Nimesulide granules for preparation of suspension for oral use 100mg, 4pcs

Composition

One package contains:

Active ingredient: nimesulide (in terms of 100% substance) 100.0 mg;

Excipients: orange flavor-42.0 mg, citric acid-30.0 mg, maltodextrin-15.0 mg, macrogol cetostearate-8.0 mg, sucrose – up to 2000.0 mg by weight

Pharmacological action

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

ATX code: M 01 AH 17.

Pharmacological properties

Pharmacodynamics :

Nimesulide is a nonsteroidal anti-inflammatory drug from the class of sulfonamides. It has anti-inflammatory, analgesic and antipyretic effects. Unlike non-selective NSAIDs, nimesulide mainly inhibits cyclooxygenase-2( COX-2), inhibits prostaglandin synthesis in the inflammatory focus, and has a less pronounced inhibitory effect on cyclooxygenase-1 (COX-1).

Pharmacokinetics:

Suction

Nimesulide is well absorbed from the gastrointestinal tract (GIT).

The maximum plasma concentration (cmax) after oral use of a single dose of nimesulide (100 mg) is reached on average in 2-3 hours and is 3-4 mg/l.

Distribution

Binding to plasma proteins is up to 97.5%.

Penetrates into the tissues of the female genital organs, where after a single dose, its concentration is about 40% of the plasma concentration. It penetrates well into the acidic environment of the inflammatory focus (40%), synovial fluid (43%). Easily penetrates through histohematic barriers.

Metabolism

Nimesulide is actively metabolized in the liver by the cytochrome P450 (CYP)2C9 isoenzyme. There is a possibility of drug interaction of nimesulide when used simultaneously with drugs metabolized by the CYP2C9 isoenzyme. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide-hydroxynimesulide, which is found in blood plasma mainly in conjugated form, in the form of glucuronate.

Deduction

The half-life (T_1/2) of nimesulide is about 1.56-4.95 hours, hydroxynimesulide-2.89-4.78 hours. Nimesulide is mainly excreted by the kidneys (about 50% of the dose taken). Hydroxynimesulide is excreted by the kidneys (65%) and with bile (35%), undergoes enterohepatic recirculation.

Use in elderly patients

The pharmacokinetic profile of nimesulide in the elderly does not change with the use of single and multiple/repeated doses.

Use in patients with kidney disease

In a short-term study conducted in patients with mild to moderate renal insufficiency (creatinine clearance 30-60 ml/min), the_cmax of nimesulide and its main metabolite was not higher than in healthy volunteers.

AUC and T_1/2 were 50% higher, but they were within the values of AUC and T_1/2observed in healthy volunteers with the use of nimesulide. Repeated use did not result in accumulation of nimesulide.

Indications

Acute pain therapy:

• pain in the lower back and / or lower back;
• pain associated with diseases of the musculoskeletal system, including tendinitis, bursitis;
• pain with bruises, sprains and dislocations of joints;
• toothache;
• symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome;
• primary algodismenorrhea.

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

Nimesulide is recommended for second-line therapy.

Use during pregnancy and lactation

Pregnancy 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 fetal pulmonary artery system, impaired renal function, which can lead to renal failure with oliguria in the fetus, an increased risk of bleeding, reduced uterine contractility, and peripheral edema in the mother. The use of nimesulide during pregnancy is contraindicated.

Breast-feedingthe use of nimesulide during breastfeeding is contraindicated.

Contraindications

• hypersensivity to the nimesulide or other components of the drug;
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose, paranasal sinuses and intolerance of acetylsalicylic acid and other NSAIDs (including in the anamnesis);
• hepatotoxic reactions to nimesulide in history;
• the simultaneous use with other drugs with potential hepatotoxicity (e. g., other NSAIDs);
• chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute phase;
• period after coronary artery bypass grafting;
• febrile syndrome and acute respiratory viral infections;
• suspected acute surgical pathology;
• peptic ulcer of the stomach or duodenum in the acute phase;
• erosive-ulcerative lesions of the gastrointestinal tract in acute phase;
• erosive-ulcerative lesions of the gastrointestinal tract in history,
• perforation or gastrointestinal bleeding in history, including those related to previous NSAIDs therapy;
• cerebrovascular bleeding, a history of other active bleeding, or diseases associated with increased bleeding;
• severe blood coagulation disorders;
• severe heart failure;
• severe renal insufficiency (creatinine clearance less than 30 ml/min);
• progressive disease of the kidneys;
• confirmed hyperkalemia;
• hepatic failure, active liver disease;
• children up to age 12 years;
• pregnancy and breastfeeding;
• alcoholism, drug addiction, lack of sucrase/isomaltase, fructose intolerance, glucose-galactose malabsorption, since the drug contains sucrose.

