Helpex® anticold neo max

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

Composition:

Active substances: paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride;

1 sachet of 4 g contains 650 mg paracetamol, 10 mg phenylephrine hydrochloride, 1.25 mg levocetirizine dihydrochloride;

Excipients:

«HelpeX® Anticold Neo MAX» with lemon flavor: colloidal anhydrous silicon dioxide, aspartame (E 951), mannitol (E 421), sucralose, sucrose, tartrazine (E 102), lemon flavor, anhydrous citric acid;

«HelpeX® Anticold Neo MAX» with raspberry flavor: colloidal anhydrous silicon dioxide, aspartame (E 951), mannitol (E 421), sucralose, sucrose, betanin (E 162), raspberry flavor.

Pharmaceutical form. Powder for oral solution.

Main physicochemical characteristics:

«HelpeX® Anticold Neo MAX» with lemon flavor: powder from pale yellow to yellow color;

«HelpeX® Anticold Neo MAX» with raspberry flavor: nearly white powder with pale pink tint, presence of dark red particles possible.

Pharmacotherapeutic group.

Analgesics and antipyretics. Anilides. Paracetamol combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological Properties

Pharmacodynamics

A combination 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, its ability to inhibit the synthesis of prostaglandins and inflammatory mediators (kinins, serotonin), and an increase in the pain sensitivity threshold.

Levocetirizine dihydrochloride is a non-sedating antihistamine agent—an active, 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 of levocetirizine for H1-histamine receptors is twice that of cetirizine. It affects the histamine-dependent phase of allergic reactions, reduces eosinophil migration, vascular permeability, and limits the release of inflammatory mediators. It prevents the development and suppresses the manifestations of allergic reactions, exerts anti-exudative, antipruritic, and anti-inflammatory effects, and does not exhibit anticholinergic or anti-serotonin activity. It does not penetrate the central nervous system.

Levocetirizine inhibits the late phase of inflammatory reaction induced by intradermal administration of kallikrein 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 due to increased cellular resistance to rhinovirus. Additionally, levocetirizine reduces secondary adhesion of Staphylococcus aureus and Haemophilus influenzae to nasopharyngeal epithelial cells infected with rhinovirus.

Phenylephrine hydrochloride is a relatively selective α1-adrenomimetic agent. It exerts weak effects on α2- and β-adrenergic receptors. Due to its vasoconstrictive effect, phenylephrine reduces swelling of the nasal mucosa, decreases nasal secretions, and improves nasal breathing by facilitating airflow through the nose. It is used for temporary relief of nasal congestion associated with acute respiratory viral infections and common cold.

Pharmacokinetics

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. The elimination half-life is 1–4 hours. It is uniformly distributed in 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 exhibit linear dependence 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 information available regarding tissue distribution of levocetirizine in humans or its penetration through the blood-brain barrier. Volume of distribution is 0.4 L/kg. Plasma protein binding is 90%.

Approximately 14% of levocetirizine undergoes metabolism in the body. Due to the low extent of metabolism and lack of enhanced inhibitory effects, drug interactions with levocetirizine (and vice versa) are unlikely.

The drug is primarily excreted 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 approximately 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%), necessitating dose adjustment. During a standard 4-hour hemodialysis session, only a small fraction (less than 10%) of levocetirizine is removed. Levocetirizine passes into breast milk.

Phenylephrine hydrochloride. The onset of action is rapid and lasts approximately 20 minutes. It is metabolized in the liver or gastrointestinal tract and excreted by the kidneys.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to any component of the medicinal product or to piperazine derivatives in medical history. Arterial hypertension, cardiovascular diseases, conduction disorders, severe ischemic heart disease, atherosclerosis, heart failure. Hyperthyroidism, pheochromocytoma. Severe impairment of liver and/or kidney function (creatinine clearance < 10 mL/min). Pancreatitis. Acute hepatitis. Thrombosis, thrombophlebitis, increased blood coagulation, and predisposition to thrombosis. Congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency. Alcoholism. Blood disorders (including severe anemia, leukopenia). Prostate hyperplasia with difficult urination, bladder neck obstruction. Diabetes mellitus. Closed-angle glaucoma. Epilepsy. Concurrent use with tricyclic antidepressants; with monoamine oxidase inhibitors (MAO inhibitors) and within 2 weeks after discontinuation of such therapy; with beta-blockers and other antihypertensive drugs, sympathomimetics. Pregnancy and breastfeeding. Do not use in children under 12 years of age.

