Nimesil - instructions for use, dose, side effects, contraindications

Excipients: macrogol, cetostearyl ether - 8.0 mg, sucrose - 1805.0 mg, maltodextrin - 15.0 mg, citric acid anhydrous - 30.0 mg, orange flavoring - 42.0 mg.

Description:Light yellow granular powder with orange smell.

Pharmacotherapeutic group:nonsteroidal anti-inflammatory drug

ATX: & nbsp

M.01.A.X Other non-steroidal anti-inflammatory drugs

M.01.A.X.17 Nimesulide

Pharmacodynamics:

Nimesulide is a non-steroidal anti-inflammatory drug from the class of sulfonamides. Has anti-inflammatory, analgesic and antipyretic effect.In contrast to nonselective NSAIDs, nimesulide, mainly inhibits cyclooxygenase-2 (COX-2), inhibits the synthesis of prostaglandins in the focus of inflammation; has a less pronounced inhibitory effect on cyclooxygenase-1 (COX-1).

Pharmacokinetics:

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

The maximum concentration in the blood plasma (C_max) after oral administration of a single dose of nimesulide, 100 mg, is achieved on average 2-3 hours and is 3-4 mg / l. Area under the curve "concentration - time" (AUC) - 20-35 mg h / l. Connection with blood plasma proteins - up to 97.5%.

Metabolized in the liver with the help of the cytochrome P450 isoenzyme (CYP)2C9. The main metabolite is the pharmacologically active parahydroxy derivative of nimesulide - hydroxynimidesulide, which is found exclusively in the form of glucuronate.

Nimesulide is excreted from the body mainly with urine (about 50% of the dose taken), in the metabolized form with feces about 29% is excreted. The half-life (T1/2) is 3.2-6 hours.

The pharmacokinetic profile of nimesulide in elderly patients and in patients with mild to moderate renal insufficiency changes with single and multiple / repeated doses.

In a study conducted in patients with mild and moderate renal failure (creatinine clearance 30-80 ml / min), C_m_Oh Nimesulide and its main metabolite were not higher than in healthy volunteers. AUC and T_1/2were 50% higher, but were within the values AUC and T_1/2, observed in healthy volunteers against the background of nimesulide. Repeated use did not result in the cumulation of nimesulide.

Indications:

- acute pain (pain in the back, lower back, pain in the musculoskeletal system, including bruises, sprains and joints dislocation, tendinitis, bursitis: toothache);

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

- primary algodismenorea.

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 the anamnesis (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs, including nimesulide;

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

- hepatotoxic reactions to nimesulide in the anamnesis;

- simultaneous use with other drugs with potential hepatotoxicity (for example, other NSAIDs);

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

- period after aortocoronary shunting;

- febrile syndrome for colds and acute respiratory viral infections;

- suspected acute surgical pathology;

- peptic ulcer of the stomach or duodenum in the phase of exacerbation; erosive-ulcerative lesion of the gastrointestinal tract; perforation or gastrointestinal hemorrhage in history;

- cerebrovascular hemorrhages in the anamnesis or other diseases, accompanied by increased bleeding;

- severe blood clotting disorders;

- severe heart failure;

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

- hepatic insufficiency or any active liver disease;

- children's age till 12 years;

- pregnancy and the period of breastfeeding;

- alcoholism, drug dependence;

- hereditary intolerance to fructose, a deficiency of sucrose-isomaltase and glucose-galactose malabsorption syndrome.

Carefully:

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

Peptic ulcer of the gastrointestinal tract in the anamnesis; infection caused by Helicobacter pylori in the anamnesis; elderly age; prolonged previous use of NSAIDs; severe physical illness.

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

Pregnancy and lactation:

Like other drugs from the class of NSAIDs 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 arterial duct, hypertension in the fetal pulmonary artery system, impaired renal function that can turn into kidney failure with oliguria in the fetus, increase the risk of bleeding, reduce contractility the appearance of peripheral edema in the mother.

Data from epidemiological studies indicate a possible increase in the risk of spontaneous abortion, the risk of heart disease and gastroschisis in the use of early-stage drugs that block the synthesis of prostaglandins. The absolute risk of cardiovascular anomalies increases from about 1% to 1.5%. It is believed that the risk increases with increasing dose and duration of use.

Data on the penetration of nimesulide in breast milk is not available.

The use of Nimesil® during pregnancy and during breastfeeding is contraindicated.

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:

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

The prepared solution is not subject to storage.

The drug Nimesil ® is used only for the treatment of patients older than 12 years.

