Nimesulide

General characteristics. Structure:

Deystuyushchiye substance: 100 mg of Nimesulide.

Excipients: lactose, microcrystallic cellulose, corn starch, polyvinylpirrolidone, Natrium benzoicum, talc, sodium glikolit starch, magnesium stearate.

Non-steroidal anti-inflammatory drug which renders pronounced antiinflammatory, analgeziruyushchy and febrifugal effect.

Pharmacological properties:

Pharmacodynamics. Non-steroidal anti-inflammatory drug from a class of sulfonanilid. Is the selection competitive inhibitor of cyclooxygenase-2 (TsOG-2) - the enzyme participating in synthesis of prostaglandins - mediators of hypostasis, an inflammation and pain.

Reversibly inhibits formation of E2 prostaglandin, both in the inflammation center, and in the ascending ways of nociceptive system, including ways of carrying out painful impulses of a spinal cord. Reduces concentration of short-lived H2 prostaglandin of which under the influence of a prostaglandinizomeraza E2 prostaglandin is formed. Reduction of concentration of E2 prostaglandin leads to decrease in extent of activation of prostanoid receptors of ER of type that is expressed in analgetic and antiinflammatory effects.

In insignificant degree affects TsOG-1, practically without interfering with formation of E2 prostaglandin from arachidonic acid in physiological conditions thanks to what the amount of side effects of drug decreases. Due to the selection action on TsOG-2 does not break synthesis of prostaglandins with cytoprotective effect in a mucous membrane of a stomach that reduces risk of development of side effects.

Nimesulide also suppresses aggregation of thrombocytes by inhibition of synthesis of an endoperoksidova of A2 thromboxane, inhibits synthesis of a factor of aggregation of thrombocytes, slows down activation of plasminogen by increase in concentration of inhibitor-1. Suppresses release of a histamine, and also reduces degree of the bronchospasm caused by influence of a histamine and acetic aldehyde.

Inhibits release of a factor of a necrosis of tumors α, causing formation of tsitokinin. It is shown that Nimesulide is capable to suppress synthesis interleykina-6 and urokinases, thereby, interfering with destruction of cartilaginous tissue. Inhibits synthesis of metalproteases (elastase, a collagenase), preventing destruction of proteoglycans and collagen of cartilaginous tissue.

Has antioxidant properties, slows down formation of toxic decomposition products of oxygen due to reduction of activity of myeloperoxidase. Besides, Nimesulide reduces formation of superoxidic anions neutrocytes and education of the free radicals who are formed at an inflammation oppresses. Interacts with glucocorticoid receptors, activating them by phosphorylation that also strengthens antiinflammatory effect of drug.

Pharmacokinetics. Absorption at intake high. Meal reduces absorption speed, without exerting impacts on its degree. Time of achievement of the maximum concentration of active agent in a blood plasma - 1-2 h. Communication with proteins of plasma makes 95%, with erythrocytes - 2%, with lipoproteins of-1%, with acid alfa1 - glycoproteins - 1%. The dose of drug does not influence extent of its linkng with blood proteins.

The maximum concentration of Nimesulide in a blood plasma reaches 3,5-6,5 mg/l. Distribution volume - 0,19-0,35 l/kg. Gets into fabrics of female generative organs where after a single dose its concentration makes about 40% of concentration in plasma. Well gets into acid medium of the center of an inflammation (40%), synovial fluid (43%). Easily gets through gistogematichesky barriers. Duration of action is about 6-8 h.

It is metabolized in a liver by fabric monooxygenases. The main metabolite – 4 hydroxynimesulide (25%) has similar pharmacological activity. The elimination half-life of Nimesulide makes 1,56 – 4,95 hours, 4 hydroxynimesulides – 2,89-4,78 hours. 4 hydroxynimesulide are removed by kidneys (65%) and with bile (35%). At prolonged use it does not kumulirutsya in an organism. At patients with a renal failure (clearance of creatinine of 1,8 - 4,8 l/h, or 30-80 ml/min.), and also at children and elderly people the pharmacokinetic profile of Nimesulide significantly is not changed.

