Instructions for Imet film-coated tablets 400 mg No. 10
Composition
active ingredient: ibuprofen;
1 film-coated tablet contains 400 mg of ibuprofen;
Excipients: corn starch, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), magnesium stearate, hypromellose, polyethylene glycol 4000, povidone (K 30), titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, oblong tablets, film-coated, with a score line on both sides and embossed with "E" on both sides of the score line on the upper side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives.
ATX code M01A E01.
Pharmacological properties
Pharmacodynamics
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which exerts a directed effect against pain, fever and inflammation by inhibiting the synthesis of prostaglandins, mediators of pain and inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation. Experimental data suggest that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when co-administered. Some pharmacodynamic studies have shown that single doses of ibuprofen 400 mg administered within 8 hours before and within 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduce the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although there is uncertainty about the applicability of these data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With irregular use of ibuprofen, a clinically significant effect is considered unlikely.
Pharmacokinetics
Absorption
When taken orally, ibuprofen is partially absorbed in the stomach and then completely in the small intestine. When taken orally as an extended-release formulation, peak plasma concentrations are reached within 1–2 hours. When taken on an empty stomach, peak serum concentrations can be reached within 45 minutes after administration.
Distribution
Binding to plasma proteins is approximately 99%.
Biotransformation
Ibuprofen is metabolized in the liver (hydroxylation, carboxylation).
Breeding
Pharmacologically inactive metabolites are completely excreted mainly in the urine (90%) and also in the bile. The half-life in healthy people and patients with liver and kidney diseases is 1.8-3.5 hours.
Linearity/nonlinearity
Linear kinetics of ibuprofen were observed at doses of 200 to 400 mg. Non-linear kinetics of the drug were observed at higher doses.
No significant differences in the pharmacokinetic profile are observed in elderly patients.
Indication
Symptomatic treatment of headaches, including migraines, toothaches, dysmenorrhea, neuralgia, back pain, joints, muscles, as well as symptoms of colds and flu.
Contraindication
Hypersensitivity to ibuprofen or to any of the excipients of the drug; hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) previously observed after taking ibuprofen, acetylsalicylic acid or other NSAIDs; active or recurrent gastric ulcer/bleeding in history (two or more severe episodes of ulceration or bleeding); history of gastrointestinal bleeding or perforation associated with the use of NSAIDs; severe hepatic or renal impairment; heart failure (class IV according to the NYHA (New York Heart Association) classification); last trimester of pregnancy (see section "Use during pregnancy or breastfeeding"); cerebrovascular or other bleeding; disorders of blood formation or blood clotting.
Interaction with other medicinal products and other types of interactions
Ibuprofen, like other NSAIDs, should not be used in combination with the following drugs:
Acetylsalicylic acid: The concomitant use of ibuprofen and acetylsalicylic acid is generally not recommended due to the possibility of an increased incidence of adverse reactions.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. However, uncertainty regarding the extrapolation of these data to the clinical situation precludes definitive conclusions that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. A clinically significant effect is unlikely with non-systematic use of ibuprofen.
Ibuprofen should be used with caution in combination with the following drugs:
Anticoagulants: NSAIDs may enhance the therapeutic effect of anticoagulants such as warfarin.
Antihypertensives (ACE inhibitors and angiotensin II antagonists), beta-blockers and diuretics: 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 with compromised renal function), the concomitant use of an ACE inhibitor, beta-blocker or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be administered with caution, especially in elderly patients. If long-term treatment is necessary, the patient should be adequately hydrated and consideration should be given to monitoring renal function at the beginning of the combination treatment and periodically thereafter. Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
Corticosteroids: may increase the risk of ulcers and bleeding in the gastrointestinal tract.
Digoxin, phenytoin, lithium: Concomitant use of ibuprofen with digoxin, phenytoin or lithium may increase the plasma concentrations of these drugs. Monitoring of serum lithium, digoxin and phenytoin concentrations is usually not necessary when used correctly.
Methotrexate: Use of ibuprofen within 24 hours before or after administration of methotrexate may lead to increased concentrations of methotrexate and increased toxic effects.
Zidovudine: There is an increased risk of haematological toxicity when zidovudine is used concomitantly with NSAIDs. There is evidence of an increased risk of haemarthrosis and haematoma in HIV-infected patients with haemophilia when zidovudine is used concomitantly with ibuprofen.
Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma glycoside levels.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Cyclosporine, tacrolimus: increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used earlier than 8–12 days after mifepristone administration, as they reduce its effectiveness.
Quinolone antibiotics: Concomitant use with ibuprofen may increase the risk of seizures.
Sulfonylureas and phenytoin: Clinical studies have shown that NSAIDs interact with antidiabetic drugs (sulfonylureas). Although no interaction between ibuprofen and sulfonylureas has been described, it is recommended to monitor blood sugar levels as a precaution when these drugs are taken concomitantly.
Probenecid and sulfinpyrazone: Medicines containing probenecid or sulfinpyrazone may delay the elimination of ibuprofen from the body.
Application features
Side effects associated with the use of ibuprofen can generally be reduced by using the minimum effective dose necessary to relieve symptoms for the shortest period of time.
Caution should be exercised when treating patients with:
systemic lupus erythematosus and mixed connective tissue disease; gastrointestinal diseases or chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease); arterial hypertension and/or heart failure; renal dysfunction; hepatic dysfunction; immediately after major surgical interventions; blood clotting disorders (ibuprofen may prolong bleeding time).
Effects on the cardiovascular and cerebrovascular systems
Patients with arterial hypertension and/or a history of mild to moderate congestive heart failure should be cautious when initiating long-term treatment (consultation with a doctor is necessary), since, as with other NSAIDs, cases of fluid retention, arterial hypertension and edema have been reported with ibuprofen therapy.
Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration. High doses (2400 mg/day) should be avoided. Patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should also be treated long-term only after careful consideration, especially if high doses of ibuprofen (2400 mg/day) are required.
Effects on the respiratory system
Bronchospasm may occur in patients who suffer from bronchial asthma or allergic diseases or have a history of these diseases.
Other NSAIDs
Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should be avoided.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Ibuprofen should be used with caution in SLE and mixed connective tissue diseases due to the increased risk of aseptic meningitis.
Effects on the kidneys
Long-term use of NSAIDs can lead to a dose-dependent decrease in prostaglandin synthesis and provoke the development of renal failure. Patients with impaired renal function, cardiac disorders, impaired liver function, patients taking diuretics, and elderly patients are at high risk of this reaction. In such patients, renal function should be monitored.
Children and adolescents with dehydration are at risk of developing kidney failure.
Effect on the liver
Caution should be exercised when treating patients with impaired liver function.
Impact on fertility in women
There is limited evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. This is reversible after discontinuation of treatment. Long-term use (at doses of 2400 mg/day and for treatment durations exceeding 10 days) of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation for infertility, the drug should be discontinued.
Effects on the gastrointestinal tract
NSAIDs should be used with caution in patients with chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated. Gastrointestinal bleeding, ulceration or perforation, which may be fatal, have been reported at any time during NSAID treatment, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs in patients with a history of ulcer, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the minimum dose. Caution should be exercised in patients receiving concomitant medications that may increase the risk of gastrotoxicity or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin) or antiplatelet agents (e.g. acetylsalicylic acid). In long-term treatment for these patients, as well as for patients who require concomitant low-dose acetylsalicylic acid or other drugs that may increase the risk for the gastrointestinal tract, the physician should consider prescribing combination therapy with misoprostol or proton pump inhibitors.
Patients with a history of gastrointestinal disorders, especially elderly patients, should report any unusual gastrointestinal symptoms (predominantly bleeding), especially gastrointestinal bleeding at the beginning of treatment. In the event of gastrointestinal bleeding or ulceration in patients receiving ibuprofen, treatment should be discontinued immediately.
Severe skin reactions
Rare serious skin reactions, which may be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs. The risk of these reactions is highest at the beginning of therapy. The onset of the reaction occurs in most cases within the first month of treatment. A case of acute generalized exanthematous pustulosis (AGEP) has also been reported after the use of ibuprofen-containing medicinal products. Ibuprofen should be discontinued at the first sign of skin rash, mucosal lesions or any other sign of hypersensitivity.
Prolonged use of any painkiller used for headaches may lead to their intensification. In such a situation, the patient should consult a doctor, and the drug should also be discontinued. A diagnosis of medication overuse headache can be assumed in patients who have frequent or daily headaches despite or as a result of regular painkiller use.
