Nimesulid-MBF - instructions for use, dose, side effects, contraindications

Excipients: sucrose (sugar) - 1.805 g, macrogol glyceryl hydroxy stearate 0.008 g, citric acid 0.03 g, maltodextrin 0.015 g, orange flavoring 0.04 g.

Description:Granules of round and irregular shape, from light yellow to yellow with inclusions of yellow color, with the smell of orange. Powder is allowed from light yellow to yellow with inclusions of yellow color.

Pharmacotherapeutic group:NSAIDs

ATX: & nbsp

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

M.01.A.X.17 Nimesulide

Pharmacodynamics:Nonsteroidal anti-inflammatory drug (NSAID), has anti-inflammatory, analgesic, antipyretic and antiplatelet effect. In contrast to other NSAIDs, it selectively inhibits cyclooxygenase-2, inhibits the synthesis of prostaglandin in the inflammatory focus; has a less pronounced inhibitory effect on cyclooxygenase-1 (less often causes side effects associated with inhibition of prostaglandin synthesis in healthy tissues).

Pharmacokinetics:

Suction. Absorption when ingested - high (eating intake reduces the rate of absorption, without affecting its degree). Time to reach the maximum concentration (TC_max) - 1,5-2,5 hours. The connection with plasma proteins is 95%, with erythrocytes -2%, with lipoproteins - 1%, with acid alpha 1-glycoproteins - 1%. The dose change does not affect the degree of binding.

Distribution. The maximum concentration is 3.5-6.5 mg / l. The volume of distribution is 0.19-0.35 l / kg. 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 by tissue monooxygenases.The main metabolite is 4-hydroxynimidesulide (25%), has similar pharmacological activity, but due to the decrease in the size of the molecules it is able to rapidly diffuse along the hydrophobic channel of cyclooxygenase-2 to the active methyl group binding center. 4-Hydroxynimidesulide is a water-soluble compound, for the elimination of which is not required glutathione and the conjugation reaction of the second phase of metabolism (sulfation, glucuronidation, etc.).

Excretion. The half-life of nimesulide is 1.56-4.95 h, 4-hydroxynimidesulide - 2.89-4.78 h.

4-hydroxynimidesulide is excreted by the kidneys (65%) and bile (35%), is subjected to enterohepatic recirculation.

Indications:

- Acute pain (pain in the back, lower back, pain in the musculoskeletal system, including bruises, sprains and joints, tendenitis, 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;

- 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 a glucose-galactose malabsorption syndrome;

- hereditary lactose intolerance, impaired absorption of glucose-galactose, deficiency of lactase.

Carefully:

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

Ulcerative lesions 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:

The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy. Contraindicated in pregnancy.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside.

The contents of the sachet are dissolved in approximately 100 ml of water at room temperature (a white suspension with a yellowish-gray hue is formed).

The prepared solution is not subject to storage.

A drug Nimesulide It is only used to treat patients older than 12 years.

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

Elderly patients: in the treatment of elderly patients, the need for correction of the daily dose is determined by the physician based on the possibility of interaction with other medicines.

Patients with renal insufficiency: in patients with renal insufficiency of mild and moderate severity (creatinine clearance 30-60 ml / min) dose adjustment is not required, while for patients with severe renal insufficiency (creatinine clearance <30 ml / min) the drug Nimesulide is contraindicated.

Patients with hepatic insufficiency

Application of the drug Nimesulide 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: 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 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: 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: 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: increased 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 "hepatic" 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 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:

Glucocorticosteroids increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSIs)_, 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 receiving 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, digoxia, 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 the simultaneous use of drugs with nimesulide, 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 the synthesis of prostaglandins, such as 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, pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine, increased activity of the "liver" transaminases), discontinue the drug immediately Nimesulide and see a doctor. Repeated use of the drug Nimesulide in such patients is contraindicated.

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

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

A drug Nimesulide should be used with caution in patients with gastrointestinal ailments 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 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 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).

A drug Nimesulide should be used with caution in 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 the drug Nimesulide, the drug should be discontinued immediately.

Given reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of the drug Nimesulide 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 drug Nimesulide should be used with extreme caution. In case of deterioration, treatment with the drug Nimesulide it is necessary to stop.

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.

The drug can cause fluid retention in the body.

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 (for example: hyperlipidemia, diabetes, smokers) drug Nimesulide Use with caution. In case of worsening, treatment with the drug Nimesulide it is necessary to stop.

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. A drug Nimesulide It is not recommended to appoint patients with intolerance to fructose, a deficiency of sucrose-isomaltose or a syndrome of glucose-galactose malabsorption.

If there are signs of "cold" or acute respiratory viral infection in the process of using the drug Nimesulide the drug should be discontinued.

Nimesulide can change the properties of platelets, so care must be taken 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 perforations, life-threatening patients, impaired renal, hepatic and cardiac function. When taking the drug Nimesulide 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 rash, lesions of mucous membranes or other signs of an allergic reaction, taking the drug Nimesulide should be stopped immediately.

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

Effect of the drug Nimesulide on the ability to manage vehicles and mechanisms has not been studied, so during the period of drug use Nimesulide caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

2 grams in heat-sealing bags of packaging combined material.

For 5, 10, 20 and 30 bags, together with instructions for use, are placed in a pack of cardboard for consumer containers.

Storage conditions:

In a dry place, at a temperature of no higher than 25 ° C.

Keep out of the reach of children

Shelf life:

2 years.

Do not use after the expiration date

Terms of leave from pharmacies:On prescription

Registration number:LP-003999

Date of registration:06.12.2016 / 02.02.2018

Expiration Date:06.12.2021

The owner of the registration certificate:MARBIOFARM, OJSC MARBIOFARM, OJSC Russia

Manufacturer: & nbsp

MARBIOFARM, OJSC Russia

Representation: & nbspMARBIOFARM, OJSCMARBIOFARM, OJSC

Information update date: & nbsp21.06.2018

Illustrated instructions

Instructions

Nimesulid-MBF (Nimesulide-MBF)