Pharmacological properties
Pharmacodynamics. combined drug, the effect of which is due to the components included in its composition. the drug exhibits analgesic (pain-relieving), anti-inflammatory, antipyretic effects. inhibits the synthesis of prostaglandins. reduces pain in the joints at rest and during movement, reduces morning stiffness and swelling of the joints, helps to increase the volume of movements.
Caffeine enhances the analgesic effect of ibuprofen and paracetamol, increases performance, and reduces fatigue and drowsiness.
Pharmacokinetics. Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. C max in blood plasma is reached 30-60 min after administration, and T ½ is 1-4 h after the use of therapeutic doses. In case of severe liver failure, it increases to 5 h. In renal failure, T ½ does not increase, however, since renal excretion is limited, the dose of paracetamol must be reduced.
Paracetamol penetrates the blood-brain barrier and also into breast milk.
Ibuprofen is rapidly absorbed from the gastrointestinal tract after oral administration. Cmax in blood plasma is reached 45 min after administration, in synovial fluid - 3 hours after administration. Ibuprofen is metabolized in the liver, excreted by the kidneys in unchanged form and as metabolites. T½ - about 2 hours.
After oral administration, caffeine is absorbed. C max in blood plasma is reached after approximately 20-60 min, T ½ - approximately 4 h.
Indication
Pain syndrome of varying intensity: dysmenorrhea and menstrual pain; headache; neuralgia; myalgia; arthralgia; toothache. increased body temperature (fever with flu and colds). as part of the complex treatment of postoperative pain, reducing the severity of symptoms of rheumatoid arthritis and osteoarthritis.
Application
Adults and adolescents over 16 years of age should take 1-2 capsules every 4-6 hours, depending on the intensity of the pain syndrome and the doctor's recommendations. The daily dose should not exceed 6 capsules. Children aged 12 to 16 years: 1 capsule 1-2 times a day. The capsule should be taken without chewing, with sufficient liquid (a glass of water). Usually the duration of treatment is 3-7 days. If there is no improvement during this time, the treatment should be reviewed.
The maximum period of use in children without consulting a doctor is 3 days. The interval between doses is at least 4 hours. Do not exceed the recommended dose.
Contraindication
Hypersensitivity to paracetamol, ibuprofen, caffeine or any component of the drug, gastric ulcer, including a history (2 or more clear episodes of exacerbation of gastrointestinal ulcer or bleeding), bleeding in the upper digestive tract or a history of perforation associated with previous treatment with NSAIDs; acute pancreatitis, severe liver and / or kidney dysfunction, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood diseases, severe anemia, leukopenia, thrombosis, thrombophlebitis, in states of increased excitement; sleep disorders; severe hypertension; organic diseases of the cardiovascular system; glaucoma; epilepsy, hyperthyroidism, decompensated heart failure, cardiac conduction disorders, severe atherosclerosis, tendency to vasospasm, coronary artery disease, prostatic hypertrophy, severe forms of diabetes mellitus, allergic reaction (e.g., barium, rhinitis, angioedema) after using acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, use of the drug simultaneously with nonsteroidal anti-inflammatory drugs, advanced age.
Do not use simultaneously with MAO inhibitors, COX-2 and within 2 weeks after stopping their use; contraindicated in patients taking tricyclic antidepressants or β-adrenergic blockers. Gilbert's syndrome. Age up to 12 years.
Side effects
The following adverse drug reactions are classified according to MedDRA terminology.
General disorders: hypersensitivity in the form of urticaria and itching; severe hypersensitivity reactions with the following manifestations: swelling of the face, tongue and larynx, shortness of breath, tachycardia, arrhythmia, decrease or increase in blood pressure, anaphylaxis, Quincke's edema, hepatorenal syndrome, exacerbation of asthma and bronchospasm.
