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

Excipients: citric acid anhydrous, sodium hydrogen carbonate, sorbitol, potassium carbonate, orange flavoring, sodium saccharinate, emetic simethicone 30% (dry weight), sodium lauryl sulfate, macrogol-6-glyceryl caprycaprate.

Description:

Round, flat-cylindrical tablets with a facet, pale yellow color with white impregnations, with a characteristic smell.

Appearance of the suspension

Suspension from white to pale yellow, with opalescence, with a characteristic odor.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID)

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 inflammatory focus; 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_m_Oh) 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%.

Nimesulide is actively metabolized in the liver by the cytochrome P450 isoenzyme (CYP)2C9. There is a possibility of drug interaction of nimesulide when used simultaneously with drugs metabolized by isoenzyme CYP2C9. The main metabolite is the pharmacologically active parahydroxy derivative nimesulide, hydroxynimidesulide, which is found in the blood plasma mainly in a conjugated form, 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 is about 29%. Only 1-3% of nimesulide is excreted unchanged.

The half-life period (T1 / 2) is 3.2-6 h.

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

In a short-term study in patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min), C_m_Oh Nimesulide and its main metabolite were not higher than in healthy volunteers. AUC and T1 / 2 were 50% higher, but were within the values AUC and T1 / 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, tendonitis, 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 NSAIDs (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 diseases (Crohn's disease, ulcerative colitis) in the phase of exacerbation;

- condition after coronary artery bypass grafting;

- 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 in the phase of exacerbation; erosive-ulcerative lesion of the gastrointestinal tract in history; perforations or gastrointestinal hemorrhages in the history, including those associated with previous therapy with NSAIDs;

- cerebrovascular hemorrhages in the anamnesis, other active bleeding or 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.

Carefully:

Severe forms of hypertension, type 2 diabetes; acute heart failure, ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, peripheral arterial disease,hemorrhagic diathesis, smoking, kidney failure (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 (see section "Special instructions").

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 in the fetus, which can progress to renal failure and lead to oligohydroamnion, an increased risk of bleeding , a decrease in contractility of the uterus, 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. It is recommended to take after eating. The tablet is dissolved in a glass of water at room temperature (a suspension of white or pale yellow color is formed), the resulting solution immediately drink.

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 tablet (100 mg of nimesulide) twice a day.

Older patients: in the treatment of elderly patients no correction of the daily dose is required.

Patients with renal insufficiency: in patients with mild and moderate renal insufficiency (creatinine clearance 30-80 ml / min), dose adjustment is not required, in patients with severe renal insufficiency (creatinine clearance < 30 ml / min) the drug Nimesil® is contraindicated.

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

To reduce the risk of undesirable side effects, use the lowest effective dose with a minimally short course. The maximum daily dose for adults and children over 12 years is 200 mg. The maximum duration of treatment with Nimesil® is 15 days.

Side effects:The frequency is classified according to the headings, depending on the occurrence of the event: Often (≥ 1/10), often (≥ 1/100, < 1/10), infrequently (≥ 1/1000, < 1/100), rarely (≥ 1/10000, < 1/1000), rarely (< 1/10000), including individual messages.

Violations of the blood and lymphatic system

Rarely: Anemia, eosinophilia, hemorrhages;

Rarely: thrombocytopenia, pancytopenia, purpura.

Immune system disorders

Rarely: hypersensitivity reactions;

Rarely: anaphylactoid reactions.

Disturbances from the skin and subcutaneous tissues

Infrequently: skin itching, skin rash, increased sweating;

Rarely: erythema, dermatitis;

Rarely: urticaria, angioedema, facial edema, erythema polyforma, 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: anxiety, 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: arterial hypertension;

Rarely: tachycardia, lability of blood pressure, flushes of blood to the face.

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, gastrointestinal bleeding, ulcer and / or perforation of the stomach or duodenum;

Rarely: gastritis, abdominal pain, indigestion, stomatitis, tarry stools.

Disturbances from the liver and bile ducts

Often: increased activity of hepatic enzymes;

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

Disorders from the kidneys and urinary tract

Rarely: dysuria, hematuria;

Rarely: renal failure, oliguria, interstitial nephritis, urinary retention.

Laboratory and instrumental data:

Rarely: hyperkalemia.

General disorders

Infrequently: peripheral edema;

Rarely: malaise, asthenia;

Rarely: hypothermia.

Overdose:

Symptoms: retardation, 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 charcoal (from 60 to 100 g for an adult person) 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:

Other non-steroidal anti-inflammatory drugs (NSAIDs):

Simultaneous use of nimesulide-containing drugs with other NSAIDs, including acetylsalicylic acid in a single dose of more than 1 g or a daily dose of more than 3 g, is not recommended.

Glucocorticosteroids increase the risk of erosive and ulcerative lesions of the gastrointestinal tract or bleeding.

