Tetralgin® H (Tetralgin® N)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCaffeine + Metamizol sodium + PhenobarbitalCaffeine + Metamizol sodium + Phenobarbital
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  • Tetralgin® H
    pills inwards 
    FPK FarmVILAR, ZAO     Russia
    • Dosage form: & nbsp

    Pills

    Composition:

    (per tablet)

    active substances-, caffeine anhydrous - 50 mg, metamizole sodium monohydrate - 300 mg, phenobarbital - 10 mg;

    Excipients: potato starch -36.31 mg, magnesium stearate-3.69 mg.
    Description:

    Tablets are of a circular planocylindrical form, from white to white with a yellowish or creamy hue of color, with a risk and a facet.

    Pharmacotherapeutic group:Analgesic combined (psychostimulating agent + NSAIDs + barbiturate)
    ATX: & nbsp

    N.02.B.B.72   Metamizole sodium in combination with psycholeptics

    Pharmacodynamics:

    Combined drug. Has analgesic and antipyretic effect. The analgesic effect develops in 20-30 minutes and reaches a maximum after 45 minutes. Pharmacological properties of the drug are due to the action of the components that make up its composition.

    Metamizol sodium is a derivative of pyrazolone, which possesses an aialgizing, antipyretic and antispasmodic effect. The mechanism of action is not fully understood. According to the results of the studies metamizole and its active metabolite (4N- methylaminoantipyrine) have a central and peripheral mechanism of action. Nonselectively inhibits cyclooxygenase and reduces the formation of prostaglandins from arachidonic acid.

    Phenobarbital refers to the barbiturate group. It interacts with the barburnate site of bisodiazepine-y-aminobutyric acid (GABA) -receptor complex, which increases the sensitivity of GABA receptors to GABA, leads to the opening of the chloride channels, which increases their entry into the cell and leads to hyperpolarization. Suppresses the sensory areas of the cerebral cortex, reduces motor activity, depresses the cerebral functions, including the respiratory center. Has no significant effect on the cardiovascular system. Reduces the tone of the smooth muscles of the gastrointestinal tract. In small doses, it exhibits a sedative effect.

    Caffeine increases the reflex excitability of the spinal cord, excites the respiratory and vasomotor centers, dilates the blood vessels of skeletal muscles, brain, heart, kidneys, reduces platelet aggregation; reduces drowsiness, a feeling of fatigue, increases mental and physical performance. In this combination caffeine in a small dose practically does not have a stimulating effect on the central nervous system, but it increases the tone of cerebral vessels and promotes the acceleration of blood flow.

    Pharmacokinetics:Metamizol sodium

    After oral administration metamizol sodium is hydrolyzed to pharmacologically active 4N-methylaminoantipyrine (MAA). Bioavailability of MAA after oral administration is 90%, which is somewhat higher than with parenteral administration. Simultaneous food intake does not have a significant effect on the pharmacokinetics of metamizole sodium.

    Clinical efficacy is mainly determined by MAL, and to a lesser extent by 4N-aminoantigine (AA) metabolites. The area under the "concentration-time" curve (AUC) AA is 25% of this value for IAA

    Metabolites 4N-acetylaminoantipyrine (AAA) and 4N-formylaminoantipyrine (FAL) have no pharmacological activity.
    All metabolites are characterized by non-linear pharmacokinetics. The clinical significance of this phenomenon is not known. In the short term, cumulation of metabolites does not play a big role.

    Metamizole sodium penetrates the placenta. Metabolites metamizole penetrate into breast milk. The connection with plasma proteins MAA is 58%, AL - 48%, FLA - 18% and ALL - 14%. After a single oral intake, 85% of the dose is found in the urine as metabolites, of which 3 ± 1% is MAA, 6 ± 3% is AL, 26 ± 8% is AAA and 23 ± 4% is FAA. Renal clearance after a single intake of 1 g of metamizole sodium inside for MAA is 5 ± 2 ml / min, AA - 38 ± 13 ml / min, ALA - 61 ± 8 ml / min and FAA - 49 ± 5 ml / min. The corresponding half-lives from plasma for MAA are 2.7 ± 0.5 h, AA - 3.7 ± 1.3 h, AAA - 9.5 ± 1.5 h and FAA - 11.2 ± 1.5 hours.

    Elderly

    In elderly patients AUC increases 2-3 times. In patients with cirrhosis of the liver, the half-lives of MAA and FAA with a single dose of the drug increase approximately 3-fold, while the half-lives of AA and AAA do not follow the same pattern. Such patients should avoid the use of high doses.

    Impaired renal function

    According to available data, with renal failure, the rate of excretion of some metabolites (AAA and FAA) decreases. Such patients should avoid the use of high doses.

