Nimesil, 100 mg 2 g 9 pcs.

Pharmacotherapeutic group: Nonsteroidal anti-inflammatory drugs (NSAIDs).

ATX code: M01AX17

Pharmacological properties

Pharmacodynamics Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) of the sulfonamide class. It has anti-inflammatory, analgesic and antipyretic effects.

Nimesulide acts as an inhibitor of cyclooxygenase enzyme responsible for the synthesis of prostaglandins and inhibits mainly cyclooxygenase 2.

Pharmacokinetics After oral administration the drug is well absorbed from the gastrointestinal tract, reaching maximum concentration in blood plasma after 2-3 hours; plasma protein binding is 97.5%; elimination half-life is 3.2-6 hours. It easily penetrates through histohematic barriers.

It is metabolized in liver by cytochrome P450 isoenzyme (CYP) 2C9. The main metabolite is pharmacologically active parahydroxy derivative of nimesulide – hydroxynimesulide. Hydroxynimesulide is excreted with bile in metabolized form (found exclusively as glucuronate – about 29%).

Nimesulide is excreted from the body mainly by the kidneys (about 50% of the taken dose). Pharmacokinetic profile of nimesulide in elderly persons does not change when administering single and multiple/repeated doses.

According to the data of experimental study, which was carried out with the participation of patients with mild to moderate degree of renal failure (creatinine clearance 30-80 ml/min) and healthy volunteers, the maximum concentration of nimesulide and its metabolite in plasma of patients did not exceed the nimesulide concentration in healthy volunteers. The area under the curve “concentration-time” (AUC) and the elimination half-life in patients with renal failure were higher by 50%, but within the pharmacokinetic values. No cumulation was observed with repeated administration of the drug.

Indications

The drug is intended for symptomatic therapy, reduction of pain and inflammation at the time of use.

Active ingredient

Composition

How to take, the dosage

Interaction

Pharmacodynamic interactions:

Glucocorticosteroids: increase the risk of gastrointestinal ulceration or bleeding.

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

Anticoagulants: NSAIDs may increase 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 combination therapy still cannot be avoided, careful monitoring of blood clotting parameters is necessary.

Diuretics

NSAIDs may decrease the effect of diuretics.

In healthy volunteers, nimesulide temporarily reduces sodium excretion with furosemide, to a lesser extent potassium excretion, and reduces the diuretic effect itself.

The co-administration of nimesulide and furosemide results in a decrease (approximately 20%) in the area under the concentration-time curve (AUC) and a decrease in the cumulative excretion of furosemide without changing the renal clearance of furosemide.

The co-administration of furosemide and nimesulide requires caution in patients with impaired renal or cardiac function.

ACE inhibitors and angiotensin-II receptor antagonists

NSAIDs may decrease the effect of antihypertensive drugs. In patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min) when ACE inhibitors, angiotensin II receptor antagonists or substances that inhibit cyclooxygenase system (NSAIDs, antiaggregants) are prescribed together, further deterioration of renal function and acute renal failure may occur, which is usually reversible. These interactions should be considered in patients taking Nimesil in combination with ACE inhibitors or angiotensin I receptor antagonists. Patients should receive sufficient fluids, and renal function should be carefully monitored after initiation of coadministration.

Pharmacokinetic interactions with other drugs:

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

Clinically significant interactions with glibenclamide, theophylline, digoxin, cimetidine and antacids (e.g., aluminum and magnesium hydroxide combination) have not been observed.

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

When nimesulide is administered less than 24 hours before or after methotrexate administration, caution is required, because in these cases, the plasma levels of methotrexate and, accordingly, the toxic effects of this drug may increase. Because of action on renal prostaglandins, inhibitors of prostaglandin synthetases, such as nimesulide, may increase nephrotoxicity of cyclosporines.

Interaction of other drugs with nimesulide :

In vitro studies have shown that nimesulide is displaced from binding sites by tolbutamide, salicylic acid and valproic acid. Although these interactions were determined in plasma, these effects were not observed during clinical use of the drug.

Special Instructions

Contraindications

With caution: severe forms of arterial hypertension, type 2 diabetes, heart failure, coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, peripheral artery disease, smoking, creatinine clearance less than 60 ml/min.

Anamnestic evidence of peptic ulcer disease, infection with Helicobacter pylori; older age; long-term prior use of NSAIDs; severe medical conditions.

Companion therapy 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). The decision to prescribe Nimesil® should be based on an individual risk-benefit assessment of the drug.

Side effects

The frequency is classified according to the headings, depending on the occurrence of the case: very often (>10), often (< 10-< 100), infrequently (< 100-< 1000), rarely (< 1000-< 10000), very rarely (< 10000).

Blood and lymphatic system disorders: rarely – anemia, eosinophilia, hemorrhages; very rarely – thrombocytopenia, pancytopenia, thrombocytopenic purpura.

Allergic reactions: infrequent – itching, rash, increased sweating; rare – hypersensitivity reactions, erythema, dermatitis; very rare – anaphylactoid reactions, urticaria, angioedema, polyform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome).

Disorders of the central nervous system: infrequent – dizziness; rarely – fear, nervousness, nightmares; very rarely – headache, somnolence, encephalopathy (Reye’s syndrome).

Sensory organ disorders: rarely – blurred vision.

Cardiovascular system disorders: infrequent – arterial hypertension, tachycardia, blood pressure lability, “hot flashes”.

Respiratory system disorders: infrequently – shortness of breath; very rarely – exacerbation of bronchial asthma, bronchospasm.

Disorders of the gastrointestinal tract: often – diarrhea, nausea, vomiting; infrequently – constipation, flatulence, gastritis; very rarely – abdominal pain, dyspepsia, stomatitis, tarry stools, gastrointestinal bleeding, ulcer and/or perforation of the stomach or duodenum.

Liver and biliary system disorders:very rarely – hepatitis, lightning hepatitis, jaundice, cholestasis, increased activity of liver enzymes.

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

General disorders: rarely – malaise, asthenia; very rarely – hypothermia.

Others: rarely – hyperkalemia.

Overdose

Similarities