Nimesulide-Teva tablets 100mg, No. 30

• Acute pain syndrome: algomenorrhea, postoperative and post-traumatic pain, arthralgia, myalgia, toothache and headache, tendinitis, bursitis.

• Symptomatic treatment of osteoarthritis, accompanied by pain syndrome (the drug is intended for symptomatic therapy, to reduce pain and inflammation at the time of use, does not affect the progression of the disease; nimesulide should be prescribed only as a second-line therapy).

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

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

1 tablet contains:

active ingredient nimesulide 100.0 mg;

excipients: sodium docusate 1.5 mg, hyprolose 0.8 mg, lactose monohydrate 153.7 mg, sodium carboxymethyl starch 35.0 mg, microcrystalline cellulose 102 100.0 mg, magnesium stearate 1.0 mg, hydrogenated vegetable oil 8, 0 mg.

• Known hypersensitivity to nimesulide or any of its constituent excipients.

• History of hypersensitivity reactions in response to taking NSAIDs (for example, bronchospasm, rhinitis, urticaria, complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose or paranasal sinuses, and intolerance to acetylsalicylic acid and other NSAIDs).

• History of gastrointestinal bleeding or perforation of the intestinal wall associated with previous NSAID treatment, erosive and ulcerative lesions of the gastric and duodenal mucosa (two or more confirmed episodes of ulceration and / or bleeding), inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation.

• Cerebrovascular bleeding, bleeding disorders with a history of bleeding, hemophilia.

• Decompensated heart failure.

• Hepatic failure or any liver disease in the acute stage, hepatotoxic reactions when using nimesulide in history, concomitant use of other potentially hepatotoxic substances.

• Severe renal failure (CC less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia. Х Postoperative period after coronary artery bypass grafting.

• Concomitant colds with high fever.

• Congenital lactose intolerance, impaired absorption of glucose-galactose, lactase deficiency.

• Children under 12 years of age.

• Third trimester of pregnancy and breastfeeding.

  Carefully

• Severe somatic diseases: ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, obliterating peripheral arterial disease, mild and moderate renal failure (CC 30-80 ml / min), anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, presence of Helicobacter pylori infection.

• Smoking, old age, prolonged use of NSAIDs, alcoholism, concomitant use of anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), oral glucocorticosteroids, selective serotonin reuptake inhibitors (including serotonin reuptake inhibitors) citalopram, fluoxetine, paroxetine and sertraline).

Pharmacodynamics

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, antipyretic and antiplatelet effects. Unlike indomethacin, it inhibits cyclooxygenase 2 (COX-2) to a greater extent than COX-1 (potentially less likely to cause side effects associated with inhibition of prostaglandin synthesis in healthy tissues, inhibiting their synthesis mainly in the focus of inflammation).

Pharmokinetics

Nimesulide is well absorbed when taken orally (food intake reduces the rate of absorption without affecting its degree). After a single dose of 100 mg of nimesulide, the maximum concentration (Cmax) in blood plasma in adults reaches 3-4 mg / l and is observed after 2-3 hours. Communication with blood plasma proteins - 95%, with erythrocytes - 2%, with lipoproteins - 1%, with acid alpha1-glycoproteins - 1%. Increasing the dose does not affect the degree of binding. The area under the concentration-time curve (AUC) is 20-35 mg h / l. There were no statistically significant differences between these parameters after a single dose and the appointment for 7 days at a dose of 100 mg 2 times a day.

The volume of distribution is 0.19-0.35 l / kg. Easily penetrates the histohematological barriers (in the tissues of the female genital organs after a single dose of nimesulide, the concentration is about 40% of the concentration in the blood plasma), incl. into the acidic environment of the focus of inflammation and synovial fluid (40% and 43%, respectively, of the concentration in the blood plasma). It is metabolized in the liver with the participation of monooxygenases, incl. cytochrome P450 (CYP) 2C9 systems.

The main metabolite, water-soluble 4-hydroxynimesulide (25%), has a pharmacological activity similar to nimesulide. Nimesulide is excreted mainly in the urine (approximately 50% of the dose taken).

The half-life (T1 / 2) of nimesulide is 3-6 hours, 4-hydroxynimesulide is 3-5 hours. 4-hydroxynimesulide is excreted by the kidneys (65%) and in the bile (35%), 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 a single and repeated administration of the drug. In patients with mild and moderate renal impairment - creatinine clearance (CC) 30-80 ml / min, Cmax of nimesulide and its main metabolite in blood plasma do not exceed those in healthy volunteers. Re-administration of nimesulide is not accompanied by its cumulation.

