Nimesil granules for preparation of suspension for oral use 100mg sachets 2g, 9pcs

Composition

1 package contains: Active ingredient: nimesulide 100 mg; Excipients: ketomacrogol 1000, sucrose, maltodextrin, citric acid anhydrous, orange flavor.

Pharmacological action

Pharmacotherapy group:  nonsteroidal anti-inflammatory drugs (NSAIDs).

ATX code: M 01 AX 17

Pharmacological properties

Pharmacodynamics Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) from the class of sulfonamides. It has anti-inflammatory, analgesic and antipyretic effects.

Nimesulide acts as an inhibitor of the cyclooxygenase enzyme responsible for prostaglandin synthesis and mainly inhibits cyclooxygenase 2.

Pharmacokinetics After oral use, the drug is well absorbed from the gastrointestinal tract, reaching a maximum concentration in blood plasma after 2-3 hours; binding to plasma proteins is 97.5%; the half-life is 3.2-6 hours. Easily penetrates through histohematic barriers.

It is metabolized in the liver by the cytochrome P450 (CYP) 2C9 isoenzyme. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide-hydroxynimesulide. Hydroxynimesulide is excreted in the bile in a metabolized form (found exclusively in the form of glucuronate – about 29%).

Nimesulide is eliminated from the body, mainly by the kidneys (about 50% of the dose taken). The pharmacokinetic profile of nimesulide in the elderly does not change with the appointment of single and multiple/repeated doses.

According to an experimental study conducted in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) and healthy volunteers, the maximum concentration of nimesulide and its metabolite in the plasma of patients did not exceed the concentration of nimesulide in healthy volunteers. The area under the concentration-time curve (AUC) and half-life in patients with renal insufficiency were 50% higher, but within pharmacokinetic values. With repeated use of the drug, accumulation is not observed.

Indications

-treatment of acute pain (back pain, low back pain; musculoskeletal pain, including injuries, sprains and dislocations of joints; tendonitis, bursitis; toothache);- symptomatic treatment of osteoarthritis with pain syndrome;- algodismenorrhea.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use.

Contraindications

-Hypersensitivity to nimesulide or to one of the components of the drug. – Hyperergic reactions (in the anamnesis), for example, bronchospasm, rhinitis, urticaria, associated with taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, including nimesulide. Hepatotoxic reactions to nimesulide (in the anamnesis). – Concomitant (simultaneous) use of drugs with potential hepatotoxicity, for example, paracetamol or other analgesic or non-steroidal anti-inflammatory drugs. – Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase. The period after coronary artery bypass grafting. – Febrile syndrome and acute respiratory viral infections. – Complete or incomplete combination of bronchial asthma, recurrent nasal or paranasal sinus polyposis with intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis). – Peptic ulcer of the stomach or duodenum in the acute phase, the presence in the anamnesis of ulcers, perforations or bleeding in the gastrointestinal tract. – The presence in the anamnesis of cerebrovascular bleeding or other bleeding, as well as diseases accompanied by bleeding. – Severe blood clotting disorders. – Severe heart failure. – Severe renal insufficiency (creatinine clearance- Liver failure or any active liver disease. – Children under 12 years of age. – Pregnancy and lactation. – Alcoholism, drug addiction.

With caution: severe hypertension, type 2 diabetes mellitus, heart failure, coronary heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral arterial diseases, smoking, creatinine clearance less than 60 ml/min.

Anamnestic data on the presence of ulcerative lesions of the gastrointestinal tract, infection caused by Helicobacter pylori; elderly age; long-term previous use of NSAIDs; severe somatic diseases.

Concomitant therapy with the following medications: anticoagulants (e. g., warfarin), antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e. g., prednisone), selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline). The decision to prescribe Nimesil® should be based on an individual risk-benefit assessment when taking the drug.

Side effects

Frequency is classified by category, depending on the occurrence of the case: very often (>10), often (><10 – <100), infrequently (<100-<1000), rarely (<1000-<10000), very rarely (

Disorders of the circulatory and lymphatic systems: rarely-anemia, eosinophilia, hemorrhages; very rarely-thrombocytopenia, pancytopenia, thrombocytopenic purpura.

Allergic reactions: infrequently-pruritus, rash, excessive sweating; rarely-hypersensitivity reactions, erythema, dermatitis; very rarely – anaphylactoid reactions, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Central nervous system disorders: infrequently-dizziness; rarely-fear, nervousness, nightmares; very rarely-headache, drowsiness, encephalopathy (Reye’s syndrome).

