Instruction for use: Pentabufen

Active substance Ibuprofen + Codeine + Caffeine + Metamizole sodium + Phenobarbital

Dosage form

Pills

Composition

One tablet contains:

Active substances:

Metamizole sodium - 300 mg

Ibuprofen 200 mg

Phenobarbital - 10 mg

Caffeine (Caffeine anhydrous) - 50 mg

Codeine phosphate hemihydrate in terms of anhydrous substance - 8 mg *

Auxiliary substances: - to obtain a tablet weighing 0.768 g

Crospovidone (Kollidon CL) 15 mg, Lodipress [lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%] 154 mg, Talc 23 mg, Calcium stearate monohydrate 8 mg

* corresponds to 6 mg of codeine in terms of anhydrous substance.

Description of dosage form

Round, flat-cylindrical tablets from white with a yellowish shade to white with a yellow shade of color with a facet and a risk, with a weak specific smell.

Pharmacological group

A nalgeziruyuschee means combined (analgesic opioid means + NSAIDs + analgesic non-narcotic means + psychostimulant + barbiturate)

Pharmacodynamics

Combined drug. Has analgesic, antipyretic and anti-inflammatory effect. Pharmacological properties of the drug are due to the action of the components that make up its composition.

Metamizole sodium is a derivative of pyrozolone, which has analgesic, 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.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid. The therapeutic effect of ibuprofen is related to the indiscriminate inhibition of the effects of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2) enzymes, which leads to inhibition of the synthesis of prostaglandins, mediators of pain, inflammation and hyperthermia. Ibuprofen has analgesic, antipyretic and anti-inflammatory effects. The analgesic effect occurs in 30 minutes and lasts 4-6 hours, the antipyretic effect occurs after 2-4 hours and lasts 4-8 hours.

Phenobarbital belongs to the barbiturate group. It interacts with the barbiturate site of benzodiazepine-γ-aminobutyric acid (GABA) - the 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, fatigue, increases mental and physical performance. In this combination, caffeine in a small dose has practically no stimulating effect on the central nervous system, but it increases the tone of the vessels of the brain and helps to accelerate blood flow.

Codeine interrupts reflexes that stimulate a prolonged cough by reducing the excitability of the cough center, and also has a weak analgesic effect due to the excitation of opioid receptors in various parts of the central nervous system and peripheral tissues, leading to stimulation of the antinociceptive system and changes in emotional perception of pain. In small doses does not cause depression of the respiratory center, does not disrupt the function of ciliated epithelium and does not reduce bronchial secretion.

Pharmacokinetics

Metamizole sodium after oral administration is hydrolyzed to pharmacologically active 4 N-methylaminoantipyrine (MAA). Bioavailability of MAA after oral administration is 90%, which is somewhat higher than with parenteral administration. Simultaneous food intake has no significant effect on the pharmacokinetics of metamizole sodium. Clinical efficacy is determined predominantly by MAA, and also to a lesser extent by 4 N -aminoantipyrine (AA) metabolites. The area under the concentration-time curve (AUC) AA is 25% of this value for the MAA. Metabolites 4 N-acetylaminoantipyrine (AAA) and 4 N-formylaminoantipyrine (FAA) do not have 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%, AA - 48%, FAA - 18% and AA - 14%. After a single oral intake, 85% of the dose is found in the urine as metabolites, of which 3 ± 1% - MAA, 6 ± 3% - AA, 26 ± 8% - AAA and 23 ± 4% - FAA. Renal clearance after a single dose of 1 g of metamizole sodium inside for MAA is 5 ± 2 ml / min, AA - 38 ± 13 ml / min, AAA - 61 ± 8 ml / min and FAA - 49 ± 5 ml / min. The corresponding half-lives from the 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, the AUC rises by 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 the available data, renal excretion of some metabolites (AAA and FAA) is reduced. Such patients should avoid the use of high doses.

Bioavailability

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

Ibuprofen

Suction

After ingestion ibuprofen is well absorbed.

Distribution

The maximum concentration (C m ax) in blood plasma when taking the drug on an empty stomach is reached after 45 minutes, with the reception during meals - after 1-3 hours. Food intake has little effect on the bioavailability of ibuprofen. Communication with blood proteins - 90%. Slowly penetrates into the joint cavity, lingers in the synovial tissue, creating in it greater concentrations than in the plasma.

Metabolism

After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into an active S-form. It is metabolized in the liver.

