Naisulide, 100 mg 20 pcs.

Pharmacotherapeutic group

NSAIDs

ATX code: M01AX

Pharmacodynamics:

Nimesulide is a nonsteroidal anti-inflammatory agent from the sulfonamide class. It has anti-inflammatory analgesic and antipyretic effects.

In contrast to non-selective NSAIDs, nimesulide mainly inhibits cyclooxygenase-2 (COX-2) inhibition of prostaglandin synthesis in the inflammation focus; it has less pronounced inhibitory effect on cyclooxygenase-1 (COX-1).

Pharmacokinetics:

Nimesulide is well absorbed from the gastrointestinal tract (GIT).

The maximum plasma concentration (Cmax) after oral administration of a single dose of nimesulide of 100 mg is reached after 2-3 hours on average and is 3-4 mg/l. Area under the curve “concentration – time” (AUC) is 20-35 mg/hl. The binding to plasma proteins is up to 975%.

Metabolized in the liver by cytochrome P450 isoenzyme (CYP)2C9. The main metabolite is pharmacologically active parahydroxy derivative of nimesulide – hydroxynimesulide, which is found only as glucuronate.

Nimesulide is excreted mainly in the urine (about 50% of the dose taken) in metabolized form with the feces about 29%.

The elimination half-life (T1/2) is 32-6 hours.

The pharmacokinetic profile of nimesulide in elderly patients and patients with mild to moderate renal impairment does not change with single and multiple/repeated doses.

Indications

– Acute pain (back pain in the lower back; pain syndrome in the musculoskeletal system including contusions sprains and dislocations of joints; tendonitis bursitis; toothache);

– symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome;

– primary algodysmenorrhea.

The drug is intended as symptomatic therapy to reduce pain and inflammation at the time of use; nimesulide is recommended for therapy as a second-line drug.

Active ingredient

Composition

1 tablet contains:

the active substance: nimesulide 50 or 100 mg;

excipients: microcrystalline cellulose, corn starch, corn starch pregelatinized, colloidal silica (aerosil), citric acid monohydrate, sodium carboxymethyl starch, type A, aspartame, talc, magnesium stearate, banana flavoring (for 50 mg dosage), pineapple flavoring (for 100 mg dosage).

How to take, the dosage

To be taken orally. Put the tablet on the tongue the tablet will quickly dissolve and you can swallow it without water.

Adults and children over 12 years of age orally (body weight over 40 kg) are prescribed 100 mg 2 times a day.

It is taken after a meal. If necessary, the tablet may be refilled with enough water.

The maximum daily dose for adults and children over 12 years is 200 mg.

Patients in the elderly:

There is no need to adjust the daily dose when treating elderly patients.

Patients with renal insufficiency:

In patients with mild to moderate renal impairment (creatinine clearance 30-60 mL/min), no dose adjustment is necessary Patients with severe renal impairment (creatinine clearance less than 30 mL/min) nimesulide is contraindicated.

Patients with hepatic impairment:

The use of nimesulide in patients with hepatic impairment is contraindicated.

The course of treatment: as prescribed by the doctor.

To decrease the chance of side effects, it is recommended to take the lowest effective dose for the shortest possible time.

The maximum duration of treatment with nimesulide is 15 days.

Interaction

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRls) such as fluoxetine increase the risk of gastrointestinal bleeding.

NSAIDs can increase the effects of anticoagulants such as warfarin. Because of the increased risk of bleeding, this combination is not recommended and is contraindicated in patients with severe coagulation disorders. If the combination therapy still cannot be avoided, careful monitoring of blood clotting parameters is necessary.

Diuretics

NSAIDs may decrease the effect of diuretics.

In healthy volunteers, nimesulide temporarily reduces sodium excretion with furosemide to a lesser extent, potassium excretion and reduces the diuretic effect itself.

The concomitant use of nimesulide and furosemide leads to a decrease (approximately 20%) in the area of the curve “concentration-time” (AUC) and reduced cumulative excretion of furosemide without changing the renal clearance of furosemide. Concomitant use of furosemide and nimesulide requires caution in patients with renal or cardiac insufficiency.

ACE inhibitors and angiotensin-II receptor antagonists

NSAIDs may decrease the effect of hypotensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) simultaneous use of ACE inhibitors, angiotensin II receptor antagonists and agents that inhibit cyclooxygenase system (NSAIDs antiaggregants) may cause further deterioration of renal function and appearance 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 concomitant use of these drugs should be performed with caution especially in elderly patients.

Patients should receive adequate fluids and renal function should be closely monitored after concomitant use.

Mifepristone

Theoretically, the potency of mifepristone and prostaglandin analogues may be reduced when used concomitantly with NSAIDs (including acetylsalicylic acid) by their antiprostaglandin effect.

Limited data show that use of NSAIDs on the day of prostaglandin analogue use has no adverse effect on the effect of mifepristone or prostaglandin analogue on cervical dilatation and does not reduce the clinical effectiveness of medical abortion.

