Therapy for acute pain, pain in the lower back and / or lumbar region;
pain syndrome associated with diseases of the musculoskeletal system, including tendinitis, bursitis;
pain with bruises, sprains and dislocations of the joints;
toothache;
symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome;
primary algomenorrhea.
The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.
Inside, after meals, drinking plenty of water.
Adults and children over 12 years of age weighing more than 40 kg: 100 mg (1 tablet) 2 times a day; the maximum daily dose is 200 mg. 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. Elderly patients do not need dose adjustment.
The minimum effective dose should be used in the shortest possible course. The duration of treatment should not exceed 15 days.
One tablet contains:
active substance: nimesulide - 100.0 mg;
excipients: microcrystalline cellulose (102) 53.95 mg, corn starch 31.00 mg, sodium starch glycolate (type A) 37.20 mg, colloidal silicon dioxide 3.10 mg, talc 3.10 mg, magnesium stearate 3.10 mg, calcium hydrogen phosphate dihydrate to obtain a tablet weighing 310 mg.
Hypersensitivity to nimesulide and other components of the drug;
complete or incomplete combination of bronchial asthma, recurrent nasal polyposis, paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including history);
history of hepatotoxic reactions to nimesulide;
simultaneous use with drugs with potential hepatotoxicity (for example, other NSAIDs);
chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis) in the acute phase;
the period after coronary artery bypass grafting;
febrile syndrome with colds and acute respiratory viral infections;
suspicion of acute surgical pathology;
peptic ulcer of the stomach or duodenum in the acute phase;
erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;
history of erosive and ulcerative lesions of the gastrointestinal tract;
a history of perforation or gastrointestinal bleeding, including those associated with previous NSAID therapy;
history of cerebrovascular bleeding, other active bleeding or diseases accompanied by increased bleeding;
severe blood clotting disorders;
severe heart failure;
severe renal failure (creatinine clearance less than 30 ml / min);
progressive kidney disease;
confirmed hyperkalemia;
liver failure, active liver disease;
children under 12 years of age;
pregnancy and the period of breastfeeding;
alcoholism, drug addiction.
Carefully
Ischemic heart disease, cerebrovascular diseases, chronic heart failure, dyslipidemia / hyperlipidemia, diabetes mellitus, arterial hypertension, peripheral arterial disease, hemorrhagic diathesis, smoking, renal failure (creatinine clearance 30-60 ml / min), anamnestic data on the development of gastrointestinal ulceration - intestinal tract, the presence of Helicobacter pylori infection, advanced age, prolonged use of NSAIDs, alcoholism, severe somatic diseases, concomitant use of anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), oral glucocorticosteroids, selective capture inhibitors serotonin (including citalopram, fluoxetine, paroxetine, sertraline).
Pharmacological properties
Pharmacodynamics
Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) from the sulfonanilide class. It has anti-inflammatory, analgesic and antipyretic effects.
Unlike non-selective NSAIDs, nimesulide mainly inhibits cyclooxygenase-2 (COX-2), inhibits the synthesis of prostaglandins in the inflammation focus; has a less pronounced inhibitory effect on cyclooxygenase-1 (COX-1).
Pharmacokinetics
Suction
Nimesulide is well absorbed from the gastrointestinal tract (GIT). The maximum concentration in blood plasma (Cmax) after oral administration of a single dose of nimesulide (100 mg) is achieved on average after 2-3 hours and is 3-4 mg / ml.
Distribution
Communication with blood plasma proteins 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 focus of inflammation (40%), synovial fluid (43%). Easily penetrates histohematogenous barriers.
Metabolism
Nimesulide is actively metabolized in the liver using the cytochrome P450 (CYP) 2C9 isoenzyme. There is a possibility of drug interaction of nimesulide while being used 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.
Withdrawal
T1 / 2 of nimesulide - about 1.56-4.95 hours, 4-hydroxynimesulide - 2.89-4.78 hours. Nimesulide is excreted mainly 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 were not higher than in healthy volunteers. AUC and T1 / 2 were 50% higher, but were within the AUC and T1 / 2 values ??observed in healthy volunteers while using nimesulide. Repeated use did not lead to the cumulation of nimesulide.
Application during pregnancy and during breastfeeding
Pregnancy
Like other drugs from the NSAID class that inhibit the synthesis of prostaglandins, nimesulide can adversely affect the course of pregnancy and / or the development of the embryo and can lead to premature closure of the ductus arteriosus, hypertension in the fetal pulmonary artery system, impaired renal function, which can turn into renal failure with oliguria in the fetus, to an increased risk of bleeding, a decrease in uterine contractility, the occurrence of peripheral edema in the mother. The use of nimesulide during pregnancy is contraindicated.
Breastfeeding period
The use of nimesulide during breastfeeding is contraindicated.
Side effect
On the part of the blood and lymphatic system
Rarely: anemia, eosinophilia, hemorrhages;
Very rare: thrombocytopenia, pancytopenia, thrombocytopenic purpura, prolonged bleeding time.
Immune system disorders :
Rarely: hypersensitivity reactions;
Very rare: anaphylactoid reactions.
Mental disorders
Rarely: fear, nervousness, nightmares.
Nervous system disorders
Uncommon: dizziness;
Very rare: headache, drowsiness, encephalopathy (Reye's syndrome).
