Nimulide, 10 mg/ml suspension 60 ml

Clinical and pharmacological group: NSAIDs. Selective COX-2 inhibitor

Pharmacological action

NSAIDs from the class of sulfonanilides, selective competitive reversible COX-2 inhibitor. It has anti-inflammatory, analgesic and antipyretic effect. It has a less pronounced inhibitory effect on COX-1.

Decreases concentration of short-lived prostaglandin H₂, a substrate for kinin-stimulated prostaglandin E₂ synthesis, in the focus of inflammation and in the ascending pathways of pain impulse conduction in the spinal cord. Reducing the concentration of prostaglandin E₂ (mediator of inflammation and pain) reduces the activation of prostanoid receptor EP type, which is manifested by analgesic and anti-inflammatory effects.

Pharmacokinetics

After oral administration, nimesulide is well absorbed from the GI tract, C_max in plasma is reached after 2-3 h on average and is 3-4 mg/L. AUC is 20-35 mg×h/l. Binding to plasma proteins is 97.5%. After a single oral dose of 100 mg, nimesulide is present in the female genital tissues at a concentration of 40% of the plasma concentration. It is metabolized in the liver with the participation of CYP2C9 isoenzyme. The main metabolite is pharmacologically active parahydroxy derivative of nimesulide – hydroxynimesulide, which is found exclusively as glucuronate. Nimesulide is excreted mainly in the urine (about 50% of the dose taken), about 29% is excreted as metabolites in the feces. T_1/2 is 3.2-6 h.

Indications

Painful menstruation (algodysmenorrhea), Back pain, Radiculitis, Headache, Lumbago, Inflamed tendons, Bursitis, Fever, Osteochondrosis, Myalgia (muscle pain), Rheumatoid arthritis, Migraine, Pain, Neck pain, Colds, Pain after injuries and operations, Joint pain (arthralgia), Sciatica, Toothache, Gout, Myositis, Sprains and strainsSore pain (pain in back, lower back; Musculoskeletal pain, including bruises, sprains and sprains of joints; tendinitis, bursitis; toothache); symptomatic treatment of osteoarthritis (osteoarthritis) with pain syndrome; primary algodysmenorrhea.

Active ingredient

Nimesulide

Composition

5 ml of the suspension contain:

The active substance:

nimesulide Br.F. 50.00 mg;

Excipients:

xanthan gum,

70% sorbitol solution,

uncrystallized. glycerin (glycerol),

sucrose,

macrogoal glyceryl hydroxystearate (Cromophor RH 40),

sodium methyl parahydroxybenzoate,

sodium propyl parahydroxybenzoate,

sodium benzoate,

silicon dioxide colloid,

sodium disulfite,

citric acid monohydrate,

hydrochloric acid (concentrated).),

Vanilla flavoring,

Mango flavoring,

Quinoline yellow dye,

Purified water.

How to take, the dosage

Ingestion, preferably before meals; in case of impaired gastric function, at the end or after meals. Adults – 100 mg 2 times a day; children – 1.5 mg/kg 2-3 times a day.

The maximum dose for children is not more than 5 mg/kg/day in 2-3 doses. No dose adjustment is required when prescribing in elderly patients.

Interaction

GCSs increase the risk of gastrointestinal ulcers or bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors, such as fluoxetine, increase the risk of gastrointestinal bleeding.

The NSAIDs may increase the effects 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 the combination therapy still cannot be avoided, it is necessary to conduct careful monitoring of blood clotting.

NSAIDs can reduce the effect of diuretics. In healthy volunteers nimesulide temporarily reduces sodium excretion under the effect of furosemide, to a lesser extent – potassium excretion and reduces the diuretic effect itself.
Concomitant use of nimesulide and furosemide leads to a decrease (approximately 20%) of AUC and reduction of cumulative excretion of furosemide without changing renal clearance of furosemide. Concomitant use of furosemide and nimesulide requires caution in patients with renal or cardiac insufficiency.