Sensory disorders: rarely – blurred vision.

Disorders of the cardiovascular system: infrequently-arterial hypertension, tachycardia, lability of blood pressure, hot flashes.

Respiratory system disorders: infrequently-shortness of breath; very rarely-exacerbation of bronchial asthma, bronchospasm.

Gastrointestinal disorders: often – diarrhea, nausea, vomiting; infrequently-constipation, flatulence, gastritis; very rarely-abdominal pain, dyspepsia, stomatitis, tarry stools, gastrointestinal bleeding, ulceration and / or perforation of the stomach or duodenum.

Disorders of the liver and biliary system: very rarely – hepatitis, lightning hepatitis, jaundice, cholestasis, increased activity of liver enzymes.

Disorders of the kidneys and urinary system: rarely-dysuria, hematuria, urinary retention; very rarely-renal failure, oliguria, interstitial nephritis.

General disorders: rarely-malaise, asthenia; very rarely – hypothermia.

Other: rarely-hyperkalemia.

Interaction

Pharmacodynamic interactions:

Glucocorticosteroids: increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine: increase the risk of gastrointestinal bleeding.

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin. Due to the increased risk of bleeding, this combination is not recommended and is contraindicated in patients with severe coagulation disorders. If combination therapy is still unavoidable, careful monitoring of blood clotting parameters is necessary.

Diuretics

NSAIDs may reduce the effect of diuretics.

In healthy volunteers, nimesulide temporarily reduces the excretion of sodium under the action of furosemide, to a lesser extent – the excretion of potassium, and reduces the actual diuretic effect.

Co-use of nimesulide and furosemide resulted in a decrease (approximately 20%) in the area under the concentration – time curve (AUC) and a decrease in the cumulative excretion of furosemide without changing the renal clearance of furosemide.

Co-use of furosemide and nimesulide requires caution in patients with impaired renal or cardiac function.

ACE inhibitors and angiotensin-II receptor

antagonists NSAIDs may reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min), concomitant use of ACE inhibitors, angiotensin II receptor antagonists, or substances that inhibit the cyclooxygenase system (NSAIDs, antiplatelet agents) may lead to further deterioration of renal function and the occurrence of acute renal failure, which is usually reversible. These interactions should be considered in patients taking Nimesil in combination with ACE inhibitors or angiotensin I receptor antagonists. Therefore, co-use of these drugs should be prescribed with caution, especially for elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after starting co-therapy.

Pharmacokinetic interactions with other medicinal products:

There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in blood plasma and its toxicity. When prescribing nimesulide to patients receiving lithium therapy, regular monitoring of the lithium concentration in the plasma should be carried out.

No clinically significant interactions were observed with glibenclamide, theophylline, digoxin, cimetidine, or antacids (for example, a combination of aluminum and magnesium hydroxides).

Nimesulide inhibits the activity of the CYP2C9 isoenzyme. When drugs that are substrates of this enzyme are taken simultaneously with nimesulide, the concentration of these drugs in plasma may increase.

Caution should be exercised when prescribing nimesulide less than 24 hours before or after taking methotrexate, as in such cases, the level of methotrexate in plasma and, accordingly, the toxic effects of this drug may increase. Due to the effect on renal prostaglandins, prostaglandin synthetase inhibitors, such as nimesulide, may increase the nephrotoxicity of cyclosporins.

Interaction of other drugs with nimesulide :

In vitro studies have shown that nimesulide is displaced from the binding sites by tolbutamide, salicylic acid, and valproic acid. Despite the fact that these interactions were determined in blood plasma, these effects were not observed during the clinical use of the drug.

How to take, course of use and dosage

Nimesil is taken orally,1 sachet (100 mg of nimesulide) twice a day. The drug is recommended to be taken after a meal. The contents of the sachet are poured into a glass and dissolved in about 100 ml of water. The prepared solution is not subject to storage. Nimesil® is only used for the treatment of patients over 12 years of age. Adolescents (12-18 years of age): based on the pharmacokinetic profile and pharmacodynamic characteristics of nimesulide, there is no need to adjust the dose in adolescents. Patients with impaired renal function: based on pharmacokinetic data, there is no need to adjust the dose in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min). Elderly patients: in the treatment of elderly patients, the need to adjust the daily dose is determined by the doctor based on the possibility of interaction with other drugs. The maximum duration of nimesulide treatment is 15 days. To reduce the risk of undesirable side effects, the minimum effective dose should be used in the shortest possible course.

