Instructions Aponil tablets 100 mg blister No. 20
Composition
active ingredient: nimesulide;
1 tablet contains nimesulide 100 mg;
Excipients: docusate sodium; hydroxypropylcellulose; lactose monohydrate; sodium starch glycolate (type A); microcrystalline cellulose; hydrogenated vegetable oil; magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat, round, light yellow tablets with a diameter of approximately 10.5 mm with a score on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A X17.
Pharmacological properties
Pharmacodynamics.
Nimesulide is a nonsteroidal anti-inflammatory drug of the methanesulfonanilide group, which exhibits anti-inflammatory, analgesic and antipyretic effects. The therapeutic effect of nimesulide is due to the fact that it interacts with the arachidonic acid cascade. Nimesulide selectively inhibits COX II (cyclooxygenase II) and suppresses the synthesis of prostaglandins in the focus of inflammation.
Nimesulide inhibits the release of the enzyme myeloperoxidase, and also inhibits the formation of free oxygen radicals, without affecting the processes of phagocytosis and chemotaxis, and inhibits the formation of tumor necrosis factor and other inflammatory mediators.
Pharmacokinetics.
After oral administration, nimesulide is rapidly absorbed from the gastrointestinal tract. The maximum concentration in blood plasma is reached after 2–3 hours. Up to 97.5% of nimesulide binds to blood plasma proteins.
The drug is actively metabolized in the liver with the participation of CYP2C9, a cytochrome P450 isoenzyme. The main product of metabolism is hydroxynimesulide - a pharmacologically active substance. The half-life is from 3.2 to 6 hours. Nimesulide is excreted from the body with urine - about 50% of the dose taken. About 29% of the dose taken is excreted with feces in a metabolized form. Only 1-3% is excreted from the body unchanged. The pharmacokinetic profile in the elderly does not change.
Indication
Treatment of acute pain. Treatment of primary dysmenorrhea.
Nimesulide should only be used as a second-line drug.
The decision to prescribe nimesulide should be made based on an assessment of all risks for the individual patient.
Contraindication
Hypersensitivity to nimesulide or any component of the drug. Hypersensitivity reactions that occurred in the past (bronchospasm, rhinitis, urticaria) in connection with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
Hepatotoxic reactions to nimesulide that have occurred in the past.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
Suspicion of acute surgical pathology.
History of gastrointestinal bleeding or perforation associated with previous use of nonsteroidal anti-inflammatory drugs (NSAIDs).
Gastric or duodenal ulcer in the acute phase, history of ulcer, perforation or bleeding in the digestive tract.
History of cerebrovascular bleeding or other hemorrhages, as well as diseases accompanied by bleeding.
Severe blood clotting disorders.
Severe heart failure.
Severe renal impairment (creatinine clearance < 30 ml/min).
Liver dysfunction.
Elevated body temperature and/or flu-like symptoms in the patient.
Children under 12 years old.
Third trimester of pregnancy and breastfeeding.
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding. Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.
Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or the elderly), the concomitant use of ACE inhibitors, angiotensin II antagonists or agents that inhibit the cyclooxygenase system may lead to further deterioration of renal function and the development of acute renal failure, which is usually reversible. These interactions should be taken into account when the patient is taking nimesulide in combination with ACE inhibitors or angiotensin II antagonists. Great caution should be exercised when using this combination, especially in the elderly. Patients should be adequately hydrated and renal function should be closely monitored after the start of this combination. Nimesulide temporarily reduces the effect of furosemide on sodium excretion, to a lesser extent on potassium excretion, and reduces the diuretic effect. The simultaneous use of furosemide and nimesulide in patients with impaired renal or cardiac function requires caution.
In healthy individuals, nimesulide rapidly reduces the sodium-excreting effect of furosemide and, to a lesser extent, the potassium-excreting effect, and also reduces the diuretic effect. Simultaneous use of nimesulide and furosemide leads to a decrease (by approximately 20%) in the area under the concentration-time curve (AUC) and a decrease in the cumulative excretion of furosemide without changes in the renal clearance of furosemide.
