Helpex® anticold neo for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HELPEX® ANTICOLD NEO for children (HELPEX® ANTICOLD NEO for children)

Composition:

Active substances: paracetamol, levocetirizine dihydrochloride;

1 sachet of 2.5 g contains paracetamol 320 mg, levocetirizine dihydrochloride 1.25 mg;

Excipients: aspartame (E 951), sucralose, raspberry flavor, colloidal anhydrous silicon dioxide, mannitol (E 421), betanin (E 162), sucrose.

Pharmaceutical form. Powder for oral solution with raspberry flavor.

Main physicochemical properties: almost white powder with a light pink tint; presence of dark red particles is possible.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol, combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

A combined medicinal product for symptomatic treatment of acute respiratory viral infections, influenza and common cold. Possesses antipyretic, analgesic, antiallergic and mild anti-inflammatory properties. Relieves symptoms of nasal congestion, rhinorrhea, lacrimation, sneezing, headache and body aches.

Paracetamol exerts analgesic, antipyretic and mild anti-inflammatory effects.

The mechanism of action of paracetamol is associated with its influence on the thermoregulatory center in the hypothalamus, ability to inhibit the synthesis of prostaglandins and inflammatory mediators (kinins, serotonin), and increased pain threshold sensitivity.

Levocetirizine dihydrochloride is a non-sedating antihistamine, the active and stable R-enantiomer of cetirizine, belonging to the group of competitive histamine antagonists. Its pharmacological action is due to blockade of H1-histamine receptors. The affinity for H1-histamine receptors is twice higher in levocetirizine than in cetirizine. It affects the histamine-dependent phase of allergic reaction development, reduces eosinophil migration, vascular permeability, and limits the release of inflammatory mediators. Prevents the development and suppresses the course of allergic reactions, exerts anti-exudative, anti-pruritic and anti-inflammatory effects, without anticholinergic or anti-serotonin activity, and does not penetrate into the central nervous system.

Levocetirizine inhibits the late phase of inflammation induced by intradermal kallikrein injection in patients. It also reduces the expression of adhesion molecules such as ICAM-1 and VCAM-1, which are markers of allergic inflammation. By reducing ICAM-1 adhesiveness, an indirect antiviral effect is achieved, since cellular resistance to rhinovirus increases. Additionally, levocetirizine reduces secondary adhesion of Staphylococcus aureus and Haemophilus influenzae to nasopharyngeal epithelial cells previously infected with rhinovirus.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. The elimination half-life is 1–4 hours. It is uniformly distributed throughout all body fluids. Plasma protein binding is variable. It is primarily excreted by the kidneys in the form of conjugated metabolites.

Levocetirizine dihydrochloride. Pharmacokinetic parameters show linear kinetics and are almost identical to those of cetirizine. It is rapidly absorbed after oral administration; food does not affect the extent of absorption but reduces its rate.

There is no data available on the distribution of levocetirizine in human tissues or its penetration through the blood-brain barrier. The volume of distribution is 0.4 L/kg. Plasma protein binding is 90%.

Approximately 14% of levocetirizine undergoes metabolism in the body. Due to its low metabolic rate and lack of enzyme inhibition enhancement, drug interactions with levocetirizine (and vice versa) are unlikely.

Drug elimination occurs mainly via glomerular filtration and active tubular secretion. The elimination half-life (T1/2) is 7.9 ± 1.9 hours; total clearance is 0.63 mL/min/kg. It does not accumulate and is completely eliminated from the body within 96 hours. 85.4% of the administered dose is excreted unchanged in urine, and about 12.9% in feces.

In patients with impaired renal function (creatinine clearance < 40 mL/min), levocetirizine clearance is reduced and elimination half-life (T1/2) is prolonged (for example, in patients undergoing hemodialysis, total clearance is reduced by 80%), requiring appropriate dose adjustment. During a standard 4-hour hemodialysis session, only a small fraction (less than 10%) of levocetirizine is removed. Levocetirizine is excreted in breast milk.

Clinical characteristics.

Indications.

