Instructions for Tamipul capsules blister No. 10
Composition
active ingredients: paracetamol, ibuprofen, caffeine;
1 capsule contains paracetamol 325 mg, ibuprofen 200 mg, caffeine 30 mg;
excipients: talc, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, gelatin, candurin (silver glitter), patent blue V (E 131), azorubine, carmoisine (E 122).
Dosage form
Capsules.
Main physical and chemical properties: hard gelatin capsules. Capsule body – white, pearlescent, cap – pink, pearlescent. Capsule contents – white powder.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Paracetamol, combinations without psycholeptics. ATX code N02B E51.
Pharmacological properties
Pharmacodynamics
A combined drug, the effect of which is due to the components that make up its composition. The drug has analgesic (pain-relieving), anti-inflammatory, antipyretic effects. Inhibits the synthesis of prostaglandins. Relieves joint pain at rest and during movement, reduces morning stiffness and swelling of the joints, helps increase the volume of movements.
Caffeine enhances the analgesic effect of ibuprofen and paracetamol. Under the influence of caffeine, diuresis is slightly increased (mainly due to a decrease in electrolyte reabsorption in the renal tubules), which causes a moderate anti-edematous effect.
Pharmacokinetics
Paracetamol.
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract (GI). Peak plasma concentrations are reached 30–60 minutes after administration, and the plasma half-life is 1–4 hours after administration in therapeutic doses. In severe hepatic insufficiency, the half-life increases to 5 hours. In renal insufficiency, the half-life does not increase, but since renal excretion is limited, the dose of paracetamol should be reduced.
Paracetamol penetrates the blood-brain barrier and also into the breast milk of breastfeeding women.
Ibuprofen.
Ibuprofen is rapidly absorbed from the gastrointestinal tract after administration. The maximum concentration in blood plasma is reached 45 minutes after administration, in synovial fluid - 3 hours after administration. Ibuprofen is metabolized in the liver, excreted by the kidneys in unchanged form and in the form of metabolites. The half-life is about 2 hours.
Caffeine.
After oral administration, caffeine is rapidly absorbed. Peak plasma concentrations are reached after approximately 20–60 minutes, with a half-life of approximately 4 hours.
Indication
Pain syndrome of varying intensity:
dysmenorrhea and menstrual pain; headache; neuralgia; myalgia; arthralgia; toothache.
Increased temperature (fever with flu and colds).
As part of the complex treatment of postoperative pain, alleviation of symptoms of rheumatoid arthritis and osteoarthritis.
Contraindication
Hypersensitivity to paracetamol, ibuprofen, caffeine or any other component of the drug, current or history of gastric ulcer (two or more clear episodes of exacerbation of ulcer or bleeding); history of upper gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs; acute pancreatitis, severe liver and/or kidney dysfunction, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood diseases, severe anemia, leukopenia, thrombosis, thrombophlebitis, states of increased excitement; sleep disorders; severe arterial hypertension; organic diseases of the cardiovascular system; angle-closure glaucoma; epilepsy, hyperthyroidism, decompensated heart failure, cardiac conduction disorders, severe atherosclerosis, tendency to vasospasm, ischemic heart disease, prostatic hypertrophy, severe forms of diabetes mellitus, allergic reaction (e.g. bronchial asthma, rhinitis, angioedema) after using acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, use of the drug simultaneously with nonsteroidal anti-inflammatory drugs, elderly patient.
Do not use with monoamine oxidase (MAO) inhibitors, cyclooxygenase-2 and within 2 weeks after stopping their use; contraindicated in patients taking tricyclic antidepressants or beta-blockers. Gilbert's syndrome. Patient age up to 12 years.
Interaction with other medicinal products and other types of interactions
With simultaneous use of paracetamol with metoclopramide and domperidone, increased absorption of paracetamol is possible, with cholesterolamine - 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.
Nonsteroidal anti-inflammatory drugs 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 may lead to increased side effects.
Taking the drug may lead to an increase in serum lithium concentrations.
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 to hepatotoxic metabolites. With the simultaneous use of paracetamol with hepatotoxic drugs, the toxic effect of the drugs on the liver increases. Simultaneous use of large doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics. Do not use simultaneously with alcohol.
