Naize - instructions for use, doses, side effects, contraindications

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) from the class of sulfonamides. Has anti-inflammatory, analgesic and antipyretic effect. Nimesulide acts as an inhibitor of the enzyme cyclooxygenase responsible for the synthesis of prostaglandins and inhibits mainly cyclooxygenase 2. Suppresses the release of histamine, inhibits the synthesis of interleukin-6 and urokinase. The drug suppresses the aggregation of platelets.

Pharmacokinetics:

Suction

After ingestion, the drug is well absorbed from the gastrointestinal tract (GIT), reaching a maximum concentration (C_mOh) in the blood plasma after 2-3 hours.

Distribution

The connection with plasma proteins is 95%, with erythrocytes - 2%, with lipoproteins - 1%, with acid alpha 1-glycoproteids - 1%. Penetrates into the tissue of the female genital organs, where after a single intake its concentration is about 40% of the concentration in the plasma. It penetrates into the acidic environment of the inflammatory focus (40%), synovial fluid (43%). Easily penetrates through the histohematological barriers.

Metabolism

Metabolized in the liver with the cytochrome P450 isoenzyme (CYP) 2C9. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide - hydroxynimidesulide.

Excretion

The half-life (T_1/2) nimesulide about 1.56-4.95 hours, hydroxynimidesulide - 2.89-4.78 hours. Nimesulide is excreted from the body, mainly by the kidneys (about 50% of the dose taken).Hydroxynimidesulide is excreted by the kidneys (65%) and bile (35%), subjected to enterohepatic recirculation.

The pharmacokinetic profile of nimesulide in elderly patients does not change with the administration of single and multiple / repeated doses.

According to the experimental study conducted with the participation of patients with mild to moderate renal failure (creatinine clearance 30-80 ml / min) and healthy volunteers, the maximum concentration of nimesulide and its metabolite in the patients plasma did not exceed the concentration of nimesulide in healthy volunteers. The area under the concentration-time curve (AUC) and half-life in patients with renal disease insufficiency were higher by 50%, but within the pharmacokinetic values. When re-taking the drug cumulation is not observed.

Indications:

- Treatment of acute pain (pain in the back, lower back, pain in the musculoskeletal system, including trauma, sprains and joints, tendenitis, bursitis, toothache);

- symptomatic treatment of osteoarthritis with pain syndrome;

- aprivileges of menopause;

The drug is intended for symptomatic therapy, reducing pain and inflammation; does not affect the progression of the disease.

Contraindications:

- Hypersensitivity to nimesulide or any auxiliary component of the drug;

- sugarase / isomaltase deficiency, fructose intolerance, glucose galactose malabsorption (Nyz® contains sucrose);

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including in history);

- erosive and ulcerative changes in the mucous membrane of the stomach and duodenum, active gastrointestinal bleeding, cerebrovascular or other bleeding;

- inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation;

- hemophilia and other bleeding disorders;

- Decompensated heart failure;

- hepatic insufficiency or any active liver disease;

- anamnestic data on the development of hepatotoxic reactions using nimesulide drugs;

- alcoholism, drug addiction;

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

- period after aortocoronary shunting;

- simultaneous reception of other hepatotoxic drugs;

- pregnancy and lactation;

- children under 12 years.

Carefully:

- Arterial hypertension, diabetes mellitus, compensated heart failure, ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, peripheral arterial disease, smoking, renal failure (creatinine clearance 30-60 ml / min);

- anamnestic data on the presence of ulcerative lesions of the gastrointestinal tract, infection caused by Helicobacter pylori;

- elderly age;

- prolonged previous use of NSAIDs;

- severe physical illnesses;

- concomitant therapy with the following drugs: anticoagulants (eg, warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).

The decision to prescribe Nyz® should be based on an individual "risk-benefit" evaluation when taking the drug.

Pregnancy and lactation:

The use of Nyz® during pregnancy and during breastfeeding is contraindicated. If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.

The use of nimesulide may adversely affect female fertility and is not recommended for women planning a pregnancy. When planning pregnancy, consultation with the doctor is necessary.

Dosing and Administration:

Nyz® is taken orally, 1 packtic (100 mg of nimesulide) twice daily. Nyz® should be taken after a meal. The contents of the sachet are poured into a beaker and dissolved in about 100 ml of water (a suspension is formed from white to light yellow). The prepared solution is not subject to storage.

The drug Nyz® is only used to treat patients older than 12 years.

Adolescents (12 to 18 years of age): 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 renal failure (creatinine clearance is 30-80 ml / min).