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 an overdose - induce vomiting, it is advisable to take activated carbon (1 g / kg body weight). Forced diuresis and hemodialysis are ineffective.

Side effects

The data of clinical and epidemiological studies indicate that long-term use of any NSAIDs (especially in high doses) can potentially be accompanied by an increase in the risk of arterial thrombosis (including manifested by myocardial infarction or ischemic stroke).

Against the background of the use of NSAIDs, the development of edematous syndrome, arterial hypertension, aggravation of the course of heart failure is possible. Very rarely, serious skin reactions have been reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Most often, various gastrointestinal disorders are observed (especially in predisposed and elderly persons): peptic ulcers, perforation of the gastrointestinal tract wall, the development of potentially severe gastrointestinal bleeding, nausea, vomiting, bloody vomiting, flatulence, abdominal pain, diarrhea, constipation, melena, stomatitis, ulcerative colitis, manifestations of gastritis are less common.

The following adverse events while taking nimesulide were identified during controlled clinical trials (marked with a '*'), as well as marketing observations with the frequency presented, classified according to the recommendations of the World Health Organization: very often (at least 10%); often (1-10%); infrequently (0.1-1%); rarely (0.01-0.1%); very rare (less than 0.01%, including isolated cases).

Allergic reactions: rarely - hypersensitivity *; very rarely - anaphylaxis.

Violations of water and electrolyte balance: rarely - hyperkalemia.

Mental disorders: rarely - anxiety, fear *, nervousness *, 'nightmares' *.

Disturbances from the nervous system and sensory organs: infrequently - dizziness *; rarely - blurred vision *; very rarely - visual impairment.

Violations of the cardiovascular system: infrequently - arterial hypertension *; rarely - tachycardia *, blood pressure lability *, 'hot flushes' of blood to the face *.

Respiratory system disorders: infrequently - dyspnea *; very rarely - bronchospasm.

Digestive system disorders: often - diarrhea *, nausea *, vomiting *; infrequently - constipation *, flatulence *, gastritis *; very rarely - abdominal pain, dyspepsia, stomatitis, melena, gastrointestinal bleeding, ulcer and perforation of the duodenum and / or stomach.

Liver and biliary tract disorders: often - increased activity of 'liver' enzymes *; very rarely - hepatitis, incl. fulminant course, jaundice, cholestasis.

Violations of the skin and subcutaneous tissues: infrequently - itching *, rash *, increased sweating *; rarely - erythema *, dermatitis *; very rarely - urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

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

Systemic disorders: infrequently - edematous syndrome *; rarely - malaise *, asthenia *; very rarely - hypothermia.

Blood disorders: rarely - anemia *, eosinophilia *; very rarely - thrombocytopenia, pancytopenia, purpura.

Drug interactions

Pharmacodynamic interactions.

The 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 enhance the anticoagulant effect of warfarin.

Patients receiving warfarin and antiplatelet agents (including clopidogrel and acetylsalicylic acid) while taking nimesulide have an increased risk of bleeding. Inhibitors of prostaglandin synthesis (NSAIDs, including nimesulide) can increase the nephrotoxicity of cyclosporine.

With simultaneous use with glucocorticosteroids and selective serotonin reuptake inhibitors, the risk of bleeding from the gastrointestinal tract increases.

NSAIDs can reduce the effectiveness of diuretics and other antihypertensive drugs. In patients with initial impairment of renal function (for example, in dehydrated patients or elderly patients with impaired renal function), concomitant administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists with COX inhibitors can lead to increased manifestations of renal failure (usually reversible). This combination should be used with caution, especially in elderly patients.

Patients should receive adequate fluid intake, and kidney function monitoring should be considered. In healthy people, nimesulide briefly reduces the severity of the natriuretic action of furosemide (to a lesser extent, potassiumuretic).

Pharmacokinetic interactions.

Concomitant administration of nimesulide and furosemide leads to a decrease (by about 20%) in AUC, without affecting its renal clearance.

NSAIDs decrease the clearance of lithium, leading to an increase in its concentration in blood plasma and toxicity. Nimesulide inhibits CYP2C9. Plasma concentrations of drugs that are substrates of this enzyme may increase with the concomitant use of the drug Nimesulide-Teva.

Caution is required when nimesulide is prescribed less than 24 hours before or after methotrexate treatment (the concentration of methotrexate in the blood plasma may increase, leading to an increase in its toxicity). In vitro studies have shown the possibility of displacing furosemide, fenofibrate, tolbutamide, salicylic and valproic acids from the connection with blood plasma proteins with nimesulide (this fact has no clinical significance).