Instructions Termidol capsules 400 mg blister No. 36
Composition
active ingredient: ibuprofen;
1 capsule contains 200 mg or 400 mg of ibuprofen;
excipients: polyethylene glycol (macrogol), potassium hydroxide, purified water;
capsule shell: gelatin; sorbitol liquid, partially dehydrated (E 420).
Dosage form
Soft capsules.
Main physicochemical properties: soft gelatin capsules of oval shape, with a seam, transparent, light yellow-brown color. The contents of the capsule are a transparent, colorless or slightly yellowish, viscous liquid.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. ATC code M01A E01.
Pharmacological properties
Pharmacodynamics.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated its effectiveness in inhibiting the synthesis of prostaglandins - mediators of pain and inflammation. Ibuprofen has analgesic, antipyretic and anti-inflammatory effects. In addition, ibuprofen reversibly inhibits platelet aggregation.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when these drugs are used concomitantly. Some pharmacodynamic studies have shown that when single doses of ibuprofen 400 mg were administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), a reduction in the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although there is uncertainty about the extrapolation 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 non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely.
Pharmacokinetics.
When taken orally, ibuprofen is rapidly absorbed, partly in the stomach and then completely in the small intestine.
After metabolism in the liver (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are completely excreted, mainly in the urine (90%), as well as in the bile.
The elimination half-life in healthy volunteers, as well as in patients with liver and kidney diseases, is 1.8–3.5 hours. Plasma protein binding is approximately 99%. With oral administration of the usual release dosage form, maximum plasma concentration is reached after 1–2 hours. Ibuprofen is detected in plasma for more than 8 hours after administration.
Indication
Symptomatic treatment of mild to moderate pain of various origins (headache, toothache, painful menstruation), including colds and fever.
Contraindication
Hypersensitivity to ibuprofen or to any of the components of the drug;
hypersensitivity reactions (e.g. bronchial asthma, rhinitis, angioedema or urticaria) previously observed after using ibuprofen, acetylsalicylic acid or other NSAIDs;
active or recurrent gastric ulcer/bleeding (two or more severe episodes of ulcer or bleeding);
history of gastrointestinal bleeding or perforation associated with the use of NSAIDs;
severe hepatic impairment, severe renal impairment, severe heart failure (NYHA class IV);
children weighing less than 20 kg (for a dose of 200 mg);
children weighing less than 40 kg or children under 12 years of age;
the last trimester of pregnancy;
cerebrovascular or other bleeding in the active phase;
hemorrhagic diathesis or blood clotting disorder;
hematopoietic disorders of unknown etiology;
severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake);
The use of the drug simultaneously with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, is contraindicated.
Interaction with other medicinal products and other types of interactions
Ibuprofen, like other NSAIDs, should not be used in combination with:
Acetylsalicylic acid, as this may increase the risk of adverse reactions, except in cases where acetylsalicylic acid (dose not exceeding 75 mg per day) has been prescribed by a doctor.
Experimental data suggest that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. However, the limitations of extrapolation of these data to the clinical situation prevent definitive conclusions that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Such clinically significant effects are considered unlikely with non-systematic use of ibuprofen.
Other NSAIDs, including selective COX-2 inhibitors:
The simultaneous use of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin.
Antihypertensives (ACE inhibitors and angiotensin II antagonists) 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 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 the elderly. 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. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium monitoring is recommended);
corticosteroids: increased risk of ulcers and bleeding in the gastrointestinal tract;
Antiplatelet agents and selective serotonin reuptake inhibitors: the risk of gastrointestinal bleeding may increase;
cardiac glycosides: NSAIDs can exacerbate cardiac dysfunction, reduce glomerular filtration function of the kidneys, and increase the level of glycosides in blood plasma;
digoxin: the blood plasma level of both drugs increases;
Lithium: there is evidence of a potential increase in plasma lithium levels;
Methotrexate: use of ibuprofen within 24 hours before or after administration of methotrexate may lead to increased concentrations of methotrexate and increased toxicity;
cyclosporine: increased risk of nephrotoxicity;
Mifepristone: NSAIDs should not be used earlier than 8-12 days after mifepristone administration, as they may reduce its effectiveness;
Tacrolimus: possible increased risk of nephrotoxicity with simultaneous use of NSAIDs and tacrolimus;
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.