    Bioavailability

    According to the clinical study, the pharmacokinetic parameters of 4-MAA when ingested 1 g of metamizole sodium (tablets) have the following values ​​(average values ​​and standard deviations): maximum plasma concentration (Cmax) is 17.3 ± 7.54 mg / l; time to reach the maximum plasma concentration (tmax) - 1.42 ± 0.54 h; area under the curve "concentration-time" (AUC) - 80.9 ± 34.1 [mghch / l]. Absolute bioavailability of 4-MAA by AUC when taking tablets is 93%.

    Phenobarbital

    When ingested completely, but relatively slowly absorbed. The maximum plasma concentration is observed 1-2 hours after administration.

    About 50% binds to plasma proteins. Evenly distributed in different organs and tissues; smaller concentrations are found in the brain tissues. Well penetrates into breast milk and through the placental barrier.

    Metabolized in the liver, induces microsomal enzymes of the liver: CYP3A4, CYP3A5, CYP3A7 (the rate of enzymatic reactions increases 10-12 times), increases the detoxification function of the liver. Cumulates in the body. Half-life is 2-4 knots.

    It is excreted by the kidneys in the form of glucuronide, 25% - unchanged.

    Caffeine

    When ingested absorption is good, occurs throughout the intestine. Absorption occurs mainly due to lipophilicity, and not water soluble ™. Time to reach the maximum concentration - 50-75 minutes after ingestion, the maximum concentration of 1.6-1.8 mg / l.Quickly distributed in all organs and tissues of the body; easily penetrates the blood-brain barrier and the placenta. The volume of distribution in adults is 0,4-0,6 l / kg, in newborns - 0,78-0,92 l / kg. The connection with blood proteins (albumin) is 25-36%. More than 90% undergo metabolism in the liver, in children of the first years of life up to - 10-15%. In adults, about 80% of the dose of caffeine is metabolized to paraxanthin, about 10% to theobromine and about 4% to theophylline. These compounds are subsequently demethylated into monomethylxanthines, and then into methylated uric acids. The half-life in adults is 3.9-5.3 hours (sometimes up to 10 hours). The excretion of caffeine and its metabolites is carried out by the kidneys (unchanged in adults, 1-2% is excreted).

    Indications:Pain syndrome of different genesis: headache, toothache, pain in muscles and joints, neuralgia, with painful menstruation, with radiculitis. As a symptomatic means to reduce fever and reduce the symptoms of "malaise" (headache, aches) with "cold" diseases.
    Contraindications:

    - Hypersensitivity to metamizol sodium and other pyrazolone derivatives, as well as to pyrazolidines, for example, phenylbutazone (including patients who suffered agranulocytosis due to the use of these drugs), caffeine, phenobarbital or other components of the drug;

    - Analgesic bronchial asthma or intolerance to analgesics (but type kranivnitsa-angioneuroticesky edema), g. patients with bronchospasm or other forms of anaphylactoid reactions (eg urticaria, rhinitis, angioedema) in response to the use of salicylates, paracetamol or non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, indomethacin or nairoksen;

    - Disturbance of bone marrow hematopoiesis (eg, after cytostatic therapy) or diseases of the hematopoietic organs;

    - Hereditary deficiency of glucose-6-phosphate dehydrogenase (hemolysis);

    - Acute intermittent hepatic porphyria (risk of developing porphyria attacks);

    - Severe diseases of the liver and (or) kidney;

    - Respiratory diseases, accompanied by shortness of breath or obstruction

    respiratory tract;

    - Myasthenia gravis;

    - Alcoholic intoxication, drug or drug dependence, including in history;

    - Pregnancy and the period of breastfeeding;

    - Children under 18 years.

    Carefully:

    Violation of the liver and / or kidney function, peptic ulcer of the stomach and duodenum in remission, glaucoma, increased excitability, advanced age, epilepsy and a tendency to seizures.

    Pregnancy and lactation:

    The drug is contraindicated for use in pregnancy. If it is necessary to use the drug during lactation, it is necessary to solve the problem of stopping breastfeeding.

    Dosing and Administration:

    Inside but 1 tablet 1-4 times a day. Tablets should be swallowed whole, with enough liquid.

    The maximum daily dose is 4 tablets. Duration of reception no more than 5 days.

    Elderly patients, patients with severe general condition and impaired creatinine clearance should reduce the dose, because they can be reduced excretion of metabolites of metamizole sodium and phenobarbital.

    Since in patients with impaired renal or hepatic function the rate of elimination of the drug is reduced, the repeated use of high doses should be avoided. In the short term, dose reduction is not required. Experience with prolonged use is absent.

    Side effects:

    Until now, there have been reports of side effects on this combination. The frequency of occurrence of the following possible side effects is unknown. When using the drug in accordance with the instructions, the occurrence of the following side effects is unlikely.

    From the immune system

    Angioedema, anaphylactoid and anaphylactic reactions.