NSAIDs can decrease the effect of hypotensive drugs. In patients with mild to moderate renal insufficiency (CKD 30-80 ml/min) concomitant use of ACE inhibitors, angiotensin II receptor antagonists and agents that inhibit COX system (NSAIDs, antiaggregants) may cause further deterioration of renal function and occurrence of acute renal failure, which is usually reversible. These interactions should be considered in patients taking nimesulide in combination with ACE inhibitors or angiotensin II receptor antagonists. Therefore, concomitant use of these drugs should be performed with caution, especially in elderly patients. Patients should receive adequate fluids, and renal function should be monitored closely after concomitant use.

Theoretically, the efficacy of mifepristone and prostaglandin analogues may be reduced when used concomitantly with NSAIDs (including acetylsalicylic acid) due to the antiprostaglandin effect of the latter. Limited data show that the use of NSAIDs on the day of prostaglandin analogue use has no adverse effect on the effect of mifepristone or prostaglandin analogue on cervical dilation and uterine contractility and does not reduce the clinical effectiveness of medical termination of pregnancy.

There is evidence that NSAIDs decrease lithium clearance, which leads to increased plasma lithium concentrations and toxicity. When using nimesulide in patients on therapy with lithium drugs, regular monitoring of plasma lithium concentration should be performed.

Nimesulide inhibits the activity of CYP2C9 isoenzyme. When concomitant use of drugs that are substrates of this enzyme with nimesulide, plasma concentrations of the latter may increase.

When nimesulide is used less than 24 hours before or after methotrexate administration, caution is required, because in these cases the plasma concentrations of methotrexate and, correspondingly, the toxic effects may increase.

Inhibitors of prostaglandin synthetases, such as nimesulide, may increase nephrotoxicity of cyclosporines because of their effect on renal prostaglandins.

Special Instructions

In case of symptoms similar to those of liver damage (anorexia, pruritus, yellowing of the skin, nausea, vomiting, abdominal pain, darkened urine, increased liver transaminases activity), nimesulide should be immediately stopped and a physician should be consulted. Repeated use of nimesulide in such patients is contraindicated.

Hepatic reactions, which in most cases are reversible, have been reported with short-term use of nimesulide.

When using nimesulide, patients should refrain from taking other analgesics, including NSAIDs (including COX-2 selective inhibitors).

With caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease) because exacerbation of these diseases is possible. The risk of gastrointestinal bleeding, peptic ulcer/perforation of the stomach or duodenum is increased in patients with a history of gastrointestinal ulcers (ulcerative colitis, Crohn’s disease), as well as in elderly patients, with increasing doses of NSAIDs, so treatment should be started with the lowest possible dose. Such patients, as well as patients who require concomitant use of low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, it is recommended to administer additional gastroprotectors (misoprostol or proton pump blockers). Patients with a history of gastrointestinal disease, especially elderly patients, should inform the physician about new gastrointestinal symptoms (especially symptoms that may indicate possible gastrointestinal bleeding).

If gastrointestinal bleeding or gastrointestinal ulcers occur in patients taking nimesulide, it should be stopped.

Given the reports of visual impairment in patients taking other NSAIDs, if any visual impairment occurs, the use of nimesulide should be stopped immediately and an ophthalmologic examination should be performed.

Nimesulide may cause fluid retention, so in patients with arterial hypertension, with renal and/or heart failure, it should be used with extreme caution. In case of worsening of the condition, treatment with nimesulide should be discontinued.

Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a small risk of myocardial infarction or stroke. There is insufficient data to exclude the risk of these events with nimesulide.

In case of signs of cold or acute respiratory infections during nimesulide use, it should be stopped immediately.

Nimesulide may change the properties of platelets, so caution should be exercised when using it in patients with hemorrhagic diathesis, but nimesulide does not replace the preventive action of acetylsalicylic acid in cardiovascular disease.