quinolone antibiotics: simultaneous administration with ibuprofen may increase the risk of seizures;
Sulfonylurea: with concomitant use, it is recommended to check blood glucose values as a precautionary measure;
probenecid and sulfinpyrazone: may delay the excretion of ibuprofen;
Phenytoin: simultaneous use with phenytoin drugs may increase its serum level;
CYP2C9 inhibitors: Concomitant use of ibuprofen with CYP2C9 inhibitors may increase the exposure of ibuprofen (CYP2C9 substrate); a study with voriconazole and fluconazole (CYP2C9 inhibitors) showed an increase in exposure of S (+)-ibuprofen by approximately 80-100%; a reduction in the ibuprofen dose should be considered when potent CYP2C9 inhibitors are used concomitantly, especially when high doses of ibuprofen are used with voriconazole or fluconazole.
Application features
The side effects of ibuprofen and the entire group of NSAIDs in general can be reduced by using the minimum effective dose necessary to treat symptoms for the shortest period of time.
Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
Caution should be exercised when treating patients with:
effects on the respiratory system – in patients who suffer from bronchial asthma or allergic diseases or have a history of these diseases, bronchospasm may occur;
effects on the cardiovascular and cerebrovascular system - patients with a history of hypertension and/or heart failure (see sections "Contraindications" and "Adverse Reactions") should start treatment with caution (doctor's consultation is required), since cases of fluid retention, hypertension and edema have been reported with ibuprofen therapy, as with other NSAIDs.
It is known from clinical trials and epidemiological data that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g. ≤1200 mg per day) may lead to an increased risk of arterial thrombotic events.
The clinical picture should also be carefully assessed before starting long-term treatment in patients with risk factors for cardiovascular complications (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required;
effects on the kidneys – in patients with impaired renal function, as renal function may deteriorate (see sections “Contraindications” and “Adverse reactions”);
effect on the liver – impaired liver function (see sections “Contraindications” and “Adverse reactions”);
effects on the digestive system - in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease (see section "Adverse reactions")), as these conditions may be exacerbated. There are reports of cases of gastrointestinal bleeding, perforation, ulcers, possibly fatal, occurring at any stage of treatment with NSAIDs, regardless of the presence of warning symptoms or the presence of severe gastrointestinal disorders in history.
The risk of gastrointestinal bleeding, perforation, and ulceration increases with increasing doses of NSAIDs, in patients with a history of ulcer, especially complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment with minimal doses. For such patients, as well as for those who require concomitant use of low-dose acetylsalicylic acid or other drugs that may increase the risk for the gastrointestinal tract, the need for combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered.
Patients with a history of gastrointestinal disorders, especially elderly patients, should be informed of any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.
Caution should be exercised when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (e.g. acetylsalicylic acid).
In the event of gastrointestinal bleeding or ulceration in patients receiving ibuprofen, treatment should be discontinued immediately;
Skin reactions – Very rarely, severe skin reactions, which can be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with NSAIDs. The risk of these reactions is highest early in treatment; in most cases, the onset of these reactions occurs within the first month of treatment. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
In exceptional cases, chickenpox can cause severe skin and soft tissue infections. It is not yet possible to exclude the possibility that NSAIDs may worsen these infections, and it is therefore recommended that ibuprofen be avoided in the event of chickenpox;
Effects on female fertility – there is limited evidence that long-term use of cyclooxygenase/prostaglandin synthesis inhibitors (applies to doses of 2400 mg per day and treatment durations exceeding 10 days) may impair female fertility by affecting ovulation. This is reversible after discontinuation of treatment.
with other NSAIDs - simultaneous use of ibuprofen with other NSAIDs, including selective COX-2 inhibitors, increases the risk of adverse reactions, so it should be avoided;
systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (see section "Adverse reactions");
congenital disorder of porphyrin metabolism – for example, acute intermittent porphyria;
surgical intervention – after extensive surgical interventions;
allergic reactions – in patients who have allergic reactions to other substances, as such patients are also at increased risk of developing hypersensitivity reactions when using ibuprofen.
In patients who suffer from hay fever, nasal polyps, chronic obstructive respiratory diseases or have a history of allergic diseases, as they are at increased risk of allergic reactions; they may have asthma attacks (so-called analgesic asthma); angioedema or urticaria.
The medicine contains sorbitol, therefore, if you have been told that you have an intolerance to some sugars, consult your doctor before taking this medicine.
