Tet 36.6® maxi with lemon flavor

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Tet 36.6® MAXI with lemon flavour (Tet 36.6® MAXI with lemon flavour)

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 flavour, quinoline yellow dye (E 104), colloidal anhydrous silicon dioxide, white sugar, sucrose.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: granular, free-flowing powder consisting of a mixture of white, pale yellow and/or yellow granules with a lemon odour.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol combinations without psycholeptics.

ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

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

Pheniramine maleate is a histamine H1-receptor blocker that reduces vascular permeability and relieves lacrimation, as well as itching of eyes and nose.

Phenylephrine hydrochloride is an α-adrenergic agonist that produces vasoconstrictive action, reducing swelling of the nasal mucosa and paranasal sinuses.

Ascorbic acid enhances nonspecific resistance of the body.

Pharmacokinetics.

Paracetamol is well absorbed, crosses the placental barrier, and passes into breast milk to a minor extent. It is metabolized by the cytochrome P450 system, excreted by the kidneys, with a half-life of 1–4 hours. 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, with a half-life of 16–18 hours; 70–83% is excreted by the kidneys.

The effect of phenylephrine hydrochloride begins rapidly and lasts approximately 20 minutes. It is metabolized in the liver or gastrointestinal tract and excreted by the kidneys.

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

Clinical characteristics.

Indications.

Symptomatic treatment of acute respiratory infections and influenza:

• elevated body temperature,
• headache,
• nasal congestion,
• rhinitis,
• muscle pain and aching.

Contraindications.

Hypersensitivity to the components of the drug; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; phenylketonuria; alcoholism; blood disorders; leukopenia; anemia; severe forms of arrhythmia, arterial hypertension, atherosclerosis, ischemic heart disease; hyperthyroidism; acute pancreatitis; prostate hypertrophy with urinary retention; bladder neck obstruction; pyloroduodenal obstruction; bronchial asthma; closed-angle glaucoma; pheochromocytoma; thrombosis; thrombophlebitis; diabetes mellitus; epilepsy; excited state; sleep disorders associated with treatment with tricyclic antidepressants, β-blockers, other sympathomimetics, appetite-suppressing or appetite-enhancing drugs, and amphetamine-like psychostimulants; concomitant therapy and within 2 weeks after administration of MAO inhibitors.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may increase when used with metoclopramide and domperidone, and decrease when used with cholestyramine (this effect is insignificant if cholestyramine is administered 1 hour apart). Long-term use of paracetamol may enhance the anticoagulant effect of warfarin and other coumarin derivatives, increasing the risk of bleeding. This effect is not pronounced with occasional use of paracetamol. Barbiturates reduce the antipyretic effect of paracetamol. Hepatotoxic drugs increase the likelihood of paracetamol accumulation and overdose. The risk of paracetamol hepatotoxicity increases with drugs that induce hepatic microsomal enzymes (barbiturates; anticonvulsants – phenytoin, phenobarbital, carbamazepine; antituberculosis drugs – rifampicin, isoniazid). Paracetamol reduces the efficacy of diuretics, may prolong the half-life of chloramphenicol; may induce hepatic metabolism of lamotrigine, thereby reducing its bioavailability and efficacy. Regular concomitant use of paracetamol and zidovudine may lead to neutropenia and increased risk of liver damage. The dose of paracetamol should be reduced when taken with probenecid, as it affects paracetamol metabolism. Paracetamol may interfere with the determination of uric acid levels by the phosphotungstic acid method. Hepatotoxicity of paracetamol may be enhanced by prolonged or excessive alcohol consumption. Do not use concurrently with alcohol.

Paracetamol should be used with caution when administered concomitantly with floxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

Phenylephrine interaction with MAO inhibitors causes a hypertensive effect; with tricyclic antidepressants (amitriptyline) – increases the risk of cardiovascular adverse reactions; with digoxin and cardiac glycosides – may lead to arrhythmias and infarction; with other sympathomimetics – increases the risk of cardiovascular adverse reactions and arterial hypertension; may reduce the effectiveness of β-blockers and other antihypertensive agents (reserpine, methyldopa, debrisoquin, guanethidine), increasing the risk of arterial hypertension and cardiovascular adverse reactions. Concurrent use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism.

