Treatment: gastric lavage, detection and correction of water-electrolyte disorders, symptomatic therapy.
Symptoms: apathy, drowsiness, nausea, vomiting, pain in the epigastric region. With maintenance therapy for gastropathy, these symptoms are usually reversible. Gastrointestinal bleeding may occur. In rare cases, it is possible to increase blood pressure, acute renal failure, respiratory depression and coma, anaphylactoid reactions.
Treatment: symptomatic. There is no specific antidote. If the overdose occurred within the last 4 hours, - induction of vomiting and / or administration of activated charcoal (from 60 to 100 g per adult) and / or osmotic laxative. Forced diuresis and hemodialysis are ineffective due to the high binding of the drug to proteins (up to 97.5%). Control of kidney and liver function is indicated.
Hypersensitivity, including to aspirin or other NSAIDs in the anamnesis (bronchospasm, rhinitis, urticaria), acute peptic ulcers, erosive and ulcerative lesions and bleeding of the gastrointestinal tract, disorders of the blood clotting system, severe renal impairment, liver failure, children under 12 years of age.
With caution: arterial hypertension, heart failure, diabetes mellitus.
hypersensitivity to nimesulide or to one of the components of the drug,
hyperergic reactions (in the anamnesis), for example, bronchospasm, rhinitis, urticaria, associated with the intake of acetylsalicylic acid or other NSAIDs, including nimesulide,
hepatotoxic reactions to nimesulide (in the anamnesis),
concomitant (simultaneous) use of drugs with potential hepatotoxicity, such as paracetamol or other analgesics or NSAIDs,
inflammatory bowel diseases (Crohn's disease, ulcerative colitis) in the acute phase,
period after coronary artery bypass grafting,
febrile syndrome in colds and acute respiratory viral infections,
complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses with intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis),
peptic ulcer of the stomach or duodenum in the acute phase, the presence of a history of ulcers, perforations or bleeding in the gastrointestinal tract,
the presence of a history of cerebrovascular hemorrhages or other bleeding, as well as diseases accompanied by bleeding,
severe blood clotting disorders,
severe heart failure,
severe renal insufficiency (creatinine Cl <30 ml / min), confirmed hyperkalemia,
liver failure or any active liver disease,
pregnancy and lactation,
alcoholism, drug addiction,
children under the age of 12.
With caution: severe forms of arterial hypertension, type 2 diabetes mellitus, heart failure, coronary heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral artery diseases, smoking, creatinine Cl less than 60 ml/min.
Anamnestic data on the presence of ulcerative lesions of the gastrointestinal tract, infection caused by Helicobacter pylori, old age, long-term previous use of NSAIDs, severe somatic diseases.
Concomitant therapy with the following drugs: anticoagulants (e.g. warfarin), antiplatelet agents (e.g. acetylsalicylic acid, clopidogrel), oral corticosteroids (e.g. prednisone), SSRIs (e.g. citalopram, fluoxetine, paroxetine, sertraline).
Decision to prescribe Enetra® it should be based on an individual assessment of the risk and benefit of taking the drug.
In the course of research in vivo There was no clinically significant interaction with glibenclamide, theophylline, warfarin, digoxin, cimetidine, and antacids. According to the results of the study, there was no clinically significant interaction. Aulin reduces the effectiveness of diuretics and, in particular, blocks the furosemide-stimulated increase in the concentration of renin in plasma. Pharmacokinetic analysis of the concentration of nimesulide in patients on continuous diuretic therapy (furosemide) revealed a clinically insignificant decrease in the volume of distribution. Enhances the effect of acetylsalicylic acid on hemostasis. Concomitant use of Aulin with salicylates or tolbutamide may affect the concentration of the latter in plasma and, consequently, their clinical effectiveness. NSAIDs reduce the clearance of lithium, which leads to an increase in plasma concentrations and the development of toxic effects (when prescribing nimesulide to patients undergoing therapy with lithium salts, it is necessary to regularly determine its concentration)
Pharmacodynamic interactions
GCS. Increase the risk of gastrointestinal ulcers or bleeding.
Antiplatelet agents and SSRIs, such as fluoxetine. Increase the risk of gastrointestinal bleeding.
Anticoagulants. NSAIDs may increase the effect of anticoagulants, such as warfarin. Due to 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, it is necessary to conduct careful monitoring of blood clotting indicators.
Diuretics. NSAIDs can reduce the effect of diuretics.
In healthy volunteers, nimesulide temporarily reduces the excretion of sodium under the action of furosemide, to a lesser extent-the excretion of potassium and reduces the actual diuretic effect.
Co-administration of nimesulide and furosemide results in a decrease (approximately 20%) in AUC and a decrease in the cumulative excretion of furosemide without changing the renal clearance of furosemide.
Co-administration of furosemide and nimesulide requires caution in patients with impaired renal or cardiac function.
ACE inhibitors and angiotensin-II receptor antagonists. NSAIDs can reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine Cl 30-80 ml / min) with the combined administration of ACE inhibitors, angiotensin II receptor antagonists or substances that suppress the COX 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 Enetra® 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 starting co-therapy.
