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

1 tablet contains: active substance nimesulide 100.0 mg; Excipients: docusate sodium 1.5 mg, giprolose 0.8 mg, lactose monohydrate 153.7 mg, carboxymethyl starch sodium 35.0 mg, cellulose microcrystalline 100.0 mg, magnesium stearate 1.0 mg, vegetable oil hydrogenated 8.0 mg.

Description:Round biconvex tablets of light yellow color with a risk on one side.

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 one of the non-steroidal anti-inflammatory drugs (NSAIDs), has anti-inflammatory, analgesic, antipyretic and antiplatelet effects.In contrast to indomethacin, it suppresses cyclooxygenase 2 (COX-2) more than COX-1 (it is less likely to cause side effects associated with the inhibition of prostaglandin synthesis in healthy tissues, inhibiting their synthesis primarily in the inflammatory focus).

Pharmacokinetics:

Nimesulide is well absorbed when ingested (eating reduces the absorption rate without affecting its degree). After a single dose of 100 mg of nimesulide, the maximum concentration (C_max) in blood plasma in adults reaches 3-4 mg / l and is observed after 2-3 hours. Communication with blood plasma proteins - 95%, with erythrocytes - 2%, with lipoproteins - 1%, with acid alpha 1-glycoproteids - 1%. The increase in dose does not affect the degree of binding.

Area under the curve "concentration-time" (AUC) is 20-35 mg h / l. Statistically significant differences between these parameters after a single dose and appointment for 7 days at a dose of 100 mg 2 times a day were not detected.

The volume of distribution is 0.19-0.35 l / kg. Easily penetrates through gistogematicheskie barriers (in the tissues of female genital organs after a single intake of nimesulide concentration is about 40% of the concentration in the blood plasma), incl.in the acidic environment of the inflammation focus and synovial fluid (40% and 43%, respectively, of the concentration in the blood plasma).

Metabolised in the liver with the participation of monooxygenases, including. cytochrome P450 systems (CYP) 2C9. The main metabolite is water-soluble 4-hydroxynimidesulide (25%), has pharmacological activity similar to nimesulide.

Nimesulide is excreted mainly with urine (approximately 50% of the dose taken). The half-life (T1/2) nimesulide - 3-6 hours, 4-hydroxynimidesulide - 3-5 hours. 4-hydroxynimidesulide is excreted by the kidneys (65%) and bile (35%), is subjected to enterohepatic recirculation.

Only 1-3% of nimesulide is excreted unchanged. Approximately 29% of the dose is excreted as a metabolite with feces.

The pharmacokinetic profile of nimesulide in elderly people does not change after a single and repeated administration of the drug.

In patients with mild to moderate renal impairment, creatinine clearance (CK) of 30-80 ml / min, C_max Nimesulide and its main metabolite in blood plasma do not exceed those of healthy volunteers. Repeated administration of nimesulide is not accompanied by its cumulation.

Indications:

- Acute pain syndrome: algodismenorea, postoperative and posttraumatic pain, arthralgia, myalgia, dental and headache, tendonitis, bursitis.

- Symptomatic treatment of osteoarthritis accompanied by pain syndrome (the drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected; nimesulide should be prescribed only as second-line therapy).

Contraindications:

- Known hypersensitivity to nimesulide or any of its adjuvants.

- Hypersensitivity reactions in the history in response to NSAID (for example, bronchospasm, rhinitis, urticaria, complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs).

- Gastrointestinal bleeding or perforation of intestinal walls in history, associated with previous treatment with NSAIDs, erosive and ulcerative lesions of the mucous membrane of the stomach and duodenum (two or more confirmed ulceration and / or bleeding episodes), inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation.

- Cerebrovascular bleeding, bleeding disorders, accompanied by bleeding in history, hemophilia.

- Decompensated heart failure.

- Hepatic insufficiency or any liver disease in the acute stage, hepatotoxic reactions when using nimesulide in a history, concomitant use of other potentially hepatotoxic substances.

