactions to NPVP, including in risk of developing of gastrointestinal bleedings and perforation, life-threatening the patient, to deterioration in function of kidneys, liver and heart. At administration of drug of Nimesil® appropriate clinical control is necessary for this category of patients.

As well as other drugs of class NPVP which inhibit synthesis of prostaglandins Nimesulide can negatively influence course of pregnancy and/or development of an embryo and can lead to premature closing of an arterial channel, hypertensia in system of a pulmonary artery, to a renal failure which can pass into a renal failure with an oligogidramniya, to increase in risk of bleedings, decrease in a kontraktilnost of a uterus, developing of peripheral hypostases. In this regard, Nimesulide is contraindicated during pregnancy and in the period of a lactation. Use of the drug Nimesil® can negatively influence female fertility and is not recommended to the women planning pregnancy. When planning pregnancy consultation with the attending physician is necessary.

There are data on emergence in rare instances of skin reactions (such as exfoliative dermatitis, Stephens-Johnson's syndrome, toxic epidermal necrolysis) on Nimesulide as well as on other NPVP. At the first symptoms of skin rash, damage of mucous membranes or other signs of allergic reaction administration of drug of Nimesil® should be stopped.

Influence of drug on ability to driving of motor transport and to control of mechanisms

Influence of the drug Nimesil® on ability to driving of motor transport and to control of mechanisms was not studied therefore during treatment by the drug Nimesil® it is necessary to be careful during the driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency is classified by headings, depending on occurrence of a case: very often (> 10), it is frequent (<10-<100), infrequently (<100-<1000), is rare (<1000-<10000), is very rare (<10000).

Disturbances from circulatory and lymphatic systems: seldom - anemia, an eosinophilia, hemorrhages; very seldom – thrombocytopenia, a pancytopenia, a Werlhof's disease.

Allergic reactions: infrequently – an itch, rash, the increased perspiration; seldom – hypersensitivity reactions, an erythema, dermatitis; very seldom - anaphylactoid reactions, a small tortoiseshell, a Quincke's disease, a poliformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease).

Disturbances from the central nervous system: infrequently – dizziness; seldom - sensation of fear, nervousness, night dreadful dreams; very seldom - a headache, drowsiness, encephalopathy (a syndrome to Reja).

Disturbances from sense bodys: seldom - indistinct sight.

Disturbances from cardiovascular system: infrequently – arterial hypertension, tachycardia, lability of arterial pressure, "inflows".

Disturbances from respiratory system: infrequently – an asthma; very seldom – an exacerbation of bronchial asthma, a bronchospasm.

Disturbances from digestive tract: often - diarrhea, nausea, vomiting; infrequently - a lock, a meteorism, gastritis; very seldom – abdominal pains, dyspepsia, stomatitis, a tar-like chair, gastrointestinal bleeding, an ulcer and/or perforation of a stomach or duodenum.

Disturbances from a liver and bile-excreting system: very seldom - hepatitis, fulminant hepatitis, jaundice, a cholestasia, increase in activity of liver enzymes

Disturbances from kidneys and an urinary system: seldom - a dysuria, a hamaturia, an urination delay; very seldom - a renal failure, an oliguria, intersticial nephrite.

General disturbances: seldom – an indisposition, an adynamy; very seldom – a hypothermia.

Others: seldom – a hyperpotassemia.

Interaction with other medicines:

Pharmakodinamichesky interactions:

Glucocorticosteroids: increase risk of developing of a gastrointestinal ulcer or bleeding.

Antithrombocytic means and the selection inhibitors of repeated absorption of serotonin (SSRIs), for example, fluoxetine: increase risk of developing of gastrointestinal bleeding.

Anticoagulants: NPVP can strengthen effect of anticoagulants, such as warfarin. Because of the increased risk of bleedings, such combination is not recommended and is contraindicated to patients with heavy disturbances of coagulation. If the combination therapy nevertheless cannot be avoided, it is necessary to carry out careful control of indicators of coagulability of blood.

Diuretics:

NPVP can reduce effect of diuretics.

At healthy volunteers Nimesulide temporarily reduces removal of sodium under the influence of furosemide, to a lesser extent - potassium removal, and reduces actually diuretic effect.

Joint reception of Nimesulide and furosemide concentration - time" (AUC) and decrease in cumulative excretion of furosemide without change of renal clearance of furosemide leads to reduction (approximately for 20%) the areas under a curve ".

Joint purpose of furosemide and Nimesulide demands care from patients with disturbances of renal or cordial functions.

