Antiflu® kids

INSTRUCTIONS FOR MEDICAL USE OF ANTIFLU® KIDS

Composition:

Active ingredients: acetaminophen, ascorbic acid, chlorpheniramine maleate;

One sachet contains: acetaminophen 160 mg, ascorbic acid 50 mg, chlorpheniramine maleate 1 mg;

Excipients: citric acid anhydrous, silicon dioxide, colloidal anhydrous silicon dioxide, sodium citrate dihydrate, corn starch, confectioner's sugar, sucrose, titanium dioxide (E 171), calcium phosphate, special red AC (E 129), raspberry flavoring.

Pharmaceutical form. Oral powder for solution.

Main physicochemical properties: free-flowing white or almost white powder containing crystalline particles, with a slight raspberry odor.

Pharmacotherapeutic group.

Analgesics and antipyretics. ATC code N02BE51.

Pharmacological Properties

Pharmacodynamics

Paracetamol has analgesic, antipyretic, and weak anti-inflammatory effects. Its mechanism of action involves inhibition of prostaglandin synthesis and influence on the thermoregulatory center in the hypothalamus.

Ascorbic acid (vitamin C), as a key component of the antioxidant and immune defense systems, enhances the body's adaptive capacity and increases resistance to infections. It actively participates in the regulation of redox processes, carbohydrate metabolism, synthesis of steroid hormones and catecholamines, and blood coagulation. It enhances collagen synthesis, stimulates regenerative processes, and normalizes capillary permeability.

Chlorpheniramine maleate is an antihistamine agent of the alkylamine class and an H\1-histamine receptor blocker. It exerts antiallergic effects and relieves rhinorrhea, lacrimation, and itching in the eyes and nose. The therapeutic effect develops within one hour after oral administration and lasts for 24 hours.

The components of the drug are metabolized independently of each other.

Pharmacokinetics

After oral administration, paracetamol is rapidly absorbed, primarily in the upper gastrointestinal tract. It quickly distributes into tissues. Protein binding in blood is less than 10%. Paracetamol is mainly metabolized in the liver: the majority is conjugated with glucuronic acid and a smaller portion with sulfuric acid. The half-life of paracetamol is 2–2.5 hours. It is prolonged in patients with liver disease.

Paracetamol is excreted in the urine (85% of a single dose is excreted within 24 hours). Excretion is significantly impaired in patients with renal excretory dysfunction, which may lead to accumulation of paracetamol and its metabolites in the body.

Ascorbic acid is actively absorbed in the small intestine. After oral administration, maximum plasma concentration is reached within 4 hours. From plasma, it readily penetrates into leukocytes, platelets, and practically all tissues. It undergoes biotransformation in the liver and is excreted in the urine: partially unchanged and partially as metabolites.

Chlorpheniramine maleate is metabolized in the liver. Its elimination half-life is 8 hours. Chlorpheniramine maleate and its metabolites are excreted in the urine.

Clinical characteristics.

Indications.

For use in children aged 2 to 12 years with influenza, acute viral respiratory infections, and colds to reduce fever and relieve headache, muscle and joint pain, rhinorrhea, sneezing, lacrimation, and other symptoms of inflammation of the mucous membranes of the upper respiratory tract and paranasal sinuses.

Contraindications.

Hypersensitivity to the components of the drug or to other antihistamines; severe hepatic dysfunction (>9 points on the Child-Pugh scale) and/or renal impairment; alcoholism; congenital glucose-6-phosphate dehydrogenase deficiency; inherited hyperbilirubinemia (including Gilbert's syndrome); blood dyscrasias, hematological disorders, marked leukopenia, anemia, thrombosis tendency; severe cardiac conduction disorders, decompensated heart failure; bladder neck obstruction; pyloroduodenal obstruction; thrombosis, thrombophlebitis; severe forms of diabetes mellitus; closed-angle glaucoma; peptic ulcer disease of the stomach and duodenum in the acute phase; age under 2 years.

Do not use together with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs. MAOIs should not be used concomitantly with antihistamines due to the potential for additive central nervous system (CNS) depression. They may prolong and enhance the anticholinergic effects of antihistamines.

Interaction with other medicinal products and other forms of interaction.

