COMPOSITION:

Active ingredient:

Nimesulide;

1 tablet contains Nimesulide 100 mg.

Additional ingredients:

Microcrystalline cellulose

Croscarmellose sodium

Magnesium stearate

Silica colloidal anhydrous.

INDICATIONS:

Treatment of acute pain. Symptomatic treatment of osteoartrosis with pain syndrome. Primary dismenorrhea.

DOSAGE:

Nimid® is administered after a precise assessment of risk/benefit ratio. It is used the minimum effective dose for the shortest period. The maximum duration of the treatment with Nimid® is 15 days.

Adults and elderly patients:

1 tablet (100 mg) 2 times per day (daily dose is 200 mg).

Children older than 12 years:

The dose adjustment is not required.

Patients with renal dysfunction:

For patients with mild or moderate renal insufficiency (creatinine clearance is 30-80 ml/min)

the dose adjustment is not necessary. The preparation is used per oral after a meal

taking enough water with one’s medicine.

ADVERSE REACTIONS:

The frequency of side effects is classified as follows:

very common (> 1/10)

common (> 1/100

< 1/10)

sometimes (> 1/1000

< 1/100)

rare (>1/10 000

< 1/1000)

very rare (<1/10 000)

unknown (it is impossible to assess them as per available data).

Blood system:

rare – anemia

eosinophilia; very rare – thrombocytopenia

pancytopenia

purpura.

Immune system:

rare – hypersensitiveness reactions

very rare – anaphylaxis;

Metabolic disorders:

rare – hyperkalemia.

Psychics:

rare – feeling of fear

nervousness

nightmares.

Nervous system:

sometimes – dizziness

very rare – headache

drowsiness and encephalopathy (Reye syndrome).

Organ of vision:

rare – blurred vision.

Hearing organ:

very rare – vertigo (dizziness). Cardio-vascular system: rare – tachycardia

hemorrhage

lability of blood pressure

flushing

and sometimes – arterial hypertension.

Respiratory system:

sometimes – shortness of breath

very rare – asthma

bronchospasm.

Gastrointestinal tract:

common – diarrhea

nausea

vomiting and sometimes – constipation

meteorism

gastritis

very rare – abdominal pain

dyspepsia

stomatitis

black bowel movements

bleeding in digestive tract

ulcers and perforation of duodenum/stomach.

Hepatobiliary system:

very rare – hepatitis

fatal fulminant hepatitis

including jaundice and cholestasis.

Skin:

sometimes – itch

skin rash

increased sweating

rare – erythema

dermatitis

very rare – urticaria

angioedema

erythema multiforme

urticaria

Stevens-Johnson syndrome and toxic epidermal necrolysis.

Urinary system:

rare – dysuria

hematuria

urinary retention

very rare – renal failure

oliguria

interstitial nephritis.

General disorders:

sometimes – edema

rare – malaise

asthenia

very rare – hypothermia.

Laboratory tests:

common – increase in liver enzymes.

Drug interactions:

Pharmacodynamic interactions:

Corticosteroids: increased risk of ulcers or gastrointestinal bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs):

increased risk of bleeding in the digestive tract.

Anticoagulants:

NSAIDs may increase the effects of anticoagulants

such as warfarin or acetylsalicinic acid

therefore

this combination is not recommended to or contraindicated in patients with severely impaired coagulation. If such combination therapy cannot be avoided

it is required a careful monitoring of blood coagulation parameters.

Diuretic agents

ACE inhibitors and angiotensin-II antagonists:

NSAIDs can reduce the effect of diuretics and other antihypertensive drugs. Some patients with renal dysfunction (e.g.

in patients with dehydration or elderly ones) the simultaneous use of ACE inhibitors

angiotensin-II antagonists or substances that inhibit cyclooxygenase system may have further impairment of renal function and occurrence of acute renal failure

which is generally reversible. These interactions should be taken into account when the patient concurrently uses Nimid® and ACE inhibitors or angiotensin-II antagonists. Patients

especially elderly

should be very careful when using such a combination. Patients should take plenty of fluid and kidney function should be carefully monitored after the start of such combination use. Nimesulide temporarily reduces the effect of Furosemide on sodium excretion

to a lesser extent – on potassium excretion

and reduces diuretic effect. Simultaneous use of Furosemide and Nimid® requires for a caution in patients with renal or cardiac dysfunction.

Pharmacokinetic interactions:

There have been reports that NSAIDs decrease lithium clearance that leads to an increase in plasma lithium level and lithium toxicity. In Nimid® administration to patients who receive lithium therapy a frequent monitoring of plasma lithium levels should be carried out.

