BISOPROLOL AUROBINDO

INSTRUCTIONS for medical use of Tet 36.6® MAXI with lemon flavor (Tet 36.6® MAXI with lemon flavor)

Composition

active substances: paracetamol, phenylephrine hydrochloride, pheniramine maleate, ascorbic acid; 1 sachet contains paracetamol 500 mg, phenylephrine hydrochloride 10 mg, pheniramine maleate 20 mg, ascorbic acid 50 mg; excipients: sodium citrate, citric acid, lemon flavor, quinoline yellow dye (E 104), colloidal anhydrous silicon dioxide, white sugar, sucrose.

Pharmaceutical form

Powder for oral solution.

Main physical and chemical properties

Granulated, loose powder, which is a mixture of white, pale yellow and/or yellow granules with a lemon smell.

Pharmacotherapeutic group

Analgesics and antipyretics. Paracetamol, combinations without psychoplegics. ATC code N02B E51.

Pharmacological properties

Pharmacodynamics

Paracetamol has antipyretic, analgesic and weak anti-inflammatory effects. It inhibits prostaglandin synthesis in the central nervous system (CNS) and blocks the transmission of pain impulses.

Pheniramine maleate is a histamine H1 receptor blocker, reduces vascular permeability, eliminates lacrimation, itching of the eyes and nose.

Phenylephrine hydrochloride is an alpha-adrenomimetic, has a vasoconstrictive effect, reduces swelling of the nasal mucosa and paranasal sinuses.

Ascorbic acid enhances the body's non-specific resistance.

Pharmacokinetics

Paracetamol is well absorbed, passes through the placental barrier, slightly penetrates into breast milk, is metabolized by the cytochrome P450 system, excreted by the kidneys, the half-life is 1-4 hours. The duration of action is 3-4 hours.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is metabolized in the liver by the cytochrome P450 system, the half-life is 16-18 hours, 70-83% is excreted by the kidneys.

The effect of phenylephrine hydrochloride occurs quickly and lasts for about 20 minutes. It is metabolized in the liver or gastrointestinal tract, excreted by the kidneys.

Ascorbic acid is quickly absorbed from the gastrointestinal tract, metabolized in the liver, excreted by the kidneys.

Clinical characteristics

Indications

Symptomatic treatment of acute respiratory infections and influenza:

• increased body temperature,
• headache,
• nasal congestion,
• chills,
• muscle pain and weakness.

Contraindications

Increased sensitivity to the components of the drug; severe liver and/or kidney function disorders; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; phenylketonuria, alcoholism; blood diseases; leukopenia; anemia; severe forms of arrhythmia, arterial hypertension, atherosclerosis, coronary heart disease; hyperthyroidism; acute pancreatitis; prostatic hyperplasia with urinary retention; obstruction of the urethra; pyloroduodenal obstruction; bronchial asthma; closed-angle glaucoma; pheochromocytoma; thrombosis; thrombophlebitis; diabetes mellitus; epilepsy; state of increased excitement; sleep disorders, concomitant treatment with tricyclic antidepressants, beta-blockers, other sympathomimetics, drugs that suppress or enhance appetite and amphetamine-like psychostimulants; concomitant treatment and 2 weeks after the use of MAO inhibitors.

Interaction with other medicinal products and other types of interactions

The rate of paracetamol absorption may increase when used with metoclopramide and domperidone, and decrease with cholestyramine (this effect is minor if cholestyramine is used 1 hour after). With prolonged use of paracetamol, the anticoagulant effect of warfarin and other coumarin derivatives may be enhanced, and the risk of bleeding may increase. With episodic use of paracetamol, this effect is not pronounced. Barbiturates reduce the antipyretic effect of paracetamol. Hepatotoxic drugs increase the likelihood of paracetamol accumulation and overdose. The risk of paracetamol hepatotoxicity increases when taking drugs that induce liver microsomal enzymes (barbiturates; anticonvulsants - phenytoin, phenobarbital, carbamazepine; antitubercular - rifampicin, isoniazid). Paracetamol reduces the effectiveness of diuretics, may prolong the half-life of chloramphenicol; may induce the metabolism of lamotrigine in the liver, thereby reducing its bioavailability and effectiveness. With regular use of paracetamol and zidovudine, neutropenia and increased risk of liver damage are possible. When taking probenecid, the dose of paracetamol should be reduced, as it affects the metabolism of paracetamol. Paracetamol may affect the results of determining the level of uric acid by the phosphor-tungstic acid method. Hepatotoxicity of paracetamol may be increased with prolonged or excessive alcohol consumption. It is not recommended to use it simultaneously with alcohol.