With caution:

• arterial hypertension;
• ischemic heart disease;
• cerebrovascular disease;
• severe heart failure;
• dyslipidemia/hyperlipidemia;
• diabetes mellitus;
• peripheral arterial disease;
• hemorrhagic diathesis;
• Smoking;
• kidney insufficiency (creatinine clearance 30-60 ml/min);
• anamnestic information about the development of erosive and ulcerative lesions of the gastrointestinal tract, the presence of Helicobacter pylori infection;
• older age;
• long-term use of nonsteroidal anti-inflammatory drugs;
• frequent alcohol use, severe somatic diseases, systemic lupus erythematosus (SLE) and other systemic connective tissue diseases;
• concomitant therapy with the following drugs: 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).

Side effects

The frequency of side effects is classified according to the frequency of occurrence of the case: very common (>1/10), common (≥ 1/100 to >< 1/10), infrequent (≥ 1/1000 to < 1/100), rare (≥ 1/10000 toDisorders of the blood and lymphatic system: rarely-anemia, eosinophilia, hemorrhages; very rarely-thrombocytopenia, pancytopenia, thrombocytopenic purpura, prolongation of bleeding time.

Immune system disorders: rarely-hypersensitivity reactions; very rarely-anaphylactoid reactions.

Mental disorders: rarely-feeling of fear, nervousness, night “nightmare” dreams.

Nervous system disorders: infrequently – dizziness; very rarely-headache, drowsiness, encephalopathy (Reye’s syndrome).

Visual disturbances: rarely-blurred vision; very rarely-visual impairment.

Hearing disorders and labyrinth disorders: vertigo is very rare.

Cardiac disorders: rarely-tachycardia, palpitation sensation.

Vascular disorders: infrequently-increased blood pressure; rarely-lability of blood pressure, “hot flashes” of blood to the skin of the face.

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

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

Liver and biliary tract disorders: often-increased activity of “liver” enzymes; very rarely-hepatitis, fulminant hepatitis (including fatal outcomes), jaundice, cholestasis.

Skin and subcutaneous tissue disorders: infrequently-pruritus, skin rash, excessive sweating; rarely-erythema, dermatitis; very rarely-urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Renal and urinary tract disorders: rarely-dysuria, hematuria, urinary retention; very rarely-renal failure, oliguria, interstitial nephritis, hyperkalemia.

General disorders and disorders at the injection site: infrequently-peripheral edema; rarely-malaise, asthenia; very rarely-hypothermia.

Interaction

Glucocorticosteroids increase the risk of erosive and ulcerative lesions of the gastrointestinal tract 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, or antiplatelet drugs, such as acetylsalicylic acid. 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.

Other nonsteroidal anti-inflammatory drugs (NSAIDs): Concomitant use of nimesulide-containing drugs with other NSAIDs, including acetylsalicylic acid in a single dose of more than 1 g or in a daily dose of more than 3 g, is not recommended.

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. Concomitant use of nimesulide and furosemide results 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. Concomitant use of furosemide and nimesulide requires caution in patients with renal or cardiac insufficiency.

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 30-60 ml/min), concomitant use of ACE inhibitors, angiotensin II receptor antagonists, and cyclooxygenase-suppressing agents (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 nimesulide in combination with ACE inhibitors or angiotensin II receptor antagonists. Therefore, concomitant use of these drugs should be carried out with caution, especially in elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after starting concomitant use.

Mifepristone. Due to the theoretical risk of changing the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be used earlier than 8-12 days after mifepristone withdrawal.

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 using nimesulide in patients undergoing lithium therapy, regular monitoring of the concentration of lithium in the blood 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 used simultaneously with nimesulide, the concentration of the latter 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 the blood plasma and, accordingly, toxic effects may increase.

Due to the effect on renal prostaglandins, prostaglandin synthetase inhibitors, such as nimesulide, may increase the nephrotoxicity of cyclosporins. 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

Inside. Adults and children over 12 years of age inside (body weight more than 40 kg) are prescribed 100 mg 2 times a day. Take after a meal with a sufficient amount of water.

The maximum daily dose for adults and children over 12 years of age is 200 mg.

Elderly patients: no daily dose adjustment is required for the treatment of elderly patients.

Patients with renal insufficiency: in patients with mild to moderate renal insufficiency (creatinine clearance 30-60 ml/min), dose adjustment is not required, in patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), nimesulide is contraindicated.

