Teplorin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TEPLORYN (TEPLORYN)

Composition:

Active substances: paracetamol, pheniramine maleate, ascorbic acid

1 sachet contains: paracetamol 500 mg, pheniramine maleate 25 mg, ascorbic acid 200 mg;

Excipients: sucrose, citric acid, sodium saccharin, raspberry flavor, colorant "Ponceau 4R" (E124).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: pale pink powder with a raspberry odor. Pink specks may be present.

Pharmacotherapeutic group. Other analgesics and antipyretics. Anilides. Paracetamol, combinations without psycholeptics.

ATC code N02BE51.

Pharmacological Properties

Pharmacodynamics

Pharmacological effects due to the components of the medicinal product:

• Pheniramine maleate — an H1-histamine receptor blocker, provides desensitization manifested by a reduced inflammatory response of the mucous membranes of the upper respiratory tract (improvement in nasal breathing, reduction in rhinorrhea, sneezing, and lacrimation);
• Paracetamol exerts antipyretic and analgesic effects, alleviating pain and fever (headache, myalgia);
• Ascorbic acid compensates for the body's requirement for vitamin C.

Pharmacokinetics

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract following oral administration. Maximum plasma concentration of paracetamol is reached within 30–60 minutes after intake. Paracetamol is rapidly distributed into all tissues. Plasma, saliva, and blood concentrations are similar. Plasma protein binding is weak. Paracetamol is primarily metabolized in the liver, forming conjugates with glucuronic acid and sulfates. A minor metabolic pathway, catalyzed by cytochrome P450, leads to the formation of a reactive intermediate (N-acetyl-benzoquinone imine), which under normal conditions is rapidly detoxified by reduced glutathione and excreted in urine after conjugation with cysteine and mercapturic acid. However, in cases of severe overdose, the amount of this toxic metabolite increases.

Excretion occurs primarily via the urine, mainly as metabolites. Approximately 90% of the administered dose is excreted by the kidneys within 24 hours, predominantly as glucuronide conjugates (60–80%) and sulfate conjugates (20–30%).

Unchanged paracetamol accounts for about 5% of the administered dose. The elimination half-life is approximately 2 hours.

In cases of severe renal impairment (creatinine clearance less than 10 ml/min), excretion of paracetamol and its metabolites is delayed.

In elderly patients, conjugation capacity remains unchanged.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is primarily excreted by the kidneys. The elimination half-life from plasma is 60–90 minutes.

Ascorbic acid is well absorbed from the gastrointestinal tract. It is primarily excreted in the urine.

Clinical characteristics

Indications

Contraindications

Hypersensitivity to the components of the medicinal product or to other antihistamines; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders; severe anemia; leukopenia; severe arterial hypertension; unstable angina; severe cardiac conduction disorders; acute phase of myocardial infarction; severe atherosclerosis; decompensated heart failure; hyperthyroidism; acute urinary retention due to prostate hypertrophy; risk of urinary retention in urethral and prostate disorders; bladder neck obstruction; pyloroduodenal obstruction; gastric and duodenal ulcer in the acute phase; closed-angle glaucoma; thrombosis; thrombophlebitis; diabetes mellitus; bronchial asthma; epilepsy; elderly age; fructose intolerance; glucose/galactose malabsorption syndrome; or sucrase-isomaltase deficiency (due to sucrose content).

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs. The medicinal product is contraindicated in patients taking tricyclic antidepressants or β-blockers. Contraindicated in urolithiasis if ascorbic acid intake exceeds 1 g per day.

Do not use in children under 15 years of age.

Interaction with other medicinal products and other forms of interaction

Unfavorable combinations

During treatment, avoid consumption of alcoholic beverages and use of medicinal products containing ethanol, as ethanol enhances the sedative effect of H1-blockers (pheniramine). Therefore, patients should refrain from driving or operating machinery.

Combinations requiring caution

Due to the presence of pheniramine, concomitant use with other sedative agents, including morphine derivatives (analgesics, antitussives, and substitution therapy), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (e.g., meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-blockers, centrally acting antihypertensives, baclofen, and thalidomide may result in central nervous system depression.

Concomitant use of pheniramine with drugs having anticholinergic (atropine-like) effects—such as imipramine-type antidepressants, most anticholinergic H1-blockers, anticholinergics, antiparkinsonian agents, atropine-like spasmolytics, disopyramide, phenothiazine neuroleptics, and clozapine—may increase undesirable anticholinergic effects such as urinary retention, constipation, and dry mouth.

Combinations requiring careful use

Concomitant use with oral anticoagulants may increase their effect, and there is an increased risk of bleeding when paracetamol is taken at maximum doses (4 g/day) for at least 4 days. The INR (International Normalized Ratio) should be monitored regularly. If necessary, the dose of oral anticoagulant may be adjusted during and after paracetamol treatment.

