Nimesil, 100 mg 2 g 30 pcs.

Pharmacodynamics

A nonsteroidal anti-inflammatory drug of the sulfonamide class. It has anti-inflammatory, analgesic and antipyretic effect.

Nimesulide acts as an inhibitor of cyclooxygenase enzyme, which is responsible for the synthesis of prostaglandins, and inhibits mainly cyclooxygenase-2.

Pharmacokinetics

After oral administration, the drug is well absorbed from the gastrointestinal tract, reaching C_max in plasma after 2-3 h. Binding to plasma proteins is 97.5%. T_1/2 is 3.2-6 hours. Easily penetrates through histohematic barriers.

Metabolized in the liver with the help of cytochrome P450 isoenzyme (CYP) 2C9. The main metabolite is pharmacologically active parahydroxy derivative of nimesulide – hydroxynimesulide.

Hydroxynimesulide is excreted with bile in metabolized form (found exclusively as glucuronate – about 29%).

Nimesulide is excreted from the body mainly by the kidneys (about 50% of the dose taken). Pharmacokinetic profile of nimesulide in elderly persons does not change when administering single and multiple/repeated doses.

According to the experimental study conducted with the participation of patients with mild to moderate renal impairment (CK 30-80 ml/min) and healthy volunteers, C_max of nimesulide and its metabolite in plasma of patients did not exceed the concentration of nimesulide in healthy volunteers. AUC and T_1/2 in patients with renal insufficiency were 50% higher, but within pharmacokinetic values. No cumulation was observed with repeated administration of the drug.

Indications

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

Active ingredient

Composition

Active ingredient:

Nimesulide 100 mg.

Associates:

ketomacrogol 1000,

sucrose,

maltodextrin,

anhydrous citric acid,

orange flavoring.

How to take, the dosage

Nimesil is taken orally, 1 sachet (100 mg nimesulide) 2 times a day. It is recommended to take the drug after meals. The contents of the sachet is poured into a glass and dissolved in about 100 ml of water.

The prepared solution should not be stored. Nimesil is used only for the treatment of patients over 12 years old.

Adolescents (aged 12 to 18 years): 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 for dose adjustment in patients with mild to moderate renal impairment (CKR 30-80 ml/min).

Patients in the elderly: When treating elderly patients, the need to adjust the daily dose is determined by the physician based on the possibility of interaction with other medications.

The maximum duration of treatment with nimesulide is 15 days.

To reduce the risk of unwanted side effects, the lowest effective dose with the shortest course possible should be used.

Interaction

Pharmacodynamic interactions:

Co-use with glucocorticosteroids increases the risk of gastrointestinal ulceration or bleeding.

Co-use with antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, increases the risk of gastrointestinal bleeding.

NSAIDs can increase the effects of anticoagulants, such as warfarin. Because of the increased risk of bleeding, this combination is not recommended and is contraindicated in patients with severe coagulation disorders. If combination therapy still cannot be avoided, careful monitoring of blood clotting parameters is necessary.

Diuretics: NSAIDs may attenuate the effects of diuretics.

In healthy volunteers, nimesulide temporarily reduces sodium excretion with furosemide, to a lesser extent, potassium excretion, and reduces the diuretic effect itself.

The co-administration 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.

The co-administration of furosemide and nimesulide requires caution in patients with impaired renal and cardiac function.

ACE inhibitors and angiotensin II receptor antagonists: NSAIDs may decrease the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (CKD 30-80 ml/min) when coadministration of ACE inhibitors, angiotensin II receptor antagonists or substances that inhibit cyclooxygenase system (NSAIDs, antiaggregants), further deterioration of renal function and acute renal failure may occur, which is usually reversible. These interactions should be considered in patients taking Nimesil in combination with ACE inhibitors or angiotensin II receptor antagonists. Therefore, co-administration of these drugs should be prescribed with caution, especially for elderly patients.

Patients should receive adequate fluids, and renal function should be carefully monitored after initiation of coadministration.

Pharmacokinetic interactions with other drugs:

There is evidence that NSAIDs decrease lithium clearance, which leads to increased plasma lithium concentrations and toxicity.

Patients receiving therapy with lithium should have their plasma lithium concentrations monitored regularly when nimesulide is prescribed.

Clinically significant interactions with glibenclamide, theophylline, digoxin, cimetidine and antacids (e.g., aluminum and magnesium hydroxide combination) have not been observed.

Nimesulide inhibits the activity of CYP2C9 isoenzyme. When concomitant use of drugs that are substrates of this enzyme with nimesulide, plasma concentrations of these drugs may increase.

When nimesulide is taken less than 24 hours before or after methotrexate administration, caution is required, because in these cases the plasma levels of methotrexate and therefore the toxic effects of this drug may increase.

Because of the effect on renal prostaglandins, inhibitors of prostaglandin synthetases, such as nimesulide, may increase nephrotoxicity of cyclosporines.