Excretion

It is excreted by the kidneys, mainly in the form of metabolites and their conjugates (unchanged not more than 1%), less excreted with bile and excreted through the intestine. T1 (half-life) - 2 hours. After oral administration, excretion of ibuprofen ends after 24 hours. Ibuprofen penetrates the placental barrier and is excreted in breast milk in an amount of less than 1 μg / ml.

Phenobarbital when taken 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 liver enzymes: CYP3A4, CYP3A5, CYP3A7 (the rate of enzymatic reactions increases 10-12 times), increases the detoxification function of the liver. Cumulates in the body. The half-life is 2-4 days. 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 solubility. The time to reach the maximum concentration is 50-75 minutes. after oral administration, 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% is metabolized 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 (in the unchanged form in adults, 1-2% is excreted).

Codeine after ingestion is rapidly absorbed. Connection with plasma proteins - 30%. TS m ah - after 2-4 hours. Metabolised in the liver to active metabolites; The isozyme CYP2D6 participates in the metabolism of the drug. 10% by demethylation passes into morphine. It is excreted by the kidneys (5-15% in the form of codeine and 10% in the form of morphine and its metabolites) and with bile. T1 - 2,5-4 hours.

Indications

Pentabufen® is used in pain syndrome of various genesis of mild and moderate intensity (including pain in joints, muscles, radiculitis, menstrual pains, neuralgia, headache and dental pain).

Contraindications

Hypersensitivity to the components of the drug; severe dysfunction of the liver and / or kidney; peptic ulcer of the stomach and duodenum in the stage of exacerbation; plantar fascial fibromatosis; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in history); amblyopia, scotoma; oppression of hematopoiesis (agranulocytosis, cytostatic or infectious neutropenia); conditions accompanied by respiratory depression; increased intracranial pressure, craniocerebral trauma; hearing loss, pathology of the vestibular apparatus; deficiency of lactase, lactose intolerance, glucose-galactose malabsorption; pregnancy and the period of breastfeeding, glaucoma; abuse of opioids, tranquilizers, sedatives in history; hemorrhagic diathesis, aplastic anemia, leukopenia; hepatic porphyria; simultaneous reception of alcohol; severe cardiovascular diseases (acute myocardial infarction, arrhythmia, arterial hypertension).

Codeine-containing drugs are contraindicated in children under the age of 12 years, as well as children and adolescents aged 12 to 18 years in the presence of respiratory pathology (eg, bronchial asthma and other chronic respiratory diseases) after a previous tonsillectomy and / or adenoidectomy, with impaired respiratory function, including neuromuscular disorders, severe heart disease, multiple injuries, or extensive surgical interventions.

With caution - gastric ulcer and duodenal ulcer in remission, gastritis, enteritis, colitis; concomitant diseases of the liver and / or kidney; chronic heart failure; blood diseases of unclear etiology; A bronchial asthma, a urticaria, a rhinitis, polyps of a mucous nose; hyperbilirubinemia; hypothyroidism; elderly age; people who have abused alcohol in their history.

pregnancy and lactation

The drug is contraindicated for use during pregnancy and during breastfeeding.

Codeine is contraindicated during breastfeeding. When administered at therapeutic doses, codeine itself and its active metabolites can be excreted into breast milk. With the usual activity of the isoenzyme CYP2D6, these substances will not affect the newborn due to very low concentrations. But with high activity in the patient of the isoenzyme CYP2D6 in the body, high amounts of the metabolite codeine-morphine can be formed, which, when released into breast milk, can cause symptoms of opioid intoxication in the newborn and lead to death. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration

Inside. 1 tablet 1-3 times a day, with water. The maximum daily dose is 4 tablets. If symptoms persist for 2-3 days after taking the drug, stop treatment and consult a doctor.

Side effects

When using the drug for 2-3 days, side effects are almost not observed. In the case of prolonged use, the following side effects may occur:

From the immune system: a high risk of developing anaphylactic reactions and agranulocytosis, which can occur at any stage of treatment. These reactions do not depend on the daily dose of the drug. Reactions of hypersensitivity: skin itch rash, urticaria, Quincke's edema, bronchospasm (triggering bronchial asthma), dyspnea.

From the gastrointestinal tract: dry mouth, abdominal pain, constipation, loss of appetite, nausea, vomiting, heartburn, anorexia, a feeling of discomfort in the epigastrium, diarrhea, flatulence, impaired liver function.