- Severe renal insufficiency (KC less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia.

- Postoperative period after aortocoronary bypass surgery.

- Associated catarrhal diseases with high fever.

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

- Children under 12 years.

- The third trimester of pregnancy and the period of breastfeeding.

Carefully:

- Severe somatic diseases: cardiac ischemia, cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, obliterating diseases of peripheral arteries, mild and moderate renal failure (CK 30-80 ml / min), anamnestic data on the development of gastrointestinal ulcer, infection Helicobacter pylori.

- Smoking, old age, long-term use of NSAIDs, alcoholism, simultaneous administration of anticoagulants (including warfarin), antiaggregants (incl.acetylsalicylic acid, clopidogrel), oral glucocorticosteroids, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine and sertraline).

Pregnancy and lactation:

The use of Nimesulide-Teva is contraindicated in the third trimester pregnancy.

Like other NSAIDs, Nimesulide-Teva is not recommended for women who are trying to get pregnant.

Inhibition of prostaglandin synthesis can have a negative effect on pregnancy and / or embryo / fetal development. The results of epidemiological studies indicate an increased risk of spontaneous abortion (miscarriages at early stages) and the development of heart defects, as well as the development of gastroschisis (developmental malformation, which is the non-growth of the anterior abdominal wall in the peripodal region, where the abdominal cavity falls out) against the background application of NSAIDs in the first trimester of pregnancy. The risk of teratogenicity and embryotoxicity increases with increasing dose and duration of treatment.

If the drug Nimesulide-Teva is taken by a woman who is trying to get pregnant,or during the first and second trimester of pregnancy, the dose and duration of treatment should be minimally possible.

During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can affect:

fetus:

- cardiopulmonary toxicity (with premature closure of the botulinum arterial duct with the development of pulmonary hypertension);

- impaired renal function, which can progress up to the development of renal failure;

mother and newborn:

- prolonged bleeding time (even with low doses);

- reduction of uterine contractions (delay and lengthening of labor).

There is no data on the isolation of nimesulide with breast milk, Nimesulide-Teva is contraindicated during breastfeeding.

Dosing and Administration:

A minimum effective dose should be given with a possibly minimally short course of treatment. The maximum duration of treatment with nimesulide is 15 days.

Adults: 100 mg of nimesulide 2 times a day after meals. In patients with renal insufficiency, the maximum daily dose is 100 mg.

Elderly persons: to reduce the daily dose is not necessary.

Children (under 12 years): the drug Nimesulide-Teva is contraindicated.

Teens (12 to 18 years): correction of the dose is not required.

Impaired renal function: dose adjustment in patients with mild to moderate renal dysfunction (CK 30-80 ml / min) is usually not required. The drug Nimesulide-Teva is contraindicated in case of severe renal dysfunction (CC <30 ml / min).

Impaired liver function: the use of Nimesulide-Teva is contraindicated.

Side effects:

Data from clinical epidemiological studies indicate that prolonged use of any NSAIDs (especially in high doses) can potentially be accompanied by an increased risk of arterial thrombosis (including manifested by myocardial infarction or ischemic stroke).

Against the background of the use of NSAIDs it is possible to develop edematous syndrome, arterial hypertension, aggravation of the course of heart failure. Very rarely reported serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Most often there are various gastrointestinal disorders (especially in predisposed and elderly persons): peptic ulcers,perforation of the gastrointestinal wall, the development of potentially severe gastrointestinal bleeding, nausea, vomiting, bloody vomiting, flatulence, abdominal pain, diarrhea, constipation, melena, stomatitis, ulcerative colitis, less frequent manifestations of gastritis.

The following undesirable phenomena with nimesulide were detected during controlled clinical trials (marked with a "*"), as well as marketing observations with the frequency reported, classified according to the recommendations of the World Health Organization: very often (at least 10%); often (1-10%); infrequently (0.1-1%); rarely (0.01-0.1%); very rarely (less than 0.01%, including individual cases).