Overdose

Symptoms: apathy, drowsiness, nausea, vomiting, epigastric pain. With maintenance therapy for gastropathy, these symptoms are usually reversible. Gastrointestinal bleeding may occur. In rare cases, increased blood pressure, acute renal failure, respiratory depression and coma, anaphylactoid reactions are possible. Treatment: Symptomatic. There is no specific antidote. If an overdose has occurred within the last 4 hours, it is necessary to induce vomiting and/or provide activated charcoal (from 60 to 100 g per adult) and / or osmotic laxative. Forced diuresis and hemodialysis are ineffective due to the high binding of the drug to proteins (up to 97.5%). Monitoring of kidney and liver function is indicated.

Special instructions

Undesirable side effects can be minimized by using the minimum effective dose of the drug in the shortest possible course. Nimesil® should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as these diseases may worsen. The risk of gastrointestinal bleeding, ulceration, or ulceration increases with increasing NSAID dose in patients with a history of ulceration, especially complicated by bleeding or perforation, as well as in elderly patients, so treatment should begin with the lowest possible dose. Patients receiving medications that reduce blood clotting or inhibit platelet aggregation also have an increased risk of gastrointestinal bleeding. If gastrointestinal bleeding or ulceration occurs in patients taking Nimesil®, treatment with the drug should be discontinued. Since Nimesil® is partially excreted by the kidneys, its dosage for patients with impaired renal function should be reduced, depending on the level of urinary excretion. There are data on the occurrence of rare cases of liver reactions. If signs of liver damage appear (pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of “liver” transaminases), stop taking the drug and consult your doctor. Despite the rarity of visual impairment in patients taking nimesulide concomitantly with other NSAIDs, treatment should be discontinued immediately. If any visual impairment occurs, the patient should be examined by an optometrist. The drug may cause fluid retention in the tissues, so patients with high blood pressure and cardiac disorders Nimesil® should be used with extreme caution. In patients with renal or cardiac insufficiency, Nimesil should be used with caution, as renal function may worsen. If the condition worsens, treatment with Nimesil should be discontinued. Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with prolonged use, may lead to a low risk of myocardial infarction or stroke. To exclude the risk of such events when using nimesulide, data are not sufficient. The drug contains sucrose, this should be taken into account in patients with diabetes mellitus (0.15-0.18 XE per 100 mg of the drug) and people who follow a low-calorie diet. Nimesil® is not recommended for patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltose deficiency. If signs of a “cold” or acute respiratory viral infection occur during treatment with Nimesil®, the drug should be discontinued. Nimesil should not be used concomitantly with other NSAIDs. Nimesulide can alter the properties of platelets, so caution should be exercised when using the drug in people with hemorrhagic diathesis, but the drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases. Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the risk of gastrointestinal bleeding and perforation, which threatens the patient’s life, deterioration of kidney, liver and heart function. When taking the drug Nimesil® for this category of patients, proper clinical monitoring is necessary. Like other NSAID drugs that inhibit prostaglandin synthesis, nimesulide can negatively affect the course of pregnancy and / or embryo development and can lead to premature closure of the ductus arteriosus, hypertension in the pulmonary artery system, impaired renal function, which can lead to renal failure with oligohydramnia, an increased risk of bleeding, reduced uterine contractility, and peripheral edema. In this regard, nimesulide is contraindicated during pregnancy and lactation. The use of Nimesil may adversely affect female fertility and is not recommended for women planning pregnancy. When planning a pregnancy, you should consult your doctor. There are reports of rare skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) to nimesulide as well as to other NSAIDs. At the first sign of skin rash, mucosal damage, or other signs of an allergic reaction, Nimesil® should be discontinued. The effect of the drug on the ability to drive motor vehicles and control mechanisms The effect of the drug Nimesil® on the ability to drive motor vehicles and control mechanisms has not been studied, therefore, during treatment with Nimesil®, caution should be exercised when driving motor vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Granules for the preparation of a suspension for oral use,100 mg. 2 g of granulate in three-layer bags (paper/ aluminum/ polyethylene).9,15 or 30 packages with instructions for use in a cardboard pack.

Storage conditions

List B. Store in a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children!

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Nimesulide

Conditions of release from pharmacies

By prescription

Purpose

For adults by doctor’s prescription, Children by doctor’s prescription, Children over 12 years of age

Indications

Osteoarthritis, Migraines, Arthritis, Osteochondrosis, Sciatica, Sprains and Sprains, Tendon Inflammation, Sciatica, Rheumatoid Arthritis, Lumbago, Myositis, Bursitis, Gout