There is evidence that NSAIDs decrease lithium clearance, which leads to increased plasma lithium concentrations and toxicity. When using nimesulide in patients on therapy with lithium medications, regular monitoring of plasma lithium concentration should be performed.

Clinically significant interactions with glibenclamide theophylline digoxin cimetidine and antacids (e.g., a combination of aluminum and magnesium hydroxide) have not been observed.

Nimesulide inhibits the activity of CYP2C9 isoenzyme. When concomitant use of drugs that are substrates of this enzyme with nimesulide, plasma concentrations of the latter may increase.

When nimesulide is taken less than 24 hours before or after methotrexate administration, caution is required since in these cases the plasma concentrations of methotrexate and the corresponding toxic effects may increase.

Inhibitors of prostaglandin synthetases, such as nimesulide, may increase nephrotoxicity of cyclosporines due to their effect on renal prostaglandins.

Special Instructions

Undesirable side effects can be minimized by using the drug at the lowest effective dose with the shortest duration of use necessary to relieve pain syndrome.

There have been reports of very rare cases of serious liver reactions, including death, associated with the use of nimesulide-containing drugs. If the symptoms similar to those of liver damage occur (anorexia, itching, yellowing of skin, nausea, vomiting, abdominal pain, darkening of urine, increased “liver” transaminases), it is necessary to stop using Naisulide® immediately and ask for medical advice. Reuse of Naisulide® in such patients is contraindicated.

Hepatic reactions have been reported, which in most cases are reversible with short-term use of nimesulide.

Patient should refrain from taking other analgesics including NSAIDs (including COX-2 selective inhibitors) while using Naisulide®.

The drug Naisulide® should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis Crohn’s disease) due to the possible exacerbation of these diseases.

The risk of gastrointestinal bleeding peptic ulcer/perforation of the stomach or duodenum is increased in patients with a history of peptic ulcer disease (ulcerative colitis Crohn’s disease) and in elderly patients with increasing doses of NSAIDs; therefore, treatment should be started with the lowest dose possible. For such patients, as well as for patients who require simultaneous use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, it is recommended to additionally prescribe gastroprotectors (misoprostol or proton pump blockers).

Patients with a history of GI disease, particularly older patients, should inform their physician if they have any new GI symptoms (especially symptoms that could indicate possible gastrointestinal bleeding).

The drug Naisulide® should be used with caution in patients taking medications that increase the risk of ulceration or bleeding (oral corticosteroids anticoagulants such as warfarin selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid).

In case of gastrointestinal bleeding or gastrointestinal ulcers in patients taking Naisulide®, treatment with the drug should be discontinued.

Given the reports of visual disturbances in patients taking other NSAIDs, if any visual disturbance occurs, the use of Naisulide® should be stopped immediately and an ophthalmologic examination should be performed.

The drug may cause fluid retention; therefore, Naisulide® should be used with extreme caution in patients with arterial hypertension with renal and/or cardiac insufficiency. In case of worsening of the condition it is necessary to stop treatment with Naisulide®.

Clinical studies and epidemiological data suggest that NSAIDs, especially at high doses and with long-term use, may lead to a low risk of myocardial infarction or stroke. There is insufficient data to exclude the risk of these events with nimesulide.

If signs of a “cold” or acute respiratory viral infection occur during the use of Nysulide®, the drug should be stopped.

Nimesulide may affect platelet function; therefore caution must be exercised when using in patients with hemorrhagic diathesis; however, the drug does not replace the preventive action of acetylsalicylic acid in cardiovascular disorders.

Elderly patients are especially prone to adverse reactions to NSAIDs including risk of gastrointestinal bleeding and perforations and life-threatening renal, hepatic and cardiac impairment. Appropriate clinical monitoring is necessary when taking Naisulide® for this category of patients.

There is evidence of rare skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when taking NSAIDs, including nimesulide. At the first signs of skin rash, mucous membranes or other signs of allergic reactions the drug Naisulide® should be stopped immediately.

The effect of the drug Naisulide® on the ability to drive vehicles and machines has not been studied; therefore during the period of using Naisulide® care should be taken when driving vehicles and performing potentially dangerous activities that require increased concentration and quick psychomotor reactions.

Contraindications

– Hypersensitivity to nimesulide or other components of the drug;

– history of hyperergic reactions (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs including nimesulide;

The complete or incomplete combination of bronchial asthma with recurrent nasal or paranasal sinus polyposis and intolerance to acetylsalicylic acid and other NSAIDs (including nimesulide).ч. history);

– history of hepatotoxic reactions to nimesulide;

– concomitant use with other drugs with potential hepatotoxicity (e.g. other NSAIDs);

– Chronic inflammatory bowel disease (Crohn’s disease ulcerative colitis) in the acute phase;

– period after coronary artery bypass grafting;

– febrile syndrome in colds and acute respiratory viral infections;

– suspected acute surgical pathology;

– gastric or duodenal ulcer in the acute phase; gastrointestinal tract erosive ulcerative lesions; history of gastrointestinal perforations or bleeding;

– A history of cerebrovascular bleeding or other conditions accompanied by increased bleeding;

– severe bleeding disorders;

– severe heart failure;

– severe renal insufficiency (creatinine clearance <30 ml/min) confirmed hyperkalemia;

– childhood under 12 years of age;

– pregnancy and period of breastfeeding;

– alcoholism drug addiction;

– hepatic insufficiency active liver disease.

