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

Excipients: cellulose microcrystalline - 101.8 mg, corn starch - 57.8 mg, sodium carboxymethyl starch - 48 mg, copovidone - 6.0 mg, polyethylene glycol - 1.6 mg, polysorbate-80 - 1.6 mg, magnesium stearate - 1.6 mg, silicon colloidal dioxide 1.6 mg.

Description:The tablets are round, biconvex in shape from light yellow to yellow, with a risk on one side and embossed in the form of a "f" on the other side.

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:Non-steroidal anti-inflammatory

drug (NSAID1) from the class of sulfoic acids. It is a selective competitive inhibitor of cyclooxygenase-2 (COX-2) - an enzyme involved in the synthesis of prostaglandin mediators of edema, inflammation and pain. Provides anti-inflammatory, analgesic and antipyretic action. Reversibly inhibits the formation of prostaglandin E2, both in the focus of inflammation, and in the ascending pathways of the nociceptive system, including ways of carrying out painful pulses of the spinal cord. Reduces concentration short-lived prostaglandin H2, from which prostaglandin isomerase forms prostaglandin E2. A decrease in the concentration of prostaglandin E2 leads to a decrease in the degree of activation of prostanoid EP receptors, which is expressed in analgesic and anti-inflammatory effects. Inhibits the release of tumor necrosis factor a. which causes the formation of cytokinins. Shown, that nimesulide is able to suppress the synthesis of interleukin-6 and urokinase, heme most inhibiting the destruction of cartilaginous tissue. Inhibits the synthesis of metalloproteases (elastase.collageniasis), preventing the destruction of anti-glycans and cartilaginous collagen. Interacts with glucocorticoid receptors, activating through phosphorylation, which also increases the anti-inflammatory effect of the drug.

Pharmacokinetics:

Suction

After oral administration nimesulide is well absorbed from the gastrointestinal tract (GIT). Eating lowers the absorption rate without affecting its degree. Time to reach the maximum concentration of active substance in blood plasma - 1,5 - 2,5 hours. The maximum concentration C_max Nimesulide in blood plasma reaches 3.5 - 6.5 mg / l.

Distribution

The connection with plasma proteins is 95%, with erythrocytes - 2%, lipoproteins - 1%, and acid alpha 1-glycoproteids - 1%. The dose of the drug does not affect the degree of its binding to blood proteins. The volume of distribution: 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 histogematic barriers.
Metabolism
Metabolized in the liver by tissue monooxygenase; 4-hydroxynimidesulide (25%) has similar pharmacological activity.
Excretion
The period of zero-elimination (T1/2) of nimesulide is 1.56 - 4.95 hours, 4-hydroxynimidesulide - 2.89 - 4.78 hours. 4-hydroxynimidesulide is excreted by the kidneys (65%) and with bile (35%), subjected to enterohepatic recirculation. Pharmacokinetics in special clinical cases
In patients with mild to moderate renal impairment (creatinine clearance 1.8 to 4.8 L / h or 30 to 80 mL / min), as well as in children and the elderly, the pharmacokinetic profile of nimesulide varies considerably.

Indications:

- rheumatoid arthritis;

- articular syndrome with exacerbation of gout;

- psoriatic arthritis;

- ankylosing spondylitis;

- osteochondrosis with radicular syndrome;

- osteoarthritis;

- myalgia of rheumatic and non-rheumatic gnesz;

- inflammation of ligaments, tendons, bursitis, including post-traumatic inflammation of soft tissues;

- pain syndrome of various geese (including in the postoperative period, in traumas, algodissmorrhoea, toothache, headache, arthralgia, lumboeishalgia).

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:- hypersensitivity to nimesulide or ancillary components of the drug;

- complete or incomplete combination of bronchial asthma, recurring nose polynomia or paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis);

- erosive and ulcerative changes in the mucosa of the stomach and duodenum (DNA), active gastrointestinal bloodedema. schlierenovascular or other bleeding;

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

- hemophilia and other bleeding disorders;

- Decompensated heart failure;

- hepatic insufficiency or any active liver disease;

- anamnestic data on the development of gsatotoxic reactions using nimesulide preparations;

- concomitant use of potentially hepatotoxic substances;

- alcoholism;

- addiction;

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

- period after aortocoronary shunting;

- pregnancy;

-period of breastfeeding; children under 12 years.