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;
• Concurrent use of paracetamol with hepatotoxic agents increases hepatotoxic effects;
• Inducers of hepatic microsomal enzymes, anticonvulsants (including phenytoin, carbamazepine, barbiturates), rifampicin, alcohol, and isoniazid may enhance the hepatotoxicity of paracetamol;
• Metoclopramide and domperidone increase, while cholestyramine, antacids, and food decrease the absorption of paracetamol;
• Salicylamide prolongs the elimination period of paracetam0l;
• Tetracycline increases the risk of anemia and methemoglobinemia caused by paracetamol;
• Increases the half-life of chloramphenicol (up to 5 times);
• Paracetamol reduces the effectiveness of diuretics.

Long-term concurrent use of paracetamol and coumarins (e.g., warfarin) enhances the anticoagulant effect of coumarins, increasing the risk of bleeding. Occasional use does not have a significant effect.

Concurrent use of paracetamol with nonsteroidal anti-inflammatory drugs increases the risk of impaired kidney function.

Regular concomitant use of paracetamol with zidovudine may lead to neutropenia and increased risk of liver damage; concurrent use with azidothymidine may lead to neutropenia.

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").

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 cause 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-dose administration 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.

Food intake does not affect the extent of drug absorption but reduces the rate of absorption.

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

Concomitant use with alcohol or central nervous system depressants in sensitive patients may additionally reduce alertness and ability to perform tasks.

Concomitant use of phenylephrine hydrochloride with indomethacin and bromocriptine may cause severe arterial hypertension; with sympathomimetic amines, digoxin, and cardiac glycosides, it increases the risk of arrhythmias and myocardial infarction; may reduce the effectiveness of β-blockers and other antihypertensive drugs (debrisoquin, guanethidine, reserpine, methyldopa), increasing the risk of arterial hypertension and cardiovascular side effects;

Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride;

α-adrenoblockers (phentolamine), phenothiazines, furosemide, and other diuretics counteract vasoconstriction.

Concomitant use of phenylephrine with ganglion blockers, adrenoblockers, Rauwolfia alkaloids, or methyldopa may lead to decreased blood pressure.

Special precautions for use.

Do not exceed the recommended dose; do not take the medicinal product simultaneously with other medications containing paracetamol, as paracetamol overdose is possible.

In case of overdose, seek immediate medical attention even if the patient feels well, due to the risk of delayed severe liver damage (see section "Overdose").

The risk of paracetamol overdose is increased in patients with alcoholic liver disease. Do not use concurrently with alcohol.

Consult a physician if symptoms worsen or persist for more than 3 days, or if headache becomes persistent.

Patients with liver disease (increased risk of hepatotoxic effects of paracetamol), kidney disease, or those taking warfarin or similar anticoagulant agents should consult a physician before using this medicinal product.

Cases of liver failure/dysfunction have been reported in patients with reduced glutathione levels, such as those with 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. Seek immediate medical attention if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic) acidosis have been reported in patients with severe underlying 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.

Exercise caution when prescribing this medicinal product to patients with Raynaud's disease.

The medicinal product may interfere with laboratory tests for blood glucose and uric acid levels.

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

Use with caution in patients prone to urinary retention and in patients at risk of seizures, as the use of this medicinal product may provoke or exacerbate seizure attacks (see section "Contraindications").

Antihistamines suppress skin allergy tests; therefore, the intake of this medicinal product should be discontinued at least 3 days before testing (elimination period).

This medicinal product contains sucrose; therefore, patients with diagnosed intolerance to certain sugars should consult their physician before taking this medicinal product.

The coloring agent tartrazine (E 102) may cause allergic reactions.

Aspartame (E 951) is a phenylalanine derivative and poses a risk for patients with phenylketonuria.

Use during pregnancy or breastfeeding.

Pregnancy

The safety of using this medicinal product during pregnancy has not been established; therefore, it is not administered to pregnant women (see section "Contraindications").

Breastfeeding

Since the active ingredients of the medicinal product pass into breast milk to some extent, breastfeeding should be discontinued during treatment with this product.

Fertility

There are no data available on the effect of this medicinal product on fertility.

Ability to affect reaction speed when driving or operating machinery.

During treatment with this medicinal product, avoid activities requiring high concentration (e.g., driving vehicles or operating potentially hazardous machinery).

Method of Administration and Dosage

Adults and children aged 12 years and older: 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 duration of treatment should not exceed 5 days.

Maximum duration of use without consulting a physician — 3 days.

Children

Do not use in children under 12 years of age.