Other: Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed very rarely. At the first signs of a hypersensitivity reaction after administration of the medicinal product, therapy should be discontinued. In such cases, both symptomatic and specialized therapy should be administered.
Ibuprofen may temporarily inhibit platelet function (affect platelet aggregation). Therefore, it is recommended to carefully monitor the condition of patients with blood clotting disorders.
Long-term use of any painkiller for headache may worsen this condition. If this condition is suspected or confirmed, consult a doctor and discontinue treatment. A diagnosis of medication overuse headache should be considered in patients who suffer from frequent or daily headaches despite (or because of) regular use of headache medications.
Habitual use of analgesic drugs, especially combinations of several analgesics, may lead to persistent renal impairment with the risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration.
There is a risk of kidney dysfunction in children and adolescents with dehydration.
When using NSAIDs with simultaneous alcohol consumption, the risk of adverse effects associated with the active substance may increase, especially from the gastrointestinal tract or central nervous system.
NSAIDs can mask symptoms of infection and fever.
Use during pregnancy or breastfeeding
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects and gastroschisis following exposure to prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of therapy.
NSAIDs should not be taken during the first two trimesters of pregnancy unless, in the opinion of the physician, the expected benefit to the patient outweighs the possible risk to the fetus. If ibuprofen is used by a woman attempting to conceive, or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible period of time.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose the following risks:
for the fetus: cardiopulmonary toxicity (characterized by premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure, accompanied by oligohydramnios;
for the mother and the newborn, at the end of pregnancy: possible increase in bleeding time, antiplatelet effect, which may develop even at very low doses; inhibition of uterine contractions, leading to delay or prolongation of labor. Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.
Breastfeeding: In limited studies, ibuprofen has been found in breast milk at very low concentrations, so it is unlikely that it would have any adverse effects on a breastfed infant. NSAIDs are not recommended during breastfeeding.
Fertility: The use of ibuprofen may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, the use of ibuprofen is not recommended in women who have difficulty conceiving.
Ability to influence reaction speed when driving vehicles or other mechanisms
If you experience dizziness, drowsiness or visual disturbances while taking ibuprofen, you should avoid driving or operating other machinery. Single use of ibuprofen or its use for a short period usually does not require any special precautions. This mainly applies to the simultaneous use of the drug with alcohol.
When used in accordance with the recommended doses and duration of treatment, the drug does not affect the reaction speed when driving or working with other mechanisms.
Method of administration and doses
Administer orally to adults and children over 12 years of age weighing 40 kg or more. A single dose for children over 12 years of age weighing 40 kg or more and adults is 1 capsule of 400 mg ibuprofen. If necessary, 1 capsule can be taken every 6 hours. The maximum daily dose is 1200 mg (3 capsules per day). Use the minimum effective dose necessary to treat symptoms for the shortest possible period of time.
For short-term use only.
Children weighing 20 to 29 kg: the recommended starting dose is 1 capsule of 200 mg ibuprofen. The maximum daily dose is 3 capsules (equivalent to 600 mg ibuprofen).
Children weighing 30 to 39 kg: The recommended starting dose is 1 capsule of 200 mg ibuprofen. The maximum daily dose is 4 capsules (equivalent to 800 mg ibuprofen). Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms.
Capsules should be taken preferably during or after meals, without chewing and with water.
Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic insufficiency. Due to the possibility of developing undesirable effects, elderly patients should be monitored especially carefully.
If in adults, symptoms of fever persist for more than 3 days and pain treatment lasts for 4 days or the symptoms of the disease worsen, you should consult a doctor to clarify the diagnosis and adjust the treatment regimen.
Patients with mild to moderate renal impairment do not require dose reduction (patients with severe renal impairment, see section "Contraindications").
No dose reduction is required in patients with mild or moderate hepatic impairment (patients with severe hepatic impairment, see section "Contraindications").
The duration of treatment is determined by the doctor individually, depending on the course of the disease and the patient's condition.
Children.
200 mg capsules – not for use in children weighing less than 20 kg.
400 mg capsules – not for use in children under 12 years of age and weighing less than 40 kg.
Overdose
The use of the drug in children in doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the dose effect is less pronounced. The half-life in case of overdose is 1.5–3 hours.