Carefully:

- cardiac ischemia;

- cerebrovascular diseases;

- compensated heart failure;

- dyslipidemia / hyperlipidemia;

- diabetes;

- diseases of peripheral arteries;

- smoking;

- renal failure (creatinine clearance 30-60 ml / min)

- anamnestic data on the development of gastrointestinal ulcer;

- infection Helicobacter pylori,

- elderly age;

- long-term use of NSAIDs;

- severe physical illnesses;

- frequent use of alcohol;

- concomitant therapy with anticoagulants (eg, warfarin, antiplatelet agents (eg, acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (GCS) (for example, prednisolone), selective serotonin reuptake inhibitors (SSRIs) (eg, citalopram, fluoxetine, paroxegin, sertraline).

Pregnancy and lactation:

Nimesulide is contraindicated in pregnancy.

If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.

Dosing and Administration:

For oral administration.

A minimum effective dose should be used with the minimum possible short course. Tablets are taken with a sufficient amount of water, preferably after eating.

Inside adults to use 100 mg 2 times / day. The maximum daily intake for adults is 200 mg.

Children over 12 years of age should take the drug in a single dose of 1.5 mg / kg of the child's body weight 2 times / day, but not more than 100 mg.

The duration of the course of treatment is not more than 5 days. If there are diseases of the digestive tract, it is advisable to take the drug at the end of the meal or after eating. Patients with chronic renal (creatinine clearance 30-60 ml / min) deficiency require a reduction in the daily dose to 100 mg.

Side effects:

The frequency of adverse reactions is classified from the incidence of the case: very often (> 1/10), often (from> = 1/100 to <1/10), infrequently (from> = 1/1000 to <1/100), rarely from> = 1/10 000 to <1/1000), very rarely (from <1/10 000), the frequency is unknown (the frequency nc can be calculated from the available data).

Allergic reactions: rarely - hypersensitivity reactions; very rarely anaphylactoid reactions.

From the central nervous system: infrequently - dizziness; rarely a feeling of fear, nervousness, "nightmarish" dreams; very rarely - headache, drowsiness, encephalopathy (Reis syndrome).

From the skin: infrequently - itching, rash, increased sweating; rarely: erythema, dermatitis; very rarely: urticaria, angioedema, facial puffiness, multiforme exudative erythema, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the urinary system: infrequently - swelling; rarely - dysuria, hematuria, urinary retention, hyperkalemia; very rarely - renal failure, oliguria, interstitial nephritis.

From the gastrointestinal tract: often - diarrhea, nausea, vomiting; infrequently - constipation, flatulence, gastritis; very rarely - abdominal pain, stomatitis, a degenerative stool, gastrointestinal bleeding, an ulcer and / or perforation of the stomach or duodenum.

From the liver and bile excretory system: often - increased "liver" transaminases; very rarely - hepatitis, fulminant hepatitis, jaundice, cholestasis.

From the hematopoiesis: rarely - anemia, eosinophilia; very rarely - thrombocytopenia, pancytopenia, purpura, prolonged bleeding time.

From the respiratory system: infrequently - shortness of breath; very rarely - exacerbation of bronchial asthma, bronchospasm.

From the sense organs: rarely - blurred vision.

From the cardiovascular system: infrequently - increased blood pressure; rarely - tachycardia, hemorrhages, "hot flashes", a feeling of palpitations.

Other: rarely - general weakness; very rarely - hypothermia, asthenia, hyperkalemia.

If any of the side effects listed in the manual are aggravated or you notice any other side effects not listed in the instructions, report it the doctor.

Overdose:

Symptoms: apathy, drowsiness, nausea, vomiting. There may be gastrointestinal bleeding, increased blood pressure, acute renal failure, respiratory depression.

Treatment: symptomatic. There is no specific antidote. In the event that an overdose has occurred within the last 4 hours, it is necessary to induce vomiting, activated carbon (60-100 g per adult), osmotic laxatives.

Forced diuresis, hemodialysis are ineffective to hams and plasma.

Interaction:

Nimesulide inhibits isoenzyme CYP2C9, so the concentration in the blood plasma of drugs metabolized by the participation of this isoenzyme, while using with nimesulide can increase.