Indications to use:

• treatment of an acute pain;

• a symptomatic treatment of a pain syndrome at an osteoarthritis;

• primary dysmenorrhea.

The decision on purpose of Nimesulide has to be based on assessment of individual factors of the patient.

Route of administration and doses:

Inside on 1 tablet (100 mg) 2 times a day after food.

For the purpose of reduction of frequency of side effects drug has to be appointed in the minimum therapeutic dose. Drug can be used no more than 15 days.

For children aged from 12 up to 18 years the daily dose also makes 100 mg, and at body weight over 40 kg - 100 mg 2 times a day.

Patients with a renal failure at clearance of creatinine have 30-80 ml/min., and also at advanced age reduction of a dose of Nimesulide is not required.

Features of use:

Side effects of use of Nimesulide can be eliminated if to carry out treatment by a short course with drug withdrawal on achievement of therapeutic action or because of inefficiency.

If at use of Nimesulide for patients biochemical changes of function of a liver are noted or arise symptoms of damage of a liver (anorexia, nausea, vomiting, an abdominal pain, dark urine), then therapy by Nimesulide it is necessary to stop. In most cases noted phenomena are completely reversible.

During therapy by Nimesulide the patient is recommended to refrain from use of other NPVS. Simultaneous use spirit of drugs from this group is not recommended.

The patients accepting Nimesulide at whom temperature increase or a grippopodobny syndrome is noted have to stop administration of drug.

To take drug at arterial hypertension, heart failure, a diabetes mellitus 2 types with caution, and also at use of the following drugs: anticoagulative means, aspirin or other types of acetylsalicylic acid, diuretic and anti-hypertensive drugs, antidepressants, methotrexate, cyclosporine.

Nimesulide should be applied with care to patients at whom tendency to bleedings, patients with diseases of the upper parts of digestive tract which had gastrointestinal bleeding in the anamnesis or having nonspecific ulcer colitis and a disease Krone and also to the patients receiving the medicines reducing coagulability of blood, or the drugs suppressing aggregation of thrombocytes was observed. Gastrointestinal bleeding or a yazvoobrazovaniye can occur at any stage of administration of drug, including at the persons who were earlier not noting these symptoms. In case of their emergence reception of Nimesulide has to be stopped.

Patients of advanced age as patients of this group are sensitive to side effects of NPVS should appoint drug with care.

As Nimesulide can exert impact on function of thrombocytes, it has to be appointed with care at patients with hemorrhagic diathesis. Nimesulide does not replace acetylsalicylic acid in prevention of cardiovascular complications.

Use of Nimesulide can worsen fertility therefore its use is not recommended at the women planning pregnancy. If at the woman infertility is noted, then use of Nimesulide has to be stopped.

Researches on influence of Nimesulide on an opportunity to manage the vehicle were not conducted, however persons who note dizziness or drowsiness after Nimesulide use, have to refrain from driving or work on the mechanisms requiring special attention.

Side effects:

Frequency is classified depending on occurrence of a case: very often (> 1/10), it is frequent (<1/10 and> 1/100), infrequently (<1/100 and> 1/1000), is rare (<1/1000 and> 1/10000), is very rare (<1/10000).

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

Central nervous system: infrequently - dizziness; seldom - feeling of fear, nervousness, dreadful dreams; very seldom - a headache, drowsiness, encephalopathy (a syndrome to Reja).

Respiratory organs: infrequently - an asthma; very seldom - bronchial asthma, a bronchospasm.

Cardiovascular system: infrequently - arterial hypertension; seldom - tachycardia, hemorrhages, "inflows".

Sense bodys: seldom - a sight illegibility, it is very rare - dizziness.

Skin and mucous covers: infrequently - an itch, rash, sweating strengthening; seldom: erythema, dermatitis; very seldom: small tortoiseshell, Quincke's disease, puffiness of the person, mnogoformny exudative erythema, including Stephens-Johnson's syndrome, toxic epidermal necrolysis (Lyell's disease).