Ascorbic acid, when taken orally, enhances iron absorption; increases levels of ethinylestradiol, penicillins, and tetracyclines; reduces blood levels of antipsychotic drugs and phenothiazine derivatives; reduces the effectiveness of heparin and indirect anticoagulants; increases the risk of crystalluria during salicylate therapy and the risk of glaucoma during glucocorticoid therapy; large doses reduce the effectiveness of tricyclic antidepressants. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their concomitant use increases iron toxicity, especially in the myocardium, potentially leading to cardiac decompensation. Prolonged use of high doses during disulfiram treatment inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taken with oral contraceptives, fruit or vegetable juices, or alkaline drinks.

Pheniramine enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents; it may inhibit the action of anticoagulants. Concurrent use of pheniramine with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol may significantly enhance its CNS depressant effects.

Special precautions for use.

Do not exceed the recommended doses. If symptoms do not improve within 5 days or are accompanied by high fever lasting more than 3 days, rash, or persistent headache, consult a physician, as these manifestations may indicate a more serious illness.

Due to the risk of severe liver damage in case of overdose, do not use simultaneously with other medications intended for symptomatic treatment of cold and rhinitis (vasoconstrictors, paracetamol-containing products). Use with caution in patients with Raynaud's disease, arterial hypertension, heart diseases, arrhythmias, bradycardia, thyroid disorders, liver or kidney diseases, acute hepatitis, glaucoma, chronic lung diseases, prostate hypertrophy (due to the risk of urinary retention), elderly patients, patients with increased blood coagulability, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The risk of hepatotoxicity is increased in patients with alcoholic liver disease or those who abuse alcohol.

Cases of metabolic acidosis with a high anion gap (high anion gap metabolic acidosis, HAGMA), resulting from pyroglutamic acidosis, have been reported in patients with severe conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and careful monitoring are recommended. Measurement of urinary 5-oxoproline levels may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

The product contains: phenylephrine, which may provoke angina attacks; and sucrose, which is contraindicated in patients with fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency. Patients with known sugar intolerance should consult their physician before taking this medication. Use with caution in patients with diabetes mellitus. May be harmful to teeth.

Consult a physician before use in cases of: liver or kidney diseases; concomitant use of warfarin or similar anticoagulants; daily use of analgesics for mild forms of arthritis; bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

The medication may affect laboratory test results for blood glucose, uric acid, creatinine, and inorganic phosphates. Fecal occult blood testing may yield false-negative results.

In patients with severe infections (e.g., sepsis), where glutathione levels are reduced, paracetamol use increases the risk of metabolic acidosis. Symptoms include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. In such cases, immediate medical attention is required.

It is not recommended to take this medication late in the day, as high doses of ascorbic acid may have a mild stimulating effect. Due to the stimulatory effect of ascorbic acid on corticosteroid hormone production, monitoring of kidney function and blood pressure is required.

Use with particular caution in patients with iron metabolism disorders (hemochromatosis, hemosiderosis, thalassemia) and in those with a history of nephrolithiasis (risk of hyperoxaluria and oxalate deposition in the urinary tract after high-dose ascorbic acid intake).

Prolonged use of high doses of ascorbic acid may accelerate its own metabolism, potentially leading to paradoxical vitamin C deficiency after discontinuation. Do not use simultaneously with other products containing vitamin C. Absorption of ascorbic acid may be altered in cases of intestinal motility disorders, enteritis, or reduced gastric secretion.

Use during pregnancy or breastfeeding.

The medication is contraindicated during pregnancy and breastfeeding. The effect of the drug on fertility has not been specifically studied. Preclinical studies have not revealed any particular effect of paracetamol on fertility when used at therapeutic doses. Adequate studies on the reproductive toxicity of phenylephrine and pheniramine in animals have not been conducted.

Ability to affect reaction speed when driving or operating machinery.

Since this medication may cause drowsiness and other adverse reactions affecting the nervous system and vision, driving vehicles or operating complex machinery is not recommended during treatment.

Dosage and Administration.

Dissolve the contents of the sachet in a glass of hot water (not boiling water) and drink. The medication may be repeated every 3–4 hours, but no more than 3 sachets per day.

Maximum duration of use – 5 days.

Children.

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

Overdose.

Paracetamol. Within the first 24 hours, symptoms include pallor, nausea, vomiting, anorexia, and abdominal pain. Following ingestion of large doses, disorientation, psychomotor agitation, dizziness, sleep disturbances, cardiac arrhythmias, pancreatitis, and hepatonecrosis may occur. The first sign of liver damage may be abdominal pain, which does not always manifest within the first 12–48 hours and may appear later, up to 4–6 days after drug administration. Liver injury typically develops within 72–96 hours after intake. Glucose metabolism disturbances and metabolic acidosis, as well as hemorrhages, may occur. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

In isolated cases, acute renal failure with tubular necrosis has been reported, which may occur even in the absence of severe liver injury, presenting as severe lumbar pain, hematuria, and proteinuria. Nephrotoxicity is possible: renal colic, interstitial nephritis, capillary necrosis.

