Auronim (Tablets) Instructions for Use

Marketing Authorization Holder

Aurobindo Pharma, Ltd. (India)

ATC Code

M01AX17 (Nimesulide)

Active Substance

Nimesulide (Rec.INN registered by WHO)

Dosage Form

Auronim

Tablets 100 mg: 20 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID. Selective COX-2 inhibitor

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID from the sulfonanilide class, a selective competitive reversible inhibitor of COX-2. It has anti-inflammatory, analgesic, and antipyretic effects. It has a less pronounced inhibitory effect on COX-1.

It reduces the concentration of short-lived prostaglandin H₂, a substrate for kinin-stimulated synthesis of prostaglandin E₂, at the site of inflammation and in the ascending pathways of pain impulse transmission in the spinal cord. The decrease in the concentration of prostaglandin E₂ (a mediator of inflammation and pain) reduces the activation of EP-type prostanoid receptors, which is manifested by analgesic and anti-inflammatory effects.

Pharmacokinetics

After oral administration, Nimesulide is well absorbed from the gastrointestinal tract. C_max in blood plasma is reached on average after 2-3 hours and is 3-4 mg/l. AUC is 20-35 mg×h/l. Plasma protein binding is 97.5%.

After a single oral dose of 100 mg, Nimesulide is present in the tissues of the female genital organs at a concentration of 40% of the plasma concentration. It is metabolized in the liver with the participation of the isoenzyme CYP2C9. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide – hydroxynimesulide, which is found exclusively as a glucuronate.

Nimesulide is excreted from the body mainly in the urine (about 50% of the administered dose), about 29% is excreted in the feces as metabolites. T_1/2 is 3.2-6 hours.

Indications

Acute pain (back pain, lower back pain; pain syndrome in the musculoskeletal system, including bruises, sprains and dislocations of joints; tendinitis, bursitis; toothache); symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome; primary dysmenorrhea.

ICD codes

Dosage Regimen

Take orally. The standard adult dose is 100 mg twice daily.

Administer the tablets after meals to reduce potential gastrointestinal irritation.

Use the lowest effective dose for the shortest duration necessary to control symptoms.

The maximum daily dose is 200 mg. Do not exceed this limit.

For acute pain, limit treatment to a maximum of 15 days.

For osteoarthritis with pain syndrome, reassess the need for continued therapy periodically.

In elderly patients, initiate treatment at the same dose. Exercise caution and monitor for adverse reactions due to a potentially increased risk of side effects.

Dosage adjustment is not typically required in patients with mild renal impairment (creatinine clearance 30-60 ml/min). Contraindicated in severe renal impairment (creatinine clearance less than 30 ml/min).

Contraindicated in patients with moderate to severe hepatic impairment. Discontinue immediately at the first sign of liver injury.

This medication is not for use in children under 12 years of age.

Adverse Reactions

From the hematopoietic system: rarely – anemia, eosinophilia, hemorrhages; very rarely – thrombocytopenia, pancytopenia, thrombocytopenic purpura.

From the immune system: rarely – hypersensitivity reactions; very rarely – anaphylactoid reactions, urticaria, angioneurotic edema.

From the skin and subcutaneous tissues: infrequently – itching, skin rash, increased sweating; rarely – erythema, dermatitis; very rarely – urticaria, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

From the nervous system: infrequently – dizziness; very rarely – headache, drowsiness, encephalopathy (Reye’s syndrome).

Mental disorders: rarely – feeling of fear, nervousness, nightmares.

From the organ of vision: rarely – blurred vision; very rarely – visual impairment.

From the organ of hearing and labyrinthine disorders: very rarely – vertigo.

From the cardiovascular system: infrequently – increased blood pressure; rarely – tachycardia, blood pressure lability, flushing, palpitation sensation.

From the respiratory system: infrequently – shortness of breath; very rarely – exacerbation of bronchial asthma, bronchospasm.

From the digestive system: often – diarrhea, nausea, vomiting; infrequently – constipation, flatulence, gastritis, gastrointestinal bleeding, gastric or duodenal ulcer and/or perforation; very rarely – abdominal pain, dyspepsia, stomatitis, tarry stools.

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

From the urinary system: rarely – dysuria, hematuria, urinary retention; very rarely – renal failure, oliguria, interstitial nephritis.

From metabolism: rarely – hyperkalemia; infrequently – peripheral edema; very rarely – hypothermia.

Other: rarely – malaise, asthenia.

Contraindications

Hypersensitivity to nimesulide; hyperergic reactions in history (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs, including nimesulide; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinus polyposis with intolerance to acetylsalicylic acid and other NSAIDs (including in history); history of hepatotoxic reactions to Nimesulide; simultaneous use with other drugs with potential hepatotoxicity (e.g., other NSAIDs); chronic inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase; period after coronary artery bypass surgery; febrile syndrome in colds and acute respiratory viral infections; suspicion of acute surgical pathology; gastric or duodenal ulcer in the acute phase; erosive-ulcerative lesions of the gastrointestinal tract; history of perforations or gastrointestinal bleeding; history of cerebrovascular bleeding or other diseases accompanied by increased bleeding; severe coagulation disorders; severe heart failure; severe renal failure (creatinine clearance <30 ml/min), confirmed hyperkalemia; children under 12 years of age (for suspension – children under 2 years of age); pregnancy, breastfeeding period; alcoholism, drug dependence; hepatic insufficiency, active liver disease.