Treatment of symptoms occurring in acute viral respiratory infections and influenza (to reduce elevated body temperature, relieve rhinitis, alleviate nasal mucosa swelling, relieve headache, and eliminate body aches).

Contraindications.

Hypersensitivity to any component of the medicinal product, history of piperazine derivatives allergy. Blood disorders (including severe anemia, leukopenia). Severe impairment of liver and/or kidney function (creatinine clearance < 10 mL/min). Congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism.

Interaction with other medicinal products and other types of interactions.

When used concomitantly with paracetamol, the following interactions may occur:

• may slow down elimination of antibiotics from the body;
• barbiturates reduce the antipyretic effect of paracetamol;
• concomitant use of paracetamol with hepatotoxic agents increases hepatotoxic effects;
• inducers of hepatic microsomal enzymes (anticonvulsants (phenytoin, barbiturates, carbamazepine), rifampicin), alcohol, and isoniazid enhance the hepatotoxicity of paracetamol;
• metoclopramide and domperidone increase, while cholestyramine, antacids, and food reduce the absorption of paracetamol;
• concomitant use of tetracycline increases the risk of anemia and methemoglobinemia caused by paracetamol;
• paracetamol reduces the effectiveness of diuretics;
• paracetamol intake may affect blood glucose and uric acid level test results.

Prolonged concomitant use enhances the anticoagulant effect of coumarins (e.g., warfarin), increasing the risk of bleeding.

Concomitant use of paracetamol with nonsteroidal anti-inflammatory agents increases the risk of kidney function impairment.

Concomitant use with flucloxacillin may result in metabolic acidosis with a high anion gap due to pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions for use").

Studies on levocetirizine regarding drug interactions have not been conducted. Studies with cetirizine (racemic mixture) showed that concomitant use with antipyrine, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide, or diazepam does not result in clinically significant adverse interactions. When used concomitantly with theophylline (400 mg/day), a slight reduction (by 16%) in total clearance of levocetirizine was observed (theophylline distribution remained unchanged). In a study of multiple dosing of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), cetirizine exposure increased by approximately 40%, while ritonavir distribution was slightly affected (-11%) with concomitant cetirizine use.

Concomitant use of cetirizine or levocetirizine with alcohol or other central nervous system depressants in susceptible patients may cause additional reduction in alertness and ability to perform tasks.

Special precautions for use.

Do not exceed the recommended dose; do not take the medicine simultaneously with other products containing paracetamol, as this may lead to paracetamol overdose, potentially causing liver failure.

Consult a physician if symptoms persist and/or are accompanied by high fever lasting more than 3 days; if headache becomes persistent.

Do not use concurrently with medicinal products containing alcohol.

Patients should consult a physician before using the medicine if they are taking analgesics daily for mild forms of arthritis; if they are taking warfarin or similar anticoagulant agents; or if they have liver (increased risk of hepatotoxic effects of paracetamol) or kidney disease.

Cases of liver failure/dysfunction have been reported in patients with reduced glutathione levels, such as in severe malnutrition, anorexia, low body mass index, or chronic alcoholism. In patients with reduced glutathione levels, for example 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. Immediate medical attention should be sought if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe conditions such as severe 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 careful monitoring. 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.

Use with caution in patients with chronic renal impairment (dose adjustment required) and in elderly patients with renal impairment (possible reduction in glomerular filtration rate).

Use with caution in patients predisposed to urinary retention (e.g., spinal cord injury, benign prostatic hyperplasia), as levocetirizine may increase the risk of urinary retention; and in patients at risk of seizures or with epilepsy.

There are no data indicating enhanced effects of sedatives when used at therapeutic doses. However, concomitant use of sedatives should be avoided during treatment with this medicine.

Antihistamines suppress skin allergy tests; therefore, the medicine should be discontinued at least 3 days before testing (elimination period).

The medicine contains aspartame, which is a source of phenylalanine; therefore, it should not be used by patients with phenylketonuria. The medicine contains sucrose; therefore, patients with diagnosed intolerance to certain sugars should consult their physician before taking this medicine.

Use during pregnancy or breastfeeding.

The medicine is intended for use in children.