From the central nervous system: headache, dizziness, decreased speed of psychomotor reactions, drug dependence (codeine), irritability, tremor, coordination disorders, anxiety, hearing loss, tinnitus, insomnia, agitation, respiratory depression, increased sweating, drowsiness, depression, fast fatigue. At long uncontrolled reception in high doses - accustoming (weakening of an anesthetizing effect).

From the cardiovascular system: heart failure, tachycardia, extrasystole, lowering blood pressure.

From the side of the kidneys and urinary tract: with prolonged intake of high doses of the drug, it is possible to develop renal dysfunction (interstitial nephritis, development of kidney failure), edematous syndrome.

On the part of the blood and lymphatic system: hemolytic anemia, very rarely - thrombocytopenia; leukopenia.

From the skin: rash, itching, hives.

Laboratory and instrumental data: increased activity of hepatic transaminases.

When using drugs containing phenobarbital, reports were received about the development of life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis).

In case of adverse reactions, including those not specified in this manual, you should stop taking the medication and consult a doctor!

Overdose

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

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

Symptoms

Acute overdose is manifested by nausea, vomiting, abdominal pain, impaired renal function - acute kidney failure (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, primary detoxification (for example, gastric lavage) or sorption therapy (for example, activated charcoal) is carried out in order to restrict the intake of the drug. The main metabolite (4 N-methylaminoantipyrine) is removed during hemodialysis, hemofiltration, gesmeperfusion and plasmafiltration. Treatment of an overdose, as well as the prevention of serious complications, may require general and special intensive medical supervision and treatment.

Ibuprofen

Symptoms

Ibuprofen in a dose of 100 mg / kg of body weight is non-toxic, doses above 400 mg / kg of body weight can cause severe intoxication.

From the side of the nervous system: headache, dizziness, blocking, drowsiness, depression, tinnitus, nystagmus, convulsions, up to coma.

There may be abdominal pain, nausea, vomiting, diarrhea.

In severe cases, overdose can cause acute renal and / or hepatic insufficiency, metabolic acidosis, lowering of blood pressure, bradycardia, tachycardia, atrial fibrillation, respiratory arrest.

Treatment of acute overdose

As soon as possible, you should rinse the stomach or induce a vomiting reflex with the subsequent intake of activated charcoal (only within an hour after intake), appoint an alkaline drink. Symptomatic treatment aimed at maintaining the vital vital functions of the body. Control and the necessary correction of the water-electrolyte balance.

In the case of frequent or prolonged seizures, anticonvulsant drugs (diazepam and lorazepam) should be used.

Phenobarbital

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

Caffeine

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.

Codeine causes constipation, urinary retention, impaired coordination of eyeball movements, miosis, suppression of the respiratory center.

Treatment: gastric lavage with activated charcoal, potassium permanganate; alkaline drink, forced diuresis, symptomatic therapy. Introduction of respiratory analeptics, atropine and a competitive physiological antagonist codeine - naloxone.

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. Metamizole sodium increases the activity of oral hypoglycemic drugs, indirect anticoagulants, glucocorticoids 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. Medative and anxiolytic drugs (tranquilizers) increase the analgesic effect of metamizole sodium. Thiamazole and cytostatics increase the risk of developing leukopenia. The effect is enhanced by codeine, H2-histamine receptor blockers and propranolol (slows inactivation). Myelotoxic 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.

Ibuprofen

It is necessary to take into account the interaction of ibuprofen with the following drugs:

- Acetylsalicylic acid and other NSAIDs: increased risk of ulcerative lesions of the gastrointestinal tract and gastrointestinal bleeding. Ibuprofen can inhibit the anti-inflammatory and antiplatelet effect of acetylsalicylic acid (aspirin) in small doses when administered simultaneously.

- Glucocorticosteroids and mineralocorticosteroids: increased risk of ulcerative lesions of the gastrointestinal tract or development of gastrointestinal bleeding.

- Hypotensive drugs and diuretics: NSAIDs can reduce the effects of diuretics and antihypertensive drugs. In some patients with impaired renal function (eg, in patients with dehydration, or in elderly patients with impaired renal function), concomitant use of ACE inhibitors, β-blockers and angiotensin II receptor inhibitors with cyclooxygenase inhibitory drugs can lead to further impairment of function kidney, including the possibility of developing acute renal failure, which is usually reversible. Therefore, this combination should be used with caution, especially in elderly patients. Patients should be sufficiently hydrated; after the beginning of combination therapy and periodically in the future they should monitor kidney function.