Paracetamol may interfere with blood glucose measurement by the glucose oxidase-peroxidase method in cases of abnormally high concentrations.

Paracetamol may affect blood urea determination when using phosphotungstic acid.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased when used with cholestyramine. Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsants (e.g., phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics.

Ascorbic acid enhances intestinal iron absorption, increases blood levels of ethinylestradiol, penicillins, and tetracyclines, and decreases blood levels of antipsychotic agents and phenothiazine derivatives. Glucocorticoids reduce body stores of ascorbic acid. Concurrent use of ascorbic acid and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, which may lead to circulatory decompensation. Ascorbic acid may be administered no sooner than 2 hours after deferoxamine injection. High doses of ascorbic acid reduce the effectiveness of tricyclic antidepressants. Absorption of ascorbic acid is reduced when taken concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as this combination has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients at risk (see "Special precautions").

Special precautions for use

In case of high body temperature or prolonged fever persisting for 5 days during treatment with the medicinal product, or if signs of superinfection appear, consult a physician to determine the appropriateness of continuing the treatment.

Ascorbic acid may alter the results of laboratory tests (blood glucose, bilirubin, transaminase activity).

Consult a physician regarding the possibility of using the medicinal product in patients with impaired kidney or liver function. A physician's consultation is also required before using the product if the patient is taking warfarin or similar anticoagulant agents.

Patients with alcoholic liver damage have an increased risk of hepatotoxic effects of paracetamol. The product may affect laboratory test results for blood uric acid levels.

Do not exceed the recommended doses.

Do not take the medicinal product together with other products containing paracetamol.

If symptoms do not resolve or if headache becomes persistent, consult a physician.

The risk of developing mainly psychological dependence may occur when exceeding the recommended doses or during prolonged treatment.

For adults with body weight over 50 kg, the total daily dose of paracetamol should not exceed 4 g.

Consumption of alcoholic beverages or use of sedatives (especially barbiturates) increases the sedative effect of pheniramine maleate; therefore, avoid using these substances during treatment.

Each sachet contains 11.5 g of sucrose, which should be considered by patients on a low-sugar diet.

Very rare cases of serious skin reactions have been reported. Patients should be informed about early signs of these serious skin reactions, such as rash or other symptoms of hypersensitivity. If such symptoms occur, the medicinal product should be discontinued.

Prescribe with special caution to patients with disorders of iron metabolism (hemochromatosis, hemosiderosis, thalassemia).

Since ascorbic acid has a mild stimulating effect, it is not recommended to take this medicinal product in the evening. Due to the stimulatory effect of ascorbic acid on corticosteroid hormone production when used in high doses, kidney function and blood pressure should be monitored.

Use the medicinal product with caution in patients with increased blood coagulability.

Prescribe with special caution to patients with a history of nephrolithiasis (risk of hyperoxaluria and oxalate precipitation in the urinary tract after high-dose ascorbic acid intake).

Prolonged use of high doses of ascorbic acid may accelerate its own metabolism, leading to paradoxical hypovitaminosis after discontinuation of treatment. Do not exceed the recommended dose.

Do not use simultaneously with other products containing vitamin C.

Absorption of ascorbic acid may be impaired in intestinal motility disorders, enteritis, or achylia (suppressed gastric secretion).

It should be noted that high-dose vitamin C intake may alter certain laboratory test parameters (uric acid, creatinine, inorganic phosphates). Fecal occult blood testing may yield false-negative results.

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

Use during pregnancy or breastfeeding

Since the effect of the medicinal product during pregnancy or breastfeeding has not been sufficiently studied, it should not be used during these periods.

Ability to influence reaction speed when driving or operating machinery

The medicinal product may significantly affect reaction speed when driving or operating machinery, causing drowsiness, especially at the beginning of treatment. Therefore, avoid driving or operating machinery during treatment.

Concurrent use of the medicinal product with alcoholic beverages, medicinal products containing ethanol, or other sedatives increases these risks.

Dosage and Administration

Administer as a solution.

Dissolve the contents of the sachet (oral powder for solution) in a sufficient amount of hot or cold water.

Dosage

This medicinal product is intended only for use in adults and children aged 15 years and older.

The dose is 1 sachet 2–3 times daily.

Always maintain an interval of 4 hours between doses.

For treatment of influenza-like conditions, it is recommended to take this medicinal product with hot water in the evening.

Duration of treatment

Maximum duration of treatment is 5 days.

In patients with severe renal impairment (creatinine clearance below 10 ml/min), the interval between doses should be at least 8 hours.

Children. Do not use in children under 15 years of age.