Allergic reactions: rarely - hypersensitivity *; very rarely anaphylaxis. Violations of the water-electrolyte balance: rarely - hyperkalemia.

Disorders of the psyche: rarely - anxiety, fear *, nervousness *, "nightmarish" dreaming *.

Disorders from the nervous system and sensory organs: infrequently - dizziness *; rarely - vagueness of vision *; very rarely - visual impairment.

Disorders from the cardiovascular system: infrequently - arterial

hypertension *; rarely - tachycardia *, lability of blood pressure *, "tides" of blood to the face *.

Disturbances from the respiratory organs: infrequently - dyspnea *; very rarely - bronchospasm.

Disorders from the digestive system: often - diarrhea *, nausea *, vomiting *; infrequently - constipation *, flatulence *, gastritis *; very rarely - abdominal pain, indigestion, stomatitis, melena, gastrointestinal bleeding, ulcer and perforation of the duodenum and / or stomach.

Disorders from the liver and bile ducts: often - increased activity of "liver" enzymes *; very rarely - hepatitis, incl. fulminant course, jaundice, cholestasis.

Disturbances from the skin and subcutaneous tissues: infrequently - itching *, rash *, increased sweating *; rarely - erythema *, dermatitis *; very rarely - urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract: rarely - dysuria *, hematuria *, urinary retention *; very rarely - renal failure, oliguria, interstitial nephritis.

Systemic disorders: infrequently - edematic syndrome *; rarely - malaise *, asthenia *; very rarely - hypothermia.

Blood disorders: rarely - anemia *, eosinophilia *; very rarely - thrombocytopenia, pancytopenia, purpura.

Overdose:

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

Treatment: symptomatic and supportive therapy. There is no specific antidote. In the first 4 hours after an overdose - it is necessary to induce vomiting, it is advisable to take activated charcoal (1 g / kg body weight). Conduction of forced diuresis and hemodialysis is ineffective.

Interaction:

Pharmacodynamic interactions. The combination of Nimesulide-Teva with other NSAIDs, including acetylsalicylic acid, in anti-inflammatory doses (> 1 g once or> 3 g per day) is not recommended.

NSAIDs increase the anticoagulant effect of warfarin. Patients receiving warfarin and antiplatelet agents (including clopidogrel and acetylsalicylic acid) against the background of nimesulide, have an increased risk of bleeding.

Inhibitors of prostaglandin synthesis (NSAIDs, incl. nimesulide) can increase the nephrotoxicity of cyclosporine.

When used simultaneously with glucocorticosteroids and selective serotonin reuptake inhibitors, the risk of bleeding from the gastrointestinal tract increases.

NSAIDs may reduce the effectiveness of diuretics and other antihypertensive drugs. In patients with initial impairment of renal function (eg, in dehydrated patients or elderly patients with impaired renal function) concomitant use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II antagonists with COX inhibitors can lead to increased manifestations of renal failure (usually reversible). This combination should be administered with caution, especially in elderly patients. Patients should receive the required amount of fluid, it is also worth considering the need to monitor kidney function.

In healthy people nimesulide short-term decreases the severity of natriuretic action of furosemide (to a lesser extent - potassium -uretic). Pharmacokinetic interaction. The concomitant use of nimesulide and furosemide results in a decrease (approximately 20%) AUC, without affecting its kidney clearance.

NSAIDs reduce the clearance of lithium, leading to an increase in its concentration in blood plasma and toxicity.

Nimesulide inhibits CYP2C9. Plasma concentrations of drugs that are substrates of this enzyme may increase with the concomitant use of Nimesulide-Teva.

Caution is required when nimesulide is prescribed less than 24 hours before or after treatment with methotrexate (plasma methotrexate concentration may increase, leading to an increase in its toxicity).