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

Older patients: in the treatment of elderly patients, the need to correct 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 and moderate renal insufficiency (creatinine clearance 30-60 ml / min), dose adjustment is not required, while for patients with severe renal insufficiency (creatinine clearance <30 ml / min), Nimesil® is contraindicated.

Patients with hepatic insufficiency:

The use of Nimesil® in patients with hepatic insufficiency is contraindicated.

To reduce the likelihood of side effects, it is recommended to take the minimum effective dose for the shortest possible time. The maximum daily dose for adults and children over 12 years is 200 mg. The maximum duration of treatment is 15 days.

Side effects:

The frequency is classified according to the headings in accordance with the recommendations of the World Health Organization, depending on the occurrence of the event: very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1/10000, <1/1000), very rarely (<1/10 000), including individual messages.

Violations of the blood and lymphatic system

Rarely: anemia, eosinophilia, hemorrhages.

Rarely: thrombocytopenia. pancytopenia, purpura thrombocytopenic.

Immune system disorders

Rarely: hypersensitivity reactions.

Rarely: anaphylactoid reactions.

Disturbances from the skin and subcutaneous tissues

Infrequently: itching, skin rash, increased sweating.

Rarely: erythema, dermatitis.

Rarely: hives,angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Disturbances from the nervous system

Infrequently: dizziness.

Rarely: headache, drowsiness, encephalopathy (Reye syndrome).

Disorders of the psyche

Rarely: a sense of fear, nervousness, nightmarish dreams.

Disturbances on the part of the organ of sight

Rarely: blurred vision.

Rarely: impaired vision.

Hearing disorders and labyrinthine disorders

Rarely: Vertigo.

Disorders from the cardiovascular system

Infrequently: increase in blood pressure.

Rarely: tachycardia, lability of blood pressure, "tides" of blood to the skin of the face, a feeling of palpitations.

Disturbances from the respiratory system

Infrequently: dyspnea.

Rarely: exacerbation of bronchial asthma, bronchospasm.

Disorders from the gastrointestinal tract

Often: diarrhea, nausea, vomiting.

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

Rarely: pain in the abdomen, dyspepsia, stomatitis, tarry stools.

Disturbances from the liver and bile ducts

Often: increased activity of "liver" enzymes.

Rarely: hepatitis, fulminant hepatitis (including lethal outcomes), jaundice, cholestasis.

Disorders from the kidneys and urinary tract

Rarely: dysuria, hematuria, urinary retention.

Rarely: renal failure, oliguria, interstitial nephritis.

Violations from the water-electrolyte exchange

Rarely: hyperkalemia.

Other

Infrequently: peripheral edema.

Rarely: malaise, asthenia.

Rarely: hypothermia.

Overdose:

Symptoms: apathy, drowsiness, nausea, vomiting, pain in the epigastric region. These symptoms are usually reversible in symptomatic and maintenance therapy. Possible increase in blood pressure, the occurrence of gastrointestinal bleeding, acute renal failure, respiratory depression, coma, anaphylactoid reactions.

Treatment: symptomatic and supportive therapy. 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 carbon (from 60 to 100 g for an adult) and / or an osmotic laxative. Forced diuresis, hemodialysis, hemoperfusion, alkalinization of urine are ineffective because of the high degree of binding of nimesulide to plasma proteins (up to 97.5%). It is necessary to monitor the status of kidney and liver function.

Interaction:

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSR/s), eg, fluoxetine, increase the risk of gastrointestinal bleeding.

NSAIDs can enhance 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 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 use of nimesulide and furosemide leads to a decrease (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.

The simultaneous use of furosemide and nimesulide requires caution in patients with renal or heart failure.

ACE inhibitors and antagonists of the angiotensin-II

NSAIDs can reduce the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min), concomitant use of ACE inhibitors, angiotensin II receptor antagonists, and agents that inhibit the cyclooxygenase system (NSAIDs, antiplatelet agents), further deterioration of kidney function and the onset of acute renal failure, which, as a rule, happens to be 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 a sufficient amount of fluid, and renal function should be carefully monitored after the onset of simultaneous 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 anti-prostaglandin effect of the latter. Limited data show that the use of NSAIDs on the day of the prostaglandin analog does not adversely affect the effect of mifepristone or prostaglandin analogue on cervical dilatation, uterine contractility and does not reduce the clinical effectiveness of drug abortion.

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 using nimesulide in patients who are on therapy with lithium drugs, regular monitoring of the concentration of lithium in 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) was not observed.