APF inhibitors and antagonists of receptors of angiotensin-II:

NPVP can reduce effect of anti-hypertensive drugs. At patients with easy and moderate degree of a renal failure (clearance of creatinine of 30-80 ml/min.) at joint purpose of the APF inhibitors, antagonists of receptors of angiotensin II or substances suppressing system of cyclooxygenase (NPVP, antiagregant), perhaps further deterioration in function of kidneys and developing of an acute renal failure which, as a rule, happens reversible. These interactions should be considered at the patients accepting Nimesil® in combination with APF inhibitors or antagonists of receptors of angiotensin II. Therefore it is necessary to appoint joint reception of these drugs with care, especially for elderly patients. Patients have to receive enough liquid, and renal function should be controlled carefully after the beginning of joint therapy.

Pharmacokinetic interactions with other medicines:

There are data that NPVP reduce clearance of lithium that leads to increase in concentration of lithium in a blood plasma and its toxicity. At purpose of Nimesulide the patients receiving therapy by lithium drugs should exercise regular control of concentration of lithium in plasma.

Clinically significant interactions with glibenclamide, theophylline, digoxin, Cimetidinum and antiacid drugs (for example, a combination of aluminum and magnesium of hydroxides) were not observed.

Nimesulide suppresses activity of an isoenzyme of CYP2C9. At a concomitant use with Nimesulide of the drugs which are substrates of this enzyme, concentration of these drugs in plasma can increase.

At purpose of Nimesulide less than in 24 hours prior to or after reception of a methotrexate it is required to be careful as in such cases methotrexate level in plasma and, respectively, toxic effects of this drug can increase.

Due to the action on renal prostaglandins, inhibitors синтетаз prostaglandins to what Nimesulide concerns, can increase nephrotoxicity of cyclosporines.

Interaction of other drugs with Nimesulide:

The researches in vitro showed that Nimesulide is forced out from places of binding by Tolbutamidum, salicylic acid and valproic acid. In spite of the fact that these interactions were defined in a blood plasma, the specified effects were not observed in the course of a clinical use of drug.

Contraindications:

• Hypersensitivity to Nimesulide or to one of drug components.
• Giperergichesky reactions (in the anamnesis) for example, the bronchospasm, rhinitis, urticaria connected with reception of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, including Nimesulide.
• Hepatotoxic reactions to Nimesulide (in the anamnesis).
• The accompanying (simultaneous) reception of medicines with a potential hepatotoxic, for example, paracetamol or others analgeziruyushchy or non-steroidal anti-inflammatory drugs.
• Inflammatory diseases of intestines (a disease Krone, nonspecific ulcer colitis) in an aggravation phase.
• The period after performing aortocoronary shunting.
• A feverish syndrome at cold and acute respiratory and viral infections.
• A full or incomplete combination of bronchial asthma, the nose recuring a polypose or okolonosovy bosoms with intolerance of acetylsalicylic acid and other NPVP (including in the anamnesis);
• A peptic ulcer of a stomach or duodenum in an aggravation phase, existence in the anamnesis of an ulcer, perforation or bleeding in digestive tract.
• Existence in the anamnesis of cerebrovascular bleedings or other bleedings, and also the diseases which are followed by bleeding.
• Heavy disturbances of a blood coagulation.
• Heavy heart failure.
• A heavy renal failure (clearance of creatinine <30 ml/min.), the confirmed hyperpotassemia.
• Liver failure or any active disease of a liver.
• Children aged up to 12 years.
• Pregnancy and period of a lactation.
• Alcoholism, drug addiction.

With care: severe forms of arterial hypertension, diabetes mellitus 2 types, heart failure, coronary heart disease, cerebrovascular diseases, дислипидемия / lipidemia, diseases of peripheral arteries, smoking, clearance of creatinine less than 60 ml/min.

Anamnestic data on existence of a canker of a GIT, the infection caused by Helicobacter pylori; advanced age; the long previous use of NPVP; heavy somatopathies.

The accompanying therapy by the following drugs: anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), peroral glucocorticosteroids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).

The decision on purpose of the drug Nimesil® has to be based on individual assessment "risk advantage" at administration of drug.

Overdose:

Symptoms: apathy, drowsiness, nausea, vomiting, pain in epigastric area. At a maintenance therapy of a gastropathy these symptoms are usually reversible. Developing of gastrointestinal bleeding is possible. Increase in arterial pressure, an acute renal failure, respiratory depression and a coma, anaphylactoid reactions is in rare instances possible.

Treatment: Symptomatic. There is no specific antidote. If the overdose happened within the last 4 hours, it is necessary to cause vomiting and/or to provide reception of absorbent carbon (from 60 to 100 g on the adult) and/or osmotic laxative. The artificial diuresis, a hemodialysis – are inefficient because of high communication of drug with proteins (to 97,5%). Control of function of kidneys and a liver is shown.

Storage conditions:

List B. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity 2 years. Not to apply after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Granules for preparation of suspension for intake, 100 mg.

On 2 g of granulate in three-layered packages (paper / aluminum / polyethylene).

On 30 packages of the application instruction in a cardboard pack.