Caution should be exercised when using paracetamol with flucloxacillin, as such concomitant use is associated with metabolic acidosis with a high anion gap, especially in patients with risk factors (see "Special instructions" section).

Interaction of phenylephrine with MAO inhibitors causes a hypertensive effect, with tricyclic antidepressants (amitriptyline) - increases the risk of cardiovascular side effects, with digoxin and cardiac glycosides - leads to arrhythmias and infarction, with other sympathomimetics increases the risk of cardiovascular side effects and arterial hypertension, may reduce the effectiveness of beta-blockers and other antihypertensive drugs (reserpine, methyldopa, debrisoquine, guanethidine) with increased risk of arterial hypertension and cardiovascular side effects. Concomitant use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism.

Ascorbic acid, when taken orally, enhances the absorption of iron; increases the level of ethinylestradiol, penicillins, tetracyclines; reduces the level of antipsychotic drugs, phenothiazine derivatives in the blood; reduces the effectiveness of heparin and indirect anticoagulants; increases the risk of crystalluria when treated with salicylates and the risk of glaucoma when treated with glucocorticosteroids; large doses reduce the effectiveness of tricyclic antidepressants. Ascorbic acid can be taken only 2 hours after injection of deferoxamine, as their concomitant use increases the toxicity of iron, especially in the myocardium, which can lead to cardiac decompensation. Long-term use of large doses can accelerate its own metabolism, and after withdrawal of treatment, a paradoxical hypovitaminosis is possible. It should not be used concomitantly with other drugs containing vitamin C. Absorption of ascorbic acid may change when intestinal motility is disturbed, enteritis or gastric secretion is reduced.

Pheniramine enhances the anticholinergic effect of atropine, spasmolytics, tricyclic antidepressants, antiparkinsonian drugs, inhibits the action of anticoagulants. Concomitant use of pheniramine with sedatives, barbiturates, tranquilizers, anesthetics, narcotic analgesics, alcohol can significantly increase its suppressive effect.

Special instructions

Do not exceed the recommended doses. If symptoms do not improve within 5 days or are accompanied by high fever, fever lasting more than 3 days, rash, or prolonged headache, you should consult a doctor, as these symptoms may be signs of a more serious illness.

In connection with the risk of severe liver damage in case of overdose, do not use it simultaneously with other drugs for symptomatic treatment of colds and chills (vasoconstrictors, paracetamol-containing). It should be prescribed with caution in case of Raynaud's disease, arterial hypertension, heart disease, arrhythmia, bradycardia, thyroid disease, liver and kidney disease, acute hepatitis, glaucoma, chronic lung disease, prostatic hyperplasia (as there is a risk of urinary retention), elderly patients, with increased blood coagulation, hemolytic anemia, chronic malnutrition, dehydration, stenosing peptic ulcer. The risk of hepatotoxicity increases in persons with alcoholic liver damage and in persons who abuse alcohol.

It is recommended to be cautious when using paracetamol with flucloxacillin due to the increased risk of metabolic acidosis with a high anion gap, especially in patients with severe renal insufficiency, sepsis, malnutrition, and other causes of glutathione deficiency (e.g., chronic alcoholism), as well as when using maximum daily doses of paracetamol. Careful monitoring, including measurement of 5-oxoproline in urine, is recommended.

The drug contains: phenylephrine, which can cause angina attacks; sucrose, which is contraindicated in patients with intolerance and impaired absorption of fructose, glucose-galactose or sucrose-isomaltose. If a patient has intolerance to some sugars, they should consult a doctor before taking this medication. It should be used with caution in patients with diabetes mellitus. It can be harmful to teeth.