With caution

Arterial hypertension, diabetes mellitus, compensated heart failure, coronary artery disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral arterial diseases, hemorrhagic diathesis, smoking, creatinine clearance 30-60 ml/min.

History of ulcerative lesions of the gastrointestinal tract; history of Helicobacter pylori infection; elderly age; long-term prior use of NSAIDs; severe somatic diseases.

Simultaneous use with the following drugs: 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 in Pregnancy and Lactation

Nimesulide is contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in moderate and severe hepatic insufficiency.

Use in Renal Impairment

Contraindicated in renal failure (creatinine clearance less than 30 ml/min).

Pediatric Use

When used in pediatrics, dosage forms intended for children should be used.

Geriatric Use

With topical application, medical supervision of the condition of elderly patients with impaired renal function, liver function, and congestive heart failure is required.

Special Precautions

If symptoms similar to signs of liver damage appear (anorexia, skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, increased activity of liver transaminases), the use of nimesulide should be stopped immediately and a doctor should be consulted. Repeated use of nimesulide in such patients is contraindicated.

Liver reactions are reported, which are reversible in most cases, with short-term use of nimesulide.

During the use of nimesulide, the patient should refrain from taking other analgesics, including NSAIDs (including selective COX-2 inhibitors).

Use with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as exacerbation of these diseases is possible. 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 be started with the lowest possible dose. Such patients, as well as patients who require simultaneous use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, are recommended to additionally prescribe gastroprotectors (misoprostol or proton pump inhibitors). Patients with a history of gastrointestinal diseases, especially elderly patients, should inform the doctor about any newly emerged gastrointestinal symptoms (especially symptoms that may indicate possible gastrointestinal bleeding).

In case of gastrointestinal bleeding or ulcerative lesions of the gastrointestinal tract in patients taking Nimesulide, it should be discontinued.

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.

Nimesulide may cause fluid retention, so it should be used with particular caution in patients with arterial hypertension, renal and/or heart failure. If the condition worsens, treatment with nimesulide must be discontinued.

Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a slight risk of myocardial infarction or stroke. There is insufficient data to exclude the risk of such events when using nimesulide.

If signs of a cold or acute respiratory viral infection appear during the use of nimesulide, it should be discontinued immediately.

Nimesulide may alter platelet properties, so caution should be exercised when using it in persons with hemorrhagic diathesis; however, Nimesulide 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 perforations, which are life-threatening to the patient, and decreased function of the kidneys, liver, and heart. When taking nimesulide for this category of patients, proper clinical monitoring is necessary.

At the first manifestations of skin rash, damage to mucous membranes, or other signs of an allergic reaction, nimesulide should be discontinued immediately.

Effect on ability to drive vehicles and operate machinery

During the use of nimesulide, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors, for example, fluoxetine, increase the risk of gastrointestinal bleeding.

NSAIDs may enhance the effect of anticoagulants such as warfarin. Due to the increased risk of bleeding, such a combination is not recommended and is contraindicated in patients with severe coagulation disorders. If combination therapy still cannot be avoided, careful monitoring of blood coagulation parameters is necessary.

NSAIDs can reduce the effect of diuretics. In healthy volunteers, Nimesulide temporarily reduces sodium excretion under the influence of furosemide, to a lesser extent – potassium excretion and reduces the diuretic effect itself. Simultaneous use of nimesulide and furosemide leads to a decrease (approximately by 20%) in AUC and a decrease in the cumulative excretion of furosemide without changing the renal clearance of furosemide. Simultaneous use of furosemide and nimesulide requires caution in patients with renal or heart failure.

NSAIDs can reduce the effect of antihypertensive drugs. In patients with mild to moderate renal failure (creatinine clearance 30-80 ml/min), with simultaneous use of ACE inhibitors, angiotensin II receptor antagonists, and agents that suppress the COX system (NSAIDs, antiplatelet agents), further deterioration of renal function and the occurrence of acute renal failure, which is usually reversible, are possible. These interactions should be considered in patients taking Nimesulide in combination with ACE inhibitors or angiotensin II receptor antagonists. Therefore, simultaneous 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 simultaneous use.

Theoretically, a decrease in the effectiveness of mifepristone and prostaglandin analogs is possible when used simultaneously with NSAIDs (including acetylsalicylic acid) due to the antiprostaglandin action of the latter. Limited data show that the use of NSAIDs on the day of prostaglandin analog use does not adversely affect the effect of mifepristone or prostaglandin analog on cervical dilation, uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.

There is evidence that NSAIDs reduce the clearance of lithium, leading to an increase in plasma lithium concentration and its toxicity. When using nimesulide in patients on lithium therapy, regular monitoring of plasma lithium concentration should be carried out.

Nimesulide inhibits the activity of the isoenzyme CYP2C9. When used simultaneously with nimesulide, drugs that are substrates of this enzyme may have increased plasma concentrations.

Caution is required when using nimesulide less than 24 hours before or after using methotrexate, as in such cases the plasma concentration of methotrexate and, accordingly, toxic effects may increase.

Due to the effect on renal prostaglandins, prostaglandin synthetase inhibitors, which include Nimesulide, may increase the nephrotoxicity of cyclosporine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.