Possible interactions when used concomitantly with acetaminophen (paracetamol):

• Slowed elimination of antibiotics from the body;
• Anticonvulsants (including phenytoin, barbiturates, carbamazepine), rifampicin, and alcohol enhance the hepatotoxic and nephrotoxic potential of acetaminophen;
• Barbiturates reduce the antipyretic effect of acetaminophen;
• Tetracycline increases the risk of anemia and methemoglobinemia induced by acetaminophen;
• Concomitant use of paracetamol with hepatotoxic agents increases the toxic effects on the liver; do not use with alcohol;
• Acetaminophen reduces the effectiveness of diuretics;
• Concurrent use of high doses of acetaminophen with isoniazid or rifampicin increases the risk of hepatotoxic syndrome;
• Enhanced effect of indirect anticoagulants, increasing the risk of bleeding;
• The absorption rate of acetaminophen increases when used with metoclopramide and domperidone, and decreases with cholestyramine;
• Long-term concomitant use with coumarin derivatives (e.g., warfarin) may potentiate their effect, increasing the risk of bleeding; patients taking oral anticoagulants should consult their physician and coagulation parameters should be monitored;
• Paracetamol (acetaminophen) intake may affect blood glucose measurements using the glucose oxidase-peroxidase method, leading to abnormally high readings;
• Paracetamol intake may affect blood urea measurements using the phosphotungstic acid method;
• Tropisetron and granisetron, 5-hydroxytryptamine type 3 antagonists, may completely block the analgesic effect of paracetamol due to pharmacodynamic interaction;
• Concurrent use of paracetamol and zidovudine increases the tendency to leukopenia (neutropenia); therefore, these drugs should not be used together unless otherwise directed by a physician;
• Absorption of ascorbic acid is reduced when used concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks;
• Orally administered ascorbic acid enhances the absorption of penicillin, tetracyclines, and iron, increases ethinylestradiol levels, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of crystalluria during salicylate therapy;
• Concurrent intake of vitamin C and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, potentially leading to circulatory decompensation; vitamin C may be taken only 2 hours after deferoxamine injection;
• High doses of the drug reduce the effectiveness of tricyclic antidepressants and phenothiazine-derived neuroleptics, decrease tubular reabsorption of amphetamine, and impair renal excretion of mexiletine;
• Ascorbic acid increases the total clearance of ethanol;
• Quinolone derivatives, calcium chloride, salicylates, and corticosteroids, when used long-term, reduce the body's ascorbic acid reserves.

Concomitant use of Antiflu® Kids with sedatives, tranquilizers, neuroleptics, and anxiolytics may significantly enhance the CNS depressant effect of chlorpheniramine maleate.

Chlorpheniramine enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents. Monoamine oxidase inhibitors (MAOIs) should not be co-administered with antihistamines due to the potential for additive CNS depression. They may prolong and intensify the anticholinergic effects of antihistamines.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, 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").

Special precautions.

Avoid concomitant use with other medications intended for symptomatic treatment of cold and flu, and medicinal products containing paracetamol. Do not exceed the recommended dose or duration of treatment. Concurrent use with other paracetamol-containing medications may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in fatal outcome.

In patients with reduced glutathione levels, e.g., during severe infections such as sepsis, the use of paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. If these symptoms occur, seek immediate medical attention.

If symptoms persist, consult a physician.

Prolonged use of high doses may lead to liver and kidney damage; multiple concomitant medications, alcoholism, alcoholic liver disease, sepsis, or diabetes mellitus may increase the risk of hepatotoxicity of paracetamol (acetaminophen) even at therapeutic doses.

Consider that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol. Consult a physician regarding the possibility of using the medication in patients with mild to moderate renal or hepatic impairment.

This medicinal product is not recommended for concomitant use with sedatives or hypnotics.

Consult a physician before using the medication if the patient is taking warfarin or similar anticoagulant agents.

Paracetamol may affect laboratory test results for blood glucose and uric acid levels.

The medication should be prescribed by a physician only after risk/benefit assessment in the following conditions: severe arterial hypertension, epilepsy, glaucoma, oxalaturia, urinary disorders, urinary retention, prostate enlargement, asthma, respiratory disorders due to bronchitis, croup, or pneumonia, thyrotoxicosis, glutathione deficiency.

Cases of metabolic acidosis with high anion gap (high anion gap metabolic acidosis (HAGMA)) as a result of pyroglutamic acidosis have been reported in patients with severe underlying conditions such as renal failure 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 is recommended, along with close monitoring of the patient. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Do not exceed the recommended dose or duration of treatment. If the medication is used for a prolonged period as directed by a physician, liver function and peripheral blood picture should be monitored.

Severe skin reactions have been reported very rarely. If skin redness, rash, blisters, or peeling occur, discontinue paracetamol and seek immediate medical assistance.

One sachet (1 dose) contains 11.6 g of sugar, which should be considered in diabetic patients and patients on a low-sugar diet. Use with caution in patients with diabetes mellitus. Concomitant intake of the medication with alkaline beverages reduces absorption of ascorbic acid; therefore, do not take the powder with alkaline mineral water. Absorption of ascorbic acid may also be impaired in intestinal dyskinesia, enteritis, and achylia.