Before using the drug, it is necessary to consult a doctor in case of liver or kidney disease; when taking warfarin or similar anticoagulants; when taking analgesics every day for mild arthritis; bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

The drug may affect the results of laboratory tests for glucose, uric acid, creatinine, inorganic phosphates in the blood. It may be a negative result of the study of hidden blood in the stool.

In patients with severe infections (sepsis), in which the level of glutathione decreases, when taking paracetamol, the risk of metabolic acidosis increases, its symptoms - deep, rapid or difficult breathing, nausea, vomiting, loss of appetite, in this case, you should immediately consult a doctor.

It is not recommended to take this medication at the end of the day, as ascorbic acid in large doses has a mild stimulating effect. Due to the stimulating effect of ascorbic acid on the production of corticosteroid hormones, monitoring of kidney function and blood pressure is required.

With special caution, the drug should be prescribed to patients with iron metabolism disorders (hemochromatosis, hemochromatosis, thalassemia), with a history of nephrolithiasis (risk of hyperoxaluria and deposition of oxalates in the urinary tract after taking large doses of ascorbic acid).

Prolonged use of large doses of ascorbic acid can accelerate its own metabolism, and after withdrawal of treatment, a paradoxical hypovitaminosis is possible. It should not be used concomitantly with other drugs containing vitamin C. Absorption of ascorbic acid may change when intestinal motility is disturbed, enteritis or gastric secretion is reduced.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy or breastfeeding. The effect of the drug on fertility has not been specifically studied. Preclinical studies have not revealed any special effect of paracetamol on fertility when used in therapeutic doses. There have been no adequate studies on the effect of phenylephrine and pheniramine on reproductive toxicity in animals.

Ability to affect the speed of reaction when driving vehicles or other mechanisms

Since the drug can cause drowsiness and other side effects from the nervous system and eyes, it is not recommended to drive a car and work with complex mechanisms when using it.

Method of use and doses

The contents of the sachet should be dissolved in a glass of hot water (not boiling) and drunk. The drug can be taken repeatedly every 3-4 hours, but no more than 3 sachets per day.

The maximum duration of use is 5 days.

Children

The drug is contraindicated in children under 14 years of age.

Overdose

Paracetamol. Within the first 24 hours, pallor of the skin, nausea, vomiting, anorexia, and abdominal pain appear. When taking large doses, disorders of orientation, psychomotor excitement, dizziness, sleep disturbances, heart rhythm, pancreatitis, and liver necrosis may be observed. The first sign of liver damage may be abdominal pain, which may not always occur within the first 12-48 hours, but may occur later, up to 4-6 days after taking the drug. Liver damage usually occurs within 72-96 hours after taking the drug. Metabolic disorders of glucose and metabolic acidosis, bleeding may occur. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia are possible.

In individual cases, acute renal failure with necrosis of the tubules has been reported, which is possible even in the absence of severe liver damage, manifested by severe back pain, hematuria, proteinuria. Nephrotoxicity is possible: kidney colic, interstitial nephritis, capillary necrosis.

The use of 10 g or more of paracetamol in adults, especially with alcohol, and more than 150 mg/kg of body weight in children, can lead to hepatocellular necrosis with the development of encephalopathy, bleeding, hypoglycemia, liver coma, and fatal outcome. In patients with risk factors (prolonged treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, or other drugs that induce liver enzymes; alcohol abuse; glutathione cachexia (gastrointestinal disorders, cystic fibrosis, HIV infection, hunger, cachexia)), the use of 5 g or more of paracetamol can lead to liver damage.

In case of overdose, immediate medical attention is required. The patient should be taken to the hospital immediately, even if there are no early symptoms of overdose. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage. Within the first hour after overdose, activated charcoal should be taken. The concentration of paracetamol in the blood should be measured after 4 hours or later (earlier concentrations are unreliable). N-acetylcysteine can be used within 24 hours after taking paracetamol, but the maximum effect occurs when used within the first 8 hours, after which its effectiveness decreases rapidly. If necessary, N-acetylcysteine should be administered intravenously according to the established dosage regimen. As an alternative, methionine can be used orally in the absence of vomiting.