Older 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 medicines.

The maximum duration of treatment with nimesulide is 15 days.

To reduce the risk of undesirable side effects, use the lowest effective dose with a minimally short course.

Side effects:

Classification of WHO frequency of development of side effects: very often - ≥1/10 appointments (> 10%); often from ≥1 / 100 to <1/10 of appointments (> 1% and <10%); infrequently - from ≥1 / 1000 to <1/100 of prescriptions (> 0.1% and <1%); rarely from ≥1 / 10,000 to <1/1000 appointments (> 0.01% and <0.1%); very rarely - <1/10000 prescriptions (<0.01%); the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

Violations of the blood and lymphatic system:

Rarely - anemia, eosinophilia, hemorrhages; very rarely - thrombocytopenia, agranulocytosis, pancytopenia, purpura thrombocytopenic.

Allergic reactions:

Rarely, hypersensitivity reactions; very rarely anaphylactoid reactions.

Disturbances from the skin and subcutaneous tissues:

Infrequent - itching, rash, increased sweating; rarely - erythema, dermatitis; very rarely - hives, angioedema,facial puffiness, multiforme exudative erythema, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Disorders from the central nervous system:

Infrequent - dizziness; rarely - a sense of fear, nervousness, "nightmarish" dreams; very rarely - headache, drowsiness, encephalopathy (Reye syndrome).

Impaired sensory organs:

Rarely - blurred vision.

Disorders from the cardiovascular system:

Infrequent - increased blood pressure; rarely - tachycardia, lability of blood pressure, "hot flashes", a feeling of palpitations.

Disturbances from the respiratory system:

Infrequent - shortness of breath; very rarely - exacerbation of bronchial asthma, bronchospasm.

Disorders from the gastrointestinal tract:

Often - diarrhea, nausea, vomiting; infrequently - constipation, flatulence, gastritis; very rarely - abdominal pain, dyspepsia, stomatitis, tarry stool, gastrointestinal bleeding, ulceration of the mucosa and / or perforation of the stomach or duodenum.

Disturbances from the liver and bile ducts:

Often - an increase in "liver" transaminases; very rarely - hepatitis, fulminant hepatitis, jaundice, cholestasis.

Disorders from the kidneys and urinary tract:

Rarely, dysuria, hematuria, urinary retention, hyperkalemia; very rarely - renal failure, oliguria, interstitial nephritis.

General disorders:

Infrequent - edema; rarely - malaise, asthenia; very rarely - hypothermia.

Overdose:

Symptoms: apathy, drowsiness, nausea, vomiting, pain in the epigastric region. There may be a gastrointestinal bleeding. 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. In case an overdose has occurred within the last 4 hours, it is necessary to induce vomiting and / or to receive activated charcoal (from 60 to 100 g per adult) and / or osmotic laxative. Forced diuresis, hemodialysis - ineffective because of the high connection of the drug with proteins.

Interaction:

Glucocorticosteroids: increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors: increase the risk of gastrointestinal bleeding.

Anticoagulants: NSAIDs can enhance the action 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 combined therapy can still be avoided, careful monitoring of blood coagulation should be carried out.

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. The simultaneous administration of nimesulide and furosemide results in a reduction (approximately 20%) of the area under the concentration-time curve (AUC) and a decrease in the cumulative excretion of furosemide without altering the renal clearance of furosemide. Co-administration of furosemide and nimesulide requires caution in patients with impaired renal or cardiac function.

ACE inhibitors and antagonists of the angiotensin-II: NSAIDs can reduce the effect of antihypertensive drugs. In patients with mild and moderate severity of renal failure (creatinine clearance 30-80 ml / min) when co-administered with ACE inhibitors,antagonists of angiotensin II receptors or substances suppressing the system of cyclooxygenase (NSAIDs, antiplatelet agents), further deterioration of kidney function and the emergence of acute renal failure, which is usually reversible. These interactions should be considered in patients taking nimesulide in combination with ACE inhibitors or antagonists of the angiotensin-II. Therefore, joint intake of these drugs should be administered with caution, especially for elderly patients. Patients should receive a sufficient amount of fluid, and renal function should be carefully monitored after the initiation of co-therapy.

There is evidence that NSAIDs reduce clearance lithium, which leads to an increase in the concentration of lithium in the blood plasma and its toxicity. When nimesulide is prescribed, patients receiving lithium therapy should be monitored regularly for plasma lithium concentrations. Clinically significant interactions with Glibenclamide, theophylline, digoxin, cimetidine and antacid preparations (for example, a combination of aluminum and magnesium hydroxides) was not observed.