From the blood and lymphatic system: hematopoietic disorders, agranulocytosis, anemia (including hemolytic and aplastic), decreased hematocrit and hemoglobin levels, sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, heart pain), leukopenia, neutropenia, pancytopenia, thrombocytopenia. The first signs are: high fever, sore throat, mouth ulcers, flu symptoms, severe exhaustion, unexplained bleeding and bruising.
Gastrointestinal disorders: abdominal pain, heartburn, ulcerative stomatitis, dyspepsia and nausea; diarrhea, flatulence, constipation and vomiting, pancreatitis, duodenitis, esophagitis; peptic ulcer, perforation or gastrointestinal bleeding, which can in some cases be fatal, especially in the elderly; exacerbation of ulcerative colitis and Crohn's disease.
Neurological disorders: headache, dizziness, irritability, nervousness, depression, drowsiness, insomnia, anxiety, psychomotor agitation, emotional instability, convulsions; aseptic meningitis.
From the sensory organs: hearing impairment, hearing loss, ringing or noise in the ears, blurred vision, change in color perception, toxic amblyopia.
Respiratory system: bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs.
On the part of the endocrine system and metabolism: hypoglycemia, up to hypoglycemic coma; decreased appetite; dryness of the mucous membranes of the eyes and oral cavity; rhinitis.
On the part of the digestive system: liver disorders; increased activity of liver enzymes, usually without the development of jaundice; hepatonecrosis (dose-dependent effect), liver failure.
On the part of the immune system: in patients with autoimmune disorders (systemic lupus erythematosus, systemic connective tissue disease) during treatment with ibuprofen, isolated cases of symptoms of aseptic meningitis were observed, namely: stiffness of the occipital muscles, headache, nausea, vomiting, fever and disorientation.
Skin and subcutaneous tissue disorders: allergic skin reactions, rash, purpura, skin peeling, itching, alopecia, photosensitivity; angioedema, severe skin reactions such as erythema multiforme (including Stevens-Johnson syndrome) and epidermal necrolysis.
Taking the drug at recommended doses with products containing caffeine may increase caffeine-related side effects, such as:
mental disorders: headache, dizziness, increased excitability, anxiety, irritability, rapid heartbeat, restlessness, insomnia due to CNS stimulation;
Gastrointestinal: nausea caused by gastrointestinal irritation.
Special instructions
In patients with impaired liver function, as well as in those taking paracetamol for a long time, it is recommended to regularly perform liver function tests. If the patient uses warfarin or similar drugs that have an anticoagulant effect, a doctor should be consulted before using the drug. Patients who take daily analgesics for mild arthritis should consult a doctor before using the drug. In patients with severe infections such as sepsis, which are accompanied by a decrease in glutathione levels, the risk of metabolic acidosis may increase when taking paracetamol. Symptoms of metabolic acidosis are deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should immediately consult a doctor if these symptoms occur. It is recommended to determine the prothrombin time when using oral anticoagulants and high doses of paracetamol. Alcohol should be avoided during treatment. Patients should be warned not to use other paracetamol-containing drugs at the same time.
Taking paracetamol may affect the results of laboratory tests for uric acid and glucose in the blood.
In case of impaired liver and kidney function, the drug should be used only as prescribed by a doctor.
In high doses (greater than 6 g per day), paracetamol is toxic to the liver. However, negative effects on the liver can occur at much lower doses in the case of alcohol consumption, the use of liver enzyme inducers or other substances that have a toxic effect on the liver.
The drug should be started with caution (after consulting a doctor) in patients who have experienced high blood pressure, fluid retention, and edema during NSAID treatment.
Side effects can be reduced by using the minimum effective dose necessary to treat symptoms for a short period of time.
Cardiovascular and cerebrovascular effects. Clinical trials and epidemiological data suggest that ibuprofen, especially at high doses (2400 mg daily), and with prolonged use may be associated with arterial thrombotic events (myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (less than 1200 mg daily) increases the risk of myocardial infarction.
Bronchospasm may occur in patients with bronchial asthma, current allergic diseases, or a history of bronchospasm.