Pharmacokinetic interactions with other drugs.
NSAIDs have been reported to reduce lithium clearance, leading to increased plasma lithium levels and lithium toxicity. When prescribing nimesulide to patients receiving lithium therapy, frequent monitoring of plasma lithium levels should be performed.
There is no clinically significant interaction with glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacids (aluminum and magnesium hydroxide combination) in vivo. Nimesulide inhibits the activity of the CYP2C9 enzyme. When used simultaneously with nimesulide, drugs that are substrates of this enzyme may increase their concentration in the blood plasma.
Caution is required if nimesulide is administered less than 24 hours before or less than 24 hours after taking methotrexate, as it may increase the serum levels of the latter and increase its toxicity.
Due to the effect on renal prostaglandin synthetase inhibitors, to which nimesulide belongs, it is possible to increase the nephrotoxicity of cyclosporines.
The effect of other drugs on nimesulide.
In vitro studies have shown that nimesulide is displaced from its binding sites by tolbutamide, salicylic acid and valproic acid. Although these interactions have been identified in plasma, these effects have not been observed during clinical use of the drug.
Application features
To reduce the risk of side effects, the minimum effective dose should be used for the shortest duration of treatment. If ineffective, therapy should be discontinued.
There have been reports of severe liver reactions, including fatal ones, with the use of nimesulide. In the event of an increase in liver enzyme levels or signs of liver damage (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine), or if laboratory liver function tests are abnormal, the drug should be discontinued. Re-administration of nimesulide to such patients is contraindicated. After short-term use of the drug, reversible liver damage was observed in most cases.
During treatment with nimesulide, it is recommended to avoid the simultaneous use of hepatotoxic drugs, analgesics, other non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, and to refrain from drinking alcohol.
Elderly patients are more likely to develop side effects from taking the drug, including gastrointestinal bleeding, perforation, cardiac, renal and hepatic dysfunction, which can be fatal. Therefore, regular clinical monitoring of the patient's condition is recommended.
Patients with toxic lesions of the digestive tract, especially the elderly, should be informed of any unusual symptoms that occur in the digestive tract, especially bleeding. This is especially important in the initial stages of treatment. Patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed of the need to exercise caution when using nimesulide. In the event of bleeding or ulceration of the digestive tract in patients receiving nimesulide, treatment with the drug should be discontinued.
Gastrointestinal bleeding, ulceration or perforation may occur at any time during treatment with the drug. In this case, concomitant warning symptoms, as well as the presence of a history of previous gastrointestinal diseases, are not always present.
NSAIDs should be prescribed with caution to patients with Crohn's disease or a history of nonspecific ulcerative colitis, as nimesulide may lead to their exacerbation.
Patients with arterial hypertension, patients with a history of heart failure, as well as patients with fluid retention and edema due to the use of NSAIDs require appropriate monitoring and consultation with a doctor. Clinical studies and epidemiological data suggest that some NSAIDs, especially in high doses and with prolonged use, carry a certain risk of arterial thrombotic events, such as myocardial infarction and stroke. There is insufficient data to exclude the risk of such events with the use of nimesulide. Patients with uncontrolled arterial hypertension, acute heart failure, established ischemic heart disease, peripheral artery disease and/or cerebrovascular disease should be prescribed nimesulide after a careful assessment of the condition. Patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, smoking, should also be carefully assessed before prescribing the drug. Patients with renal or heart failure should be prescribed the drug with caution, as renal function may deteriorate. In case of deterioration of the condition, treatment should be discontinued. Since nimesulide may affect platelet function, it should be prescribed with caution to patients with hemorrhagic diathesis. However, nimesulide does not replace acetylsalicylic acid in the prevention of cardiovascular diseases.
The use of nonsteroidal anti-inflammatory drugs may mask fever associated with an underlying bacterial infection. In the event of fever or flu-like symptoms in patients taking nimesulide, the drug should be discontinued.