Pharmacokinetic interactions with other drugs
Lithium preparations. 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 prescribing nimesulide to patients receiving lithium therapy, regular monitoring of the concentration of lithium in the plasma should be carried out.
No clinically significant interactions with glibenclamide, theophylline, digoxin, cimetidine, or antacids (e.g., a combination of aluminum and magnesium hydroxides) were observed.
Nimesulide inhibits the activity of the CYP2C9 isoenzyme. When taking drugs that are substrates of this enzyme simultaneously with nimesulide, the concentration of these drugs in the plasma may increase.
When prescribing nimesulide less than 24 hours before or after taking methotrexate, caution is required, since in such cases, the level of methotrexate in the plasma and, accordingly, the toxic effects of this drug may increase.
Due to the effect on renal PG, COX inhibitors, such as nimesulide, can increase the nephrotoxicity of cyclosporins.
Interaction of other drugs with nimesulide
Researches in vitro It was shown that nimesulide is displaced from the binding sites by tolbutamide, salicylic acid and valproic acid, but these effects were not observed during clinical use of the drug.
Allergic reactions: most often — rash, urticaria, itching, erythema, angioedema, in isolated cases — Stevens-Johnson syndrome and epidermal necrolysis.
From the gastrointestinal tract: often-heartburn, nausea, gastralgia, abdominal pain, diarrhea, constipation, rarely — peptic ulcers, perforated ulcers, gastrointestinal bleeding.
From the side of the hepatobiliary system: changes in liver enzymes (transaminases), often temporary and reversible, in isolated cases — acute hepatitis, lightning liver failure (several deaths).
From the nervous system: drowsiness, headache, restlessness, dizziness.
From the urinary system: oliguria, edema, isolated hematuria,
kidney failure.
From the blood and lymphatic system: in isolated cases
leukopenia, anemia, agranulocytosis, prolonged bleeding time, hematuria, purpura, thrombocytopenia.
From the respiratory system: in isolated cases-anaphylactic reactions in the form of dyspnea, asthma attacks, mainly in patients with allergies to aspirin (acetylsalicylic acid) and other NSAIDs.
The frequency is classified by category, depending on the occurrence of the case: very often (>10), often (>100–<10), infrequently (>1000–<100), rarely (>10000–<1000), very rarely (<10000).
Disorders of the circulatory and lymphatic systems: rarely-anemia, eosinophilia, hemorrhages, very rarely-thrombocytopenia, pancytopenia, thrombocytopenic purpura.
Allergic reactions: infrequently-itching, rash, excessive sweating, rarely-hypersensitivity reactions, erythema, dermatitis, very rarely-anaphylactoid reactions, urticaria, angioedema, erythema polyforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).
Violations of the central nervous system: infrequently-dizziness, rarely-a feeling of fear, nervousness, nightmarish dreams, very rarely-headache, drowsiness, encephalopathy (Reye's syndrome).
Sensory disorders: rarely-blurred vision.
Violations by the CCC: infrequently-arterial hypertension, tachycardia, blood pressure lability, hot flashes.
Respiratory system disorders: infrequently-shortness of breath, very rarely-exacerbation of bronchial asthma, bronchospasm.
Disorders of the gastrointestinal tract: often-diarrhea, nausea, vomiting, infrequently-constipation, flatulence, gastritis, very rarely-abdominal pain, dyspepsia, stomatitis, tar-like stools, gastrointestinal bleeding, ulcers and / or perforation of the stomach or duodenum.
Disorders of the liver and biliary system: very rarely-hepatitis, lightning hepatitis, jaundice, cholestasis, increased activity of liver enzymes.
Disorders of the kidneys and urinary system: rarely-dysuria, hematuria, urinary retention, very rarely-renal failure, oliguria, interstitial nephritis.
General violations: rarely-malaise, asthenia, very rarely — hypothermia.
Other: rarely-hyperkalemia.
For symptomatic therapy, reducing the intensity of pain and inflammation at the time of use (does not affect the progression of the disease) in the following conditions and diseases:
rheumatoid arthritis,
articular cider in acute gout,
psoriatic arthritis,
ankylosing spondylitis,
osteochondrosis with radicular syndrome,
osteoarthritis,
myalgia of rheumatic and non-rheumatic origin,
inflammation of ligaments, tendons, bursitis (including post-traumatic inflammation of soft tissues),
pain syndrome of various origins (including in the postoperative period, with injuries, algodismenorrhea, toothache, headache, arthralgia, lumboishialgia).
Osteoarthritis, osteoarthritis, pain syndrome in extraarticular lesions (tendinitis, bursitis, bruises, sprains, etc.), toothache and inflammation, primary dysmenorrhea (symptomatic treatment).
treatment of acute pain (back pain, lower back pain, pain syndrome in the pathology of the musculoskeletal system, including injuries, sprains and dislocations of joints, tendinitis, bursitis),
toothache,
symptomatic treatment of osteoarthritis with pain syndrome,
dysalgomenorrhea.
