Nimesulide tablets 100 mg

Instructions for use Nimesulide tablets 100 mg

International Nonproprietary Name: Nimesulide

Trade Name: Nimesulide

Dosage Form: tablets

Composition per one tablet:

Active substance: nimesulide
100.0 mg.

Excipients: calcium hydrogen phosphate dihydrate - 75.0 mg, corn starch - 54.0 mg, microcrystalline cellulose 101 – 40 mg, sodium starch glycolate (type A) - 35.0 mg, magnesium stearate - 3.0 mg, colloidal silicon dioxide - 2.0 mg, talc - 1.0 mg.

Description

Round, biconvex tablets, light yellow or yellow in color.

Pharmacotherapeutic group: nonsteroidal anti-inflammatory drug (NSAID).

ATC Code: M01AX17

Pharmacological properties

Pharmacodynamics:

Nonsteroidal anti-inflammatory drug (NSAID) from the sulfonanilide class.

It is a selective, competitive inhibitor of cyclooxygenase-2 (COX-2) - an enzyme involved in the synthesis of prostaglandin inflammatory mediators at the site of injury. The inhibitory effect on COX-1 is less pronounced, therefore nimesulide less frequently causes side effects associated with the inhibition of prostaglandin synthesis in healthy tissues. It has anti-inflammatory, analgesic, and antipyretic effects.

Pharmacokinetics

Absorption

Absorption after oral administration is high. Food intake reduces the rate of absorption without affecting its extent. Time to reach maximum concentration (T_max) – 1.5 - 2.5 hours.

Distribution

Plasma protein binding is 95%, with erythrocytes – 2%, with lipoproteins – 1%, with acidic alpha-1-glycoproteins – 1%.

Changing the drug dose does not affect its degree of binding to blood proteins. Maximum concentration (C_max) of nimesulide in blood plasma – 3.5 - 6.5 mg/L. Volume of distribution – 0.19 - 0.35 L/kg. Penetrates into tissues of the female reproductive organs, where after a single dose its concentration is about 40% of the plasma concentration. Penetrates well into the acidic environment of the inflammation site (40%), synovial fluid (43%). Easily crosses histohematic barriers.

Metabolism

Metabolized in the liver by tissue monooxygenases.

The main metabolite – 4-hydroxynimesulide (25%) has similar pharmacological activity but, due to reduced molecular size, is able to diffuse through the hydrophobic channel of COX-2 to the active binding site of the methyl group.

Excretion

The half-life (T_1/2) of nimesulide is 1.56 - 4.95 hours, of 4-hydroxynimesulide - 2.89-4.78 hours. 4-hydroxynimesulide is excreted by the kidneys (65%) and with bile (35%), undergoes enterohepatic recirculation.

In patients with renal insufficiency (creatinine clearance 1.8 - 4.8 L/h or 30-80 ml/min), as well as in children and elderly individuals, the pharmacokinetic profile of nimesulide does not change significantly.

Indications for use

The drug is intended for symptomatic therapy, to reduce pain and inflammation at the time of use; it does not affect the progression of the disease.

• pain syndrome in musculoskeletal disorders, as well as pain syndrome in musculoskeletal injuries;
• joint syndrome during acute gout attacks;
• psoriatic arthritis;
• pain syndrome of various origins: dysmenorrhea, toothache, headache, lumbosacral radiculopathy (sciatica).

Contraindications

• hypersensitivity to nimesulide and drug components (complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinusitis and intolerance to acetylsalicylic acid and other NSAIDs (including history);
• erosive-ulcerative changes of the gastric and duodenal mucosa in the acute stage;
• gastrointestinal bleeding or perforation of the intestinal wall in the past,
• inflammatory bowel diseases (ulcerative colitis, Crohn's disease) in the acute phase;
• cerebrovascular bleeding,
• history of coagulation disorders accompanied by bleeding,
• hemophilia; 
• hepatic insufficiency or any active liver disease;
• history of hepatotoxic reactions while taking nimesulide preparations;
• concomitant use of hepatotoxic substances;
• alcoholism;
• drug addiction;
• severe renal failure (creatinine clearance less than 30 ml/min); progressive kidney disease;
• pregnancy;
• breastfeeding period;
• children under 12 years of age;
• decompensated heart failure;
• severe coagulation disorders;
• confirmed hyperkalemia;
• period after coronary artery bypass graft surgery;
• broncho-obstructive diseases of the respiratory system;
• colds accompanied by high body temperature