Interactions of other drugs with nimesulide:

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

Special Instructions

Unwanted side effects can be minimized by using the lowest effective dose of the drug for the shortest possible course.

Nimesil should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), since exacerbation of these diseases is possible.

The risk of gastrointestinal bleeding, ulcers or perforation increases with increasing dosage of NSAIDs in patients with a history of ulcers, especially complicated by bleeding or perforation, as well as in elderly patients, so treatment should be started with the lowest possible dose. Patients receiving drugs that reduce blood clotting or inhibit platelet aggregation also have an increased risk of gastrointestinal bleeding.

If gastrointestinal bleeding or ulcers occur in patients taking Nimesil, treatment with the drug should be stopped.

Because 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 occur (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkened urine, increased “liver” transaminase activity) the drug should be stopped and a physician should be consulted.

Although visual disturbances are rare in patients who have taken nimesulide concomitantly with other NSAIDs, treatment should be stopped immediately. If any visual disturbance occurs, the patient should be examined by an ophthalmologist.

The drug may cause fluid retention in the tissues, so patients with high blood pressure and with cardiac abnormalities should use Nimesil 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 stopped.

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

The drug contains sucrose; this should be considered in patients with diabetes mellitus (0.15-0.18 units per 100 mg of the drug) and those who follow a low-calorie diet. Nimesil is not recommended for patients with rare hereditary diseases of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltose deficiency.

In case of signs of a “cold” or acute respiratory viral infection during treatment with Nimesil, the drug should be stopped.

Nimesil should not be used simultaneously with other NSAIDs.

Nimesulide may change platelet properties; therefore caution should be exercised when using the drug in patients with hemorrhagic diathesis, but the drug does not replace the preventive action of acetylsalicylic acid in cardiovascular disease.

Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the occurrence of gastrointestinal bleeding and life-threatening perforations, deterioration of kidney, liver, and heart function. Adequate clinical monitoring is required when taking Nimesil for this category of patients.

. As other drugs of NSAID class, which inhibit prostaglandin synthesis, nimesulide may negatively influence pregnancy and/or fetal development and may lead to premature closure of the arterial duct, hypertension in pulmonary artery system, impaired renal function, which may develop into renal failure with oligodyramnios, increased bleeding risk, decreased uterine contractility, occurrence of peripheral edema. In this regard, nimesulide is contraindicated during pregnancy and lactation. The use of Nimesulide may adversely affect female fertility and is not recommended for women planning to become pregnant. It is necessary to consult with the attending physician if pregnancy is planned.

There is evidence of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) to nimesulide as well as to other NSAIDs in rare cases.

At the first signs of skin rash, mucous membrane lesions or other signs of an allergic reaction, the use of Nimesulide should be stopped.

The effect of the drug Nimesil on driving and operating machinery has not been studied, therefore during treatment with Nimesil care should be taken when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Side effects

Hematopoietic system: seldom – anemia, eosinophilia, hemorrhagic syndrome; very rarely – thrombocytopenia, pacitopenia, thrombocytopenic purpura.

Allergic reactions: infrequently – itching, rash, increased sweating; rarely – hypersensitivity reactions, erythema, dermatitis; very rarely – anaphylactoid reactions, urticaria, angioneurotic edema, erythema polyform, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome).

CNS disorders: infrequent dizziness, rarely – anxiety, nervousness, nightmares; very rarely – headache, somnolence, encephalopathy (Reye syndrome).

Withthe visual organ: rarely – blurred vision.

Cardiovascular system disorders: infrequent – arterial hypertension, tachycardia, blood pressure lability, “hot flashes”.

In the respiratory system: infrequent – shortness of breath; very rare – exacerbation of bronchial asthma, bronchospasm.

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

Remote urinary system disorders:Rarely – dysuria, hematuria, urinary retention; very rarely – renal failure, oliguria, interstitial nephritis.

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

Others: rarely – hyperkalemia.

Overdose

Symptoms: apathy, drowsiness, nausea, vomiting, and epigastric pain.

With supportive 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, and anaphylactoid reactions may occur.

Treatment: conduct symptomatic therapy. There is no specific antidote. If overdose occurred within the last 4 hours, it is necessary to induce vomiting and/or provide activated charcoal (60 to 100 g in adults) and/or osmotic laxative. Forced diuresis, hemodialysis are ineffective due to high protein binding of the drug (up to 97.5%). Monitoring of renal and hepatic function is indicated.

Pregnancy use

Like other drugs of NSAID class that inhibit the synthesis of prostaglandins, nimesulide may adversely affect the course of pregnancy and/or the development of the embryo and may lead to premature closure of the arterial duct, hypertension in the pulmonary artery system, impaired renal function, which may develop into renal failure with oligodyramnios, increased bleeding risk, reduced uterine contractility, the occurrence of peripheral edema.

In this regard, the drug is contraindicated in pregnancy and during breastfeeding.

Similarities