Patients with hepatic insufficiency: the use of nimesulide in patients with hepatic insufficiency is contraindicated.

Course of treatment: as prescribed by your doctor. To reduce the likelihood of side effects, it is recommended to take the minimum effective dose for the shortest possible time. The maximum duration of nimesulide treatment is 15 days.

Overdose

Symptoms: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with symptomatic and supportive care. Possible increase in blood pressure, gastrointestinal bleeding, acute renal failure, respiratory depression, coma, anaphylactoid reactions.

Treatment: Symptomatic and supportive therapy. There is no specific antidote. If symptoms of overdose occur within 4 hours after taking the drug, it is necessary to induce vomiting, and/or provide activated charcoal (from 60 to 100 g for an adult) and / or an osmotic laxative. Forced diuresis, hemodialysis, hemoperfusion, and urinary alkalinization are ineffective due to the high degree of binding of nimesulide to plasma proteins (up to 97.5%). It is necessary to monitor the state of kidney and liver function.

Description

A mixture of powder and granules from almost white to light yellow color with an orange smell. Color variations are allowed. The finished suspension is white to light yellow in color with an orange smell.

Special instructions

Undesirable side effects can be minimized by using the drug at the lowest effective dose with the minimum duration of use necessary for the relief of pain.

There are data on very rare cases of serious liver reactions, including cases of fatal outcome associated with the use of nimesulide-containing drugs. If you experience symptoms similar to those of liver damage (anorexia, pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of “liver” transaminases), you should immediately stop using nimesulide and consult a doctor. Repeated use of nimesulide in such patients is contraindicated. After 2 weeks of using the drug, monitoring of liver function indicators (“transaminases”) is necessary. Liver reactions, which in most cases are reversible, have been reported with short-term use of the drug. During the use of nimesulide, the patient should refrain from taking other analgesics, including NSAIDs (including selective COX-2 inhibitors).

Nimesulide 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, peptic ulcer/perforation of the stomach or duodenum increases in patients with a history of ulcerative lesions of the gastrointestinal tract (ulcerative colitis, Crohn’s disease), as well as in elderly patients, with an increase in the dose of NSAIDs, so treatment should begin with the lowest possible dose. Such patients, as well as patients who require concomitant use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, are recommended to take additional gastroprotectors (misoprostol or proton pump blockers). Patients with a history of gastrointestinal diseases, especially elderly patients, should inform the doctor about new gastrointestinal symptoms (especially those that may indicate possible gastrointestinal bleeding). Nimesulide should be used with caution in patients taking medications that increase the risk of ulceration or bleeding (oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid). If gastrointestinal bleeding or ulcerative lesions of the gastrointestinal tract occur in patients taking nimesulide, treatment with the drug should be stopped immediately.

Given reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of nimesulide should be stopped immediately and an ophthalmological examination should be performed.

The drug can cause fluid retention in the tissues, so patients with arterial hypertension, renal and/or heart failure, coronary heart disease, peripheral artery disease and/or cerebrovascular diseases, with the presence of risk factors for developing cardiovascular diseases (for example: hyperlipidemia, diabetes mellitus, smokers) nimesulide should be used with extreme caution. If the condition worsens, treatment with nimesulide should be discontinued.

Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with prolonged use, may lead to a slight increase in the risk of myocardial infarction or stroke. To exclude the risk of such events when using nimesulide, data are not sufficient.

If signs of a “cold” or acute respiratory viral infection occur during the use of nimesulide, the drug should be discontinued.

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 life-threatening perforations, and decreased kidney, liver, and heart function. When taking nimesulide for this category of patients, proper clinical monitoring is necessary.

There are reports of rare skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when taking NSAIDs, including nimesulide. At the first appearance of skin rash, mucosal lesions, or other signs of an allergic reaction, nimesulide should be discontinued immediately.

The use of the drug may negatively affect female fertility and is not recommended for women planning pregnancy.

Influence on the ability to drive vehicles and mechanisms

The effect of nimesulide on the ability to drive vehicles and mechanisms has not been studied, however, taking into account undesirable reactions from the nervous system (dizziness, drowsiness), it is necessary to refrain from driving vehicles and other mechanisms.

Form of production

Granules for the preparation of a suspension for oral use,100 mg. 2.0 g each in disposable bags made of multi-layer packaging material (polyethylene terephthalate-polypropylene-aluminum-polyethylene). By 4,5,6,7,8,10,20 or 30 bags together with the instructions for use are placed in a pack of cardboard.

Storage conditions

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

Dosage form

Oral suspension