    On the part of the organs of hematopoiesis

    Agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia, pancytopenia.

    From the nervous system

    Psychomotor agitation, anxiety, tremor, anxiety, dizziness, epileptic seizures, increased reflexes, insomnia; paradoxical reaction in the elderly (unusual stimulation), increased fatigue, drowsiness, decreased speed of psychomotor reactions, drug dependence.

    From the side of the cardiovascular system

    Heart palpitations, tachycardia, increased blood pressure, lower blood pressure.

    On the part of the respiratory system, the organs of the thorax and the mediastinum Tachypnea, bronchosiastic syndrome, analgesic bronchial asthma.

    From the digestive system

    Nausea, vomiting, exacerbation of peptic ulcer (caffeine), constipation.

    From the skin and subcutaneous tissues Rash (including persistent), itching, hives.

    If unwanted reactions occur, including those not indicated in the instructions, contact your doctor.
    Overdose:

    To date, cases of overdose with this combination have not been reported.

    Caffeine (more than 300 mg per dose or more than 1 g per day)

    Symptoms

    Common symptoms are anxiety, nervousness, anxiety, insomnia, mental agitation, muscle twitching, confusion, convulsions. In severe overdose, hyperglycemia may occur. Cardiac disorders are manifested by tachycardia and arrhythmia.

    Treatment

    Dose reduction or caffeine withdrawal.

    Metamizol sodium (more than 1 g per reception, more than 3 g per day)

    Symptoms

    Acute overdose is manifested by nausea, vomiting, abdominal pain, impaired renal function / esophagus, renal insufficiency (for example, as a manifestation of interstitial nephritis) and, rarely, symptoms from the central nervous system (dizziness, drowsiness, coma, convulsions) and a decrease in blood pressure, leading to tachycardia and shock.

    With a high overdose, the excretion of rubric acid can stain the urine red.

    Treatment

    The specific antidote is not known. In case of a recent overdose, in order to limit the intake of the drug, primary detoxification (for example, gastric lavage) or sorption therapy (for example, Activated carbon). The main metabolite (4N-methylaminoantipyri) is removed during hemodialysis, haemofiltration, hemoperfusion and plasmafiltration.

    Treatment of an overdose, as well as the prevention of serious complications, may require general and special intensive medical supervision and treatment. Phenobarbital

    When taking Tetradgin® H, an overdose of phenobarbital is unlikely: one package of the drug (20 tablets) contains one maximum single dose of phenobarbital.

    Interaction:

    Metamizol sodium Enhances the effects of ethanol.

    It is not recommended to simultaneously use radiocontrast drugs, colloidal blood substitutes and penicillin.

    With the simultaneous use of cyclosporine, the concentration of the latter in the blood decreases, so when they are used simultaneously, the concentration of cyclosporin should be monitored.

    Mstamizol sodium increases the activity of oral hypoglycemic drugs, indirect anticoagulants, glucocorticosteroids and indomethacin.

    Phenylbutazone, barbiturates and other inducers of microsomal liver enzymes with simultaneous use reduce the effectiveness of metamizole sodium. Simultaneous use with other non-narcotic analgesics, tricyclic antidepressants, contraceptive hormonal drugs and allopurinol may lead to an increase in their toxicity.

    Medagivnye and anxiolytic drugs (tranquilizers) enhance the analgesic effect of megamysol sodium.

    Thiamazole and cytostatics increase the risk of developing leukopenia.

    The effect is enhanced codeine, H2-histamine receptor blockers and propranolol (slows inactivation).

    Myelogoxic drugs increase the manifestation of hematoxicity of the drug. The simultaneous use of metamizole sodium and methotrexate may increase the hematotoxicity of the latter, especially in elderly patients.

    With the simultaneous use of metamizole sodium and chlorpromazine may develop severe hypothermia.

    Phenobarbital

    Interaction with other drugs is due, mainly, to the ability of phenobarbital to induce cytochrome P450 (mainly isoenzyme CYP3A4).

    Reduces antibacterial activity of antibiotics and sulfonamides,

    antifungal activity of griseofulvin (reduces absorption).

    Reduces the effectiveness of indirect anticoagulants, glucocorticosteroids, doxycycline, estrogens and other drugs metabolized by microsomal enzymes of the liver. Sleeping effect is reduced with simultaneous administration of atropine, belladonna extract, dextrose, thiamine, nicotinic acid, analeptics and psychostimulants.

    When combined with reserpine, the anticonvulsant effect decreases, under the influence of amitriptyline, nialamide, diazepam, chlordiazene oxide - is amplified.

    Acetazolamide, alkalinizing urine, reduces the reabsorption of phenobarbital in the kidneys and weakens its effect.

    Strengthens the effect of alcohol, neuroleptics, narcotic analgesics, muscle relaxants, sedatives and hypnotics.