There was not clinically significant interaction in concomitant usage of Nimesulide with Glibenclamid

Theophyllin

Warfarin

Digoxin

Cimetidine and antacids (combination of aluminium and magnesium hydroxide).

Nimesulide inhibits CYP2C9 enzyme action. Therefore

concentration of agents

which are substrates of this enzyme

may be increased in their concurrent usage with Nimid®. It is necessary to be careful if Nimesulide is used less than 24 hours before or after the use of Methotrexate because of possible increasing of Methotrexate concentration in plasma and its toxicity.

Pregnancy and lactation:

Nimesulide administration can disturb women fertility and is not recommended for women planning to become pregnant.

It is not recommended to administer Nimid® to women who have problems with becoming pregnant or if they are on the examination because of infertility.

Nimid® administration is contraindicated in III trimester of pregnancy.

Like other non-steroidal anti-inflammatory drugs Nimid® is not recommended to administer to women who are planning to become pregnant.

Like other non-steroidal anti-inflammatory drugs

which inhibit prostaglandin synthesis

Nimesulide may bring to premature arterial (Botallo’s) duct closure

pulmonary hypertension

oliguria

oligohydramnios. There is an increased risk of bleeding

uterine insufficiency and peripheral oedema. There are single reports on renal failure in infants born by women who have used Nimesulide in late pregnancy.

This preparation is not used in I and II trimesters of pregnancy.

Since it is not known whether Nimesulide is excreted in breast milk it is not recommended to use Nimid® during lactation period.

Children:

Nimesulide is not used in children under 12 years old.

PRECAUTIONS:

Nimesulide should be used only as a second line. Decision on Nimesulide administration should be based on the assessment of risks for individual patients.

Unwanted side effects can be minimized by taking the least effective dose for the shortest period of administration required for symptoms control. In case of treatment ineffectiveness (reduction of disease symptoms)

this preparation therapy should be discontinued. There were reports on cases of liver severe reactions

including fatal ones

during Nimesulide use. Patients with symptoms similar to symptoms of liver lesion during Nimid® treatment

such as anorexia

nausea

vomiting

abdominal pain

fatigue

dark urine

or patients

which laboratory parameters of liver function are abnormal

should stop this preparation usage. Re-administration of Nimesulide to such patients is contraindicated. It is necessary to avoid other analgesics use during Nimid® treatment. It is necessary to avoid concomitant use of other NSAIDs

including selective cyclooxygenase-2. Patients who used Nimesulide and who have symptoms similar to flu or colds should discontinue its use. There are increased incidences of adverse reactions associated with NSAIDs

especially possible bleeding and perforation in the digestive tract that may be dangerous for a patient

in elderly patients. Ulcer bleeding or perforation of the digestive tract may threaten the life of a patient

especially if there is an evidence of such phenomena in anamnesis in patients during usage of any other NSAIDs (without limitation period). The risk of such events is increased together with NSAID dose increasing in patients with GIT ulcers in anamnesis

especially complicated by bleeding or perforation

as well as in elderly patients. The treatment in such patients should be started with the least effective dose. For these patients

as well as for those who use concurrently low-dose of acetylsalicinic acid or other medicines that increase the risk of complications in the digestive tract

it should be considered the possibility of combination therapy with such medicines as misoprostol or proton pump inhibitors. Patients with toxic lesion of the digestive tract

especially elderly ones

should inform about any unusual symptoms that occur in the digestive tract

especially about bleeding. Patients who use concomitant medications that may increase the risk of ulcers or bleeding

such as corticosteroids

anticoagulants

selective serotonin reuptake inhibitors

antiplatelet agents (acetylsalicylic acid)

should be informed about the need of caution during the use of Nimesulide. In case of bleeding or GIT ulcers in patients who use Nimid® this preparation treatment should be discontinued. It is necessary to administer NSAIDs with caution to patients with Crohn’s disease or ulcerative colitis in anamnesis

since Nimesulide may aggravate them. Patients with hypertension and/or heart failure in anamnesis

as well as those with water retention and edema due to the use of NSAIDs

require an appropriate state monitoring and a doctor’s advice. Clinical studies and epidemiological data suggest that some NSAIDs

especially in high doses and in long-term use

can lead to insignificant risk of arterial thrombotic episodes

for example

myocardial infarction and stroke. There is no sufficient data concerning exclusion of the risk of such events occurrence during Nimesulide use. Nimesulide should be administered to patients with uncontrolled arterial hypertension

acute cardiac insufficiency

known coronary heart disease

peripheral arterial disease and/or cerebrovascular disease only after a precise assessment of their states. It is also necessary to carefully assess the states of patients with risk factors of cardiovascular diseases

such as hypertension

hyperlipidemia

diabetes and smoking

before this preparation administration. It should be administered to patients with renal or heart failure with caution due to possible worsening of renal function. In case of recrudescence the treatment should be stopped. It is necessary a thorough clinical control under elderly patients due to possible development of bleeding and perforation of the digestive tract

renal liver or heart impairment. Since Nimesulide may affect platelet function

it should be administered with caution in patients with hemorrhagic diathesis. However