- Potassium-sparing diuretics: simultaneous use of ibuprofen and potassium-sparing diuretics can lead to hyperkalemia (it is recommended to monitor the potassium content in the blood).

- Indirect anticoagulants, antiaggregants, fibrinolytics: NSAIDs may enhance the effects of indirect anticoagulants, such as warfarin.

- Thrombolytics: with simultaneous use with thrombolytic drugs (alteplase, streptokinase, urokinase), the risk of bleeding increases.

- Selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.

- Lithium preparations, digoxin, phenytoin: Combined therapy with ibuprofen with lithium preparations, digoxin or phenytoin may increase the serum concentrations of these drugs.

- Methotrexate: the use of ibuprofen at a dose of 200 mg for 24 hours before or after the administration of methotrexate may lead to an increase in the concentration of methotrexate in the blood plasma and the increase in its toxic effect.

- Baclofen: There are clinical data indicating that NSAIDs can increase plasma concentrations of baclofen.

- Zidovudine: There is evidence that the risk of hemarthrosis and hematoma increases in HIV-infected patients with hemophilia who are receiving both zidovudine and ibuprofen.

- Quinolones: data from animals indicate that NSAIDs may increase the risk of seizures associated with the use of quinolones. Patients taking both quinolones and ibuprofen simultaneously have an increased risk of seizures.

- Cyclosporine, tacrolimus, gold preparations: the risk of nephrotoxicity may be increased by decreasing the synthesis of prostaglandins in the kidneys. During combined therapy, renal function should be carefully monitored, especially in elderly patients. Ibuprofen increases the plasma concentration of cyclosporine and the likelihood of its hepatotoxic effects.

- Mifepristone: because NSAIDs can reduce the effectiveness of mifepristone, NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

- Drugs that block tubular secretion: may increase the plasma concentration of ibuprofen.

- Hypoglycemic drugs for oral administration, derivatives of sulfonylureas: as a precautionary measure, it is recommended to monitor the concentration of glucose in the blood when they are used together.

- Sulfinpyrazone, probenecid: when combined with ibuprofen, the inhibition of ibuprofen excretion is possible.

- Aminoglycosides: ibuprofen may reduce the clearance of aminoglycosides, which may increase the nephrotoxicity and hepatotoxicity of these drugs.

- Cefamandol, cefoperazone, cefotetan, valproic acid, plikamycin: may increase the incidence of hypoprothrombinemia when co-administered with ibuprofen.

-Microsomal oxidation inductors (phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants): when combined, they increase the production of hydroxylated active metabolites, increasing the risk of severe intoxication.

- Urikozuric drugs: ibuprofen reduces the effectiveness of uricosuric drugs.

- Estrogens, ethanol: with the simultaneous use of ibuprofen may increase the side effects of estrogens, ethanol.

- Antacids and colstiraamine: drugs reduce the absorption of ibuprofen.

- Caffeine: Caffeine increases the analgesic effect of ibuprofen.

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, glucocorticoids, 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, analgesics and psychostimulants. When combined with reserpine, anticonvulsant action decreases, under the influence of amitriptyline, nialamide, diazepam, chlordiazepoxide - is amplified. Acetazolamide, alkalinizing urine, reduces the reabsorption of phenobarbital in the kidneys and weakens its effect.

Caffeine: with the combined use of caffeine and barbiturates, primidone, anticonvulsant drugs (hydantoin derivatives, especially phenytoin), it is possible to increase metabolism and increase caffeine clearance. Simultaneous use with cimetidine, oral contraceptives, disulfiram, ciprofloxacin, norfloxacin leads to a decrease in the metabolism of caffeine in the liver, slowing its elimination and increasing the concentration in the blood. When used with caffeinated drinks and other drugs that stimulate the central nervous system, excessive stimulation of the central nervous system is possible. Caffeine is an adenosine antagonist (large doses of adenosine may be required). Mexiletine reduces caffeine withdrawal to 50%; nicotine increases the rate of caffeine withdrawal. Large doses of caffeine (more than 300 mg / day) can cause the development of life-threatening cardiac arrhythmias or a pronounced increase in blood pressure when combined with monoamine oxidase (MAO) inhibitors, furazolidone, procarbazine and selegiline. 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. Joint use of caffeine with β-adrenoblockers can lead to mutual suppression of therapeutic effects: with β-adrenomimetics - to additional stimulation of the central nervous system and other additive toxic effects.

