Trialgin
Trialgin: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Obsolete name: Tetralgin N
Latin name: Trialgin
ATX code: N02BB72
Active ingredient: metamizole sodium (Metamizole sodium) + caffeine (Caffeine) + phenobarbital (Phenobarbital)
Producer: OOO NPO PharmVILAR (Russia); Noventis s.r.o. (Noventis, sro) (Czech Republic)
Description and photo update: 2020-25-02
Trialgin is a combined agent of analgesic and antipyretic action.
Release form and composition
The drug is produced in the form of tablets: from white to white with a yellow or cream shade, flat-cylindrical, round, with a line and a chamfer (10 pcs. In a blister strip, 20 pcs. In a polymer bottle; in a cardboard box 1-2 packs or 1 bottle and instructions for use of Trialgin).
1 tablet contains:
- active ingredients: metamizole sodium monohydrate - 300 mg, anhydrous caffeine - 50 mg, phenobarbital - 10 mg;
- additional components: magnesium stearate - 3.69 mg; potato starch - 36.31 mg.
Pharmacological properties
Pharmacodynamics
Trialgin is a combined preparation with analgesic and antipyretic effects. After taking it, the onset of analgesic action is observed after 20-30 minutes, and the maximum effect - after 45 minutes. The pharmacological properties of the drug are due to the action of the active substances included in its composition:
- metamizole sodium: refers to non-steroidal anti-inflammatory drugs (NSAIDs), pyrazolone derivatives; exhibits antipyretic, analgesic and antispasmodic effect, the mechanism of its action is not fully established; in accordance with the results of the studies carried out, metamizole and its active metabolite (4N-methylaminoantipyrine) are characterized by a central and peripheral mechanism of action; the drug non-selectively inhibits cyclooxygenase and reduces the production of prostaglandins from arachidonic acid;
- caffeine: is a psychostimulant; helps to increase the reflex excitability of the spinal cord, stimulation of the respiratory and vasomotor centers; leads to a decrease in platelet aggregation and an expansion of the blood vessels of skeletal muscles, myocardium, kidneys, and brain; helps to reduce drowsiness and fatigue, increase mental and physical performance; caffeine is included in the composition of the drug in a small dose and has almost no stimulating effect on the central nervous system (CNS), at the same time it causes an increase in the tone of the cerebral vessels and acceleration of blood flow;
- phenobarbital: belongs to the group of barbiturates; binds to the barbiturate site of benzodiazepine-γ-aminobutyric acid (GABA) - a receptor complex, as a result of which it increases the sensitivity of GABA receptors to GABA, ensures the opening of chlorine channels, promoting an increase in their entry into the cell, which leads to hyperpolarization; inhibits sensory areas of the cerebral cortex, reduces motor activity, suppresses cerebral functions, including the respiratory center; does not significantly affect the cardiovascular system (CVS); reduces the tone of smooth muscles of the gastrointestinal tract (GIT), in low doses has a sedative effect.
Pharmacokinetics
Metamizole sodium
After oral administration of Trialgin, the active substance is converted by hydrolysis into the pharmacologically active 4N-methylaminoantipyrine (MAA), the bioavailability of which after oral use is 90%, which is slightly higher than with parenteral administration. The pharmacokinetics of metamizole sodium does not undergo a significant change while taking the drug with food. Clinical efficacy is mainly determined by MAA, and also to some extent by metabolites of 4N-aminoantipyrine (AA). The area under the concentration-time curve (AUC) for AA is 25% of that for MAA.
The metabolites 4N-formylaminoantipyrine (FAA) and 4N-acetylaminoantipyrine (AAA) do not exhibit pharmacological activity. All metamizole derivatives are characterized by nonlinear pharmacokinetics, the clinical significance of this phenomenon has not been determined. In the case of short-term use of the drug, the accumulation of metabolites is not of great importance. Metamizole sodium passes through the placenta, and the products of its metabolism are excreted in breast milk.
MAA binds to blood plasma proteins by 58%, AA - by 48%, FAA - by 18% and AAA - by 14%. After a single oral administration, up to 85% of the administered dose is detected in the urine in the form of metabolites, of which FAA - 23 ± 4%, AAA - 26 ± 8%, AA - 6 ± 3%, MAA - 3 ± 1%.