There have been rare reports of severe skin reactions with NSAIDs, some of which can be fatal, such as: exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Patients are at very high risk of such reactions if they have previously had a reaction during the first month of treatment. Aponil should be discontinued at the first signs of skin rash, mucosal lesions or other allergic manifestations.
Cases of fixed drug eruption (FDE) have been reported with nimesulide. Nimesulide should not be re-administered to patients with a history of FDE associated with nimesulide (see section 4.8).
Nimesulide may impair female fertility and is not recommended for women attempting to conceive. Nimesulide is not recommended for women who are unable to conceive or are undergoing investigation for infertility.
The drug contains lactose, so it should not be used in patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Use during pregnancy or breastfeeding.
Pregnancy. The use of nimesulide is contraindicated in the last trimester of pregnancy.
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or foetal development. Epidemiological data suggest that use of prostaglandin synthesis inhibitors in early pregnancy increases the risk of spontaneous abortion, foetal heart defects and gastroschisis. The absolute risk of cardiovascular malformation increases from less than 1% to approximately 1.5%. The risk is thought to increase with dose and duration of exposure.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis. When used in women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose and duration of treatment should be used.
The use of nimesulide from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of the drug. In addition, narrowing of the ductus arteriosus in the fetus has been observed after administration of the drug in the second trimester of pregnancy, which in most cases disappeared after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, nimesulide should not be taken unless absolutely necessary. If nimesulide is used in women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose and the shortest possible duration of treatment should be used.
It may be advisable to monitor the fetus for oligohydramnios and ductus arteriosus in case of exposure to nimesulide for several days, starting from the 20th week of gestation. Pregnant women should discontinue nimesulide if oligohydramnios or ductus arteriosus is detected.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can lead to the development of the following in the fetus:
pneumocardial toxic lesion (with premature closure of the ductus arteriosus and hypertension in the pulmonary artery system);
renal dysfunction, which may progress to renal failure with the development of oligohydramnios.
In the mother and fetus at the end of pregnancy, it is possible:
increased bleeding time, anti-aggregation effect, which can occur even when using very low doses of the drug;
suppression of uterine contractile activity, which can lead to a delay or prolongation of the period of labor.
Therefore, nimesulide is contraindicated in the third trimester of pregnancy.
Breastfeeding. Since it is not known whether nimesulide passes into breast milk, the use of the drug is contraindicated during breastfeeding.
Fertility: Nimesulide may impair female fertility and is therefore not recommended for use in women attempting to conceive. Women who are unable to conceive or who are undergoing investigation of infertility should consider discontinuing nimesulide. If pregnancy occurs during treatment with nimesulide, the physician should be informed.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect of nimesulide on the ability to drive and perform work requiring increased attention has not been studied. However, patients who experience dizziness or drowsiness after taking nimesulide should refrain from driving and performing work requiring increased attention.
Method of administration and doses
In order to minimize possible unwanted side effects, the minimum effective dose should be used for the shortest possible time.
The maximum duration of the treatment course is 15 days.
Adults: The recommended dose is 100 mg 2 times a day after meals, washed down with sufficient liquid.
Elderly: No dose adjustment is required.
Children over 12 years of age: No dose adjustment is required.
Patients with renal impairment. No dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance 30-80 ml/min). In severe renal impairment (creatinine clearance <30 ml/min), the drug is contraindicated.
Patients with impaired liver function. The use of nimesulide for the treatment of patients with impaired liver function is contraindicated (see "Contraindications").
Children.
The drug is contraindicated in children under 12 years of age.