Liver and bile-excreting system: often - increase in "hepatic" transaminases; very seldom - hepatitis, jaundice, a cholestasia; extremely - seldom quickly developing hepatitis, including from the death.

Kidneys and urinary system: infrequently - hypostases; seldom - a dysuria, a hamaturia, an ischuria, a hyperpotassemia; very seldom - a renal failure, an oliguria, intersticial nephrite.

Bodies of a hemopoiesis: seldom - anemia, an eosinophilia; very seldom - thrombocytopenia, a pancytopenia, a purpura, lengthening of a bleeding time.

Allergic reactions: seldom - hypersensitivity reactions; very seldom - anaphylactoid reactions.

General reactions: seldom - the general weakness; very seldom - a hypothermia.

Interaction with other medicines:

At simultaneous use of Nimesulide to the following drugs there is a competition of drugs for communication with proteins of plasma: with digoxin; Phenytoinum and drugs of lithium; diuretics and antihypertensives; other NPVS; cyclosporine; methotrexate and antidiabetic means.

Action of the medicines reducing coagulability of blood amplifies at their simultaneous use with Nimesulide. At the patients accepting warfarin and drugs of acetylsalicylic acid the risk of bleedings therefore this combination is not recommended increases. If appointment cannot be avoided, then the dose of warfarin has to be under strict laboratory control.

Nimesulide can reduce effect of furosemide on removal of sodium and, to a lesser extent, on removal of potassium and diuretic action. Joint purpose of furosemide and Nimesulide leads to decrease (approximately for 20%) removal of furosemide without reduction of renal clearance.

Use of Nimesulide within 24 hours to or later can increase a possibility of approach of side effects at reception of a methotrexate.

Lithium level in plasma increases at a concomitant use of drugs of lithium and Nimesulide therefore serumal concentration of lithium has to be controlled more carefully.

Because of high extent of linkng of Nimesulide with proteins of plasma patients who are at the same time treated hydantoin and streptocides have to be under observation of the doctor, undergoing inspection through short periods.

Nimesulide can strengthen nefrotoksichny effect of cyclosporine.

Contraindications:

Hypersensitivity in the anamnesis to Nimesulide, drug excipients;

Existence in the anamnesis of reactions of hypersensitivity ("aspirinovy" asthma, bronchospasm, allergic rhinitis or defeat of integuments) at use of other NPVP groups;

The peptic ulcer of a stomach and 12-perstny gut in an aggravation phase recuring erosive cankers of digestive tract, bleeding from digestive tract in the anamnesis;

Existence in the anamnesis of data on hepatotoxic reactions to Nimesulide, and also combined use with potentially gepatotoksichny substances (paracetamol or other anesthetizing drugs);

Abnormal liver function;

alcoholism, drug addiction, medicinal dependence;

Heavy disturbances of coagulability of blood;

Renal failure (clearance of creatinine less than 30 ml/min.);

Heavy heart failure;

Patients with fever or a grippopodobny syndrome (feeling of weakness, fatigue, a fever or heat);

Pregnancy (third trimester), lactation period;

Children's age (up to 12 years).

Overdose:

Symptoms: apathy, drowsiness, nausea, vomiting. They are, as a rule, reversible at drug withdrawal. There can be gastrointestinal bleeding. Arterial hypertension, an acute renal failure, respiratory depression can meet, but is very rare.

Treatment: the symptomatic treatment of the patient and the supporting care of it is required. There is no specific antidote. If the overdose happened within the last 4 hours, it is necessary to cause vomiting, to provide reception of absorbent carbon (60-100 g on the adult), osmotic laxatives. The artificial diuresis and a hemodialysis are inefficient because of high communication of drug with proteins.

Storage conditions:

List B. In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. 1 or 2 blister strip packagings together with a leaf insert in secondary packaging from a cardboard bandbox.