Systemic lupus erythematosus and systemic connective tissue diseases cause an increased risk of aseptic meningitis.
Chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) may worsen.
Symptoms of increased blood pressure and/or heart failure due to severe liver dysfunction may be exacerbated and/or fluid retention may occur.
The drug should be used with caution in patients receiving concomitant therapy with drugs that increase the risk of ulceration or bleeding, in particular oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid. If necessary, combination therapy with protective drugs (misoprostol or proton pump inhibitors) should be carried out, especially in patients who require long-term use of low doses of acetylsalicylic acid.
Liver disease increases the risk of liver damage from paracetamol. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.
Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur very rarely in association with the use of NSAIDs. The risk of these reactions is highest at the beginning of treatment, with the first manifestations appearing in most cases within the first month of treatment.
With prolonged use of analgesics in large doses, a headache may occur, which cannot be treated by increasing the dose of the drug. Prolonged and uncontrolled use of analgesics can lead to chronic kidney damage with the risk of renal failure (analgin nephropathy).
There is insufficient evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis can cause impairment of female reproductive function through effects on ovulation. This phenomenon is reversible after discontinuation of treatment.
Gastrointestinal bleeding, ulceration, or perforation, which can be fatal, may occur with all NSAIDs, with or without worsening symptoms or a history of serious cardiovascular events.
Patients who have experienced gastrointestinal disturbances should report any unusual abdominal symptoms (especially gastrointestinal bleeding) at the beginning of treatment.
One capsule of the drug contains approximately the same dose of caffeine as a cup of coffee. When using Tetramol, it is necessary to limit the intake of medications, food and drinks containing caffeine, since a large amount of caffeine can cause nervousness, irritability, insomnia, and sometimes - rapid heartbeat.
You should consult a doctor before using the drug.
If symptoms persist, you should consult a doctor.
Do not take the drug simultaneously with other products containing paracetamol, ibuprofen or caffeine.
Use during pregnancy and breastfeeding. Do not use during pregnancy and breastfeeding.
Children: The drug should not be used in children under 12 years of age.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. In cases where adverse reactions from the nervous system are observed during treatment, you should refrain from driving vehicles and working with mechanisms.
Interactions
With simultaneous use of paracetamol with metoclopramide and domperidone, increased absorption of paracetamol is possible, with cholesterinamine - decreased absorption.
In case of long-term continuous use of paracetamol, the anticoagulant effect of warfarin and other coumarins may be enhanced, increasing the risk of bleeding.
NSAIDs may enhance the effects of anticoagulants such as warfarin and weaken the effects of blood pressure-lowering drugs or diuretics.
Concomitant use of other nonsteroidal anti-inflammatory drugs increases the risk of side effects.
Corticosteroids: increase the risk of gastrointestinal side effects.
Taking the drug may cause an increase in the concentration of lithium in the blood plasma.
Concomitant use with methotrexate may lead to poisoning.
Barbiturates reduce the antipyretic effect of paracetamol.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate the activity of liver microsomal enzymes, may enhance the toxic effect of paracetamol on the liver due to an increase in the degree of conversion of the drug into hepatotoxic metabolites. With the simultaneous use of paracetamol with hepatotoxic drugs, the toxic effect of drugs on the liver increases. Simultaneous use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics. Do not use simultaneously with alcohol.
Cimetidine, hormonal contraceptives, isoniazid enhance the effect of caffeine. Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics and sedatives, is an antagonist of anesthetics and other drugs that depress the central nervous system, a competitive antagonist of adenosine drugs, ATP. With simultaneous use of caffeine with ergotamine, the absorption of ergotamine in the gastrointestinal tract improves, with thyroid-stimulating agents - the thyroid effect increases. Caffeine reduces the concentration of lithium in the blood.
Should not be used in combination with:
acetylsalicylic acid, unless a low dose of acetylsalicylic acid (not higher than 75 mg/day) has been prescribed by a doctor, as this may lead to side effects; other NSAIDs, as this may lead to an increased incidence of side effects.
