Nimesulide-Teva, tablets 100 mg 20 pcs

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID)

ATX code: M01AX17

Pharmacological properties

Pharmacodynamics. Nimesulide belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs), has anti-inflammatory, analgesic, antipyretic and antiaggregant effects. Unlike indomethacin, it inhibits cyclooxygenase 2 (COX-2) to a greater extent than COX-1 (potentially less often causing side effects associated with inhibition of prostaglandin synthesis in healthy tissues, inhibiting their synthesis mainly in the focus of inflammation).

Pharmacokinetics. Nimesulide is well absorbed when taken orally (eating reduces the rate of absorption without affecting its degree). After a single administration of 100 mg of nimesulide the maximum concentration (C_max) in blood plasma in adults reaches 3-4 mg/l and is observed after 2-3 hours. Binding with plasma proteins is 95%, with erythrocytes – 2%, with lipoproteins – 1%, with acidic alpha1-glycoproteins – 1%. Increasing the dose does not affect the degree of binding.

The area under the curve “concentration-time” (AUC) is 20-35 mg h/l. No statistically significant differences were found between these parameters after a single dose and administration for 7 days in a dose of 100 mg twice a day.

The volume of distribution is 0.19-0.35 l/kg. It easily penetrates through histohematic barriers (in female genital tissues after a single nimesulide administration its concentration is about 40% of the blood plasma concentration), including acidic environment of the inflammatory focus and synovial fluid (40% and 43% of the blood plasma concentration, respectively).

It is metabolized in liver with participation of monooxygenases, including cytochrome P450 (CYP) 2C9 system. The main metabolite is water-soluble 4-hydroxynimesulide (25%), which has pharmacological activity similar to nimesulide.

Nimesulide is excreted mainly in the urine (approximately 50% of the dose taken). The half-life (T_1/2) of nimesulide is 3-6 hours, of 4-hydroxynimesulide – 3-5 hours. 4-hydroxynimesulide is excreted by the kidneys (65%) and with the bile (35%); it undergoes enterohepatic recirculation.

Only 1-3% of nimesulide is excreted unchanged. Approximately 29% of the dose is excreted as a metabolite in the feces.

The pharmacokinetic profile of nimesulide in the elderly does not change after single and repeated administration of the drug.

In patients with mild to moderate renal impairment – creatinine clearance (CK) 30-80 ml/min, C_max of nimesulide and its main metabolite in plasma are not higher than those of healthy volunteers. Repeated administration of nimesulide is not accompanied by its cumulation.

Indications

Active ingredient

Composition

How to take, the dosage

The lowest effective dose should be administered with the shortest possible course of treatment. The maximum duration of treatment with nimesulide is 15 days.

Adults:100 mg nimesulide 2 times daily after meals. In patients with renal insufficiency, the maximum daily dose is 100 mg.

Elderly persons:reducing the daily dose is not necessary.

Children (under 12 years): The drug Nimesulide-Teva is contraindicated.

Adolescents (12 to 18 years):dose adjustment is not required.

Kidney function impaired:dose adjustment in patients with mild to moderate renal function impairment (CK 30-80 ml/min) is usually not required. Nimesulide-Teva is contraindicated in patients with severe renal impairment (CKR < 30 ml/min).

Hepatic impairment:The use of Nimesulide-Teva is contraindicated.

Interaction

Pharmacodynamic interactions. Combination of Nimesulide-Teva with other NSAIDs, including acetylsalicylic acid, in anti-inflammatory doses (≥ 1 g once or ≥ 3 g per day) is not recommended.

NSAIDs increase the anticoagulant effect of warfarin. Patients receiving warfarin and antiaggregants (including clopidogrel and acetylsalicylic acid) while taking nimesulide have an increased risk of bleeding.

Inhibitors of prostaglandin synthesis (NSAIDs, including nimesulide) may increase nephrotoxicity of cyclosporine.

Concomitant use with glucocorticosteroids and selective serotonin reuptake inhibitors increases the risk of gastrointestinal bleeding.

NSAIDs may decrease the effectiveness of diuretics and other antihypertensive drugs. In patients with initial renal dysfunction (e.g., dehydrated patients or elderly patients with impaired renal function) concomitant administration of angiotensin-converting enzyme inhibitors (ACE) or angiotensin II antagonists with COX inhibitors may lead to increased manifestations of renal failure (usually reversible). This combination should be administered with caution, especially in elderly patients. Patients should get the necessary amount of fluids, and it is also worth considering the necessity of monitoring renal function.

In healthy subjects, nimesulide briefly reduces the severity of the natriuretic effect of furosemide (to a lesser extent, of the potassium-uretic effect).

Pharmacokinetic interactions. Concomitant administration of nimesulide and furosemide results in a decrease (approximately 20%) in AUC without affecting its renal clearance.

NSAIDs decrease clearance of lithium, leading to increased plasma concentrations and toxicity.

Nimesulide inhibits CYP2C9. Plasma concentrations of drugs that are substrates of this enzyme may increase with concomitant use of the drug Nimesulide-Teva.

Caution is required when nimesulide is administered less than 24 hours before or after treatment with methotrexate (plasma concentrations of methotrexate may increase, leading to increased toxicity).

The in vitro studies have shown the possibility of nimesulide displacing furosemide, fenofibrate, tolbutamide, salicylic acid and valproic acid from plasma protein binding (this fact has no clinical significance).

Special Instructions

The functional state of the liver should be monitored every 2 weeks. In case of signs of liver damage (skin itching, jaundice, nausea, vomiting, abdominal pain, darkened urine, increased activity of “liver” transaminases) the treatment should be stopped immediately.