Nimesulide suppresses activity isoenzyme CYP2C9. With simultaneous use with nimesulid drugs, which are substrates of this enzyme, the concentration of the latter in the plasma can increase.

When nimesulide is administered less than 24 hours before or after application 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, to which nimesulide, can increase nephrotoxicity cyclosporins.

Special instructions:

Unwanted side effects can be minimized when the drug is used in the minimum effective dose with the minimum duration of application necessary to relieve the pain syndrome.

There are data on very rare cases of serious reactions from the liver, including deaths associated with the use of nimesulide-containing drugs.If symptoms similar to those of liver damage (anorexia, skin itch, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of "liver" transaminases), immediately stop using Nimesil® and consult a doctor. Repeated use of Nimesil® in such patients is contraindicated.

It is reported on the reactions of the liver, which in most cases are reversible, with short-term use of the drug.

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

The drug Nimesil® should be used with caution in patients with gastrointestinal diseases in history (ulcerative colitis, Crohn's disease), as possible exacerbation of these diseases.

The risk of gastrointestinal bleeding, peptic ulcer / perforation of the stomach or duodenum is increased in patients with an ulcerative lesion of the gastrointestinal tract (ulcerative colitis, Crohn's disease) in the anamnesis, as well as in elderly patients, with an increase in the dose of NSAIDs, so treatment should be started with the lowest possible dose.Such patients, as well as patients who require the simultaneous use of low doses of acetylsalicylic acid or other agents that increase the risk of complications from the gastrointestinal tract, it is recommended to additionally appoint a method of gastroprotectors (misoprostol or proton pump blockers). Patients with a history of gastrointestinal disease, especially elderly patients, should inform the doctor of newly diagnosed GI symptoms (especially symptoms that may indicate possible gastrointestinal bleeding).

Nimesil® should be administered with caution to patients taking drugs that increase the risk of ulceration or bleeding (oral corticosteroids, anticoagulants, for example warfarin, selective serotonin reuptake inhibitors or antiplatelet agents, for example, acetylsalicylic acid).

In the case of gastrointestinal bleeding or ulcerative lesions of the gastrointestinal tract in patients taking Nimesil®, the drug should be discontinued immediately.

Given reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of Nimesil® should be immediately discontinued and an ophthalmological examination performed.

The drug can cause fluid retention, so in patients with hypertension, with renal and / or heart failure, Nimesil® should be used with extreme caution. In case of deterioration, treatment with Nimesil® should be stopped.

Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with prolonged use, can lead to an insignificant risk of myocardial infarction or stroke. To exclude the risk of such events occurring when nimesulide is used, data is insufficient.

Patients with hypertension, with renal and / or heart failure, coronary heart disease, peripheral arterial disease and / or cerebrovascular disease, with risk factors for cardiovascular disease (eg, hyperlipidemia, diabetes, smokers), Nimesil® should use with extreme caution.In case of deterioration, treatment with Nimesil® should be stopped.

The composition of the drug includes sucrose, this should be taken into account for patients suffering from diabetes (0.15-0.18 XE per 100 mg of the drug) and those who observe a low-calorie diet. Nimesil® drug is not recommended for patients with intolerance to fructose, sucrose-isomaltose deficiency or glucose-galactose syndrome malabsorption.

If there are signs of "cold" or acute respiratory viral infection during use of the drug Nimesil® the drug should be discontinued. Nimesulide It can change the properties of platelets, so caution should be exercised when using the drug in patients with hemorrhagic diathesis, but the drug does not replace the prophylactic effect of aspirin in cardiovascular diseases.

Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including the risk of gastrointestinal bleeding and perforation, threatening the patient's life, reduced kidney function, liver and heart. When taking Nimesil® for this category of patients, proper clinical control 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 manifestations of skin rashes, lesions of mucous membranes or other signs of an allergic reaction, the drug Nimesil® should be stopped immediately.

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

The influence of Nimesil® on the ability to drive vehicles and mechanisms has not been studied, therefore, during the period of application of Nimesil®, caution should be exercised when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Granules for the preparation of a suspension for oral administration, 100 mg.

Packaging:

2 grams of granules in a three-layer sachet (paper / aluminum foil / polyethylene). For 9, 15 or 30 bags with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011439 / 01

Date of registration:18.08.2010

The owner of the registration certificate:Laboratory Guidotti SpALaboratory Guidotti SpA Italy

Manufacturer: & nbsp

Laboratorios MENARINI, S.A. Spain

Information update date: & nbsp07.05.2015

Illustrated instructions

Instructions

Nimesil® (Nimesil® )