Masking the symptoms of underlying infections
Imet® may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment and thereby complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When Imet® is used for fever or to relieve pain in an infection, monitoring for the infectious disease is recommended. In the case of home treatment, the patient should consult a doctor if symptoms persist or worsen (see also section “Adverse reactions. Infections and infestations”).
In exceptional cases, chickenpox can cause serious skin and soft tissue infections. It is currently not possible to completely exclude the possibility of an association between the use of NSAIDs and the worsening of such infections. Therefore, it is advisable to avoid the use of ibuprofen in case of chickenpox.
With simultaneous use of alcohol during treatment with NSAIDs, the risk of adverse reactions associated with the active substance, in particular from the gastrointestinal tract or central nervous system, may increase.
Ability to influence reaction speed when driving vehicles or other mechanisms
When used in accordance with the recommended doses and duration of treatment, the drug does not affect the speed of reaction when driving or operating other mechanisms. Patients who experience dizziness, drowsiness, disorientation or visual disturbances while taking NSAIDs should refrain from driving or operating mechanisms. These phenomena are exacerbated when the drug is combined with alcohol.
Use during pregnancy or breastfeeding
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects and gastroschisis following exposure to prostaglandin synthesis inhibitors during early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is thought to increase with dose and duration of treatment. In animals, the use of prostaglandin synthesis inhibitors has been associated with an increased incidence of pre- and post-implantation loss and embryo/foetal lethality. In addition, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.
Ibuprofen should not be taken during the first two trimesters of pregnancy unless clearly necessary. Women trying to conceive or during the first and second trimesters of pregnancy should use the lowest possible dose of ibuprofen for the shortest possible period of time.
In the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may carry risks for the fetus such as cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension) and renal dysfunction, which may progress to renal failure with oligohydramnios; for the mother at the end of pregnancy and the newborn - increased bleeding time, antiplatelet effect, which may occur even at very low doses; inhibition of uterine contractions, which leads to a delay or increase in the duration of labor. In this regard, ibuprofen is contraindicated in the third trimester of pregnancy.
In studies, ibuprofen has been found in breast milk in very small amounts, so it is unlikely that it would have any negative effects on a breastfed infant.
Method of administration and doses
For oral administration for short-term use.
Adults and children aged 12 and over
The drug should be taken 1 tablet every 4 hours. The tablets should be swallowed whole with plenty of liquid, during or after meals.
Do not take more than 3 tablets in 24 hours. The maximum daily dose is 1200 mg.
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time necessary to relieve symptoms (see also section "Special instructions").
If complaints persist for more than 3 days in children and more than 4 days when treating pain in adults, you should consult a doctor.
Patients with sensitive stomachs are recommended to take Imet® with meals.
Elderly patients do not require special dosage.
Patients with mild or moderate renal and hepatic impairment do not require dose adjustment.
Children
Do not use in children under 12 years of age.
Overdose
In children, the use of more than 400 mg/kg of ibuprofen may cause symptoms of intoxication. In adults, the dose-response effect is less pronounced. The half-life in overdose is 1.5–3 hours.
Symptoms
In most patients in clinical trials, the use of significant amounts of NSAIDs caused only nausea, vomiting, epigastric pain or, very rarely, diarrhea. Tinnitus, headache, dizziness and gastrointestinal bleeding may also occur. In more severe poisoning, toxic lesions of the central nervous system may occur, which manifest as drowsiness, nystagmus, visual disturbances, sometimes - an excited state and disorientation or coma. Sometimes patients experience convulsions. In severe poisoning, hyperkalemia and metabolic acidosis, acute renal failure, liver damage, arterial hypotension, respiratory failure and cyanosis may occur. In patients with bronchial asthma, exacerbation of the course of asthma may occur.
Treatment
Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring vital signs until the condition returns to normal. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour of ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkaline agents may be administered to accelerate the excretion of acidic ibuprofen in the urine.
In case of frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. In case of bronchial asthma, bronchodilators should be used.
Adverse reactions
Gastrointestinal reactions are the most common and are mostly dose-dependent. Adverse reactions are least common when the maximum daily dose is 1200 mg.