Elderly patients are particularly susceptible to adverse reactions to NSAIDs, including risk of gastrointestinal bleeding and life-threatening perforations, decreased renal, liver and cardiac function. Appropriate clinical monitoring is necessary when taking nimesulide for this patient population.

In case of the first manifestations of skin rash, mucosal lesions or other signs of an allergic reaction, nimesulide should be stopped immediately.

Impact on driving and other machinery

When using nimesulide, caution should be exercised when driving motor transport and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

• Hypersensitivity to nimesulide;
• hyperergic reactions in the history (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other NSAIDs, including nimesulide.
• complete or incomplete combination of bronchial asthma, recurrent nasal or paranasal sinus polyposis with intolerance to acetylsalicylic acid and other NSAIDs (incl. history);
• Hepatotoxic reactions to nimesulide in history;
• Concomitant use with other drugs with potential hepatotoxicity (e.g. other NSAIDs);
• Chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute phase;
• period after coronary artery bypass grafting;
• fever syndrome with colds and SARS;
• Gastric or duodenal ulcer in the acute phase;
• Gastrointestinal erosive lesions;
• perforations or gastrointestinal bleeding in the history;
• cerebrovascular bleeding in the history or other diseases accompanied by increased bleeding;
• severe clotting disorders;
• severe heart failure;
• severe renal insufficiency (CK<30 ml/min), confirmed hyperkalemia;
• children under 12 years of age;
• alcoholism, drug addiction;
• hepatic failure, active liver disease.

With caution

Artial hypertension, diabetes mellitus, compensated heart failure, CHD, cerebrovascular disease, dyslipidemia/hyperlipidemia, peripheral artery disease, hemorrhagic diathesis, smoking, IQ 30-60 ml/min.

A history of peptic ulcer disease; history of infection caused by Helicobacter pylori; advanced age; long-term prior use of NSAIDs; severe medical conditions.

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

Side effects

Blood system: rare – anemia, eosinophilia, hemorrhages; very rare – thrombocytopenia, pancytopenia, thrombocytopenic purpura.

The immune system: rare – hypersensitivity reactions; very rare – anaphylactoid reactions, very urticaria, angioedema.

Skin and subcutaneous tissue disorders: infrequent – itching, skin rash, increased sweating; rare – erythema, dermatitis; very rare – hives, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome).

Nervous system disorders: infrequent dizziness; very rare headache, somnolence, encephalopathy (Reye’s syndrome).

Psychiatric disorders: rarely – fear, nervousness, nightmares.

An organ of vision: rarely – blurred vision; very rare – visual impairment.

Hearing organ and labyrinth disorders: very rare – vertigo.

Cardiovascular system: infrequent – increase of blood pressure; rare – tachycardia, BP lability, “rushes” of blood to the face, a feeling of palpitations.

Respiratory system: infrequent dyspnea; very rare – exacerbation of bronchial asthma, bronchospasm.

The digestive system: often – diarrhea, nausea, vomiting; infrequent – constipation, flatulence, gastric bleeding, gastric or duodenal ulcer and/or perforation; very rare – abdominal pain, dyspepsia, stomatitis, tarry stools.

Hepatic and biliary tract disorders: often – increased activity of “liver” enzymes; very rare – hepatitis, fulminant hepatitis (including fatal outcomes), jaundice, cholestasis.

Urinary system disorders: rarely – dysuria, hematuria, urinary retention; very rarely – renal failure, oliguria, interstitial nephritis.

Metabolism: rarely – hyperkalemia; rarely – peripheral edema; very rarely – hypothermia.

Others: rarely – malaise, asthenia.

Pregnancy use

Nimesulide is contraindicated in pregnancy and during breastfeeding.

Similarities

Naiz, Nimesil, Nimesulide, Nemulex, Nimesulide-TEVA, Nimulide, Nimesan tablets 100 mg 20 pcs, Naisulide, Mialais