Research in vitro have shown that nimesulide can be displaced from furosemide, fenofibrate, tolbutamide, salicylic and valproic acid due to protein binding to blood plasma (this fact has no clinical significance).

Special instructions:

Every 2 weeks, the functional state of the liver should be monitored. If there are signs of liver damage (pruritus, jaundice, nausea, vomiting, abdominal pain, darkening of urine, increased activity of "liver" transaminases), discontinue treatment immediately.

Given the possibility of visual impairment in patients taking NSAIDs, if such symptoms appear, treatment should be stopped immediately and an ophthalmological examination performed.

The drug may cause fluid retention, and therefore patients with high blood pressure or signs of congestive heart failure nimesulide should be used with extreme caution.

Patients should be under regular medical supervision if they take drugs along with nimesulide, which also have ulcerogenic effects on the gastrointestinal tract. Do not use the drug simultaneously with other NSAIDs (including selective inhibitors of COX-2) and non-narcotic analgesics.

Nimesulide reduces platelet aggregation, but it is unable to replace the prophylactic use of antiplatelet agents (acetylsalicylic acid, clopidogrel, ticlopidine) in cardiovascular diseases.

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

The risk of adverse events can be reduced by using the lowest effective dose of Nimesulide-Teva for the shortest possible period.

Patients who develop symptoms on the background of taking Nimesulide-Teva,Characteristic for liver damage (eg, anorexia, nausea, vomiting, pain in the right upper quadrant, increased fatigue, darkening of urine), or an increase in the activity of "liver" transaminases, the appointment of nimesulide should be discontinued. These patients should also not re-appoint nimesulide.

Patients who developed signs of concomitant catarrhal disease (for example, there was an increase in body temperature), the appointment of nimesulide should be discontinued.

When using NSAIDs, it is possible to develop cases of bleeding, ulceration and perforation of the walls of the stomach or intestine. The risk of their development is higher with the appointment of high doses of NSAIDs, when they are taken by patients with a stomach ulcer and duodenal ulcer in an anamnesis, as well as elderly persons. If therapy is required in these cases, consideration should be given to the need for concomitant use of misoprostol or proton pump inhibitors.

Patients (especially those with a history of history and elderly people) should be warned about the need to tell the doctor about any unusual abdominal symptoms (especially those that occur early in the treatment).

The cases of fluid retention and development of edematous syndrome on the background of NSAID administration are described, and therefore patients with arterial hypertension and / or congestive heart failure, coronary heart disease, peripheral arterial diseases and / or cerebrovascular diseases require very careful monitoring. The same precautions should be taken when nimesulide is prescribed to patients with an increased risk of developing cardiovascular diseases (eg, hyperlipidemia, diabetes and smoking).

In patients with impaired renal function, caution should be exercised in prescribing Nimesulide-Teva (further deterioration of their function may be possible), with a decrease in creatinine clearance, treatment should be discontinued.

Nimesulide should be used with caution in patients with hemorrhagic diathesis, since it can reduce platelet aggregation.

The risk of serious skin reactions (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) is higher at the beginning of the treatment with NSAIDs (most of these reactions appear during the first month of treatment).Treatment with Nimesulide-Teva should be discontinued when the first signs of rash, mucosal damage or other manifestations of hypersensitivity occur.

The drug Nimesulide-Teva contains lactose monohydrate. Patients with congenital lactose intolerance, impaired glucose-galactose absorption or lactase deficiency should not take this medication.

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

The effect of Nimesulide-Teva on the rate of psychomotor reactions has not been specifically studied. However, patients who experience dizziness or drowsiness after taking Nimesulide-Teva, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 100 mg.

Packaging:For 10 tablets in a blister of PVC / aluminum foil. For 1, 2, 3 or 6 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 25 ° C in a dry, protected from light place. Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002427

Date of registration:09.04.2014

Expiration Date:09.04.2019

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp14.08.2015

Illustrated instructions

Instructions

Nimesulide-Teva (Nimesulid-Teva)