Naisulide, tablets 100 mg 20 pcs

Pharmacotherapeutic group

NSAIDs

ATX code: M01AX

Pharmacodynamics:

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) of the sulfonamide class. It has anti-inflammatory analgesic and antipyretic effects. Nimesulide belongs to new generation of NSAIDs which mechanism of action is related to selective inhibition of cyclooxygenase II and influence on several other factors: inhibition of platelet-activating factor of tumor necrosis factor alpha, inhibition of proteinases and histamine.

Pharmacokinetics:

Intake

After oral administration is well absorbed from the gastrointestinal tract (GIT). Maximum plasma concentration (Cmax) after oral administration is reached on average after 2-3 hours.

Distribution

Binding with plasma proteins – 95% with erythrocytes – 2% with lipoproteins – 1% with acidic alpha1-glycoproteins – 1%. It penetrates into the tissues of the female genitalia where after a single administration its concentration is about 40% of the blood plasma concentration. It penetrates well into the acidic environment of the inflammation focus (40%) and synovial fluid (43%). Easily penetrates through histohematic barriers.

Metabolism

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

Elimination

The half-life of nimesulide (T1/2) is about 156-495 hours for hydroxinesulide – 289-478 hours.

Nimesulide is excreted mainly through the kidneys (about 50% of the dose taken) hydroxinesulide is excreted through the kidneys (65%) and with the bile (35%) undergoes enterohepatic recirculation.

Pharmacokinetics in special groups of patients

In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) and in children and elderly persons the pharmacokinetic profile of nimesulide does not change significantly.

Repeated use does not lead to cumulation of the drug.

Indications

Rheumatoid arthritis joint syndrome with gout exacerbation; psoriatic arthritis; ankylosing spondylitis; osteochondrosis with radicular syndrome; osteoarthritis; myalgia of rheumatic and non-rheumatic genesis; inflammation of ligaments tendon bursitis including post-traumatic inflammation of soft tissues; pain syndrome of different genesis (including in the post-operative period with injuries algodysmenorrhea toothache headache arthralgia lumboishalgia).

The drug is intended as symptomatic therapy to reduce pain and inflammation at the time of use has no effect on the progression of the disease.

Active ingredient

Nimesulide

Composition

1 tablet contains:

active ingredient: nimesulide 100 mg;

excipients: microcrystalline cellulose, lactose monohydrate, potato starch, povidon K-30, sodium carboxymethyl starch (sodium starch glycolate), talc, magnesium stearate.

How to take, the dosage

For oral administration. The lowest effective dose of the drug should be used for the shortest possible course.

The tablets are taken with plenty of liquid, preferably after meals. In case of gastrointestinal diseases, the drug is recommended to be taken at the end of a meal or after a meal.

Adults: 100 mg 2 times a day. The maximum daily dose for adults is 200 mg.

Children over 12 years of age: 100 mg up to twice daily.

The duration of the course of treatment is not more than 15 days.

Patients with chronic renal insufficiency of mild to moderate severity (creatinine clearance 30-60 ml/min) do not require dose adjustment.

Interaction

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) increase the risk of gastrointestinal bleeding.

Anticoagulants

NSAIDs may increase the effect 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 under the effect of furosemide to a lesser extent, potassium excretion and reduces the diuretic effect itself. Concomitant use of nimesulide and furosemide leads to a decrease (approximately 20%) of the area under 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 inhibiting cyclooxygenase system (NSAIDs antiaggregants) may cause further decrease 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.

This combination of drugs should be administered with caution especially in elderly patients. Patients should receive adequate fluid intake and renal function should be monitored closely after initiation of concomitant therapy.

Mifepristone

Theoretically, the potential for decreased efficacy of mifepristone and prostaglandin analogues with NSAIDs (including acetylsalicylic acid) is increased 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.

The concomitant use of nimesulide with salicylates or other nonsteroidal anti-inflammatory drugs is not recommended because of the increased risk of gastrointestinal tract ulceration. Nimesulide displaces salicylic acid when it binds to plasma receptors.

There is evidence that NSAIDs decrease clearance of lithium which leads to increased plasma concentrations of lithium and its toxicity. When nimesulide is administered to patients receiving 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., aluminum and magnesium hydroxide combination) have not been observed.

Nimesulide inhibits the activity of CYP2C9 isoenzyme. When concomitant use of drugs metabolized with nimesulide, plasma concentrations of the latter may increase.

In concomitant use with antiepileptic drugs (valproic acid) antifungal drugs (ketoconazole) anti-tuberculosis drugs (isoniazid) amiodarone methotrexate methyldopa amoxicillin in combination with clavulanic acid an additive hepatotoxic effect is possible.

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

In connection with action on renal prostaglandins, inhibitors of prostaglandin synthetases such as nimesulide may increase nephrotoxicity of cyclosporine.

In vitro studies have shown that nimesulide is displaced from binding sites by tolbutamide by salicylic acid. Although these interactions have been determined in plasma, these effects were not observed during clinical use of the drug.

Special Instructions

The drug should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis Crohn’s disease) because exacerbation of these diseases is possible.

The risk of gastrointestinal bleeding/perforation of the stomach or duodenum increases with increasing dosage of NSAIDs in patients with a history of gastric or duodenal ulcers, especially complicated by bleeding or perforation and in older patients so treatment should be started at the lowest dose possible.

In patients receiving drugs that reduce blood clotting or inhibit platelet aggregation there is also an increased risk of gastrointestinal bleeding. If gastrointestinal bleeding or peptic ulcer occurs in patients taking Naisulide®, treatment should be discontinued.