The simultaneous use of caffeine with MAO inhibitors can cause a dangerous increase in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesics-antipyretics, potentiates the effects of xanthine derivatives, alpha- and beta-adrenomimetics, and psychostimulants.
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 from the gastrointestinal tract improves, with thyroid-stimulating drugs - the thyroid effect increases. Caffeine reduces the concentration of lithium in the blood.
Should not be used in combination with:
acetylsalicylic acid, unless the dose of acetylsalicylic acid (not higher than 75 mg per day) has been prescribed by a doctor, as this may lead to a risk of side effects;
other non-steroidal anti-inflammatory drugs (NSAIDs). This may lead to an increased incidence of side effects.
Ibuprofen should be used with caution in combination with:
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 prescribed 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. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
Anticoagulants: Nonsteroidal anti-inflammatory drugs may increase the therapeutic effect of anticoagulants such as warfarin.
Antiplatelet agents and selective serotonin reuptake inhibitors: The risk of gastrointestinal bleeding may be increased.
Cardiac glycosides: Heart failure may worsen, glomerular filtration rate may decrease, and plasma glycoside levels may increase.
Cyclosporines: There is some evidence of a possible drug interaction that is likely to lead to an increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be taken for 8–12 days after mifepristone administration, as this may reduce the effectiveness 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 may increase the risk of seizures.
Sulfonylurea drugs. Possible enhancement of the effect.
Application features
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 Tamiflu®.
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 be increased when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should consult a doctor immediately if these symptoms occur.
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, adverse 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 consultation with a doctor) in patients who have experienced increased blood pressure, fluid retention, and edema during treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Side effects can be reduced by using the minimum effective dose needed to treat symptoms for a short period of time.
Effects on the cardiovascular and cerebrovascular systems
Clinical trials and epidemiological data suggest that ibuprofen, especially at high doses (2400 mg daily), and long-term use may be associated with a small increased risk of arterial thrombotic events (myocardial infarction or stroke). Overall, epidemiological data do not suggest that low doses of ibuprofen (less than 1200 mg daily) may be associated with an increased risk of myocardial infarction. In patients with uncontrolled hypertension, congestive heart failure, established coronary artery disease, peripheral artery disease and/or cerebrovascular disease, long-term treatment should only be initiated after careful consideration by the physician. In patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes mellitus, smoking), long-term treatment with NSAIDs should only be initiated after careful consideration.
Bronchospasm may occur in patients with bronchial asthma or allergic diseases at present, or with a history of indications of bronchospasm.
Systemic lupus erythematosus and systemic connective tissue diseases increase the risk of aseptic meningitis.
Chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) as these diseases may worsen.
Symptoms of high blood pressure and/or heart failure due to severe liver dysfunction may worsen and/or fluid retention may occur.
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.
Effect on the liver
Liver dysfunction. Liver disease increases the risk of liver damage from paracetamol. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.
Impact on fertility in women
There is limited evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. However, this effect is reversible and disappears 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 are unable to conceive or are undergoing investigation for infertility, this medicinal product 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, perforation, and ulceration, 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.
Patients with a history of gastrointestinal disorders, especially elderly patients, should be informed of 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.
Skin and subcutaneous tissue disorders: Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur with NSAIDs. The highest risk of such reactions is observed in the early stages of therapy, in most cases the onset of such reactions occurs within the first month of treatment.
The drug should be discontinued at the first signs of skin rash, pathological changes in the mucous membranes, or any other signs of hypersensitivity.
With prolonged use of painkillers in high doses, a headache may occur, which cannot be treated by increasing the dose of the drug. Prolonged and uncontrolled use of painkillers can lead to chronic kidney damage with the risk of kidney failure (analgesic nephropathy).
One capsule of this drug contains approximately the same dose of caffeine as a cup of coffee. When using Tamiflu®, it is necessary to limit the intake of medications, food and drinks containing caffeine, since large amounts 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.
The medicine contains E 122, which may cause allergic reactions.
Ability to influence reaction speed when driving vehicles or other mechanisms
If adverse reactions from the nervous system are observed during treatment with the drug, you should refrain from driving vehicles and working with other mechanisms.
Use during pregnancy or breastfeeding
Do not use during pregnancy or breastfeeding.
