Instructions for use Affida Fort-nimesulide granules for oral suspension 100 mg sachet 2 g No. 30
Composition
active ingredient: nimesulide;
1 sachet of 2 g of granules contains nimesulide 100 mg;
excipients: cetomacrogol 1000, maltodextrin, citric acid, sucrose, orange flavoring.
Dosage form
Granules for oral suspension.
Main physicochemical properties: straw-yellow granules.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A X17.
Pharmacological properties
Pharmacodynamics.
Affida fort-nimesulide is a nonsteroidal anti-inflammatory drug of the methanesulfonanilide group, which exhibits anti-inflammatory, analgesic and antipyretic effects. The therapeutic effect of the drug is due to the fact that it interacts with the arachidonic acid cascade and reduces the biosynthesis of prostaglandins by inhibiting cyclooxygenase.
Pharmacokinetics.
In the human body, Affida fort-nimesulide is well absorbed when taken orally, reaching a maximum concentration in blood plasma after 2-3 hours. Up to 97.5% of nimesulide binds to plasma proteins. Nimesulide is actively metabolized in the liver with the participation of CYP2C9, an isoenzyme of cytochrome P450. The main metabolite is a parahydroxy derivative, which also has pharmacological activity. 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 elderly patients does not change.
Indication
Treatment of acute pain, 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 the risks for the individual patient.
Contraindication
Known hypersensitivity to nimesulide or any component of the drug. History of hyperergic reactions (bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. History of hepatotoxic reactions to nimesulide.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
History of gastrointestinal bleeding or perforation associated with previous use of nonsteroidal anti-inflammatory drugs.
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.
Liver dysfunction.
Patients with fever and/or flu-like symptoms.
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 (SSRIs): increased risk of gastrointestinal bleeding.
Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin or acetylsalicylic acid, which makes this combination contraindicated in patients with severe coagulation disorders. If such combination therapy cannot be avoided, careful monitoring of blood coagulation parameters is necessary.
Diuretics, angiotensin-converting enzyme 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 elderly patients), 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 considered when the patient uses Affida fort-nimesulide together with ACE inhibitors or angiotensin II antagonists. Great caution should be exercised when using such a combination, especially in elderly patients. Patients should receive sufficient fluids, and renal function should be carefully monitored after the start of such a combination. Nimesulide temporarily weakens the effect of furosemide on the excretion of sodium and, to a lesser extent, the excretion of potassium, and also reduces the diuretic effect. The combined use of furosemide and Affida fort-nimesulide in patients with impaired renal or cardiac function requires caution.
Pharmacokinetic interactions with other drugs.
There have been reports that NSAIDs reduce lithium clearance, leading to increased plasma lithium levels and lithium toxicity. When prescribing Affida fort-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 Affida fort-nimesulide, drugs that are substrates of this enzyme may increase their plasma concentration. Caution is required if nimesulide is prescribed less than 24 hours before or less than 24 hours after taking methotrexate, since it is possible to increase the level of the latter in the blood serum and increase its toxicity.
Due to their effect on renal prostaglandins, synthetase inhibitors, to which nimesulide belongs, may 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
Undesirable side effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms.
If the treatment is ineffective (reduction in symptoms of the disease), therapy with the drug should be discontinued.
During treatment with nimesulide, it is recommended to avoid the simultaneous use of hepatotoxic drugs, as well as to refrain from drinking alcohol. The use of nonsteroidal anti-inflammatory drugs may mask an increase in body temperature associated with a background bacterial infection. In the event of an increase in body temperature or the appearance of flu-like symptoms in patients using nimesulide, the drug should be discontinued.
There have been reports of serious liver reactions during treatment with Affida fort-nimesulide, including fatal cases with nimesulide preparations. Patients who experience symptoms similar to those of liver damage, such as anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine, or patients whose laboratory liver function tests are abnormal, should discontinue the drug. Re-administration of nimesulide to such patients is contraindicated. During treatment with the drug, the patient should refrain from taking other analgesics. Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Patients taking nimesulide who develop flu-like symptoms should discontinue its use.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially possible bleeding and perforation in the digestive tract, which can be fatal.