With caution

Ischemic heart disease, chronic heart failure (NYHA functional class II-IV), cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, obliterating peripheral arterial diseases, hemorrhagic diathesis, smoking, mild and moderate renal failure (CrCl 30-60 ml/min), systemic lupus erythematosus and other autoimmune diseases. History of ulcerative gastrointestinal lesions, presence of Helicobacter pylori infection. Elderly age, long-term use of nonsteroidal anti-inflammatory drugs, alcohol abuse, smoking,  severe somatic diseases, concomitant treatment with anticoagulants (e.g., warfarin), antiplatelet agents (e.g.,  acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

Use during pregnancy and breastfeeding

Not recommended for women planning pregnancy.

Contraindicated for use during pregnancy and lactation. However, there are currently no scientific data on the embryotoxic and tocolytic effects of nimesulide.

Dosage and Administration

Adults and children over 12 years old: orally, 1 tablet (100 mg) twice daily. The maximum daily dose for adults is 200 mg. Tablets should be taken with a sufficient amount of water, preferably after meals. In the presence of gastrointestinal diseases, the drug is advisable to take at the end of a meal or after eating.

Patients with chronic renal insufficiency require a reduction in the daily dose to 100 mg.

The minimum effective dose should be used for the shortest possible course.

The duration of the treatment course should not exceed 15 days.

Instructions for use of Nimesulide in children and the elderly

Nimesulide tablets should be prescribed only if the patient has reached 12 years of age. Use in children under 12 years is contraindicated. Exceptions are possible only when the effectiveness of treatment outweighs the risks to the patient's health. In such a situation, the doctor may prescribe Nimesulide, selecting an individual treatment regimen and dosage.

Adjustment of the frequency and amount of drug intake when prescribed to elderly patients is not required. In this situation, Nimesulide is taken according to the general instructions for use, as with adult patients.

IMPORTANT! It must be taken into account that exceeding the daily dosage of the drug is not allowed. Otherwise, the risk of negative reactions from the body increases. If a patient misses a dose, the dosage should not be increased at the next application. In case of a long break in treatment, it is necessary to consult a doctor again to clarify a new drug regimen or adjust the existing one.

Adverse reactions

Frequency of adverse effects is classified according to incidence: Very common (>1/10), Common – (from ≥ 1/100 to < 1/10), Uncommon (from ≥ 1/1000 to < 1/100), Rare (from ≥ 1/10000 to < 1/1000), Very rare (< 1/10000), Frequency not known (cannot be estimated from the available data).

Allergic reactions: Rare – hypersensitivity reactions; Very rare – anaphylactoid reactions. 

Central nervous system disorders: Uncommon – dizziness; Rare – feeling of fear, nervousness, "nightmarish" dreams; Very rare – headache, drowsiness, encephalopathy (Reye's syndrome).

Skin and subcutaneous tissue disorders: Uncommon – pruritus, rash, increased sweating; Rare - erythema, dermatitis; Very rare - urticaria, angioedema, facial swelling, erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Renal and urinary disorders: Uncommon  – edema; Rare – dysuria, hematuria, urinary  retention, hyperkalemia; Very rare – renal failure, oliguria, interstitial nephritis.

Gastrointestinal disorders: Common – diarrhea, nausea, vomiting; Uncommon - constipation, flatulence, gastritis; Very rare – abdominal pain, stomatitis, tarry stools, gastrointestinal bleeding, ulcer and/or perforation of the duodenum and/or stomach.

Hepatobiliary disorders: Common – increased "liver" transaminases; Very rare – hepatitis, fulminant hepatitis, jaundice, cholestasis.