Do not use this medicinal product in patients with fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency due to the presence of sucrose (saccharose). If you have been diagnosed with intolerance to certain sugars, consult your physician before taking this medicinal product.

If high body temperature or prolonged fever persists for 3 days despite treatment, or if signs of superinfection appear, consult a physician.

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

Do not take this medication with other cold and flu remedies containing paracetamol or antihistamines. If symptoms persist, consult a physician. If headache becomes persistent, consult a physician as well.

Chlorpheniramine maleate may mask symptoms of hypersensitivity reactions and interfere with skin test results. Therefore, discontinue use of the medication several days before such procedures.

Use during pregnancy or breastfeeding.

Not recommended.

Ability to affect reaction speed when operating vehicles or machinery.

Due to the potential for drowsiness following chlorpheniramine maleate administration, children should avoid activities requiring high concentration for 4 hours after taking the medication.

Method of Administration and Dosage

Administer orally, regardless of food intake, after dissolving the contents of the sachet in a glass of hot (not boiling) water. The recommended amount of water for dissolving the powder is usually the volume that a child can drink in one intake (100–200 mL). The single dose for children aged 2–5 years is the contents of 1 sachet; for children aged 6–12 years – the contents of 2 sachets. If necessary, repeat administration every 4–6 hours, but no more than 4 sachets per day. The maximum duration of use without medical consultation is 3 days. Further use is possible only under medical supervision.

Children

Do not use in children under 2 years of age. Medical advice should be sought before administering the medication to children aged 2–5 years.

The maximum dose for children is up to 100 mg/kg per day or 4000 mg per day.

Overdose

Cases of overdose with Antiflu® Kids have not been reported. Symptoms of overdose consist of intoxication manifestations related to individual active ingredients.

In patients with risk factors, therapeutic doses of paracetamol may cause symptoms of overdose when used concomitantly with certain medications (see section "Interaction with other medicinal products and other forms of interaction") and in diseases that increase oxidative stress and deplete glutathione reserves in the liver (prolonged fasting, sepsis, diabetes mellitus).

The most significant effects of acute intoxication are hepatotoxicity – hepatocellular damage due to binding of active metabolites of paracetamol to liver cell proteins. At therapeutic doses, these metabolites bind to glutathione and form non-toxic conjugates. In massive overdose, SH-group donor reserves (which support glutathione formation) in the liver become depleted. This leads to accumulation of toxic metabolites and hepatocyte necrosis, resulting in progressive liver dysfunction, potentially progressing to hepatic coma.

Symptoms of overdose caused by acetaminophen within the first 24 hours include pallor, nausea, vomiting, anorexia, general weakness, and abdominal pain. The patient's condition may appear to improve within 24–48 hours, although symptoms may persist.

Following ingestion of large doses, psychomotor agitation or central nervous system depression, increased sweating, dizziness, and sleep disturbances may also occur.

Occasionally, nephrotoxicity has been observed, including renal colic, interstitial nephritis, and acute renal failure with acute tubular necrosis, which may manifest as severe pain in the lumbar region, hematuria, proteinuria, and may develop even in the absence of severe liver damage. In severe cases, liver damage (hepatocellular necrosis) and worsening liver function may occur, potentially progressing to hepatic encephalopathy, hepatic coma, cerebral edema, and fatal outcome. Clinical signs of liver damage may not appear within 12–48 hours after overdose. Liver size rapidly increases. Disorders of glucose metabolism, hypokalemia, and metabolic acidosis (including lactic acidosis) may occur, along with elevated liver transaminase activity, increased bilirubin, prolonged prothrombin index, and hemorrhages. Urine output decreases; mild azotemia may be observed. Liver damage in children may develop after administration of more than 150 mg/kg body weight. Common clinical manifestations appearing after 3–5 days include jaundice, fever, hemorrhagic diathesis, hypoglycemia, hepatic odor from the mouth, and liver failure.

Ingestion of 5 g or more of paracetamol may lead to liver damage 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 intake; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)).

Arrhythmia (disturbance of heart rhythm) and pancreatitis have also been reported. Following large doses, disturbances in orientation may occur from the central nervous system.

With prolonged use at high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

Chronic intoxication includes various liver injuries. Data on chronic toxicity, and especially nephrotoxicity of paracetamol, are controversial. With prolonged use, peripheral blood analysis should be monitored.

In case of chlorpheniramine maleate overdose, anticholinergic (atropine-like) symptoms may occur: mydriasis, photophobia, dryness of skin and mucous membranes, elevated body temperature (hyperpyrexia), tachycardia, intestinal atony, facial flushing. Typically, symptoms of central nervous system excitation occur first (psychomotor agitation, psychosis, hallucinations, tremor, motor coordination disturbances, hyperreflexia, seizures), followed by depression, drowsiness, impaired consciousness, accompanied by respiratory disturbances and cardiovascular system dysfunction (arrhythmias, extrasystoles, reduced pulse rate, decreased arterial pressure up to circulatory failure and fatal outcome).