Ulceration, bleeding or perforation of the digestive tract can be life-threatening, especially if there is a history of similar events in the patient while taking any other NSAIDs (without a prescription). The risk of such events increases with increasing NSAID dose in patients with a history of gastrointestinal ulcer, especially complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be started with the lowest possible effective dose. For these patients, as well as for those taking concomitant low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, combination therapy with protective agents, such as misoprostol or proton pump inhibitors, should be considered.
Patients with toxic lesions of the digestive tract, especially elderly patients, should report 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, selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed of the need to exercise caution when using nimesulide.
If a patient receiving Affida Fort-Nimesulide experiences bleeding or ulcers in the digestive tract, treatment with the drug should be discontinued.
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 a history of hypertension and/or heart failure, as well as patients with fluid retention and edema due to NSAID use, require appropriate monitoring and medical advice.
Clinical trials and epidemiological data suggest that some NSAIDs, especially at high doses and with long-term use, may carry a small risk of arterial thrombotic events, such as myocardial infarction and stroke. There is insufficient data to exclude a risk of such events with nimesulide.
Patients with uncontrolled hypertension, acute heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be prescribed nimesulide after careful assessment of the condition. The same should be done before prescribing the drug to patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, smoking.
Patients with impaired renal function or heart failure should be treated with caution due to the possibility of worsening renal function. If the patient's condition worsens, treatment should be discontinued.
Elderly patients should be carefully monitored for the possibility of bleeding and perforation in the digestive tract, deterioration of renal, hepatic or cardiac function. 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.
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. In most cases, if such reactions occurred during the first month of previously prescribed treatment, the risk of their occurrence in patients is significantly increased. Afida fort-nimesulide should be discontinued at the first signs of skin rash, mucosal lesions and other allergic manifestations.
The use of nimesulide may impair female fertility and is not recommended for women attempting to conceive. Nimesulide is not recommended for women who have difficulty conceiving or who are undergoing investigation for infertility.
Affida fort-nimesulide contains sucrose, therefore it should not be prescribed to patients with hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Use during pregnancy or breastfeeding
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or foetal development. Epidemiological data suggest that the use of prostaglandin synthesis inhibitors in early pregnancy may increase 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.
Nimesulide should not be taken during the first and second trimesters of pregnancy unless clearly necessary. If the drug 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.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can lead to the development of the following in the fetus:
In the mother and fetus at the end of pregnancy, it is possible:
Therefore, nimesulide is contraindicated in the third trimester of pregnancy.
The use of nimesulide may impair fertility in women, so the drug is not recommended for women trying to conceive. For women who experience difficulty conceiving or are undergoing infertility studies, nimesulide should be discontinued.
As an NSAID that inhibits prostaglandin synthesis, nimesulide can cause premature closure of the ductus arteriosus, pulmonary hypertension, oliguria, oligohydramnios. The risk of bleeding, labor weakness and peripheral edema increases. There are isolated reports of renal failure in infants whose mothers used nimesulide at the end of pregnancy. Animal studies have shown atypical reproductive toxicity of the drug, but there are no reliable data on the use of nimesulide in pregnant women. The potential risk for humans has not been determined, therefore, the use of nimesulide in the I and II trimesters of pregnancy is not recommended.
Since it is not known whether nimesulide passes into breast milk, its use is contraindicated during breastfeeding.
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
Studies on the effect of nimesulide on the ability to drive or use machines have not been conducted, but if patients experience headache, dizziness, or drowsiness while taking nimesulide, they should refrain from driving or operating machinery.
Method of administration and doses
To minimize possible unwanted side effects, the minimum effective dose should be used for the shortest possible time. It is recommended to take after meals.
The maximum duration of the treatment course is 15 days.
Adults: 100 mg nimesulide (1 single-dose packet) 2 times a day after meals.
Elderly patients: No dose adjustment is required.
Children over 12 years of age: No dose adjustment is required.
Patients with renal impairment. For patients with mild or moderate renal impairment (creatinine clearance 30-80 ml/min), dose adjustment is not required, while severe renal impairment (creatinine clearance <30 ml/h) is a contraindication to the use of Affida fort-nimesulide.
Dissolve the contents of the packet in a glass of water and take orally.
Children
The use of nimesulide in children under 12 years of age is contraindicated.