Renal clearance after a single dose of metamizole sodium at a dose of 1 g is equal for AAA 61 ± 8 ml / min, FAA - 49 ± 5 ml / min, AA - 38 ± 13 ml / min, MAA - 5 ± 2 ml / min.
The corresponding half-lives (T 1/2) from plasma are for FAA - 11.2 ± 1.5 hours; AAA - 9.5 ± 1.5 h; AA - 3.7 ± 1.3 h; MAA - 2.7 ± 0.5 h.
According to the results of a clinical study, the pharmacokinetic parameters of 4-MAA after oral administration of metamizole sodium in the form of tablets at a dose of 1 g have the following mean values and standard deviations: AUC - 80.9 ± 34.1 (mg × h / l); maximum concentration (C max) - 17.3 ± 7.54 mg / l; the period of reaching the maximum plasma concentration (T max) is 1.42 ± 0.54 hours. The absolute bioavailability of this metabolite by AUC when using tablets is 93%.
In elderly patients, the AUC of metamizole sodium increases by 2–3 times.
In patients with liver cirrhosis, T 1/2 of FAA and MAA metabolites with a single dose increase approximately 3 times, while T 1/2 for AAA and AA does not follow a similar pattern. Patients in this group need to avoid taking high doses of the drug.
Caffeine
When taken orally, caffeine is well absorbed throughout the intestine. Absorption occurs primarily as a result of lipophilicity rather than water solubility. After oral administration, C max is 1.6–1.8 mg / l, T max is 50–75 minutes. Caffeine is actively distributed throughout all organs and tissues of the body, easily passes through the blood-brain barrier (BBB) and the placenta.
The volume of distribution (V d) in newborns is 0.78–0.92 l / kg; in adults - 0.4-0.6 l / kg. The connection with blood proteins (mainly albumin) is 25–36%. Over 90% of caffeine is metabolized in the liver; in children of the first years of life, this figure is less than 10-15%.
In adults, approximately 80% of the dose of caffeine taken is metabolized into paraxanthine, 10% into theobromine, 4% into theophylline. Subsequently, these compounds are demylylated into monomethylxanthines, and then into methylated uric acids. In adults, T 1/2 varies on average from 3.9 to 5.3 hours. In rare cases, caffeine is excreted from the body up to 10 hours. The elimination of the substance and its metabolites is performed by the kidneys, in an unchanged form in adults, from 1 to 2% of caffeine is excreted …
Phenobarbital
After oral administration, phenobarbital is absorbed completely, but at a low rate. C max in plasma is noted after 1–2 hours. About 50% binds to plasma proteins.
The active substance is evenly distributed over different tissues and organs, in lower concentrations it is detected in the tissues of the brain. It passes well through the placenta and enters breast milk.
The process of biotransformation occurs in the liver, while phenobarbital induces such liver microsomal enzymes as CYP3A7, CYP3A5 and CYP3A4 - the course of enzymatic reactions is accelerated 10-12 times. It enhances the detoxification function of the liver, accumulates in the body. T 1/2 varies from 2 to 4 days. It is excreted by the kidneys in the form of glucuronide and unchanged (25%).
Indications for use
Trialgin is recommended for use as an analgesic for pain syndrome of various origins: toothache, headache, neuralgia, pain in joints and muscles, algodismenorrhea, pain in sciatica.
As a symptomatic agent, Trialgin is used to reduce elevated body temperature and ease the severity of headache, aches and other symptoms of malaise in case of colds.