Emergency treatment for antihistamine poisoning consists of symptomatic and supportive therapy, including mechanical ventilation.

Emergency measures: The patient must be immediately transported to a hospital intensive care unit, even if early symptoms of overdose are absent. Continuous monitoring of vital functions, laboratory parameters, and cardiovascular status should be ensured. Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Treatment with activated charcoal should be considered if an excessive dose of paracetamol was ingested within the past hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Gastric lavage should be performed within 6 hours after suspected acetaminophen overdose. Hemodialysis and hemoperfusion enhance substance elimination. Cytotoxic effects can be reduced by administration of SH-group donors (oral methionine or intravenous cysteamine or N-acetylcysteine) within 10 hours after overdose, as they bind to active metabolites and promote detoxification. N-acetylcysteine may be effective up to 48 hours after poisoning. Antidote efficacy sharply decreases after this period.

Symptoms of ascorbic acid overdose: There are no data indicating that this medicinal product may cause overdose when used according to recommendations. After single ingestion of excessive doses, nausea, vomiting, bloating and abdominal pain, itching, skin rash, and increased excitability may occur. With prolonged use at high doses, suppression of the islet apparatus of the pancreas (pancreatic function should be monitored), development of cystitis, and accelerated formation of calculi (urates, oxalates) are possible. Effects of ascorbic acid overdose may be attributed to severe hepatotoxicity resulting from paracetamol overdose.

High doses of ascorbic acid (more than 3,000 mg) may cause temporary osmotic diarrhea and gastrointestinal disturbances.

Treatment: Gastric lavage, administration of alkaline drinks, activated charcoal, or other absorbents.

Adverse Reactions

In most cases, the medicinal product is well tolerated.

The following adverse effects may occur:

• Blood system: anemia, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency), thrombocytopenia, thrombocytosis, hyperprothrombinemia, erythropenia, neutrophilic leukocytosis, agranulocytosis, thrombocytopenic purpura, leukopenia, bruising or bleeding;
• Respiratory system: bronchospasm in patients sensitive to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs;
• Gastrointestinal tract: dyspepsia, nausea, vomiting, dry mouth, discomfort and pain in the epigastric region, hypersalivation, decreased appetite, heartburn, diarrhea;
• Endocrine system: hypoglycemia up to hypoglycemic coma, damage to the pancreatic islet apparatus (hyperglycemia, glucosuria), and impaired glycogen synthesis up to the development of diabetes mellitus;
• Hepatobiliary system: impaired liver function, increased liver enzyme activity, usually without jaundice, hepatonecrosis (dose-dependent effect);
• Immune system: hypersensitivity reactions (including allergic reactions), anaphylactic reactions, and anaphylactic shock;
• Nervous system: headache, dizziness, psychomotor agitation and disorientation, anxiety, fear, sleep disturbances, somnolence, insomnia, confusion, coma, seizures, dyskinesia, behavioral changes;
• Cardiovascular system: tachycardia, reflex bradycardia, dyspnea, chest pain, increased blood pressure, arrhythmia, myocardial dystrophy (dose-dependent effect with prolonged use);
• Urinary system: renal colic and interstitial nephritis, urinary retention and difficulty in urination, aseptic pyuria; with prolonged use in high doses – damage to the glomerular apparatus of the kidneys, crystalluria, formation of urate, cystine and/or oxalate stones in the kidneys and urinary tract;
• Eye organs: accommodation disorders, dry eyes, mydriasis, visual disturbances, increased intraocular pressure;
• Metabolism and nutrition disorders: disturbances in zinc and copper metabolism, hypokalemia; metabolic acidosis with high anion gap – frequency "unknown" (cannot be estimated from available data);
• Skin and subcutaneous tissues: itching, skin and mucous membrane rashes (usually generalized rash, erythema, urticaria), allergic and angioneurotic edema, acute generalized exanthematous pustulosis, localized drug dermatitis, Stevens-Johnson syndrome (including other forms of erythema multiforme), toxic epidermal necrolysis (Lyell's syndrome), including fatal outcomes.

Description of specific adverse reactions

Metabolic acidosis with high anion gap

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

Reporting of adverse reactions after marketing authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

Powder, dosed at 12 g, in packets made of paper laminated with aluminum foil and polyethylene. 5 packets per cardboard box.

Supply category. Over-the-counter.

Manufacturer.

Contract Pharmacal Corporation.

Manufacturer's address and place of business.

135 Adams Avenue, Hauppauge, New York, 11788, USA.