Antiplatelet agents and selective inhibitors of re-uptakeserotonin CSSRIs), eg, fluoxetine, increase the risk of gastrointestinal bleeding.

Anticoagulants: NSAIDs can enhance the action of anticoagulants, such as warfarin or drugs that have an antiplatelet effect, such as acetylsalicylic acid. Because of the increased risk of bleeding, this combination is not recommended for patients with severe coagulation disorders. If it is not possible to cancel combination therapy, careful monitoring of indicators blood coagulability.

Diuretics

NSAIDs can reduce the effect of diuretics.

In healthy volunteers nimesulide when used simultaneously with furosemide transiently reduces the excretion of sodium ions and to a lesser extent - the excretion of potassium; 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 cardiacinsufficiency.

Angiotensin converting enzyme (ACE) and angiotensin II receptor antagonists

NSAIDs can reduce the effect of antihypertensive drugs. Patients with mild to moderate renal severity of failure (creatinine clearance of 30-80 ml / min) while the use of ACE inhibitors, angiotensin II receptor antagonists and drugs suppressing system cyclooxygenase (NSAIDs, antiplatelet agents) may further decrease in renal function, including the development of acute renal failure, which usually is 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 adequate amounts of fluids, and the indicators of renal function should be closely monitored in case of simultaneous application.

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 pharmacokinetic interactions with glibenclamide, theophylline, digoxin, cimetidine, warfarin and antacids (for example, a combination of aluminum and magnesium hydroxides) was not observed.

Nimesulide suppresses the activity of the 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 may increase and, accordingly, the severity of toxic effects may increase.

In connection with the effect on renal prostaglandins, inhibitors of prostaglandin synthetases, to which nimesulide, can increase nephrotoxicity cyclosporins.

In connection with the theoretical risk of change in efficiency mifepristone under the influence of inhibitors of prostaglandin synthesis, NSAIDs should not be used earlier than 8 to 12 days after the withdrawal of mifepristone.

Research in vitro showed that nimesulide expelled from binding sites tolbutamide, salicylic acid and valproic 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:

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 the patient has symptoms similar to the symptoms of liver damage (anorexia, skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, deviation from the normal values of the results of the "liver tests"), the patient should 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.

It reported the occurrence of gastrointestinal bleeding, ulceration or perforation of ulcers that can pose a threat to the patient's life, while taking all NSAIDs during the whole treatment period - like the appearance of symptoms-precursors, and without them, and regardless of the presence of severe disease from the gastrointestinal tract in the anamnesis. Risk of gastrointestinal bleeding, peptic ulcer or perforation ulcer is increased in patients with the presence of ulceration gastrointestinal tract (ulcerative colitis, Crohn's disease) in history and in the elderly, with increasing NSAID dose, however, treatment should begin 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 any unusual symptoms from the gastrointestinal tract (especially the 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.

The drug can cause fluid retention in the body.

In patients with uncontrolled arterial hypertension, with congestive heart failure, coronary heart disease, peripheral arterial disease and / or cerebrovascular disease, renal failure, risk factors for cardiovascular disease diseases (for example, hyperlipidemia, diabetes, smokers), 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 a slight increase in the risk of myocardial infarction or stroke. To exclude the risk of such events occurring when nimesulide is used, data is insufficient.

Nimesil® contains sorbitol (sorbitol), therefore its use in patients with hereditary intolerance to fructose is contraindicated.

If there are signs of fever or acute respiratory viral infection during the use of 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 perforations, life-threatening patients, impaired renal, hepatic and cardiac function. When taking Nimesil® for this category of patients, proper clinical control is necessary.

There are data on the occurrence of rare cases of severe skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) with NSAIDs, including nimesulide. The greatest risk of development of skin reactions in patients occurs at the beginning of therapy. 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 effect of Nimesil® on the ability to drive vehicles and mechanisms has not been studied. However, if headache, dizziness or drowsiness occurs after taking Nimesil®, you should refrain from controlling the vehicle and other mechanisms.

Form release / dosage:Tablets are effervescent, 100 mg.

Packaging:

10 tablets per polypropylene tube, capped with a lid of low density polyethylene, containing silica gel.

1 tube with instructions for use in a cardboard pack.

Storage conditions:

At a temperature of no higher than 25 ° C in a tightly closed tube.

Keep out of the reach of children!

Shelf life:

3 years.

After the first opening of the tuba - 6 months.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004523

Date of registration:31.10.2017

Expiration Date:31.10.2022

The owner of the registration certificate:Berlin-Chemie, AGBerlin-Chemie, AG Germany

Manufacturer: & nbsp

E-PHARMA Trento S.p.A. Italy

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp23.11.2017

Illustrated instructions

Instructions

Nimesil® (Nimesil®)