With simultaneous use with antiepileptic drugs (valproic acid), proti fungal preparations (ketoconazole), antituberculous drugs (isoniazid), amiodarone, methotrexate, methyldopa, amoxicillium in combination with clavulanic acid, additive hepatotoxic effect is possible. Care should be taken if the interval between taking nimesulide and methotrexate is less than 24 hours. Nimesulide may increase the possibility of side effects with simultaneous administration of methotrexate.

It is possible to increase the nephrotoxicity of cyclosporine when used simultaneously with nimesulide.

Nimesulide can reduce the oral bioavailability of furosemide, therefore, reduces the effectiveness of furosemide action on glomerular filtration, renal blood flow. The simultaneous use of nimesulide and furosemide requires caution in patients with impaired renal and cardiac function.

Simultaneous reception of nimesulide with warfarin and similar anticoagulants, acetylsalicylic acid ns is recommended, hack as the risk of bleeding increases. Nimesulide contraindicated in patients with severe blood clotting disorder.

There are data that non-steroidal anti-inflammatory drugs reduce the clearance of lithium, which leads to an increase in the concentration of lithium in the blood plasma and increase its toxicity. Therefore, simultaneous use of nimesulide and lithium, it is necessary to regularly control the concentration of lithium in the blood plasma. Clinically significant interactions of nimesulide with glibenclamide, theophylline, digoxin, cimetidine and antacids (combinations of aluminum and magnesium compounds) have not been identified.

Non-steroidal anti-inflammatory drugs can reduce the effectiveness of diuretics and other antihypertensive drugs. In patients with initial impairment of renal function (for example, in dehydrated patients or elderly patients with impaired renal function) concomitant administration of inhibitors angiotensin converting enzyme (AIF) or angiotensin II antagonists with TS0G inhibitors may lead to an increase in renal insufficiency (usually reversible). This combination should be administered with caution, especially in elderly patients.Patients should receive the necessary amount of fluid, and there is also the question of the need for monitoring the function of the kidneys.

Special instructions:

Since imimesulide is partially excreted by the kidneys, its dose for patients with impaired renal function should be reduced, depending on the creatinine clearance values.

Given reports of visual impairment in patients taking other NSAIDs. treatment should be stopped immediately, if any visual impairment occurs, and the patient should be examined by an oculist.

The drug can cause fluid retention in tissues, so patients with high blood pressure and cardiac disorders nimesulide should be used with extreme caution.

Patients should undergo regular medical supervision if they take medications along with nimesulide, for which the effect on the gastrointestinal tract is characteristic. If there are signs of liver damage (itchy skin, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, increased activity of "liver" transaminases), then stop taking the drug and consult a doctor.Hc should be used simultaneously with other NSAIDs.

During treatment with nimesulide, 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 does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

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

After 2 weeks of using the drug, it is necessary to monitor the biochemical parameters of liver function.

Gastrointestinal bleeding or ulcer / perforation can develop at any time with the use of the drug, with or without symptomatic symptoms. as with the existence of gastrointestinal complications in the anamnesis, and without them. The risk of their development is higher with the appointment of high doses NSAIDs, when taken by patients with ulcers stomach and duodenum in anamnesis, as well as elderly persons. When the need for therapy in these cases should consider the need for concomitant use of misoprostol or proton pump inhibitors.If there is a gastrointestinal bleeding or ulcers of the gastrointestinal tract, the drug should be discarded.

In elderly patients the most frequent side effects are when taking the drug, including gastrointestinal bleeding, perforation, cardiac, renal, and hepatic dysfunction, therefore regular clinical monitoring of the condition of these patients is recommended.

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

The drug can cause drowsiness, dizziness and blurred vision, you need to be careful when driving and taking other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets of 100 mg. For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2, 3 or 10 contour mesh packages together with the instruction for medical use are placed in a pack of cardboard box.

Packaging:(10) - packings, cellular, outline (1) - packs, cardboard
(10) - packings cellular planimetric (10) - packs cardboard
(10) - packings, cellular, outline (2) - packs, cardboard
(10) - packings, cellular, outline (3) - packs, cardboard

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not take it beyond the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002835

Date of registration:23.01.2015

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Information update date: & nbsp14.08.2015

Illustrated instructions

Instructions

Nimesulide (Nimesulid)