Overdose
Symptoms of acute overdose with nonsteroidal anti-inflammatory drugs (NSAIDs) are usually limited to the following: apathy, drowsiness, nausea, vomiting, epigastric pain. These symptoms are usually reversible with supportive therapy. Gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression, coma are possible, but such phenomena occur rarely. There have been reports of anaphylactoid reactions when using therapeutic doses of NSAIDs and in case of their 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 case of symptoms of overdose or after the use of a large dose of the drug within 4 hours after its administration, patients can be prescribed artificial vomiting and/or taking activated charcoal (60-100 g for adults), and/or taking an osmotic laxative. Forced diuresis, increasing urine alkalinity, hemodialysis and hemoperfusion may be ineffective due to the high degree of binding of nimesulide to blood plasma proteins. Kidney and liver function should be monitored.
Adverse reactions
The adverse reaction data presented in the table are obtained from clinical trials and post-marketing studies. The frequency of adverse events is classified as follows: very common (> 1/10); common (> 1/100, but < 1/10); uncommon (> 1/1000, but < 1/100); rare (> 1/10000, but < 1/1000); very rare (< 1/10000), unknown (cannot be estimated from the available data).
| From the circulatory and lymphatic systems | Rarely | Anemia, eosinophilia |
| Very rare | Thrombocytopenia, pancytopenia, purpura | |
| On the part of the immune system | Rarely | Increased sensitivity |
| Very rare | Anaphylaxis | |
| Metabolic | Rarely | Hyperkalemia |
| From the psyche | Rarely | Feelings of fear, nervousness, night terrors |
| From the nervous system | Sometimes | Dizziness |
| Very rare | Headache, drowsiness,
encephalopathy (Reye's syndrome) | |
| From the organs of vision | Rarely | Blurred vision |
| Very rare | Vision disorders | |
| From the side of the hearing aid and labyrinth | Very rare | Vertigo (dizziness) |
| Heart disorders | Rarely | Tachycardia |
| Vascular disorders | Sometimes | Arterial hypertension |
| Rarely | Hemorrhage, blood pressure lability, hot flashes | |
| Respiratory, thoracic and mediastinal disorders | Sometimes | Dyspnea |
| Very rare | Asthma, bronchospasm | |
| From the digestive tract | Often | Diarrhea, nausea, vomiting |
| Sometimes | Constipation, flatulence, gastritis, bleeding in the digestive tract, ulcer and perforation of the duodenum or stomach | |
| Very rare | Abdominal pain, dyspepsia, stomatitis, black stools | |
| Hepatobiliary disorders | Often | Increased liver enzymes |
| Very rare | Hepatitis, fulminant hepatitis, fatal, including jaundice, cholestasis | |
From the skin and its appendages | Sometimes | Itching, rash, increased sweating |
| Rarely | Erythema, dermatitis | |
| Very rare | Urticaria, angioedema, facial edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis | |
| Renal and urinary disorders | Rarely | Dysuria, hematuria, urinary retention |
| Renal failure, oliguria, interstitial nephritis | |
| General disorders and local drug reactions | Sometimes | Edema |
| Rarely | Malaise, asthenia | |
| Very rare | Hypothermia | |
The most common adverse reactions observed with nonsteroidal anti-inflammatory drugs (NSAIDs) are gastrointestinal. Peptic ulcers, perforations or bleeding in the gastrointestinal tract, which can sometimes be life-threatening, especially in elderly patients, may occur. 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.
Clinical and epidemiological studies suggest that some NSAIDs, especially at high doses and with prolonged use, may be associated with a small increased risk of arterial thrombotic events, such as myocardial infarction or stroke.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Packaging
1 sachet or 3, 6, 30, or 999 sachets, connected three by three with a perforation line, in a cardboard box.
Vacation category
According to the recipe.
Producer
Fine Foods and Pharmaceuticals N.T.M. S.P.A./Fine Foods & Pharmaceuticals NTMSPA
Location of the manufacturer and its business address
Via Grignano, 43 - 24041 Brembate (BG), Italy.
Applicant
Delta Medical Promotions AG.
Applicant's location
26 Oetenbachgasse, Zurich 8001, Switzerland.