Clinical trial data suggest that the use of ibuprofen, especially at high doses (2400 mg per day), slightly increases the risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
Adverse reactions occurring with ibuprofen are classified by organ system and frequency of occurrence: very common (> 1/10), common (> 1/100 - < 1/10), uncommon (> 1/1000 - < 1/100), rare (> 1/10000 - < 1/1000), very rare (< 1/10000) and frequency unknown (cannot be estimated due to limited available data).
Heart disorders
Very rare: palpitations, heart failure, myocardial infarction.
Digestive tract disorders
Common: gastrointestinal complaints such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation and minor gastrointestinal bleeding, which in exceptional cases may cause anaemia.
Uncommon: gastrointestinal ulcers with the possibility of bleeding and perforation (sometimes fatal, especially in elderly patients), ulcerative stomatitis, exacerbation of colitis and Crohn's disease, gastritis.
Very rare: esophagitis, pancreatitis, formation of diaphragmatic intestinal strictures.
Frequency unknown: dyspepsia, melena, hematemesis, jaundice.
Nervous system disorders
Uncommon: central nervous system disorders such as headache, dizziness, insomnia, agitation, irritability or fatigue.
Rare: vertigo.
Very rare: aseptic meningitis (see below), some symptoms of which (rigidity of the neck muscles, headache, nausea, vomiting, fever or disorientation) may occur in patients with existing autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease.
Frequency unknown: paresthesia, drowsiness.
Kidney and urinary system disorders
Very rare: acute renal failure, papillary necrosis, especially with prolonged use, associated with increased blood urea levels and edema, hypernatremia (sodium retention), scanty urination.
Frequency unknown: renal failure, nephrotoxicity including interstitial nephritis and nephrotic syndrome.
Hepatobiliary disorders
Very rare: liver dysfunction, liver damage, especially with long-term therapy, liver failure, acute hepatitis.
Vascular disorders
Very rare: arterial hypertension.
Frequency unknown: arterial thrombosis (myocardial infarction or stroke).
Skin and subcutaneous tissue disorders
Rare: various skin rashes.
Very rare: severe forms of skin reactions such as Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis, hair loss.
Frequency unknown: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, acute generalized exanthematous pustulosis (AGEP).
Blood and lymphatic system disorders
Very rare: anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur with prolonged treatment, the first signs of which are fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
Mental disorders
Rare: mental disorders, depression, insomnia, agitation, hallucinations, confusion.
Uncommon: with prolonged treatment, visual disturbances and optic neuritis may occur.
Hearing and labyrinth disorders
Rare: with prolonged treatment, ringing in the ears and dizziness are possible.
Immune system disorders
Uncommon: hypersensitivity reactions accompanied by skin rash, urticaria and itching, as well as asthma attacks (in some cases with a decrease in blood pressure).
Very rare: severe hypersensitivity reactions, symptoms of which may include swelling of the face, tongue and larynx, shortness of breath, tachycardia, hypotension, anaphylactic reactions, angioedema or severe shock.
Frequency unknown: airway reactivity, including bronchial asthma, asthma exacerbation, bronchospasm.
Infections and infestations
Very rare: Exacerbations of inflammation associated with infection (e.g. development of necrotizing fasciitis) have been described in association with the use of NSAIDs. This may be related to the mechanism of action of NSAIDs.
If signs of infection occur or worsen while taking ibuprofen, the patient is advised to seek immediate medical attention. It should be checked whether anti-infective/antibacterial therapy is indicated.
General disorders
Malaise and fatigue, irritability.
Laboratory studies
Very rare: decreased hemoglobin level.
Description of selected adverse reactions
Hypersensitivity reactions have been reported following treatment with ibuprofen. These include non-specific allergic reactions and anaphylaxis, respiratory tract reactions including bronchial asthma, exacerbation of asthma, bronchospasm or dyspnoea, various skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema, and less commonly exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
The mechanism of pathogenesis of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (due to temporal association with drug intake and resolution of symptoms after drug withdrawal). In particular, isolated cases of symptoms of aseptic meningitis (such as neck stiffness, headache, nausea, vomiting, fever or disorientation) have been reported during ibuprofen treatment of patients with autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
No special storage conditions are required. Keep the medicine out of the reach of children.
Packaging
10 tablets in a blister; 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
BERLIN-CHEMI AG.
Location of the manufacturer and its business address
Glienicker Weg 125, 12489 Berlin, Germany.