Artial hypertension diabetes mellitus compensated heart failure ischemic heart disease cerebrovascular disease dislipidemia/hyperlipidemia peripheral artery disease hemorrhagic diathesis smoking creatinine clearance 30-60 ml/min.

History of gastrointestinal ulcers; history of infection with Helicobacter pylori; advanced age; long-term prior use of NSAIDs; severe medical conditions.

Simultaneous use with the following medications: anticoagulants (e.g., warfarin) antiplatelet agents (e.g., acetylsalicylic acid clopidogrel) oral glucocorticosteroids (e.g., prednisolone) selective serotonin reuptake inhibitors (e.g., citalopram fluoxetine paroxetine sertraline).

Side effects

Frequency is classified according to World Health Organization guidelines according to the occurrence of the case: very common (≥1/10) common (≥1/100 < 1/10) infrequent (≥1/1000 < 1/100d) rare (≥1/10000 < 1/1000) very rare (< 1/10000) including individual reports.

Blood and lymphatic system disorders

Rare: anemia eosinophilia hemorrhages;

Very rare: thrombocytopenia pancytopenia purpura thrombocytopenic.

Immune system disorders

Rare: hypersensitivity reactions;

Very rare: anaphylactoid reactions.

Skin and subcutaneous tissue disorders

Infrequent: itching skin rash increased sweating;

Rare: erythema dermatitis;

Very rare: urticaria angioneurotic edema facial edema polyform erythema Stevens-Johnson syndrome toxic epidermal necrolysis (Lyell’s syndrome).

Nervous system disorders

Infrequent: dizziness;

Very rare: headache drowsiness encephalopathy (Reye’s syndrome).

Mental disorders

Rarely: feelings of fear nervousness nighttime “nightmares” dreams.

Visual disturbances

Rare: blurred vision;

Very rare: visual disturbances.

Hearing and labyrinth disorders

Very rare: Vertigo.

Cardiovascular system disorders

Infrequent: increased blood pressure;

Rarely: tachycardia lability of blood pressure “rushes” of blood to the facial skin feeling of palpitations.

Respiratory system disorders

Infrequent: shortness of breath;

Very rare: exacerbation of bronchial asthma bronchospasm.

Gastrointestinal disorders

Often: diarrhea nausea vomiting;

Infrequent: 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 lightning (fulminant) hepatitis (including fatal outcomes) jaundice cholestasis.

Renal and urinary tract disorders

Rare: dysuria hematuria urinary retention;

Very rare: renal failure oliguria interstitial nephritis.

Disorders of water-electrolyte metabolism

Rarely: hyperkalemia.

Other

Infrequent: peripheral edema;

Rare: malaise asthenia;

Very rare: hypothermia.

Overdose

Symptoms: apathy drowsiness nausea vomiting epigastric pain. These symptoms are usually reversible with symptomatic and supportive therapy. Increased blood pressure may occur gastrointestinal bleeding acute renal failure respiratory depression coma anaphylactoid reactions.

Treatment: symptomatic and supportive therapy. There is no specific antidote. If overdose occurred within the last 4 hours it is necessary to induce vomiting and/or ensure intake of activated charcoal (60 to 100 g per adult) and/or osmotic laxative. Forced diuresis hemoperfusion hemoperfusion urine alkalinization is ineffective due to the high degree of nimesulide binding to blood plasma proteins (up to 975%). It is necessary to monitor the state of renal and hepatic function.

Pregnancy use

Nimesulide, like other NSAIDs that inhibit prostaglandin synthesis, may adversely affect pregnancy and/or fetal development and may result in premature closure of the fetal pulmonary artery system with hypertension, renal dysfunction that may progress to renal failure with fetal oliguria, increased bleeding risk, decreased uterine contractility, and peripheral edema in the mother.

The data obtained in epidemiological studies suggest a possible increase in the risk of spontaneous abortion and the risk of cardiac malformation and gastroschisis when prostaglandin synthesis blockers are used early in pregnancy. The absolute risk of cardiovascular abnormality increases from about 1% to 15%. The risk is thought to increase with increasing dose and duration of use.

The use of Naisulide® is contraindicated in pregnancy and during breastfeeding.

The use of nimesulide may have a negative effect on female fertility and is not recommended for women planning pregnancy. It is necessary to consult with the attending physician when planning a pregnancy.

There are no data on penetration of nimesulide into the breast milk.

Similarities