Overdose
Symptoms of acute overdose with nonsteroidal anti-inflammatory drugs (NSAIDs) are usually limited to the following manifestations: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with supportive therapy. Gastrointestinal bleeding may occur. Less commonly, arterial hypertension, acute renal failure, respiratory depression, coma may occur. There have been reports of anaphylactoid reactions when using therapeutic doses of NSAIDs and in case of overdose. There is no specific antidote. Treatment of overdose is symptomatic and supportive. There is no data on the removal of nimesulide by hemodialysis, but if we take into account the high degree of binding of nimesulide to plasma proteins (up to 97.5%), dialysis is unlikely to be effective. In the presence of symptoms of overdose or after the use of a large dose of the drug within 4 hours after its administration, patients may be prescribed: artificial induction of vomiting and/or administration of activated charcoal (60–100 g for adults), and/or administration of an osmotic laxative. Forced diuresis, increased urine alkalinity, hemodialysis and hemoperfusion may be ineffective due to the high degree of binding of nimesulide to plasma proteins. Kidney and liver function should be monitored.
Side effects
The frequency of side effects was defined as follows: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000), including isolated cases.
From the blood system: rarely - anemia, eosinophilia; very rarely - thrombocytopenia, pancytopenia, purpura.
On the part of the immune system: rarely - hypersensitivity reactions; very rarely - anaphylaxis.
Metabolic disorders: rarely - hyperkalemia.
On the part of the psyche: rarely - feelings of anxiety, nervousness, night terrors.
From the nervous system: infrequently - dizziness; very rarely - headache, drowsiness, encephalopathy (Reye's syndrome).
On the part of the organs of vision: rarely - blurred vision; very rarely - visual impairment.
From the side of the organs of hearing and vestibular apparatus: very rarely - vertigo (dizziness).
From the cardiovascular system: rarely - tachycardia; infrequently - arterial hypertension; rarely - hemorrhage, blood pressure fluctuations, hot flashes.
On the part of the respiratory system: infrequently - shortness of breath; very rarely - asthma, bronchospasm.
On the part of the digestive tract: often - diarrhea, nausea, vomiting; infrequently - constipation, flatulence, gastritis, bleeding in the digestive tract, ulcer and perforation of the duodenum or stomach; very rarely - gastritis, abdominal pain, dyspepsia, stomatitis, black stools.
From the hepatobiliary system: often - increased liver enzymes; very rarely - hepatitis, fulminant hepatitis with fatal outcome, including jaundice, cholestasis.
Skin: often - itching, skin rashes, increased sweating; rarely - erythema, dermatitis; very rarely - urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency unknown - fixed drug rash (see section "Special instructions").
From the urinary system: rarely - dysuria, hematuria; very rarely - urinary retention, renal failure, oliguria, interstitial nephritis.
General disorders: infrequently - edema; rarely - malaise, asthenia; very rarely - hypothermia.
Laboratory indicators: often - increased liver enzymes.
The most common adverse reactions observed with nonsteroidal anti-inflammatory drugs (NSAIDs) are gastrointestinal. Peptic ulcers, perforations or bleeding in the digestive tract may occur, which are sometimes life-threatening, especially in elderly patients. The following adverse reactions have been reported after the use of this group of drugs: nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, black stools, bloody vomiting, ulcerative stomatitis, exacerbation of colitis and Crohn's disease. Gastritis has been observed less frequently. There have been reports of edema, hypertension and heart failure as reactions to the use of NSAIDs. Very rarely, skin reactions such as blistering, Stevens-Johnson syndrome and toxic epidermal necrolysis may occur with the use of NSAIDs. There is evidence that some NSAIDs, especially at high doses and with long-term use, slightly increase the risk of arterial thrombotic complications, such as myocardial infarction or stroke.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging, out of the reach of children.
Packaging
10 tablets in a blister. 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
1. Medochemie LTD (Central Factory).
2. Medochemie Limited.
Location of the manufacturer and address of its place of business
1. 1-10 Constantinoupoleos Street, Limassol, 3011, Cyprus.
2. Agios Athanassios Industrial Area, Michail Irakleous 2, Agios Athanassios, Limassol, 4101, Cyprus / Agios Athanassios Industrial Area, Michail Irakleous 2, Agios Athanassios, Limassol, 4101, Cyprus.
In case of adverse reactions and questions regarding the safety of the drug, please contact us via the feedback form on the website: www.ukraine.medochemie.com