    Caffeine

    Caffeine is an adenoside antagonist (large doses of adenosine may be required). With the joint use of caffeine and barbiturates, primidone, anticonvulsant drugs (hydantoin derivative, especially phenytoin) it is possible to increase metabolism and increase caffeine clearance; cymethidine, oral contraceptives, disulfiram, ciprofloxacin, norfloxacin - a decrease in the metabolism of caffeine in the liver (slowing its elimination and increasing blood concentrations). Caffeine-containing beverages and other medicines that stimulate the central nervous system may cause excessive stimulation of the central nervous system. Mexiletin - reduces caffeine withdrawal by 50%; nicotine - Increases the speed of caffeine removal. Inhibitors of monoamine oxidase, furazolidone, procarbazine and selegiline - large doses of caffeine (more than 300 mg / day) can cause the development of life-threatening heart arrhythmias or a pronounced increase in blood pressure. Caffeine reduces the absorption of calcium in the gastrointestinal tract. Reduces the effectiveness of narcotic and hypnotic drugs.Increases the excretion of lithium drugs with urine. Accelerates absorption and enhances the action of cardiac glycosides, increases their toxicity. Co-administration with beta-adrenergic blockers can lead to mutual suppression of therapeutic effects; from p-adrenomimetics - to additional stimulation of the central nervous system and other additive toxic effects. Caffeine can reduce the clearance of geofillin and, possibly, other xanthines, increasing the possibility of additive pharmacodynamic and toxic effects.
    Special instructions:

    The drug should not be taken more than 5 days in a row.

    Due to the caffeine content in the preparation The drug should be administered with caution to patients with gout, hyperthyroidism and arrhythmia.

    When using the drug should limit the consumption of products containing caffeine, as excessive intake of caffeine can lead to nervousness, irritability, insomnia and, in some cases, increased heart rate. Due to the content of sodium metamizole in the preparation

    If the increased body temperature and symptoms of "malaise" in case of "cold" diseases are maintained while taking the drug within 48 hours, you should consult a doctor.

    With prolonged (more than 5 days) use of the drug, control of the picture of peripheral blood and the functional state of the liver is necessary.

    Against the background of long reception of high doses of the drug in connection with the content of metamizole sodium, it is possible to develop agranulocytosis or thrombocytopenia, therefore, if an unmotivated rise in temperature, chills, sore throats, difficulty swallowing, stomatitis, and the development of phenomena of vaginitis or proctitis, immediate withdrawal of the drug is necessary. With the development of pancytopsy, the drug should be immediately discontinued and the general blood test should be monitored until the parameters return to normal. All patients should be advised to seek medical help immediately if there are signs and symptoms reminiscent of blood disorders (eg, weakness, infection, persistent fever, bruising, bleeding, pallor) during treatment. Termination of therapy should not be postponed until laboratory results are obtained.

    Against the background of the use of high doses of metamizole sodium, life-threatening severe skin reactions have been described: Stevens-Johnson syndrome (SDS) and toxic epidermal necrolysis (TEN). When there are signs of SS or TENS (such as a progressive skin rash, often accompanied by blisters or ulceration of the mucous membrane), treatment with metamizole should be stopped immediately and never restarted.

    Patients with atopic bronchial asthma and pollinosis have an increased risk of developing allergic reactions.

    Abdominal pain

    It is inadmissible to use the drug to relieve acute pain in the abdomen (until finding out their cause).

    Due to the content of phenobarbital in the preparation

    Avoid prolonged use of the drug due to the possibility of cumulation of phenobarbital in the body and the development of addiction or drug dependence. Excipients

    One tablet contains 0.85 mmol (19.64 mg) of sodium, which must be taken into account in individuals. controlling the intake of sodium from food (on a diet low in salt / sodium).

    Effect on the ability to drive transp. cf. and fur:

    The drug does not influence or weakly affect the coordination of movements, but contains substances (caffeine, phenobarbital), which have a pronounced effect on the central nervous system, and therefore, during the treatment period, care must be taken when driving vehicles, working with mechanisms and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

    Form release / dosage:

    Pills. For 10 tablets in a contour mesh package or but 20 tablets into a polymer bottle with a lid.

    1-2 contour squares or 1 bottle together with instructions for use are placed in a pack of cardboard.

    Packaging:
    Storage conditions:

    In a dry, the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    Do not use after the expiration date.

    Terms of leave from pharmacies:Without recipe
    Registration number:LP-002856
    Date of registration:09.02.2015
    The owner of the registration certificate:FPK FarmVILAR, ZAO FPK FarmVILAR, ZAO Russia
    Manufacturer: & nbsp
    NOVENTIS, s.p.o. Czech Republic
    Representation: & nbspFPK FarmVILAR CJSC FPK FarmVILAR CJSC Russia
    Information update date: & nbsp09.02.2015
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