If symptoms similar to those of liver disease occur (anorexia, itching of the skin, yellowing of the skin, nausea, vomiting, abdominal pain, darkened urine, increased “liver” transaminases), discontinue use and seek medical advice immediately.

Patients with arterial hypertension, cardiac disorders, cerebrovascular diseases should use the drug with caution. If the condition worsens, treatment with the drug should be stopped.

Because nimesulide is partially excreted by the kidneys, its dose for patients with impaired renal function should be reduced depending on creatinine clearance values. In case of worsening of renal function the drug should be discontinued.

Nimesulide may change platelet function; therefore caution should be exercised when using in patients with hemorrhagic diathesis; however, the drug does not replace the prophylactic effect of acetylsalicylic acid in patients with cardiovascular disease.

When treating with Naisulide®, it is recommended to avoid concomitant use of hepatotoxic analgesics other NSAIDs (except for low doses of acetylsalicylic acid used in antiplatelet doses) and consumption of ethanol.

In patients taking nimesulide together with cardiac doses of acetylsalicylic acid, combined therapy with gastroprotective agents (proton pump inhibitors or misoprostol) should be used.

Elderly patients are particularly susceptible to adverse reactions to NSAIDs including the risk of gastrointestinal bleeding and perforations and life-threatening renal hepatic and cardiac impairment. Appropriate clinical monitoring of these patients is necessary when administering the drug to this category of patients.

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.

Effect on the ability to drive vehicles and machines:

The effect of the drug on the ability to drive vehicles and machines has not been studied so during the period of using the drug care should be taken when driving vehicles and performing potentially dangerous activities requiring high concentration and quick psychomotor reactions.

Contraindications

– Hypersensitivity to nimesulide or other components of the drug;

– complete or incomplete combination of bronchial asthma with recurrent polyposis of the nose or sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including anamnesis);

– anamnestic evidence of the development of hepatotoxic reactions when using nimesulide preparations;

– concomitant use with other drugs with potential hepatotoxicity;

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

– period after coronary artery bypass grafting;

– gastric and duodenal mucosal erosive-ulcerative changes active gastrointestinal bleeding;

– history of cerebrovascular bleeding;

– hemophilia and other blood clotting disorders;

– decompensated heart failure;

– severe renal failure (creatinine clearance <30 ml/min) progressive renal disease confirmed hyperkalemia;

– hepatic insufficiency or any active liver disease;

– alcoholism drug dependence;

– lactase deficiency lactose intolerance glucose-galactose malabsorption;

– pregnancy and breastfeeding period;

– childhood under 12 years of age.

Cautions:

Artial hypertension diabetes mellitus compensated heart failure ischemic heart disease cerebrovascular disease dyslipidemia/hyperlipidemia peripheral artery disease smoking frequent use of alcohol renal failure (creatinine clearance 30-60 ml/min).

History of gastrointestinal ulcers; presence of Helicobacter pylori; elderly age; long-term prior use of NSAIDs; severe somatic diseases.

Continue therapy with the following medications: anticoagulants (e.g., warfarin) antiaggregants (e.g., acetylsalicylic acid clopidogrel) oral glucocorticosteroids (e.g., prednisolone) selective serotonin reuptake inhibitors (e.g., citalopram fluoxetine paroxetine sertraline).

Side effects

WHO Classification of the incidence of side effects:

Very common (≥1/10) common (≥1/100 < 1/10) infrequent (≥1/1000 < 1/100) rare (≥1/10000< 1/1000) very rare (< 1 /10000) including individual reports.

Blood and lymphatic system disorders

Rare: anemia eosinophilia hemorrhages;

Very rare: thrombocytopenia agranulocytosis pancytopenia purpura thrombocytopenic prolongation of bleeding time.

Immune system disorders

Rare: hypersensitivity reactions;

Very rare: anaphylactoid reactions.

Skin and subcutaneous tissue disorders

Infrequent: skin itching skin rash increased sweating;

Rare: erythema dermatitis;

Very rare: urticaria angioneurotic edema facial edema multiform exudative 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.

Sensory disturbances

Rarely: blurred vision.

Cardiovascular system disorders

Infrequent: increased blood pressure;

Rarely: tachycardia lability of blood pressure “flushes” 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;

Very rare: abdominal pain dyspepsia stomatitis tarry stools gastrointestinal bleeding gastric or duodenal ulcer and/or perforation.

Liver and biliary tract disorders

Often: increased activity of “liver” enzymes;

Very rare: hepatitis fulminant hepatitis 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. Gastrointestinal bleeding may occur. In rare cases, increased blood pressure, gastrointestinal bleeding, acute renal failure, respiratory depression, coma anaphylactoid reactions may occur.

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 for an adult) and/or osmotic laxative. Forced diuresis hemodialysis is ineffective due to the high degree of nimesulide binding to blood plasma proteins. It is necessary to monitor the state of renal and hepatic function.

Pregnancy use

The use of nimesulide during pregnancy and during breastfeeding is contraindicated.

If it is necessary to use nimesulide during breastfeeding, breastfeeding should be stopped.

The use of nimesulide may adversely affect female fertility and is not recommended for women planning to become pregnant. It is necessary to consult with the attending physician when planning a pregnancy.

Similarities

Naiz, Nimesil, Nimesulide, Nemulex, Nimesulide-TEVA, Nimulide, Nimesan tablets 100 mg 20 pcs, Mialais