COMPOSITION:

Active substance: nimesulide;

1 sachet (2 g of granules) contains nimesulide 100 mg;

excipients:

Lactose monohydrate, Povidone, Sodium saccharin, Citric acid, monohydrate; Flavour orange DC 100 PH, Colloidal anhydrous silica.

INDICATIONS:

Treatment of acute pain. Symptomatic treatment of osteoarthritis with pain syndrome. Primary dysmenorrhea.

DOSAGE:

For the purpose of appearance prevention and for subsidence of adverse reaction manifestations the preparation should be used during the shortest period of time and in the minimum effective dose. The drug should be administered only after precise assessment of risk/advantage ratio.

The drug is taken orally after meal. For adults and children aged 12 or above – is 1 sachet (100 mg) 2 times per day – in the morning and in the evening.

Content of the sachet dissolve before use in 1 glass of warm water and drink at once.

Maximum duration of treatment is 15 days.

Dosage adjustment for elderly patients is not required.

For the patients with decreased kidney function, for patients with mild and moderate severity of renal failure (creatine clearance is 380 ml/min), there is no need in dose correction.

ADVERSE REACTIONS:

The following criteria were used for evaluation of incidence rate of adverse reactions:

very often (≥ 1/10); often (≥ 1/100 < 1/10); not often (≥ 1/1000 < 1/100); seldom (≥ 1/10000 <1/1000); very seldom (< 1/10000), including individual cases.

Drug interactions:

Pharmacodynamic interaction.

Corticosteroids:

Risk of gastrointestinal ulcer or bleeding increases.

Antiplatelet agents and selective serotonin reuptake inhibitor (SSRI): Risk of gastrointestinal bleeding increases.

Anticoagulants:

NAID can potentiate such anticoagulants as warfarin and acetylsalicylic acid, that is why such combination is not recommended and forbidden for patients with severe impaired coagulation. If such combined therapy could not be avoided, a strict blood-clotting factor control should be conducted.

Diuretic agents, angiotensin converting enzyme inhibitors and antagonist of angiotensin-II.

NAID can depress diuretic actions and other antihypertensive preparations. Concomitant administration of ACE inhibitors, antagonist of angiotensin-II or cyclooxygenase inhibitors for some patients with kidney failure (patients with symptoms of dehydration or elderly patients) can further lead to deterioration of renal function and occurrence of acute renal failure, which is, as a rule, invertible. These interactions have to be considered, when the patient concomitantly uses Nimid® with ACE inhibitors or antagonist of angiotensin-II. It is necessary to be very careful, using such combination, especially for elderly people. Patients have to attain enough quantity of liquid, and renal function must be strictly controlled after the beginning of such combination administration. Nimesulide temporarily reduces the effect of furosemide on the excretion of sodium, in lesser degree, on excretion of kalium, as well as reduces the diuretic effect. Concomitant administration of furosemide and Nimid® requires carefulness from the patients with impaired renal function or heart.

Pharmacokinetic interaction with other medicinal preparations.

There were reports that NAID reduces clearance of lithium resulting in increase of lithium levels in the blood plasma and toxic effects of lithium preparations. Therefore in concomitant use of Nimid® and lithium therapy, lithium levels in blood plasma should be monitored closely. There were no clinically significant interactions observed in case of concomitant use of nimesulide and glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacid medications (combination of aluminum and magnesium hydroxide).

Nimesulide inhibits CYP 2C9 enzyme action. Therefore, plasma concentration of drugs that are substrates of this enzyme may be increased when Nimid® is used concomitantly.

Caution is required when nimesulide is used less than 24 h before or after the intake of methotrexate, as the serum level of methotrexate and its toxicity may increase.

Pregnancy and lactation:

Pregnancy:

Administration of Nimid® is contraindicated in the third trimester of pregnancy.

Administration of nimesulide can affect women’s fertility and is not recommended for women planning to become pregnant.

Like other nonsteroidal anti-inflammatory drugs which inhibit prostaglandin synthesis, Nimid® may bring on premature arterial (Botallo’s) duct closure, pulmonary hypertension, oliguria, oligohydramnios.

There is an increased risk of bleeding, uterine atony and peripheral edema. Given the lack of data on preparation use in pregnant women, it is not recommended to administer it in the 1st and 2nd trimesters of pregnancy.

Lactation:

As it is unknown if nimesulide is excreted into the breast milk, the drug use is contraindicated during the breast feeding.

Children:

The drug is contraindicated in children.

The preparation is contraindicated for children under age of 12 years.

PRECAUTIONS:

Nimesulide should be used only like a second line preparation. Decision about nimesulide prescription should be made on the basis of evaluation of all risks to the particular patient.