Phenylephrine. Hyperhidrosis, psychomotor excitement or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmia, tremor, hyperreflexia, convulsions, nausea, vomiting, irritability, restlessness, arterial hypertension, and in severe cases - coma. To eliminate hypertensive effects, alpha-receptor blockers can be used intravenously, and for the elimination of convulsions - diazepam.

Pheniramine. Atropine-like symptoms occur: mydriasis, photophobia, dryness of the skin and mucous membranes, hyperthermia, atony of the intestine. CNS depression leads to disorders of the respiratory and cardiovascular systems (bradycardia, arterial hypotension, collapse). Symptoms caused by the mutual potentiation of the parasympatholytic effect of pheniramine and the sympathomimetic effect of phenylephrine: drowsiness, which can be followed by excitement (especially in children) or CNS depression, vision disturbances, rash, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disorders, bradycardia. There is no specific antidote for the treatment of overdose with antihistamine drugs. Standard first aid should be provided, including administration of activated charcoal, saline laxative, and standard measures to support the cardiovascular system. Stimulants should not be used, and for the treatment of arterial hypotension, vasoconstrictor agents can be used.

Ascorbic acid. Nausea, vomiting, or diarrhea (which disappear after its cancellation); bloating and abdominal pain, itching, skin rash, increased excitability. Doses over 3000 mg can cause temporary osmotic diarrhea and gastrointestinal disorders, disorders of zinc, copper, and iron metabolism, cardiomyopathy, and with prolonged use in large doses, suppression of the function of the insulin apparatus of the pancreas and glucosuria is possible. Overdose can lead to changes in renal excretion of ascorbic and uric acid during acetylation of urine with the formation of oxalate stones.

Symptomatic treatment: within the first 6 hours, it is necessary to rinse the stomach, and within the first 8 hours - to introduce methionine orally or cysteine or N-acetylcysteine intravenously.

Side effects

From the skin and subcutaneous tissue: rash, itching, dermatitis, urticaria, multiform exudative erythema, Stevens-Johnson syndrome, Lyell's syndrome.

From the immune system: hypersensitivity reactions, including anaphylactic shock, angioedema.

Neurological disorders: headache, dizziness, tremor, anxiety, nervousness, irritability, feeling of fear, insomnia, drowsiness, confusion, hallucinations, psychomotor excitement, disorientation, depressive state, paresthesia, tinnitus, in individual cases - coma, convulsions, dyskinesia, behavioral changes.

From the respiratory system: bronchospasm in patients sensitive to acetylsalicylic acid and NSAIDs.

From the organs of vision: vision and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

From the gastrointestinal tract: nausea, vomiting, heartburn, dry mouth, discomfort and abdominal pain, constipation, diarrhea, meteorism, anorexia, aphthae, hypersalivation, hemorrhage, irritation of the mucous membranes.

From the hepatobiliary system: liver function disorders, hypertransaminasemia, usually without jaundice, liver necrosis (when using high doses).

From the endocrine system: hypoglycemia, up to hypoglycemic coma.

From the blood and lymphatic system: anemia, including hemolytic, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnea, chest pain), bruising or bleeding, thrombocytopenia, neutropenia, agranulocytosis, leukopenia, pancytopenia.

From the kidneys and urinary system: nephrotoxicity, interstitial nephritis, capillary necrosis, dysuria, urinary retention, and difficulty urinating, kidney colic, kidney failure.

Cardiac disorders: arterial hypertension, tachycardia, bradycardia, increased heart rate, arrhythmia, dyspnea, chest pain, angina attacks.

Other: general weakness, malaise.

In contrast to antihistamine drugs of the second generation, the use of pheniramine is not associated with the prolongation of the QT interval and cardiac arrhythmia.

Reporting suspected adverse reactions after registration of the medicinal product is important. This allows monitoring the ratio of benefit/risk when using this medicinal product. Medical and pharmaceutical workers, as well as patients or their authorized representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product through the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store at a temperature not exceeding 25 °C. Store in a place inaccessible to children.

Packaging

23 g in a sachet, 5 or 10 sachets in a pack.

Release category

Without a prescription.

Manufacturer

Private Joint-Stock Company "Lekhim-Kharkiv).

Location of the manufacturer and address of the place of its activity

Ukraine, 61115, Kharkiv region, Kharkiv, Severina Pototskogo street, 36.