Method of administration and doses
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 from 12 to 16 years of age: 1 capsule 1–2 times a day. The capsule should be taken without chewing, with sufficient liquid (a glass of water). The usual 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 for children without consulting a doctor is 3 days.
The interval between doses is at least 4 hours.
Do not exceed the recommended dose.
Children
The drug should not be used in children under 12 years of age.
Overdose
With long-term use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, leukopenia are possible. When taking high doses, central nervous system (CNS) disorders (dizziness, psychomotor agitation, impaired orientation and attention, insomnia, tremor, nervousness, anxiety) are possible, and from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).
In case of overdose, increased sweating, psychomotor agitation or CNS depression, 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 the drug in a dose of more than 150 mg/kg of body weight. In patients with risk factors (long-term use of carbamazepine, phenobarbitone, 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.
Treatment. In case of overdose, urgent medical attention is required, even if symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage. Treatment with activated charcoal should be considered if an overdose of paracetamol has been taken within 1 hour. The concentration of paracetamol in the blood plasma should be measured 4 hours or later after ingestion (earlier concentrations are unreliable).
N-acetylcysteine treatment can be used within 24 hours of paracetamol ingestion, but the maximum protective effect occurs when it is used within 8 hours of ingestion.
The effectiveness of the antidote decreases sharply after this time. If necessary, the patient should be given intravenous N-acetylcysteine according to current guidelines. In the absence of vomiting, oral methionine may be used as a suitable alternative in remote areas outside the hospital.
Symptoms of caffeine overdose. Large doses of caffeine can cause rapid breathing, extrasystole, dizziness, affective state, epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmia, stimulation of the central nervous system (insomnia, restlessness, agitation, anxiety, syndrome of increased neuro-reflex excitability, headache, tremor, convulsions, nervousness and irritability). Clinically important symptoms of caffeine overdose are also associated with liver damage by paracetamol.
Treatment: There is no specific antidote. However, supportive measures, such as beta-adrenergic antagonists, may alleviate cardiotoxic effects.
Symptoms of ibuprofen intoxication. In most patients who participated in clinical studies, the use of significant amounts of nonsteroidal anti-inflammatory drugs caused only nausea, vomiting, epigastric pain or, very rarely, diarrhea. Tinnitus, headache and bleeding from the digestive tract may also occur. In more severe poisoning, toxic lesions of the central nervous system may occur in the form of drowsiness, 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 course of the disease is possible. The use of more than 400 mg/kg in children 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.
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 of the drug. Intravenous diazepam or lorazepam should be used for frequent or prolonged seizures. Bronchodilators should be used for the treatment of bronchial asthma.
Adverse reactions
The following adverse drug reactions are classified according to MedDRA terminology.
On the part of the immune system: hypersensitivity in the form of urticaria and itching; severe hypersensitivity reactions with manifestations such as 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 bronchial asthma and bronchospasm.
Nervous system: headache, dizziness, irritability, nervousness, depression, drowsiness, insomnia, anxiety, psychomotor agitation, emotional instability, convulsions, paresthesias, aseptic meningitis, some symptoms of which (rigidity of the occipital muscles, headache, nausea, vomiting, fever or disorientation) may occur in patients with existing autoimmune diseases, such as systemic lupus erythematosus, mixed connective tissue disease.
From the blood and lymphatic system: disorders of the hematopoietic system, 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, gastritis, 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.
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.
Cardiac: heart failure, edema.
Vascular disorders: arterial thrombosis (myocardial infarction or stroke).
From the endocrine system and changes in metabolism: hypoglycemia, up to hypoglycemic coma; decreased appetite; dryness of the mucous membranes of the eyes and oral cavity; rhinitis.
Liver: liver disorders, increased activity of liver enzymes, hepatonecrosis (dose-dependent effect), liver failure, hepatitis and jaundice may occur with prolonged treatment.
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.
General disorders: malaise and fatigue.
Laboratory tests: decreased hemoglobin level.
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 stimulation of the central nervous system;
Gastrointestinal: nausea caused by gastrointestinal irritation.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C, out of the reach of children.
Packaging
10 capsules in a blister; 1 blister in a package.
Vacation category
Without a prescription.
Producer
JSC "Grindex".
Location of the manufacturer and its business address
Krustpils St., 53, Riga, LV-1057, Latvia.