Violations of the organ of vision
Rarely: blurred vision;
Very rare: visual impairment.
Hearing and labyrinth disorders
Very rare: vertigo.
Heart disorders
Rare: tachycardia, palpitations.
Vascular disorders
Uncommon: increased blood pressure;
Rarely: lability of blood pressure, 'hot flushes' of blood to the skin of the face.
Respiratory, Chest and Mediastinal Disorders
Uncommon: shortness of breath;
Very rare: exacerbation of bronchial asthma, bronchospasm.
Gastrointestinal disorders
Often: diarrhea, nausea, vomiting;
Uncommon: constipation, flatulence, gastritis, gastrointestinal bleeding, ulcer and / or perforation of the stomach or duodenum;
Very rare: abdominal pain, dyspepsia, stomatitis, tarry stools.
Liver and biliary tract disorders
Often: increased activity of 'liver' enzymes;
Very rare: hepatitis, fulminant (fulminant) hepatitis (including deaths), jaundice, cholestasis.
Skin and subcutaneous tissue disorders
Uncommon: itching, skin rash, excessive sweating;
Rarely: erythema, dermatitis;
Very rare: urticaria, angioedema, facial edema, erythema multiforme, Stevenson-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).
Kidney and urinary tract disorders
Rarely: dysuria, hematuria, urinary retention;
Very rare: renal failure, oliguria, interstitial nephritis, hyperkalemia.
General disorders and disorders at the injection site
Uncommon: peripheral edema;
Rarely: malaise, asthenia;
Very rare: hypothermia.
Overdose
Symptoms: nausea, vomiting, drowsiness, apathy, gastrointestinal bleeding, increased blood pressure, acute renal failure, respiratory depression, anaphylactic reactions, coma.
Treatment: symptomatic and supportive treatment is recommended. There is no specific antidote for nimesulide. Patients admitted to the hospital with symptoms of an overdose of the drug (within 4 hours after taking it or after taking a high dose) are recommended to wash the stomach, take activated carbon (for adults - 1 g / kg body weight) and / or an osmotic-type laxative. There are no data on the possibility of removing nimesulide by hemodialysis. Forced diuresis, hemodialysis are ineffective due to the high connection of the drug with proteins.
Interaction with other medicinal products
Pharmacodynamic interactions
Glucocorticosteroids increase the risk of gastrointestinal erosive and ulcerative lesions or bleeding. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, increase the risk of gastrointestinal bleeding.
Anticoagulants: NSAIDs can 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 for patients with severe coagulation disorders. If the combination therapy still cannot be avoided, it is necessary to carefully monitor the blood clotting parameters.
Other non-steroidal anti-inflammatory drugs (NSAIDs): The simultaneous 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 can reduce the effect of diuretics.
In healthy volunteers, nimesulide temporarily reduces the excretion of sodium by furosemide, to a lesser extent - excretion of potassium and reduces the actual diuretic effect.
The simultaneous use of nimesulide and furosemide leads to a decrease (by 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 simultaneous use of furosemide and nimesulide requires caution in patients with renal or heart failure.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists: NSAIDs can reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-60 ml / min) with the simultaneous use of ACE inhibitors, angiotensin II receptor antagonists and agents that suppress the cyclooxygenase system (NSAIDs, antiplatelet agents), 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, the simultaneous use of these drugs should be carried out with caution, especially in elderly patients. Patients should receive adequate amounts of fluids,and renal function should be carefully monitored if used concomitantly. Mifepristone: due to the theoretical risk of a change in the effectiveness of mifepristone under the influence of inhibitors of prostaglandin synthesis, NSAIDs should not be used earlier than 8-12 days after discontinuation of mifepristone. There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in the blood plasma and its toxicity. When using nimesulide in patients on therapy with lithium preparations, regular monitoring of the concentration of lithium in the blood plasma should be carried out.than 8-12 days after discontinuation of mifepristone. There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in the blood plasma and its toxicity. When using nimesulide in patients on therapy with lithium preparations, regular monitoring of the concentration of lithium in the blood plasma should be carried out.than 8-12 days after discontinuation of mifepristone. There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in the blood plasma and its toxicity. When using nimesulide in patients on therapy with lithium preparations, regular monitoring of the concentration of lithium in the blood plasma should be carried out.
Clinically significant interactions with glibenclamide, theophylline, digoxin, cimetidine and antacids (for example, a combination of aluminum and magnesium hydroxides) were not observed.
Nimesulide inhibits the activity of the isoenzyme CYP2C9. With the simultaneous use of drugs that are substrates of this enzyme with nimesulide, the concentration of the latter in plasma may increase.
When prescribing nimesulide less than 24 hours before or after using methotrexate, caution is required, since in such cases, the concentration of methotrexate in the blood plasma and, accordingly, the toxic effects may increase.
In connection with the effect on renal prostaglandins, inhibitors of prostaglandin synthetases, which include nimesulide, can increase the nephrotoxicity of cyclosporins.
Influence on the ability to drive vehicles and mechanisms
Due to the fact that nimesulide can cause dizziness and drowsiness, it is necessary to refrain from driving and engaging in activities that require increased concentration of attention and speed of psychomotor reactions.