Overdose

Related to ascorbic acid

Ascorbic acid is well tolerated. It is a water-soluble vitamin, and excess amounts are excreted in urine. However, prolonged use of high-dose vitamin C may suppress the function of the pancreatic islet apparatus, requiring monitoring of pancreatic status. Overdose may alter renal excretion of ascorbic and uric acids during urinary acidification, increasing the risk of precipitation of oxalate calculi. Administration of high doses of ascorbic acid may cause vomiting, nausea, or diarrhea, which resolve after discontinuation of ascorbic acid.

Related to pheniramine

Pheniramine overdose may cause convulsions (especially in children), disturbances of consciousness, and coma.

In case of pheniramine overdose, anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, and intestinal atony. Central nervous system depression may lead to respiratory and cardiovascular system dysfunction (bradycardia, arterial hypotension, collapse).

Related to paracetamol

There is a risk of intoxication in elderly individuals and, especially, in young children (therapeutic overdose and accidental poisoning occur quite frequently). Paracetamol overdose can be fatal. Symptoms within the first 24 hours include pallor, nausea, vomiting, anorexia, and abdominal pain.

Liver damage may become evident 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to hemorrhage and hypoglycemia. Acute renal failure with acute tubular necrosis may present with severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Single doses exceeding 10 g of paracetamol in adults and 150 mg/kg body weight in children may cause hepatocellular lysis, potentially leading to complete and irreversible necrosis, resulting in hepatic failure, metabolic acidosis, encephalopathy, which in turn may lead to coma and death.

Elevated levels of liver transaminases, lactate dehydrogenase, and bilirubin, along with increased prothrombin levels, may be observed 12–48 hours after ingestion.

In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs inducing liver enzymes; regular excessive ethanol consumption; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), administration of 5 g or more of paracetamol may lead to liver damage. With prolonged use of the drug in high doses, hematological complications may include aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. High-dose intake may cause central nervous system effects such as dizziness, psychomotor agitation, and disorientation; urinary system effects may include nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

Emergency measures:

• Immediate hospitalization;
• Determination of initial plasma paracetamol concentration;
• Immediate removal of the ingested drug by gastric lavage;
• Administration of the antidote N-acetylcysteine either intravenously or orally. The antidote should be administered as early as possible, preferably within 10 hours of overdose;
• Symptomatic therapy.

Adverse Reactions

Blood and lymphatic system disorders: anemia, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia; thrombosis, hyperprothrombinemia, erythrocytopenia, thrombocytopenia, neutrophilic leukocytosis, agranulocytosis, purpura, leukopenia, neutropenia, bruising or bleeding.

Immune system disorders: anaphylaxis, anaphylactic shock, hypersensitivity skin reactions, including pruritus, skin and mucous membrane rashes (usually erythematous, urticaria, purpura), angioneurotic edema, erythema multiforme (including Stevens–Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

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

Gastrointestinal disorders: dry mouth, nausea, heartburn, vomiting, constipation, epigastric pain, diarrhea, liver function disturbances, increased liver enzyme activity, usually without jaundice development, hepatonecrosis (dose-dependent effect).

Endocrine system disorders: hypoglycemia up to hypoglycemic coma.

Nervous system disorders: rarely – headache, dizziness, sleep disturbances, insomnia, sedation or drowsiness, confusion, hallucinations, nervousness, impaired motor coordination, tremor; in individual cases – coma, seizures, dyskinesia, behavioral changes, increased excitability; disturbances of balance and memory, inattention, dizziness, especially in elderly patients. Anticholinergic effects, such as dry mucous membranes, constipation, accommodation disturbances, mydriasis, palpitations, risk of urinary retention. Orthostatic hypotension.

Cardiovascular system disorders: in isolated cases – tachycardia, myocardial dystrophy (dose-dependent effect with prolonged use), orthostatic hypotension.

Metabolism and nutrition disorders: disturbances in zinc and copper metabolism; metabolic acidosis with high anion gap (frequency unknown).

Renal and urinary system disorders: urinary retention and difficulty in urination, aseptic pyuria.

Skin disorders: eczema.

Eye disorders: dry eyes, mydriasis, accommodation disturbances.

With prolonged use in high doses: glomerular kidney apparatus damage, crystalluria, formation of urate, cystine and/or oxalate calculi in kidneys and urinary tract; damage to the islet apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the development of diabetes mellitus.

Adverse reactions associated with ascorbic acid: when used in doses exceeding 1 g per day – irritation of the gastrointestinal mucosa, renal failure, arterial hypertension.

Description of selected adverse reactions

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

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. Sachets of 12.75 g; 10 sachets per cardboard box.

Availability category. Over-the-counter.

Manufacturer. LLC "ASTRAFARM".

Manufacturer's address and location of business activity 6, Kyivska St., Vyshneve, Buchanskyi district, Kyiv region, 08132, Ukraine.

Marketing Authorization Holder. LLC "BERKANA+".

Address of Marketing Authorization Holder 20/1 Pushkina St., m. Bohodukhiv, Bohodukhiv district, Kharkiv region, 62103, Ukraine.