Contraindications
Absolute:
- severe liver and / or kidney damage;
- acute intermittent hepatic porphyria;
- lesions of hematopoietic organs or disorders of bone marrow hematopoiesis (including due to cytostatic therapy);
- respiratory disease with airway obstruction or shortness of breath;
- myasthenia gravis;
- hereditary deficiency of glucose-6-phosphate dehydrogenase (hemolysis);
- alcohol intoxication, drug / drug dependence, including data in the anamnesis;
- age up to 18 years;
- pregnancy and lactation;
- intolerance to analgesics (of the type urticaria - angioedema) or analgesic bronchial asthma, i.e. with the development of bronchospasm or other forms of anaphylactoid reactions, such as rhinitis, urticaria, angioedema, in response to the use of paracetamol, salicylates, including NSAIDs or NSAIDs or NSAIDs diclofenac, naproxen, indomethacin;
- hypersensitivity to any constituents of Trialgin, as well as to other pyrazolone derivatives and pyrazolidines, including phenylbutazone (including in persons who have undergone agranulocytosis as a result of using these drugs).
Relative (Trialgin therapy requires caution in the presence of the following diseases / conditions):
- peptic ulcer and 12 duodenal ulcer in remission;
- impaired liver and / or kidney function;
- increased excitability;
- glaucoma;
- epilepsy and a predisposition to seizures;
- elderly age.
Trialgin, instructions for use: method and dosage
Trialgin tablets are taken orally, they must be swallowed whole with a sufficient amount of liquid.
Recommended dosage: 1–4 times a day, 1 tablet, the maximum daily dose should not exceed 4 tablets. The duration of treatment is no more than 5 days.
In severe general condition and impaired creatinine clearance (CC), it is necessary to reduce the dose, since in these cases, a reduced excretion of metabolites of metamizole sodium and phenobarbital is possible.
Side effects
Against the background of the use of a combination of metamizole sodium, caffeine and phenobarbital, undesirable side reactions have not been recorded so far.
The incidence of the possible disorders listed below is unknown:
- hematopoietic organs: thrombocytopenia, leukopenia, pancytopenia, aplastic anemia, agranulocytosis;
- CVS: palpitations, increase / decrease in blood pressure (BP), tachycardia;
- immune system: anaphylactoid and anaphylactic reactions, angioedema;
- CNS: anxiety, dizziness, anxiety, tremor, insomnia, psychomotor agitation, increased reflexes, epileptic seizures; paradoxical reaction in the elderly (unusual agitation), drowsiness, excessive fatigue, drug dependence, a decrease in the speed of psychomotor reactions;
- skin and subcutaneous tissues: itching, urticaria, rash (including persistent);
- digestive system: nausea, vomiting, constipation, worsening peptic ulcer disease (caffeine);
- respiratory system, chest and mediastinal organs: tachypnea, bronchial obstruction syndrome, analgesic bronchial asthma.
The occurrence of these effects when using Trialgin according to the recommended dosage regimen is unlikely.
Overdose
Until now, cases of overdose of Trialgin have not been registered.
Metamizole sodium
Taking metamizole sodium in a single dose of more than 1 g or in a daily dose of more than 3 g can cause the following symptoms of acute overdose: nausea, abdominal pain, vomiting, renal impairment / acute renal failure (including interstitial nephritis); rarely - a decrease in blood pressure, causing tachycardia and shock; reactions from the central nervous system - drowsiness, dizziness, convulsions, coma. Against the background of a high overdose, urine may turn red as a result of excretion of rubazonic acid.
In order to limit the absorption of the drug in case of a recent overdose, gastric lavage or intake of activated charcoal is recommended. The main metabolite of the drug, MAA, is removed by hemodialysis, hemofiltration, plasma filtration and hemoperfusion. It may also require the appointment of general and special intensive medical supervision and symptomatic therapy.
Caffeine
The main symptoms of a caffeine overdose (if taken in a single dose above 0.3 g or in a daily dose - above 1 g) may be nervousness, insomnia, anxiety, anxiety, muscle twitching, mental agitation, convulsions, confusion. In case of a significant overdose, hyperglycemia, tachycardia, arrhythmias may develop.
The development of caffeine intoxication while taking Trialgin may require a dose reduction or discontinuation of the drug.
Phenobarbital
Taking into account that 20 Trialgin tablets contain only one maximum single dose of phenobarbital, while taking the drug, the risk of phenobarbital overdose is minimal.
special instructions
Trialgin should not be used for more than 5 days in a row.
In case of need for prolonged therapy exceeding 5 days, the functional state of the liver and the patient's peripheral blood picture should be monitored.