Ability to affect reaction speed when driving or operating machinery.

Patients should refrain from activities requiring high psychomotor reaction speed.

Dosage and Administration

Children aged 6 to 10 years: 1 sachet up to 4 times daily.

Intervals between doses should be at least 4 hours.

Dissolve the contents of the sachet in a glass of hot water and drink. The recommended amount of water for dissolving the powder for children is usually the volume the child drinks in one intake (100–200 mL).

Do not exceed the recommended dose. The maximum duration of use without medical consultation is 3 days. Further use is possible only under medical supervision.

Children

The medicinal product is intended for use in children aged 6 to 10 years.

Overdose

Liver damage may occur in adults who have taken 10 g or more of paracetamol, or 5 g in the presence of risk factors, and in children who have taken more than 150 mg/kg body weight.

In paracetamol overdose, symptoms develop within the first 24 hours: pallor, nausea, vomiting, loss of appetite, abdominal pain.

The first clinical and biochemical signs of liver damage may appear 12–48 hours after overdose. Glucose metabolism disorders, hypokalemia, and metabolic acidosis (including lactic acidosis) may occur, along with increased hepatic transaminase activity, elevated bilirubin levels, prolonged prothrombin index, and hemorrhages.

Occasionally, nephrotoxicity has been observed from the urinary system, 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 impaired liver function may occur, which can progress to hepatic encephalopathy, hepatic coma, cerebral edema, and may be fatal.

In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; alcoholism; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), the use of 5 g or more of paracetamol may lead to liver damage.

Cardiac arrhythmia and acute pancreatitis have also been reported, usually accompanied by liver function disorders and hepatotoxicity.

After ingestion of large doses, disturbances in orientation may occur from the central nervous system.

With prolonged use of the drug in high doses, blood disorders may develop, including aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia.

Treatment of overdose: In case of overdose, prompt medical assistance is required. The patient should be immediately transported to a hospital, even if early symptoms of overdose are absent.

Symptoms may be limited to nausea and vomiting and may not reflect the severity of overdose or risk of organ damage. Gastric lavage should be performed within the first hours after suspected overdose. Activated charcoal treatment may be beneficial if the 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). Intravenous administration of N-acetylcysteine should be initiated within 24 hours after paracetamol ingestion according to current guidelines. Maximum efficacy is achieved within 8 hours after paracetamol intake; thereafter, the antidote's effectiveness decreases sharply. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital.

Symptoms of levocetirizine dihydrochloride overdose may include drowsiness in adults and initial excitation and increased irritability followed by drowsiness in children.

Treatment of overdose. There is no specific antidote for levocetirizine. In case of overdose symptoms, symptomatic and supportive therapy is recommended. Gastric lavage may be considered shortly after drug ingestion. Hemodialysis is ineffective for removing levocetirizine from the body.

Adverse Reactions

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

Nervous system disorders: drowsiness, headache, increased fatigue, weakness, asthenia, tremor, seizures, paresthesia, dizziness, syncope, dysgeusia.

Psychiatric disorders: sleep disturbances, aggression, excitement, insomnia, suicidal thoughts, hallucinations, depression.

Eye disorders: visual disturbances, blurred vision.

Cardiac disorders: palpitations, tachycardia.

Renal and urinary disorders: dysuria, urinary retention.

Ear and labyrinth disorders: vertigo.

Respiratory system disorders: bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs, dyspnea.

Gastrointestinal disorders: nausea, vomiting, dry mouth, abdominal pain, diarrhea, constipation, increased appetite.

Hepatobiliary disorders: liver function abnormalities, increased liver enzyme activity, usually without development of jaundice, hepatitis.

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

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

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

Metabolism and nutrition disorders: metabolic acidosis with a high anion gap.

General disorders: edema, weight gain.

Description of selected adverse reactions

Metabolic acidosis with a high anion gap as a result of pyroglutamic acidosis has 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 suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging.

2.5 g of powder in sachets; 6 sachets in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer: Alpex Pharma SA.

Manufacturer's address and place of business.

Via Cantonale, 6805 Mezzovico-Vira, Switzerland.