Nimesulide suppresses the activity of the isoenzyme CYP2C9. With concomitant administration with nimesulide of drugs metabolized with the participation of this isoenzyme, the concentration of these drugs in the plasma may be exceeded,

When used simultaneously with antiepileptic drugs (valproic acid), antifungal agents (ketoconazole), antituberculous drugs (isoniazid), amiodarone, methotrexate, methyldopa, amoxicillin in combination with clavulanic acid an additive hepatotoxic effect is possible.

Due to the high degree of binding of nimesulide to plasma proteins, patients concurrently taking sulfonyl amides should be under the supervision of a doctor, passing the examination at short intervals. When nimesulide is prescribed less than 24 hours before or after taking methotrexate caution is required, as in such cases the concentration of methotrexate in the plasma and, accordingly, the toxic effects of this drug may increase. In connection with the effect on renal prostaglandins, inhibitors of prostaglandin synthetases, to which nimesulide, can increase nephrotoxicity cyclosporins.

Research in vitro showed that nimesulide expelled from binding sites tolbutamide, salicylic acid. Despite the fact that these interactions were determined in blood plasma, these effects were not observed during the clinical application of the drug.

Special instructions:

Nyyz ® should be used with caution in patients with gastrointestinal ailments in history (ulcerative colitis, Crohn's disease), since it may exacerbate these diseases.

The risk of gastrointestinal bleeding, ulcers / perforations of the stomach or duodenum increases with the increase in the dose of NSAIDs in patients with a history of stomach ulcer or duodenal ulcer, especially complicated by bleeding or perforation, and also in elderly patients, so treatment should be started with the least possible dose.

Patients receiving medications that reduce blood clotting or suppress platelet aggregation also increase the risk of gastrointestinal bleeding.In the event of gastrointestinal bleeding or gastric or duodenal ulcers in patients taking Nyz®, treatment should be discontinued.

When using the drug for more than two weeks, it is necessary to monitor the liver function (activity "liver" transaminase).

If there are signs of liver damage (itchy skin, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of "liver" transaminases), stop taking the drug and consult a doctor.

Patients with hypertension, cardiac disorders, cerebrovascular diseases, Nyz ® should be administered with caution. In case of deterioration, treatment with Nyz® should be stopped.

Since Nyz® is partially excreted by the kidneys, its dose for patients with impaired renal function should be reduced, depending on the creatinine clearance. If the kidney function worsens, the drug should be discarded.

The composition of the drug includes sucrose (0.15-0.18 XE per 100 mg of the drug), this should be taken into account for patients suffering from diabetes and people who follow a low-calorie diet.

Nyz® is not recommended for patients with rare hereditary diseases of intolerance to fructose, malabsorption of glucose-galactose or insufficiency of sucrose-isomaltase.

The drug can change the properties of platelets, so you need to be careful when using the drug in people with hemorrhagic diathesis, but the drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

During treatment with Naise®, it is recommended that simultaneous use of hepatotoxic drugs, analgesics, other NSAIDs (with the exception of low doses of acetylsalicylic acid used in antiplatelet doses) and the use of ethanol should be avoided.

Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the risk of gastrointestinal bleeding and gastrointestinal perforations that threaten the patient's life, as well as worsening kidney, liver and heart function. When taking Naise® for this category of patients, regular clinical monitoring of the condition of these patients is necessary.

The risk of gastrointestinal bleeding, ulcers, or perforations is increased when taking high doses of nimesulide, in patients with a stomach ulcer or duodenal ulcer in the anamnesis, in the elderly. These patients should begin treatment with the lowest dose. In these patients, as well as individuals who take nimesulide together with cardiac doses of acetylsalicylic acid, combined therapy should be used in conjunction with gastroprotectors (proton pump inhibitors or misoprostol).

To reduce the risk of adverse events, a minimally effective dose of nimesulide should be used with the minimum possible short course.

Effect on the ability to drive transp. cf. and fur:

The influence of Nyz® on the ability to drive vehicles and control mechanisms has not been studied, therefore, during the period of treatment with Nize®, caution should be exercised when driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Granules for the preparation of a suspension for oral administration, 100 mg.

Packaging:

2 grams per package of combined material (paper / foil / polyethylene).

For 9, 15 or 30 packets together with the instruction for use are put in a pack from cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003413

Date of registration:15.01.2016

Expiration Date:15.01.2021

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp21.06.2018

Illustrated instructions

Instructions

Naise® (Naise®)