Caffeine can reduce the clearance of theophylline and, possibly, other xanthines, increasing the possibility of additive pharmacodynamic and toxic effects.

Codeine

Pharmacodynamicsinteraction: chloramphenicol inhibits the metabolism of codeine in the liver and thereby enhances its action in the body. With the simultaneous use of drugs, depressing the central nervous system (hypnotics, antipsychotic, etc.), it is possible to increase the sedative effect and depressant effect on the respiratory center. Codeine enhances the effect of ethanol on the psychomotor function.

Pharmacodynamics interaction: chloramphenicol inhibits the metabolism of codeine in the liver and thereby enhances its action in the body. With the simultaneous use of drugs, depressing the central nervous system (hypnotics, antipsychotic, etc.), it is possible to increase the sedative effect and depressant effect on the respiratory center. Codeine enhances the effect of ethanol on the psychomotor function.

Pharmacokinetic interaction: when using codeine in large doses, the action of cardiac glycosides can be intensified, since in connection with impaired peristalsis, absorption decreases. Adsorbents, astringents and enveloping agents can reduce the absorption of codeine in the gastrointestinal tract.

special instructions

It is necessary to have medical control during the period of taking the drug. When using the drug for more than 5 days, control of peripheral blood and the functional state of the liver is necessary. Taking the drug may make it difficult to diagnose an acute pain syndrome in the abdomen. In the period of productive cough, the drug is able to suppress the cough reflex, which can lead to the accumulation of sputum in the lumen of the bronchi and, consequently, to worsen the patient's condition.

Avoid prolonged use of the drug, since the codeine and phenobarbital contained in it can cause the development and formation of drug dependence.

During the treatment with Pentabufen® it is necessary to refrain from drinking alcohol because of the worsening of tolerability of the drug.

Pentabufen® should not be taken to patients who have previously been hypersensitive to taking medications containing methamizole sodium. The sodium metamizole contained in the preparation can stain the urine red, but this has no clinical significance.

Pentabufen® should be taken with caution in elderly patients who show signs of intoxication more often.

It should avoid taking the drug to patients with peptic ulcer disease in the stomach and duodenal ulcers in the acute phase, as well as patients with severe renal and hepatic insufficiency.

In patients with impaired renal function, excretion of codeine is slowed, so it is recommended to extend the intervals between doses of the drug. If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the test. The drug is not recommended for patients with high activity of cytochrome P450 enzymes (CYP2D6).

Long-term use of the drug may lead to the development of codeine dependence. Phenobarbital is addictive. Formation of dependence can occur with long uncontrolled administration of the drug. In this case, the intervention of an expert in narcology is required.

Athletes should remember that the drug contains codeine and is doping.

The involvement of the CYP2D6 isoenzyme in metabolism

Codeine is metabolized by the isoenzyme CYP2D6 to the active metabolite - morphine. If the patient's activity is insufficient, or if the enzyme is absent in the body, it is not possible to achieve a sufficient analgesic effect in the treatment. Presumably, 7% of the population of the Caucasoid race has insufficient activity of CYP2D6. With high activity of codeine metabolism, there is an increased risk of developing undesirable effects of opioid toxicity even when taking the drug at recommended doses. In patients in this group, codeine is rapidly metabolized to morphine, which in plasma reaches higher concentrations than the rest of the population.

Common symptoms of opioid toxicity include: confusion, drowsiness, shallow breathing, narrowing of the pupils, nausea, vomiting, constipation and lack of appetite. In severe cases, a circulatory and respiratory collapse, which is dangerous to the life of the patient, may develop.

The expected frequency of high isoenzyme activity in different populations is presented below:

Population

Frequency %

Africans / Ethiopians 29%

African Americans 3.4 - 6.5%

The Mongoloid race 1,2 - 2%

European race 3.6-6.5%

Greeks 6.0%

Hungarians 1.9%

Northern Europeans 12%

Influence on ability to drive vehicles, mechanisms

When taking Pentabufen®, it is necessary to refrain from carrying out potentially dangerous activities requiring an increased concentration of attention and speed of psychomotor reactions (vehicle management, work with moving mechanisms, dispatcher and operator work).

Form of issue

Pills. For 10 tablets in a planar cell package. One or two contour mesh packs, together with the instructions for use, are placed in a pack of cardboard.

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

2 years.

Do not use the drug after the expiration date.

Conditions of leave from pharmacies

On prescription.