The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use.
Selective inhibitor of cyclooxygenase, an enzyme involved in the synthesis of PG. The functional group in nimesulide is sulfonylide. In research in vivo and in vitro it was found that nimesulide mainly inhibits cyclooxygenase II, the synthesis of which prevails in the process of inflammation, and has a minimal effect on cyclooxygenase I, which has a protective effect on the gastric or renal mucosa. In an inflammatory reaction, it affects neutrophils at the second stage of the cellular response. Effectively reduces the production of oxidants during the interaction of neutrophils with chemotaxis factors (direct cellular action), while not reducing the locomotor properties of the cell and does not limit the absorption efficiency of neutrophils during phagocytosis. It acts as an activator of hypochloric acid in the process of phagocytosis (recycling process). Prevents the formation of chloramine in neutrophils and toxic tissue damage by chlorinated oxidants in inflammatory processes
Nimesulide is an NSAID from the class of sulfonamides. It has anti-inflammatory, analgesic and antipyretic effects. Nimesulide acts as an inhibitor of the COX enzyme responsible for the synthesis of PG and mainly inhibits COX-2.
When taken orally, it is well absorbed. After a single dose of 100 mg C max in plasma, it is noted after 2-3 hours and is 3-4 mg/l. AUC = 20-35 mg/l/h. There was no statistical difference between the above data and the values obtained when using the drug at a dose of 100 mg 2 times a day for 7 days. Up to 97.5% of the substance binds to plasma proteins.
It is metabolized in the liver. The main metabolite is the parahydroxy form, which has pharmacological activity. The estimated time before the appearance of the metabolite in the circulatory system is insignificant and is 0.8 hours, but the formation constant is small and significantly less than the absorption constant of nimesulide. Hydroxynimesulide is the only metabolite in the plasma and is almost completely free. T1/2 it is from 3.2 to 6 hours. It is mainly excreted in the urine (approximately 50% of the administered dose). Only 1-3% is excreted unchanged. Hydroxynimesulide, the main metabolite, is found only in the form of glucuronide. Approximately 29% of the injected substance is released after biotransformation with feces.
The kinetic profile of nimesulide does not change in elderly patients with single and repeated administration.
With minor renal impairment (creatinine Cl 30-80 ml / min) C max nimesulide and its metabolites do not exceed the level in healthy volunteers. Repeated use of the drug does not lead to accumulation. It is contraindicated in patients with impaired liver function due to the high risk of accumulation.
After oral administration, the drug is well absorbed from the gastrointestinal tract, reaching Cmax in blood plasma after 2-3 hours, the bond with plasma proteins is 97.5%, T1/2 It is 3.2-6 hours. It easily penetrates through histohematic barriers.
It is metabolized in the liver by the cytochrome P450CUR 2C9 isoenzyme. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide-hydroxynimesulide. Hydroxynimesulide is excreted in the bile in a metabolized form (found exclusively in the form of glucuronate-about 29%).
Nimesulide is excreted from the body, mainly by the kidneys (about 50% of the dose taken).
The pharmacokinetic profile of nimesulide in the elderly does not change with the administration of single and multiple/repeated doses.
According to an experimental study conducted with patients with mild to moderate renal insufficiency (creatinine Cl 30-80 ml / min) and healthy volunteers, Cmax The concentration of nimesulide and its metabolite in the plasma of patients did not exceed the concentration of nimesulide in healthy volunteers. AUC and T1/2 in patients with renal insufficiency, they were 50% higher, but within the values of pharmacokinetic parameters. With repeated administration of the drug, no accumulation is observed.
Nimesulide
Inside, after eating. The contents of the bag are dissolved in 80-100 ml of water. The prepared solution is not subject to storage.
Adults: the recommended dosage is 100 mg (1 table). or 1 bag of pellets) 2 times a day. If necessary, the dosage can be increased to 200 mg 2 times a day, depending on the severity of the disease. The duration of treatment depends on the clinical effect.
Patients over 65 years of age are recommended to use the minimum effective dose of the drug.
Patients with minor renal impairment (creatinine Cl — 30-80 ml/min) do not need to adjust the dose. When prescribing the drug to patients with renal insufficiency (creatinine Cl < 30 ml/min), caution should be exercised (if necessary, the dosage in such patients can be reduced).
Inside, after the meal. 1 pack each. (100 mg of nimesulide) 2 times a day. The contents of the bag are poured into a glass and dissolved in about 100 ml of water. The prepared solution is not subject to storage.
Enetra® it is used only for the treatment of patients older than 12 years.
Teenagers (from 12 to 18 years old). 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 to adjust the dose in patients with mild to moderate forms of renal insufficiency (creatinine Cl 30-80 ml/min).
Elderly patients. In the treatment of elderly patients, the need to adjust the daily dose is determined by the doctor based on the possibility of interaction with other drugs.
The maximum duration of treatment with nimesulide is 15 days.
To reduce the risk of undesirable side effects, the minimum effective dose should be used in the shortest possible course.