Blood and lymphatic system disorders: Rare – anemia, eosinophilia; Very rare – thrombocytopenia, pancytopenia, purpura, prolonged bleeding time.

Respiratory, thoracic and mediastinal disorders: Uncommon – dyspnea; Very rare – exacerbation of bronchial asthma, bronchospasm.

Eye disorders: Rare – blurred vision.

Cardiac and vascular disorders: Uncommon – increased blood pressure; Rare – tachycardia, palpitations, hemorrhages, flushing, palpitations.

Other: Rare – general weakness; Very rare – hypothermia, asthenia, hyperkalemia.
If any of the adverse effects mentioned in the instructions worsen, or if you notice any other adverse effects not listed, inform your doctor.

Overdose

Symptoms: Apathy, drowsiness, nausea, vomiting. Development of gastrointestinal bleeding, as well as increased blood pressure, acute renal failure, respiratory depression are possible.

Treatment: Symptomatic. There is no specific antidote. If overdose symptoms occur within 4 hours of ingestion, induce vomiting, take activated charcoal (60-100 g for an adult) and osmotic laxatives. Forced diuresis and hemodialysis are ineffective due to the high protein binding of the drug.

Drug interactions

• Concurrent use of nimesulide with salicylates or other nonsteroidal anti-inflammatory drugs is not recommended due to an increased risk of ulceration of the gastrointestinal tract.
• Use of nonsteroidal anti-inflammatory drugs is not recommended within 8-12 days after taking mifepristone.
• When used concomitantly with anticonvulsants (valproic acid), antifungal drugs (ketoconazole), anti-tuberculosis drugs (isoniazid), amiodarone, methotrexate, methyldopa, amoxicillin in combination with clavulanic acid, an enhanced hepatotoxic effect is possible.
• Nimesulide should not be taken with anticoagulants such as warfarin,  as it enhances their anticoagulant effect. Due to the increased risk of bleeding, such combination is not recommended and is contraindicated in patients with severe coagulation disorders.

Nonsteroidal anti-inflammatory drugs  may reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) with concurrent use of ACE inhibitors, angiotensin II receptor antagonists and agents that suppress the cyclooxygenase system (NSAIDs, antiplatelet agents), further deterioration of renal function and occurrence of acute renal failure, which is usually reversible, is possible. These interactions should be considered in patients taking nimesulide in combination with ACE inhibitors or angiotensin II receptor antagonists.  Therefore, concurrent use of these drugs should be done with caution, especially in elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after initiation of concurrent use.

Nimesulide may reduce the effect of furosemide. In healthy volunteers, nimesulide temporarily reduced sodium excretion induced by furosemide, to a lesser extent potassium excretion, and reduced the diuretic effect itself. Concurrent use of nimesulide and furosemide requires caution in patients with renal or cardiac insufficiency.

Nimesulide may increase the likelihood of adverse effects when taken concomitantly with  methotrexate.

Plasma lithium levels increase with concurrent use of lithium preparations and nimesulide.

Nimesulide may enhance the nephrotoxic effect of cyclosporine on the kidneys.

Use of the drug with glucocorticosteroids, serotonin reuptake inhibitors, and antiplatelet agents increases the risk of gastrointestinal bleeding.

Nimesulide inhibits the CYP2C9 isoenzyme, therefore the plasma concentration of drugs metabolized by this isoenzyme may increase when used concomitantly with nimesulide.

Theoretically, a decrease in the effectiveness of mifepristone and prostaglandin analogs is possible when used concomitantly with NSAIDs (including acetylsalicylic acid) due to the antiprostaglandin action of the latter.

No clinically significant interactions of nimesulide with glibenclamide, theophylline, digoxin, cimetidine, and antacids (combination of aluminum and magnesium compounds) have been identified.

Caution is required if nimesulide is administered less than 24 hours before or after methotrexate use, as in such cases the plasma concentration of methotrexate and its toxic effects may increase.

