Naisulide granules for preparation of suspension for oral use sachets 100mg, 30pcs

Composition

1 sachet contains:

Active ingredient:

nimesulide 100 mg;

excipients:

sugar (sucrose),

maltodextrin,

cetomacrogol 1000 (macrogol cetostearyl ether),

citric acid anhydrous,

orange flavor.

Pharmacological action

Pharmacotherapy group: nonsteroidal anti-inflammatory drug (NSAID)CodATH: M 01 AH 17 Pharmacological Properties Pharmacodynamics

Nimesulide is a nonsteroidal anti-inflammatory drug from the class of sulfonamides. It has anti-inflammatory, analgesic and antipyretic effects. Unlike non-selective NSAIDs, nimesulide mainly inhibits cyclooxygenase-2( COX-2), inhibits prostaglandin synthesis in the inflammatory focus, and has a 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 use of a single dose of nimesulide,100 mg, is reached on average in 2-3 hours and is 3-4 mg/l. The area under the concentration – time curve (AUC) is 20-35: mg / h x l. Plasma protein binding is up to 97.5%.

It is metabolized in the liver by the cytochrome P450 (CYP)2C9 isoenzyme. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide-hydroxynimesulide, which is found exclusively in the form of glucuronate. Nimesulide is mainly excreted in the urine (about 50% of the dose taken), and about 29% is excreted in the feces in the metabolized form. The half-life (T 1/2) is 3.2-6 hours

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

In a study conducted in patients with mild to moderate renal insufficiency (creatine clearance and 30-80 ml/min), the Cmax of nimesulide and its main metabolite was not higher than in healthy volunteers. AUC and T 1/2 were 50% higher, but they were within the values of AUC and T 1/2 observed in healthy volunteers with the use of nimesulide. Repeated use did not result in accumulation of nimesulide.

Indications

• acute pain (back pain, low back pain; musculoskeletal pain,
• including bruises, sprains and dislocations of joints; tendinitis, bursitis; toothache);
• symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome;
• primary algodismenorrhea.

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

Contraindications

• hypersensitivity to nimesulide or other components of the drug;
• hyperergic reactions in anamnesis (bronchospasm, rhinitis, urticaria) associated with
• the use of acetylsalicylic acid or other NSAIDs, including nimesulide;
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose or around the sinuses with intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis);
• hepatotoxic reactions to nimesulide in history;
• the simultaneous use with other drugs with potential hepatotoxicity (e. g., other NSAIDs);
• chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute phase;
• after the coronary artery bypass surgery;
• febrile syndrome and acute respiratory viral infections;
• suspected acute surgical pathology;
• peptic ulcer of the stomach or duodenum in the acute phase; erosive-ulcerative lesions of the gastrointestinal tract perforation or gastrointestinal bleeding in history;
• cerebrovascular bleeding or history of other diseases, accompanied by an increased risk of bleeding;
• severe violations of coagulability of blood;
• severe heart failure;
• severe renal impairment (creatine clearance and on < 30 ml/min), confirmed hyperkalemia;
• children up to age 12 years;
• pregnancy and breastfeeding;
• alcoholism, drug addiction;
• hereditary fructose intolerance, sucrase deficiency-isomaltase syndrome
• of malabsorption of glucose-galactose;

With caution

Arterial hypertension, diabetes mellitus, compensated heart failure, ischemic heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral arterial diseases, hemorrhagic diathesis, smoking, creatine clearance and 30-60 ml/min.

A history of ulcerative lesions of the gastrointestinal tract; a history of infection caused by Helicobacter pylori; advanced age; long-term previous use of NSAIDs; severe somatic diseases.

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

Side effects

Frequency is classified according to the recommendations of the World Health Organization, depending on the occurrence of the case:  very common ≥), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥ 1/10000, <1/1000), very rare, including individual messages

Disorders of the blood and lymphatic system

Rarely:  anemia, eosinophilia, hemorrhages;

Very rare:  thrombocytopenia, pancytopenia, and thrombocytopenic purpura.

Immune system disorders

Rarely:  hypersensitivity reactions;

Very rare:  anaphylactoid reactions.