Given the possibility of visual impairment in patients taking NSAIDs, if such symptoms occur, treatment should be stopped immediately and an ophthalmologic examination should be performed.

The drug may cause fluid retention; therefore, nimesulide should be used with extreme caution in patients with high blood pressure or signs of congestive heart failure.

Patients should be under regular medical supervision if along with nimesulide they also take drugs for which the gastrointestinal tract is also characterized by ulcerogenic effects. The drug should not be used simultaneously with other NSAIDs (including COX-2 selective inhibitors) and non-narcotic analgesics.

Nimesulide decreases platelet aggregation; however, it cannot replace prophylactic anticoagulants (acetylsalicylic acid, clopidogrel, ticlopidine) in cardiovascular diseases.

The use of the drug may adversely affect female fertility (not recommended for women planning to become pregnant).

The risk of adverse events may be reduced by using the lowest effective dose of Nimesulide-Teva for the shortest possible period.

Patients who develop symptoms associated with liver damage while taking Nimesulide-Teva (e.g., anorexia, nausea, vomiting, right-sided pain, increased fatigue, darkened urine) or who have increased liver transaminase activity should discontinue nimesulide. These patients should also not be repeatedly prescribed nimesulide.

Patients who have developed signs of a concomitant cold (e.g., increased body temperature), the prescription of nimesulide should be discontinued.

When using NSAIDs, bleeding, ulceration or perforation of the stomach or intestinal wall may occur. The risk of their development is higher when prescribing high doses of NSAIDs, when taking them in patients with a history of gastric or duodenal ulcers, as well as in elderly persons. Concomitant use of misoprostol or proton pump inhibitors should be considered if therapy is necessary in these cases.

Patients (especially those with a history of poor treatment and the elderly) should be cautioned to report any unusual abdominal symptoms (especially in the early stages of treatment) to their physician.

In cases of fluid retention and edema syndrome with NSAIDs, patients with arterial hypertension and/or congestive heart failure, coronary heart disease, peripheral arterial disease and/or cerebrovascular disease require special close monitoring. The same precautions should be taken when prescribing nimesulide for patients with increased risk of cardiovascular disease (e.g., hyperlipidemia, diabetes mellitus and smoking).

In patients with impaired renal function caution is required when prescribing Nimesulide-Teva (further deterioration of their function is possible); if creatinine clearance decreases, treatment should be discontinued.

Nimesulide should be used with caution in patients with hemorrhagic diathesis because it may decrease platelet aggregation.

The risk of serious skin reactions (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) when taking NSAIDs is higher at the beginning of treatment (most of these reactions appear within the first month of treatment). Nimesulide-Teva therapy should be discontinued when the first signs of rash, mucosal lesions or other manifestations of hypersensitivity appear.

The drug Nimesulide-Teva contains lactose monohydrate. Patients with congenital lactose intolerance, impaired glucose-galactose absorption or lactase deficiency should not take this drug.

Influence on the ability to drive and operate vehicles The effect of the drug Nimesulide-Teva on the speed of psychomotor reactions has not been specifically studied. However, patients who have dizziness or somnolence after taking Nimesulide-Teva should be careful when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Contraindications

Side effects

The data of clinical and epidemiological studies suggest that long-term use of any NSAID (especially in high doses) may potentially be accompanied by an increased risk of arterial thrombosis (including manifested by myocardial infarction or ischemic stroke).

With NSAID use the development of edema syndrome, arterial hypertension and worsening of the course of heart failure are possible. Serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been rarely reported.

A variety of gastrointestinal disorders (especially in predisposed and elderly individuals) have been observed more frequently: Peptic ulcers, perforation of the gastrointestinal wall, development of potentially severe gastrointestinal bleeding, nausea, vomiting, bloody vomiting, flatulence, abdominal pain, diarrhea, constipation, melena, stomatitis, ulcerative colitis, and less frequently, manifestations of gastritis are observed.

The following adverse events against nimesulide have been identified in controlled clinical trials (marked with “*”), as well as in marketing authorization studies with the reported frequency, classified according to the recommendations of the World Health Organization: very common (at least 10%); common (1-10%); infrequent (0.1-1%); rare (0.01-0.1%); very rare (

Overdose

Symptoms:apathy, drowsiness, nausea, vomiting, gastrointestinal bleeding, increased blood pressure, acute renal failure, respiratory depression.

Treatment:Symptomatic and supportive therapy. There is no specific antidote. In the first 4 hours after overdose – should cause vomiting, it is advisable to take activated charcoal (1 g/kg body weight). Carrying out forced diuresis and hemodialysis is ineffective.

Pregnancy use

The use of the drug Nimesulide-Teva is contraindicated in the third trimester of pregnancy.

Like other NSAIDs, the drug Nimesulide-Teva is not recommended for women trying to become pregnant.

Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/fetal development. Epidemiological studies show an increased risk of spontaneous abortion (early miscarriage) and development of heart defects and gastroschisis (malformation which is a malformation of the anterior abdominal wall in the perianal region in which abdominal organs fall out) when using NSAIDs in the first trimester of pregnancy. The risk of teratogenicity and embryotoxicity increases with increasing dose and duration of treatment.

If Nimesulide-Teva is taken by a woman who is trying to become pregnant or during the first and second trimesters of pregnancy, the dose and duration of treatment should be as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can affect:

the fetus:

– cardiopulmonary toxicity (with premature closure of the botallic arterial duct with development of pulmonary hypertension);

– renal dysfunction, which may progress to the development of renal failure;

the mother and the newborn:

– prolongation of bleeding time (even when low doses are administered);

– reduction of uterine contractions (delayed and prolonged labor).

There are no data on excretion of nimesulide with the breast milk, the drug Nimesulide-Teva is contraindicated during breastfeeding.

Similarities