Special warnings and precautions

Since nimesulide is partially excreted by the kidneys, for patients with impaired renal function, the drug dose must be reduced depending on creatinine clearance levels. If creatinine clearance decreases, treatment should be discontinued.

Given reports of visual impairment in patients taking other NSAIDs, treatment should be stopped immediately. If any visual disturbance occurs, the patient should be referred for examination by an ophthalmologist.

Should be used with caution in patients with high blood pressure and cardiac disorders, due to the drug's ability to cause fluid retention in tissues.

Patients should be under regular medical supervision if they are taking nimesulide along with other drugs that also have an ulcerogenic effect on the gastrointestinal tract.

The drug should not be used concurrently with other nonsteroidal anti-inflammatory drugs (including selective COX-2 inhibitors) and non-narcotic analgesics.

Patients undergoing treatment for gastrointestinal diseases and taking nimesulide concurrently should undergo regular medical monitoring.

When using NSAIDs, cases of bleeding, ulceration, and perforation of the stomach or intestinal walls may occur. The risk is higher when high doses of NSAIDs are prescribed, and when taken by patients with a history of gastric and duodenal ulcers, as well as elderly individuals. If therapy is necessary in these cases, the need for concomitant use of misoprostol or proton pump inhibitors should be considered.

After two weeks of drug use, monitoring of biochemical indicators of liver function is necessary.

If signs of liver damage appear (skin itching, jaundice, nausea, vomiting, abdominal pain, dark urine, increased levels of "liver" transaminases), stop taking the drug and consult your doctor.

Patients should be warned to report any unusual abdominal symptoms to their doctor.

The drug may alter platelet properties but does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular diseases.

Use with caution in patients with hemorrhagic diathesis, as it may reduce platelet aggregation.

Use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy.

The risk of adverse events can be reduced by using the lowest effective dose for the shortest possible period.

Treatment with the drug should be discontinued at the first signs of rash, mucosal damage, or other manifestations of hypersensitivity.

Effects on ability to drive and use machines

Caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Dosage form

Tablets 100 mg.

10 tablets in a blister strip made of polyvinyl chloride film and printed lacquered aluminum foil.

1, 2, or 3 blister packs, together with the instructions for use, are placed in a cardboard carton.

Storage conditions

In a dry place, protected from light and moisture, at a temperature not exceeding 25 °C. Keep out of reach of children.

Prescription status

By prescription.

Shelf life

2 years. Do not use after the expiration date printed on the packaging.

Name and address of the legal entity in whose name the registration certificate is issued / Organization accepting claims:

JSC "AVVA RUS", Russia

 121614,  Moscow, Krylatskie Kholmy st., 30, building 9.

Tel/Fax: +7 (495) 956-75-54.

avva.com.ru

Production site address:

JSC "AVVA RUS", Russia, 610044, Kirov region, Kirov, Luganskaya st., 53a

Tel. +7 (8332) 25-12-29;  +7 (495) 956-75-54

Where to buy?

The main distribution points for the drug are pharmacies and pharmacy chains. To purchase the medicine, it is necessary to make an appointment with a doctor in advance to obtain all necessary prescriptions and a prescription. Without a prescription, a pharmacy pharmacist has the right not to dispense the drug. Due to the presence of certain contraindications and possible complications from individual organs and systems, self-medication and self-prescription of medications is not allowed!

The price of Nimesulide tablets may vary slightly in different pharmacies. This may be due to the region of distribution and the pricing policy of a particular pharmacy chain or individual pharmacy. All pricing issues fall within the competence of the retail distributor; the manufacturer cannot influence this process.

If you purchase the drug through a pharmacy, you must check its quality compliance. First, check the expiration date on the packaging. Expired medications must not be used for treatment under any circumstances.

Secondly, carefully study the instructions for use of Nimesulide, familiarize yourself with the indications and contraindications, as well as possible complications and risks.

Finally, take the drug only according to the regimen determined by your doctor, do not exceed the recommended dosages to avoid negative reactions from the body. If health deteriorates as a result of taking the drug, it is necessary to interrupt treatment and consult a doctor for additional advice.