During treatment with Trialgin, it is required to limit the consumption of products that include caffeine, since excessive intake of the latter aggravates the risk of insomnia, irritability, nervousness, and in some cases, tachycardia.
With caution, it is recommended to carry out therapy for persons with hyperthyroidism, gout, arrhythmia due to the presence of caffeine in the Trialgin tablets.
If an elevated body temperature and symptoms of colds persist for 48 hours after starting treatment, you should consult a doctor.
Against the background of long-term use of Trialgin in high doses, due to its constituent metamizole sodium, the threat of agranulocytosis or thrombocytopenia increases. As a result, if there is a sore throat, chills, unmotivated rise in temperature, difficulty swallowing, stomatitis, as well as signs of proctitis or vaginitis, it is necessary to urgently cancel the drug.
If pancytopenia is detected, therapy should also be stopped immediately and a complete blood count should be monitored until its indicators normalize.
If during treatment there is the development of such side effects as pallor, bruising, general weakness, persistent fever, infections, bleeding, as well as other possible signs of blood disorders, you should stop taking Trialgin and consult a doctor.
In the presence of atopic bronchial asthma and pollinosis, there is an increased threat of allergic reactions.
Against the background of the use of metamizole sodium in large doses, cases of the development of severe skin reactions - Stevens-Johnson syndrome and toxic epidermal necrolysis were recorded. If possible signs of these complications arise in the form of a progressive skin rash, often accompanied by ulceration of the mucous membrane or blisters, it is necessary to immediately stop taking Trialgin.
It is forbidden to take Trialgin to relieve acute abdominal pain until the cause of their development is established.
With prolonged use in the body, the accumulation of phenobarbital is possible.
Patients on a diet low in salt (sodium) should take into account that 1 tablet of Trialgin contains 0.85 mmol (19.64 mg) of sodium.
Influence on the ability to drive vehicles and complex mechanisms
During the period of therapy, due to the possible development of undesirable phenomena on the part of the central nervous system, caution is required when driving a car and controlling other complex mechanisms.
Application during pregnancy and lactation
During pregnancy, treatment with Trialgin is contraindicated.
If it is necessary to take an analgesic during lactation, it is necessary to resolve the issue of stopping breastfeeding.
Pediatric use
Trialgin therapy is contraindicated in patients under 18 years of age.
With impaired renal function
In renal failure (including moderate / mild), the rate of elimination of some metabolites of sodium metamizole (AAA and FAA) decreases. Such patients need to avoid repeated administration of high doses of the drug. With short therapy, dose adjustment is not required. There is no experience of long-term drug therapy.
Trialgin is contraindicated in patients with severe renal impairment.
For violations of liver function
In the presence of severe liver dysfunctions, as well as acute intermittent hepatic porphyria, due to the aggravated risk of seizures of this disease, Trialgin is contraindicated.
In patients with moderate / mild liver dysfunction, the rate of elimination of the drug is reduced, so they need to refrain from repeated use of high doses. With short-term therapy, dose reduction is not required. There is no experience of long-term treatment with the drug.
Use in the elderly
Since elderly people may experience a reduced excretion of metabolites of metamizole sodium and phenobarbital, they need to reduce the dose of Trialgin.
Drug interactions
Due to the combined composition of Trialgin, against the background of concomitant treatment with other drugs, it is required to take into account the likelihood of pharmacological interaction of each of its active components.
Metamizole sodium:
- other non-narcotic analgesics, hormonal contraceptives, tricyclic antidepressants, allopurinol: the risk of increased toxicity of these drugs is aggravated;
- oral antidiabetic agents, glucocorticosteroids (GCS), indirect anticoagulants, indomethacin: the activity of these agents increases;
- barbiturates, phenylbutazone and other inducers of liver microsomal enzymes: weaken the therapeutic effect of sodium metamizole;
- sedatives and anxiolytics (tranquilizers): enhance the analgesic effect of metamizole sodium;
- cyclosporine: the content of this substance in the blood decreases, therefore it is required to monitor its concentration;
- blockers of H2-histamine receptors, codeine, propranolol: the effect of these drugs is enhanced (inactivation slows down);
- cytostatics, thiamazole: the risk of leukopenia is aggravated;
- chlorpromazine: increased likelihood of severe hypothermia;
- myelotoxic drugs: increase the manifestation of hematotoxicity of metamizole sodium;
- ethanol: its effect is enhanced;
- methotrexate: the risk of increased hematotoxicity of this substance increases, especially in the elderly;
- colloidal blood substitutes, radiopaque drugs, penicillin: simultaneous use of these drugs with Trialgin is not recommended.