Skin and subcutaneous tissue disorders

Infrequently:  itching, skin rash, excessive sweating;

Rarely:  erythema, dermatitis;

Very rare:  urticaria, angioedema, facial edema, erythema multiforme, Stevens – Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Nervous system disorders

Infrequently:  dizziness;

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

Mental disorder

Rarely:  feeling of fear, nervousness, night “nightmare” dreams.

Visual disturbances

Rarely:  blurred vision.

Very reoko:  visual impairment.

Hearing disorders and labyrinth disorders

Very rare: vertigo.

Disorders of the cardiovascular system

Infrequently:  increased blood pressure;

Rarely:  tachycardia, lability of blood pressure, “flushes” of blood to the skin of the face, palpitation sensation.

Respiratory system disorders

Infrequently:  shortness of breath;

Very rare:  exacerbation of bronchial asthma, bronchospasm.

Gastrointestinal disorders

are Common:  diarrhea, nausea, and vomiting.

Infrequently:  constipation, flatulence, gastritis, gastrointestinal bleeding, ulceration and / or perforation of the stomach or duodenum;

Very rare:  abdominal pain, dyspepsia, stomatitis, tarry stools

Liver and biliary tract disorders

are common:  increased activity of “liver” enzymes;

Very rare:  hepatitis, fulminant hepatitis (including fatal outcomes), jaundice, cholestasis.

Kidney and urinary tract disorders

Rarely:  dysuria, hematuria, urinary retention;

Very rare:  renal failure, oliguria, interstitial nephritis.

Disorders of water and electrolyte metabolism

Rarely:  hyperkalemia.

Other services

Infrequently:  peripheral edema;

Rarely:  malaise, asthenia;

Very rare:  hypothermia.

Interaction

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antithrombotic agents and selective serotonin reuptake inhibitors

(SSRls)* for example, fluoxetine increases the risk of gastrointestinal bleeding.

NSAIDs may enhance the effects 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 is still unavoidable, careful monitoring of blood clotting parameters is necessary.

Diuretics

NSAIDs may 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.

Concomitant use of nimesulide and furosemide results in a decrease (approximately 20%) in the area of the concentration – time curve (AUC) and a decrease in the 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 angioteisin-II receptor antagonists

NSAIDs may reduce the effect of antihypertensive drugs.In patients with mild to moderate renal insufficiency (creatine clearance and 30-80 ml / min), concomitant use of ACE inhibitors, angiotensin II receptor antagonists, and cyclooxygenase-suppressing agents (NSAIDs, antiplatelet agents) may lead to 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, concomitant use of these drugs should be carried out with caution, especially in elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after starting concomitant use.

Mifepristone

Theoretically, it is possible to reduce the effectiveness of mifepristone and prostaglandin analogues when used simultaneously with NSAIDs (including acetylsalicylic acid) due to the antiprostaglandin action of the latter. Limited data show that the use of NSAIDs on the day of use of a prostaglandin analog does not adversely affect the effect of mifepristone or a prostaglandin analog on cervical dilatation, uterine contractility, and does not reduce the clinical effectiveness of medical termination of pregnancy.

There is evidence that NSAIDs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in blood plasma and its toxicity. When using nimesulide in patients undergoing lithium therapy, regular monitoring of the concentration of lithium in the blood plasma should be carried out.

There were no clinically significant interactions with glibenclaiide, theophylline, – digostin, cimetidine, or antacids (for example, a combination of aluminum and magnesium hydroxides).

Nimesulide inhibits the activity of the CYP2C9 isoenzyme. When drugs that are substrates of this enzyme are used simultaneously with nimesulide, the concentration of the latter in plasma may increase.

Caution should be exercised when prescribing nimesulide less than 24 hours before or after the use of methotrexate, as in such cases, the concentration of methotrexate in the blood plasma and, accordingly, toxic effects may increase.

Due to the effect on renal prostaglandins. prostaglandin synthetase inhibitors, such as nimesulide, may increase the nephrotoxicity of cyclosporins.

How to take, course of use and dosage

Inside, the contents of the sachet are dissolved in approximately 100 ml of water at room temperature (a white or light yellow suspension is formed).

The prepared solution is not subject to storage.

The drug Nisulide is used only for the treatment of patients over 12 years of age.

Adults and children over 12 years of age: 1 sachet twice a day, after meals.

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.