Ingestion of 10 g or more of paracetamol by adults, especially with alcohol, or over 150 mg/kg body weight in children, may lead to hepatocellular necrosis, resulting in encephalopathy, hemorrhages, hypoglycemia, hepatic coma, and fatal outcome. In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may cause liver damage.

In case of overdose, immediate medical assistance is required. The patient should be taken to hospital immediately, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Activated charcoal should be administered within the first hour after overdose. Paracetamol blood concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but maximum efficacy is achieved when administered within the first 8 hours; after this, its effectiveness declines rapidly. If intravenous administration of N-acetylcysteine is required, it should be given according to the established dosing schedule. Alternatively, in the absence of vomiting, oral methionine may be used.

Phenylephrine. Symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmia, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension, and in severe cases, coma. To counteract hypertensive effects, an intravenous α-receptor blocker may be administered; for seizures, diazepam may be used.

Pheniramine. Anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, intestinal atony. CNS depression leads to respiratory and cardiovascular system dysfunction (bradycardia, arterial hypotension, collapse). Symptoms due to mutual potentiation of the parasympatholytic effect of pheniramine and the sympathomimetic effect of phenylephrine include drowsiness, which may progress to agitation (especially in children) or CNS depression, visual disturbances, skin rash, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disturbances, and bradycardia. There is no specific antidote for antihistamine overdose. Standard emergency care should be provided, including administration of activated charcoal, a saline laxative, and standard supportive measures for the cardiopulmonary system. Stimulants must not be used; vasoconstrictors may be used to treat arterial hypotension.

Ascorbic acid. Symptoms include nausea, vomiting, or diarrhea (which resolve after discontinuation); bloating and abdominal pain, itching, skin rashes, and increased excitability. Doses exceeding 3000 mg may cause temporary osmotic diarrhea and gastrointestinal disturbances, disturbances in zinc and copper metabolism, myocardial dystrophy; prolonged use in high doses may suppress the function of the pancreatic islet apparatus and lead to glucosuria. Overdose may lead to changes in renal excretion of ascorbic and uric acids during acetylation of urine, resulting in precipitation of oxalate stones.

Treatment is symptomatic: gastric lavage should be performed within the first 6 hours, and oral methionine or intravenous cysteamine or N-acetylcysteine should be administered within the first 8 hours.

Adverse Reactions

Skin and subcutaneous tissue disorders: rash, pruritus, dermatitis, urticaria, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.

Immune system disorders: hypersensitivity reactions, including anaphylactic shock and angioedema.

Nervous system disorders: headache, dizziness, tremor, restlessness, nervousness, irritability, feeling of fear, insomnia, somnolence, confusion, hallucinations, psychomotor agitation, disorientation, depressive state, paresthesia, tinnitus, in individual cases – coma, convulsions, dyskinesia, behavioral changes.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and NSAIDs.

Eye disorders: visual disturbances and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

Gastrointestinal disorders: nausea, vomiting, heartburn, dry mouth, abdominal discomfort and pain, constipation, diarrhea, flatulence, anorexia, aphthae, hypersalivation, hemorrhage, mucosal irritation.

Hepatobiliary disorders: liver function abnormalities, hypertransaminasemia (usually without jaundice), hepatonecrosis (with high-dose administration).

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

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

Renal and urinary disorders: nephrotoxicity, interstitial nephritis, capillary necrosis, dysuria, urinary retention and difficulty in urination, renal colic, renal failure.

Cardiac disorders: arterial hypertension, tachycardia, bradycardia, palpitations, arrhythmia, dyspnea, chest pain, angina attacks.

Metabolic and nutritional disorders: frequency unknown (cannot be estimated from available data) – metabolic acidosis with high anion gap.

Other: general weakness, malaise.

Unlike second-generation antihistamines, pheniramine use is not associated with QT interval prolongation or cardiac arrhythmia.

Description of selected adverse reactions.

Metabolic acidosis with high anion gap. Cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging. 23 g in sachets, 5 or 10 sachets per pack.

Availability. Over-the-counter.

Manufacturer. Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of business activity.
Ukraine, 61115, Kharkiv region, Kharkiv, Severin Pototskoho Street, 36.