Symptoms. Most patients who have taken clinically significant amounts of NSAIDs have experienced only nausea, vomiting, epigastric pain, and very rarely diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may occur, manifested as vertigo, drowsiness, and sometimes agitation and disorientation or coma. Sometimes patients experience convulsions. In severe poisoning, hyperkalemia and metabolic acidosis may develop, and an increase in prothrombin time/prothrombin index may be observed, possibly due to effects on circulating blood clotting factors. Acute renal failure, liver damage, hypotension, respiratory failure, and cyanosis may develop. In patients with bronchial asthma, exacerbation of the disease may occur.
Treatment. Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring cardiac and 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. Intravenous diazepam or lorazepam should be used for frequent or prolonged seizures. Bronchodilators should be used for the treatment of acute asthma.
There is no specific antidote.
Adverse reactions
The list of adverse reactions observed after treatment with ibuprofen includes all adverse reactions known during short-term use of the drug, as well as those observed during long-term therapy with high doses in patients with rheumatism. The stated frequency of adverse reactions exceeding the "very rare" level mentioned during short-term use of daily doses of the drug with a maximum daily dose of ibuprofen 1200 mg for oral dosage forms.
The development of adverse reactions to the drug depends mainly on the dose and individual characteristics of the body.
The most commonly observed adverse reactions are related to the gastrointestinal tract. Peptic ulcers, perforation or gastrointestinal bleeding may occur, sometimes with fatal outcomes, especially in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported during use of the drug. Gastritis has been reported less frequently.
The risk of gastrointestinal bleeding is mainly dose-related and duration-dependent. There have been reports of oedema, hypertension and heart failure associated with NSAID treatment.
Clinical studies show that the use of ibuprofen, especially at high doses (2400 mg per day), may cause a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Hypersensitivity reactions have been reported:
nonspecific allergic reactions and anaphylaxis;
airway reactivity, such as asthma, asthma exacerbation, bronchospasm, shortness of breath;
various skin reactions, such as itching, urticaria, angioedema, less commonly - exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
The patient should immediately inform the doctor and stop taking the drug if any of the above symptoms occur.
Infections and infestations: Exacerbation of inflammation associated with infection (e.g. development of necrotizing fasciitis), which may coincide with the use of NSAIDs.
Symptoms of aseptic meningitis with stiff neck, headache, nausea, vomiting, fever or confusion have been observed with ibuprofen in patients with existing autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease.
From the blood and lymphatic system: hematopoietic disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
In this case, the patient should be advised to stop using this medicinal product to avoid any self-medication with analgesics or antipyretics, and to consult a doctor.
During long-term therapy, blood counts should be checked regularly.
Immune system disorders: hypersensitivity reactions including urticaria and pruritus, as well as asthma attacks; 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); exacerbation of asthma, bronchospasm.
On the part of the psyche: psychotic reactions, depression.
Nervous system: headache, dizziness, insomnia, anxiety, irritability or increased fatigue.
On the part of the organs of vision: visual impairment.
From the organs of hearing and balance: tinnitus, hearing loss.
From the side of the cardiac system: palpitations, heart failure and myocardial infarction.
From the vascular system: arterial hypertension, vasculitis; edema.
On the part of the digestive tract: dyspepsia, heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, minor blood loss from the gastrointestinal tract, which in exceptional cases can cause anemia; peptic ulcer, perforation or gastrointestinal bleeding, ulcerative stomatitis, exacerbation of colitis and Crohn's disease, gastritis; esophagitis, pancreatitis, formation of intestinal diaphragm-like structures.
The patient should immediately discontinue the drug and consult a doctor if upper abdominal pain or melena or vomiting blood occurs.
Liver: impaired liver function, liver damage, especially in case of prolonged therapy, liver failure, acute hepatitis.
Skin and subcutaneous tissue disorders: various skin rashes; severe forms of skin reactions such as bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), alopecia. In some cases, chickenpox can be a source of serious infectious complications of the skin and soft tissues; rashes accompanied by eosinophilia and systemic symptoms (DRESS syndrome).
Renal and urinary disorders: acute renal failure (papilonecrosis) and increased blood uric acid concentration; increased blood uric acid concentration; edema, especially in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure, therefore, renal function should be regularly checked.
Laboratory tests: decreased hemoglobin level.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 capsules in a blister, 1 blister in a pack.
10 capsules in a blister, 3 blisters in a pack.
12 capsules in a blister, 3 blisters in a pack.
Vacation category
Without a prescription.
Producer
JSC "KYIV VITAMIN FACTORY".
Location of the manufacturer and address of its place of business.
04073, Ukraine, Kyiv, Kopylivska St., 38.