Patients with renal insufficiency: in patients with mild or moderate renal insufficiency (creatinine clearance 30-60 ml/min), no dose adjustment is required, while in patients with severe renal insufficiency (creatinine clearance

Patients with hepatic insufficiency:

The use of Naisulide* in patients with hepatic insufficiency is contraindicated.

To reduce the likelihood of side effects, it is recommended to take the minimum effective dose for as short a time as possible.

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

The maximum duration of treatment is 15 days.

Overdose

Symptoms: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with symptomatic and supportive care.

Possible increase in blood pressure, gastrointestinal bleeding, acute renal failure, respiratory depression, coma, anaphylactoid reactions.

Treatment: symptomatic and supportive care. There is no specific antidote. If an overdose has occurred within the last 4 hours, it is necessary to induce vomiting. or provide activated charcoal (60 to 100 g per adult) and / or an osmotic laxative. Forced diuresis, hemodialysis, hemoperfusion, and urinary alkalinization are ineffective due to the high degree of binding of nimesulide to plasma proteins (up to 97.5%). It is necessary to monitor the state of kidney and liver function.

Special instructions

Undesirable side effects can be minimized by using the drug at the lowest effective dose with the minimum duration of use necessary for the relief of pain.

There are data on very rare cases of serious liver reactions, including cases of fatal outcome associated with the use of ni mesul-containing drugs. If you experience symptoms similar to those of liver damage (anorexia, pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of “liver” transam and naz), you should immediately stop using the drug Nisulide and consult a doctor. Repeated use of Naisulide in such patients is contraindicated.

Liver reactions, which in most cases are reversible, have been reported with short-term use of the drug.

During the use of Naisulide, the patient should refrain from taking other analgesics, including NSAIDs (including selective COX-2 inhibitors).

Naisulide should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as these diseases may worsen.

The risk of gastrointestinal bleeding, peptic ulcer/perforation of the stomach or duodenum increases in patients with a history of ulcerative lesions of the gastrointestinal tract (ulcerative colitis, Crohn’s disease), as well as in elderly patients, with an increase in the dose of NSAIDs, so treatment should begin with the lowest possible dose. Such patients, as well as patients who require concomitant use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, are recommended to take additional gastroprotectors (misoprostol or proton pump blockers).

Patients with a history of gastrointestinal diseases, especially elderly patients, should inform the doctor about new gastrointestinal symptoms (especially those that may indicate possible gastrointestinal bleeding).

Niculide 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).

If gastrointestinal bleeding or ulcerative lesions of the gastrointestinal tract occur in patients taking Nisulide, treatment with the drug should be discontinued.

Taking into account reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of Naisulide should be stopped immediately and an ophthalmological examination should be performed.

The drug may cause fluid retention, so in patients with arterial hypertension, renal and/or heart failure, the drug Nisulide should be used with extreme caution. If the condition worsens, treatment with Nisulide should be discontinued.

Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with prolonged use, may lead to a low risk of myocardial infarction or stroke. To exclude the risk of such events when using nimesulide, data are not sufficient. The drug contains sucrose, this should be taken into account in patients with diabetes mellitus (0.15-0.18 XE per 100 mg of the drug) and people who follow a low-calorie diet. Naisulide is not recommended for patients with fructose intolerance, sucrose-isomaltose deficiency, or glucose-galactose malabsorption syndrome. If signs of a “cold” or acute respiratory viral infection occur during the use of Nisulide, the drug should be discontinued. Nimesulide can alter the properties of platelets, so caution should be exercised when using the drug in people with hemorrhagic diathesis, but the drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases. Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the risk of gastrointestinal bleeding and life-threatening perforations, and decreased kidney, liver, and heart function. When taking Nisulide prepagate for this category of patients, proper clinical monitoring is necessary.

There are data on the occurrence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when taking NSAIDs, including nimesulide. At the first appearance of skin rash, mucosal lesions, or other signs of an allergic reaction, Naisulide should be discontinued immediately.

Effect of the drug on the ability to drive vehicles and other mechanisms

The effect of the drug Nisulide on the ability to drive vehicles and mechanisms has not been studied, so during the use of the drug Nisulide, care should be taken when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Nimesulide

Conditions of release from pharmacies

By prescription

Dosage form

Oral suspension