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.