Caffeine:
- oral contraceptives, cimetidine, disulfiram, norfloxacin, ciprofloxacin: inhibit the metabolism of caffeine in the liver, as a result of which its elimination slows down and its content in the blood increases;
- caffeine-containing drinks and other drugs that stimulate the central nervous system: the risk of overstimulation of the central nervous system is aggravated;
- primidone, barbiturates, anticonvulsants (hydantoin derivative, especially phenytoin): can increase the metabolism of caffeine, as a result of which its clearance increases;
- furazolidone, monoamine oxidase inhibitors (MAO), selegiline, procarbazine: a significant increase in blood pressure or the occurrence of life-threatening arrhythmias is possible when the drug is combined in daily doses above 0.3 g with these agents;
- mexiletine: reduces the excretion of caffeine by 50%;
- β-adrenomimetics: additional stimulation of the central nervous system and other additive toxic effects may occur;
- calcium preparations: absorption of these agents in the gastrointestinal tract is weakened;
- nicotine: the rate of caffeine elimination increases;
- sleeping pills and narcotic drugs: their effectiveness decreases;
- cardiac glycosides: absorption is accelerated, the effect is enhanced and the toxicity of these agents increases;
- β-blockers: the risk of mutual suppression of therapeutic effects increases;
- lithium preparations: their elimination with urine increases;
- xanthines, including theophylline: it is possible to reduce the clearance of these drugs and increase the risk of developing additive pharmacodynamic and toxic effects;
- adenosine: it may be necessary to increase the dose of this substance, since caffeine is its antagonist.
Phenobarbital (its interaction with other drugs / substances is mainly related to its ability to induce cytochrome P450, mainly the isoenzyme CYP3A4):
- diazepam, amitriptyline, chlordiazepoxide, nialamide: their anticonvulsant effect is enhanced;
- sulfonamides, antibiotics: the antibacterial activity of these funds is weakened;
- reserpine: the anticonvulsant effect is weakened;
- griseofulvin: absorption of this substance decreases and, as a result, its antifungal activity;
- nicotinic acid, thiamine, belladonna extract, dextrose, atropine, psychostimulants, analeptics: hypnotic effect is weakened;
- muscle relaxants, narcotic analgesics, antipsychotics, sedatives and hypnotics, alcohol: their effect is enhanced;
- indirect anticoagulants, corticosteroids, doxycycline, estrogens and other drugs metabolized with the participation of microsomal liver enzymes: phenobarbital weakens their pharmacological activity;
- acetazolamide: reduces the reabsorption of phenobarbital in the kidneys and reduces its effect (due to alkalinization of urine).
Analogs
Trialgin analogs are Tetralgin, Piralgin, Pentalgin Plus, Santotitralgin, Pentalgin-N, Santoperalgin, Andipal, Pentalgin-ICN, Quintalgin, Sedalgin Plus, etc.
Terms and conditions of storage
Store out of the reach of children, protected from moisture and light, at a temperature not exceeding 25 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Available without a prescription.
Reviews about Trialgin
The few reviews about Trialgin are mostly positive. Patients note that the drug quickly and effectively relieves pain syndrome of various etiologies, brings down fever and weakens the symptoms of colds.
Occasionally they indicate a weak action of Trialgin with severe pain. Also, the disadvantages of the analgesic include a large number of contraindications.
Price for Trialgin in pharmacies
The average price for Trialgin, tablets 300 + 50 + 10 mg (metamizole sodium + caffeine + phenobarbital) varies in the range from 177 to 336 rubles. for 20 pcs. packaged.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