Overdose

Paracetamol

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

Symptoms of paracetamol overdose may develop within the first 24 hours and include pallor, nausea, vomiting, loss of appetite, and abdominal pain.

Clinical and biochemical signs of liver damage typically appear 12–48 hours after overdose. Cases of cardiac arrhythmias and pancreatitis have been reported, usually associated with impaired liver function and hepatotoxicity. Hypoglycemic coma, thrombocytopenia, disturbances in glucose metabolism, metabolic acidosis, hypokalemia, elevated liver transaminase activity, increased bilirubin levels, prolonged prothrombin time, and hemorrhages may occur.

Occasionally, nephrotoxic effects involving the urinary system have been observed, including renal colic, interstitial nephritis, and acute renal failure with acute tubular necrosis, which may present as severe lumbar pain, hematuria, and proteinuria, and may develop even in the absence of severe liver injury.

Large doses may lead to hepatocellular necrosis, resulting in encephalopathy, impaired consciousness, hepatic coma, acute renal failure, and potentially fatal outcomes.

In patients with risk factors [long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs that induce liver enzymes; alcoholism; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may result in liver injury.

Prolonged use of the drug in high doses may lead to hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia.

Treatment of overdose: In case of suspected overdose, the patient should be taken to a hospital immediately, even if early symptoms are absent.

Symptoms may be limited to nausea and vomiting and may not reflect the severity of overdose or the risk of organ damage. Gastric lavage should be performed within the first hours after suspected overdose.

Administration of activated charcoal 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 measurements are unreliable).

Intravenous administration of N-acetylcysteine should be initiated within 24 hours after paracetamol ingestion, according to current guidelines. The maximum antidote effect is achieved within 8 hours after paracetamol intake; beyond this time, antidote efficacy decreases sharply.

In the absence of vomiting, oral methionine may be used as an alternative treatment in remote areas outside hospital settings.

Levocetirizine dihydrochloride

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

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

Phenylephrine hydrochloride

Overdose manifests with cardiovascular system symptoms and respiratory depression. Symptoms may include nervousness, headache, dizziness, insomnia, nausea, vomiting, elevated blood pressure, or reflex bradycardia, tachycardia, palpitations, and urinary retention.

Treatment of overdose. To counteract hypertensive effects, intravenous α-adrenergic blockers are administered; in case of seizures, diazepam is indicated.

Adverse Reactions

Immune system disorders: hypersensitivity reactions, including pruritus, urticaria, rash (generalized, erythematous), angioneurotic edema, anaphylactic shock; erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Eye disorders: visual and accommodation disturbances, blurred vision, oculogyria (involuntary circular eye movements), mydriasis, increased intraocular pressure.

Nervous system disorders: sedative effect, somnolence when exceeding the therapeutic dose, insomnia, dizziness, syncope, weakness, asthenia, increased fatigue, decreased mental and physical performance, mood changes, dysphoria, headache, paresthesia, seizures, tremor, tic, dysgeusia, dyskinesia, dystonia, memory impairment, restlessness, anxiety.

Psychiatric disorders: sleep disturbances, psychomotor agitation, hallucinations, apathy, depression,
aggression, insomnia, suicidal thoughts, nightmares, nervousness, irritability, fear, disorientation.

Cardiovascular system disorders: increased blood pressure, decreased blood pressure, tachycardia, palpitations, chest pain.

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

Renal and urinary system disorders: urethral and vesical sphincter spasm, dysuria, enuresis, urinary retention, difficulty in micturition, renal colic, nephrotoxicity.

Gastrointestinal disorders: nausea, vomiting, dry mouth, gastrointestinal discomfort, epigastric pain, diarrhea, constipation, increased appetite, heartburn, flatulence, hypersalivation.

Ear and labyrinth disorders: vertigo, tinnitus.

Hepatobiliary disorders: liver function abnormalities, increased liver enzyme activity, hepatitis, hepatic failure.

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

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

Musculoskeletal and connective tissue disorders: myalgia, arthralgia.

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

General disorders: malaise, edema, weight gain, fever.

Description of selected adverse reactions

Metabolic acidosis with a high anion gap, resulting from 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.

If any adverse reactions occur, the drug should be discontinued and medical advice should be sought immediately.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug 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 via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

4 g of powder in sachets; 10 sachets in a cardboard pack.

Availability. Over-the-counter.

Manufacturer. Alpex Pharma SA.

Manufacturer's address and location of business activity.

Via Cantonale, 6805 Mezzovico-Vira, Switzerland.