Unwanted adverse effects can be minimized by using minimal effective dose with minimal duration of the treatment, necessary for control of disease symptoms. In case of lack of efficacy of treatment (reducing of the disease symptoms) therapy with this preparation must be discontinued. There were reports on severe reactions on the part of the liver, including fatal, while nimesulide usage. Patients experience symptoms similar to liver disease during Nimid® therapy, for example, anorexia, nausea, vomiting, gastric pain, fatigability, dark urine, or patients, whose laboratory reports on hepatic function deviate from normal values, should stop preparation administration. It is forbidden to rechallenge nimesulide to those patients. During the treatment with Nimid®, it is recommended to avoid concomitant use of other analgesics. They should avoid simultaneous administration of other NAID, including Cox-2 selective inhibitors. Patients, who used nimesulide and who has got flu-like symptoms, should discontinue drug use. Elderly patients has a high frequency of adverse reaction on NAID, especially it concerns possible bleedings and perforations in digestive tract, which could be fatal for the patient. Ulcer, bleedings or perforations in the digestive tract can be dangerous to life of the patient, especially if in the history there are data that similar effects had appeared while using by the patient any other NAID (without a statute of limitations). Risk of similar phenomena increases along with NAID dose increasing of the patients which has in the history ulcer in the gastrointestinal tract, especially complicated with bleeding or perforation, as well as in elderly patients. For such patients therapy should be started with the minimum effective dose. For these patients, as well as for those, who uses concomitantly small doses of acetylsalicylic acid or some other preparations, increasing risk of digestive tract sequelae emergency, should be considered a possibility of combined treatment using protective agents, for example misoprostol or proton-pump inhibitor. Patients with the toxic damage of the digestive tracts, especially elderly people, should inform about any abnormal symptoms, appeared in the digestive tract, especially bleedings. It is especially important in the beginning of treatment. Patients, who use concomitantly preparations, which can increase a risk of ulcer or bleeding emergence, such as corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed about necessity to be careful while nimesulide usage. In case of emergence of gastrointestinal bleeding or ulcer in a patient, who uses Nimid®, treatment should be discontinued. Caution should be exercised when prescribing NAID to patients with Crohn’s disease or nonspecific ulcerative colitis in anamnesis, as far as nimesulide can lead to its exacerbation. For patients with arterial hypertension and/or heart failure in anamnesis, as well as for patients with fluid retention or NAID related edemas, appropriate condition control and consultation of the physician are necessary.

Clinical studies and epidemiological data permit to make a conclusion that some NAID, especially in a high dose and in long-term treatment, can lead to imperceptible risk of arterial thrombotic episodes, for example myocardial infraction and

insult. It is insufficient data for exclusion of such phenomena emergency while usage of nimesulide. For the patients with uncontrolled arterial hypertension, acute heart failure, identified ischemic heart disease, peripheral vascular disease and / or cerebrovascular disease nimesulide should be prescribed only after sound condition judgment. The same conditions should be hold while prescribing the preparation to the patients with the risk factor of cardiovascular disease development, for example while arterial hypertension, hyperlipidemia, pancreatic diabetes, and smocking. For patients with kidney or heart failure, the preparation should be carefully prescribed because of kidney functions loop. In case of deconditioning of a patient, treatment should be discontinued. Strict clinical control; should be realized for elderly patients because of the possible development of gastrointestinal bleeding and perforations, kidney, liver and heart failure. As far as nimesulide can influence on thrombocyte function, it should be carefully prescribed for patients with hemorrhagic diathesis. However nimesulide does not substitute acetylsalicylic acid for prevention of cardiovascular disease. Nimide® should be immediately withhold, if there are any exanthema, blennosis and any other hypersensitivity reaction manifestations. Nimide® contains lactose, that is why it should not be prescribed for patients with hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-maltase deficiency.

Overdose:

Symptoms:

Somnolence, nausea, vomiting, and anticardium pain are observed; also, gastrointestinal bleeding, arterial hypertension, acute renal failure, respiratory depression, anaphylactoid reactions and coma may occur in case of overdose.

Treatment:

There is no specific antidote. In case of overdose, symptomatic therapy is required.

It is necessary to perform gastric lavage and use activated carbon within the first four hours. Haemodialysis is not effective.

Hepatic and renal function monitoring is necessary.

Ability to influence reaction velocity while driving or operating any other mechanisms.

No studies on the effect of nimesulide on the ability to drive and perform the work requiring increased concentration of attention have been performed. However, patients experiencing dizziness or somnolence after receiving nimesulide should refrain from driving and performing the work requiring increased concentration of attention.

CONTRAINDICATIONS:

Known hypersensivity to the nimesulide or any other component of the drug. Hyperergic reactions, which took place in the past (bronchospasm, rhinitis, urticaria), connected with the administration of the acetylsalicylic acid or to other non-steroidal anti-inflammatory drugs (NAID). Hepatotoxic responses on nimesulide, which took place in the past. Active gastric or duodenal ulcer, recurrent ulcer or bleedings in the digestive tract, cerebrovascular bleedings or other diseases accompanying by bleedings. Hard disruption of blood coagulation. Severe cardiac failure. Severe kidney and liver failure. Fever and flu-like symptoms, assumption of acute surgical pathology. Do not use simultaneously with other preparations, which can cause hepatotoxic response. Alcoholism, drug abuse.

PHARMACOLOGICAL PROPERTIES:

* Pharmacodynamics. Nimesulide is an active substance with anti-inflammatory, analgesic and antipyretic properties. Nimesulide selectively inhibits COG II (cyclooxygenase II) and depresses the synthesis of prostaglandins in the focus of inflammation.

* Nimesulide inhibits the release of myeloperoxidase and formation of free oxygen radicals without affecting phagocytosis and free oxygen radical formation without affecting the processes of phagocytosis and chemotaxis; it inhibits formation of tumor necrosis factor and other mediators of inflammation.

Pharmacokinetics:

Nimesulide is quickly absorbed from gastro-intestinal tract after ingestion. Maximum plasma concentration of nimesulide occurs within 2 – 3 hours after ingestion. 97.5% of nimesulide is bound with plasma proteins.

The preparation is metabolized in liver; the main metabolism product is hydroxynimesulide, a pharmacologically active substance. Approximately 65% of the ingested dose is excreted with urine and the rest 35% with faeces.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties: Pale yellow granules with orange odor.

Shelf-life:

3 years

Storage:

Store at a temperature no more than 25°C. Keep out of reach of children.

Package:

2 g in each sachet. 30 sachets in a cartoon box.

Conditions of supply:

By prescription.