Nimesulide tablets 100mg, No. 20

• 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.

»сследовани¤ in vitro показали, что нимесулид вытесн¤етс¤ из мест св¤зывани¤ толбутамидом, салициловой кислотой и вальпроевой кислотой. Ќесмотр¤ на то, что данные взаимодействи¤ были определены в плазме крови, указанные эффекты не наблюдались в процессе клинического применени¤ препарата.

ќсобые указани¤

Ќежелательные побочные эффекты можно свести к минимуму при применении препарата в минимальной эффективной дозе при минимальной длительности применени¤, необходимой дл¤ купировани¤ болевого синдрома. »меютс¤ данные об очень редких случа¤х серьезных реакций со стороны печени, в том числе, случа¤х летального исхода, св¤занных с применением нимесулидсодержащих препаратов. ѕри по¤влении симптомов, схожих с признаками поражени¤ печени (анорекси¤, кожный зуд, пожелтение кожных покровов, тошнота, рвота, боли в животе, потемнение мочи, повышение активности Ђпеченочныхї трансаминаз) следует немедленно прекратить применение нимесулида и обратитьс¤ к врачу. ѕовторное применение нимесулида у таких пациентов противопоказано. ѕосле 2-х недель применени¤ препарата необходим контроль показателей функции печени (Ђтрансаминазыї).

—ообщаетс¤ о реакци¤х со стороны печени, имеющих в большинстве случаев обратимый характер, при кратковременном применении препарата.

¬о врем¤ применени¤ нимесулида пациент должен воздерживатьс¤ от приема других анальгетиков, включа¤ Ќѕ¬ѕ (в т.ч. селективные ингибиторы ?ќv-2). Ќимесулид следует примен¤ть с осторожностью у пациентов с желудочно-кишечными заболевани¤ми в анамнезе (¤звенный колит, болезнь  рона), поскольку возможно обострение этих заболеваний.

–иск возникновени¤ желудочно-кишечного кровотечени¤, пептической ¤звы/перфорации желудка или двенадцатиперсной кишки повышаетс¤ у пациентов с наличием ¤звенного поражени¤ ? “ (¤звенный колит, болезнь  рона) в анамнезе, а также у пожилых пациентов, с увеличением дозы Ќѕ¬ѕ, поэтому лечение следует начинать с наименьшей возможной дозы. “аким пациентам, а также пациентам, которым требуетс¤ одновременное применение низких доз ацетилсалициловой кислоты или других средств, повышающих риск возникновени¤ осложнений со стороны желудочно-кишечного тракта, рекомендуетс¤ дополнительно назначать прием гастропротекторов (мизопростол или блокаторы протонной помпы). ѕациенты с заболевани¤ми ? “ в анамнезе, в особенности, пожилые пациенты, должны сообщать врачу о вновь возникших симптомах со стороны ? “ (особенно о симптомах, которые могут свидетельствовать о возможном желудочно-кишечном кровотечении).

Ќимесулид следует назначать с осторожностью пациентам, принимающим препараты, увеличивающие риск изъ¤звлени¤ или кровотечени¤ (пероральные кортикостероиды, антикоагул¤нты, например, варфарин, селективные ингибиторы обратного захвата серотонина или антитромбоцитарные средства, например, ацетилсалицилова¤ кислота).

¬ случае возникновени¤ желудочно-кишечного кровотечени¤ или ¤звенного поражени¤ ? “ у пациентов, принимающих нимесулид, лечение препаратом необходимо немедленно прекратить.

”читыва¤ сообщени¤ о нарушени¤х зрени¤ у пациентов, принимавших другие Ќѕ¬ѕ, при по¤влении любого нарушени¤ зрени¤ применение нимесулида должно быть немедленно прекращено и проведено офтальмологическое обследование.

ѕрепарат может вызывать задержку жидкости в ткан¤х, поэтому пациентам с артериальной гипертензией, с почечной и/или сердечной недостаточностью, ишемической болезнью сердца, заболевани¤ми периферических артерий и/или цереброваскул¤рными заболевани¤ми, с наличием факторов риска развити¤ сердечно-сосудистых заболеваний (например, гиперлипидемией, сахарным диабетом, у кур¤щих) нимесулид следует примен¤ть с особой осторожностью. ¬ случае ухудшени¤ состо¤ни¤, лечение нимесулидом необходимо прекратить.

 линические исследовани¤ и эпидемиологические данные позвол¤ют сделать вывод о том, что Ќѕ¬ѕ, особенно в высоких дозах и при длительном применении, могут приводить к незначительному увеличению риска возникновени¤ инфаркта миокарда или инсульта. ?л¤ исключени¤ риска возникновени¤ таких событий при применении нимесулида данных недостаточно.

ѕри возникновении признаков Ђпростудыї или острой респираторно-вирусной инфекции в процессе применени¤ нимесулида прием препарата должен быть прекращен. Ќимесулид может измен¤ть свойства тромбоцитов, поэтому необходимо соблюдать осторожность при применении препарата у лиц с геморрагическим диатезом, однако препарат не замен¤ет профилактического действи¤ ацетилсалициловой кислоты при сердечно-сосудистых заболевани¤х.

ѕожилые пациенты особенно подвержены неблагопри¤тным реакци¤м на Ќѕ¬ѕ, в том числе, риску возникновени¤ желудочно-кишечных кровотечений и перфораций, угрожающим жизни пациента, снижению функций почек, печени и сердца. ѕри приеме нимесулида дл¤ данной категории пациентов необходим надлежащий клинический контроль.

There is evidence of the occurrence of rare cases of severe skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when taking NSAIDs, including nimesulide. At the first manifestations of a skin rash, damage to the mucous membranes or other signs of an allergic reaction, nimesulide should be discontinued immediately.

The use of the drug may adversely affect female fertility and is not recommended for women planning a pregnancy.

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.