Ibuprofen should be used with caution in combination with:
antihypertensives and diuretics: nonsteroidal anti-inflammatory drugs may reduce the therapeutic effect of these drugs.
Diuretics increase the risk of nephrotoxic effects.
Anticoagulants: NSAIDs may increase the therapeutic effect of anticoagulants such as warfarin.
Antiplatelet and selective serotonin inhibitors: increased risk of gastrointestinal bleeding.
Cardiac glycosides: may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.
Cyclosporines: there is some evidence of a possible drug interaction that increases the risk of nephrotoxicity.
Mifepristone: NSAIDs should not be taken for 8-12 days after mifepristone use, as this may reduce the effect of mifepristone.
Tacrolimus: increased risk of nephrotoxicity.
Lithium and methotrexate: There is evidence of a potential increase in plasma levels of lithium and methotrexate.
Zidovudine: There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients receiving concomitant treatment with zidovudine and ibuprofen.
Quinolone antibiotics: concomitant use increases the risk of seizures.
Overdose
With prolonged use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, leukopenia are possible. When taking high doses, disorders of the central nervous system (dizziness, psychomotor agitation, impaired orientation and attention, insomnia, tremor, nervousness, restlessness) are possible, and from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).
In case of overdose, increased sweating, psychomotor agitation or depression of the central nervous system, drowsiness, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystole, tremor, hyperreflexia, and convulsions may occur.
Symptoms of paracetamol overdose. Liver damage is possible in adults who have taken 10 g or more of paracetamol and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes, alcohol abuse, insufficiency of the glutathione system, for example, digestive disorders, HIV infection, starvation, cystic fibrosis, cachexia), taking 5 g or more of paracetamol can lead to liver damage. In the first 24 hours: pallor, nausea, vomiting, anorexia and abdominal pain, hepatonecrosis, increased activity of hepatic transaminases, increased prothrombin index. Liver damage may become apparent 12-48 hours after excessive doses of the drug. Glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, coma, and death. AKI with acute tubular necrosis may develop even in the absence of severe renal damage. Cardiac arrhythmias and pancreatitis have also been reported.
Symptoms of caffeine overdose. High doses of caffeine can cause rapid breathing, extrasystole, dizziness, a state of affect, epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmia, stimulation of the CNS (insomnia, restlessness, agitation, anxiety, syndrome of increased neuro-reflex excitability, headache, tremor, convulsions, nervousness and irritability). Clinically significant symptoms of caffeine overdose are also associated with liver damage by paracetamol.
Treatment: There is no specific antidote. However, supportive measures, such as the use of beta-blockers, may reduce the cardiotoxic effect.
Symptoms of ibuprofen intoxication. In most patients who participated in clinical studies, the use of a significant amount of NSAIDs caused only nausea, vomiting, epigastric pain or very rarely diarrhea. Tinnitus, headache and bleeding from the digestive tract may occur. In more severe poisoning, toxic lesions of the CNS in the form of drowsiness may occur, sometimes - nervous excitement and disorientation or coma. Sometimes patients have convulsions. In severe poisoning, metabolic acidosis may occur; the prothrombin index may be increased, possibly due to the effect on blood clotting factors. Acute renal failure and liver damage may occur. In patients with bronchial asthma, exacerbation of the disease may occur. The use of more than 400 mg/kg in children may cause symptoms of intoxication. In adults, the effects are less pronounced. The half-life in case of overdose is 1.5-3 hours.
Treatment may be symptomatic and supportive, and may include airway clearance and monitoring of cardiac symptoms and vital signs until the condition returns to normal. Oral administration of activated charcoal is recommended within 1 hour of ingestion of a potentially toxic amount. Diazepam or lorazepam IV should be used for frequent or prolonged seizures. Bronchodilators should be used for asthma.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C, out of the reach of children.