Nimesulide does not substitute acetylsalicylic acid in cardiovascular disease prevention. Nimid® should be withdrawn when the first signs of skin rash

mucous membranes lesions and other phenomena of allergic reaction occur.

In case of body temperature increase or flu-like symptoms occurrence in patients using Nimesulide

the preparation should be withdrawn.

Overdose:

Symptoms of acute overdose with non-steroidal anti-inflammatory drugs (NSAIDs) are usually as follows: apathy

drowsiness

nausea

vomiting

epigastric pain. These symptoms are usually reversible in supportive treatment. Gastrointestinal bleeding

hypertension

acute renal failure

respiratory depression

coma are possible

however

such phenomena are rare. There have been reports about anaphylactoid reactions during the use of therapeutic doses of NSAIDs and their overdose. There is no specific antidote.

The treatment of overdose is symptomatic and supportive one. There is no data concerning Nimesulide excretion via dialysis

but if the high degree of Nimesulide binding to plasma proteins (up to 97.5%) is taken into account

it is unlikely that dialysis will be effective.

In case of symptoms of overdose or after the use of a large dose of the preparation within 4 hours after its intake the following measures may be administered to patients:

Artificial vomiting turn up and/or intake of activated charcoal (60 – 100 g for adults)

and/or intake of osmotic laxative agent. Forced diuresis

increase of urine alkalinity

hemodialysis and hemoperfusion may be ineffective due to high degree of Nimesulide binding to plasma proteins. Renal and hepatic function should be monitored.

Ability to influence reaction velocity while driving or operating any other mechanisms. Nimid® influence on ability to drive a car and perform a work requiring a high attention has not been studied. However

patients who have dizziness or drowsiness during Nimesulide use should avoid driving a car and work requiring a high attention.

CONTRAINDICATIONS:

Known hypersensitivity to Nimesulide or any preparation components. Hyperergic reactions in anamnesis (bronchospasm

rhinitis

urticaria) due to the use of acetylsalicinic acid or other non-steroidal anti-inflammatory drugs; hepatotoxic reaction to Nimesulide in anamnesis; acute gastric and duodenum peptic ulcer

recurrent GIT ulcers

cerebrovascular bleeding or other lesions associated with bleeding; severe disorders of blood coagulability; severe kidney or hepatic insufficiency; fever and flu-like symptoms

suspected acute surgical pathology. It is not concurrently used with other medicines

which may potentially cause hepatotoxic reactions. Alcoholism

drug dependence. III trimester of pregnancy or lactation period. Children age less 12 years old.

PHARMACOLOGICAL PROPERTIES:

Nonsteroidal anti-inflammatory and anti-rheumatic medicines. Code АТС М01А Х17.

Pharmacodynamics:

Nimesulide is a non-steroidal anti-inflammatory drug of methanesulfonamide group

which has anti-inflammatory

analgesic and antipyretic actions. Medicinal effect of Nimid® is caused by it interaction with a cascade of arachidonic acid and reduces the biosynthesis of prostaglandins via cyclooxygenase inhibiting.

Pharmacokinetics:

Nimesulide is well absorbed in a human organism in per oral use

reaching the maximal plasma concentration in 2 – 3 hours. About 97.5% of Nimesulide are bound to plasma proteins. Nimesulide is actively metabolized in liver via CYP2C9 isoenzyme of P450 cytochrome. The main metabolism product is para hydroxy derivative

which has a pharmacological activity. Half-life period is 3.2 to 6 hours. Nimesulide is excreted from the organism with the urine – approximately 50% of the used dose. Approximately 29% of the used dose are excreted with faeces in a metabolised form. Only 1 – 3% are excreted from the organism as unchanged ones. Pharmacokinetic profile in elderly patients is not changed.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties:

pale yellow

round

plain on both sides tablets.

Shelf-life:

3 years.

Storage:

Store at a temperature not more 25°C in a dry

protected from light place.

Keep it out of reach of children.

Package:

There are 10 tablets in a blister

there is 1 blister in a carton package; there are 10 packages in a carton box.

Conditions of supply:

By prescription.