Helpex® anticold neo

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

Composition:

Active substances: paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride;

1 sachet of 4 g contains paracetamol 500 mg, levocetirizine dihydrochloride 1.25 mg, phenylephrine hydrochloride 10 mg;

Excipients:

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

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

Pharmaceutical form. Oral powder for solution.

Main physicochemical properties:

HelpeX® Anticold NEO with lemon flavor: powder from pale yellow to yellow in color;

HelpeX® Anticold NEO with raspberry flavor: nearly white powder with a pale pinkish hue, presence of dark red particles possible.

Pharmacotherapeutic group.

Analgesics and antipyretics. Anilides. Paracetamol, combinations without psycholeptics.

ATC code N02B E51.

Pharmacological properties.

Pharmacodynamics.

A combined medicinal product for symptomatic treatment of acute respiratory viral infections, influenza, and common cold. Has 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.

Levocetirizine dihydrochloride is a non-sedating antihistamine agent, 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 of levocetirizine for H1-histamine receptors is twice higher than that of cetirizine. It affects the histamine-dependent stage of allergic reaction development, reduces eosinophil migration, vascular permeability, and limits the release of inflammatory mediators. Prevents the development and suppresses manifestations of allergic reactions, exerts anti-exudative, antipruritic, and anti-inflammatory effects. It does not exert anticholinergic or anti-serotonergic effects and does not penetrate into the central nervous system.

Levocetirizine inhibits the late phase of inflammatory reaction induced in patients by intradermal administration of kallikrein. It also reduces the expression of adhesion molecules such as ICAM-1 and VCAM-1, which are markers of allergic inflammation. Due to the reduction in ICAM-1 adhesiveness, an indirect antiviral effect is achieved, as cellular resistance to rhinovirus increases. Additionally, levocetirizine reduces secondary adhesion of Staphylococcus aureus and Haemophilus influenzae to nasopharyngeal epithelial cells previously 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 nasal mucosal swelling, decreases nasal secretion volume, and improves nasal breathing by facilitating airflow through the nose. It is used for temporary relief of nasal congestion in acute respiratory viral infections and colds.

Pharmacokinetics.

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

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

There is no available information 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 its low metabolic rate and lack of increased inhibitory effect, drug interactions with levocetirizine (and vice versa) are unlikely.

Drug excretion occurs mainly via glomerular filtration and active tubular secretion. 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 (e.g., in patients undergoing hemodialysis, total clearance is reduced by 80%), necessitating appropriate dose adjustment. During a standard 4-hour hemodialysis session, only a small fraction (less than 10%) of levocetirizine is removed. It passes into breast milk.

Phenylephrine hydrochloride. The effect begins rapidly 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 occurring with acute respiratory viral infections and influenza (to reduce elevated body temperature, relieve rhinitis, alleviate nasal mucosal edema, relieve headache, and eliminate body aches).

Contraindications.

Hypersensitivity to any component of the medicinal product, history of piperazine derivatives. 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). Acute hepatitis. Pancreatitis. Thrombosis, thrombophlebitis, increased blood coagulation and predisposition to thrombosis, tendency to vascular spasm. Congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency. Alcoholism. Blood disorders (including severe anemia, leukopenia). Prostate hyperplasia with urinary retention, bladder neck obstruction. Diabetes mellitus. Closed-angle glaucoma. Concomitant use with tricyclic antidepressants; with MAO inhibitors and within 2 weeks after discontinuation of such agents; beta-blockers and other antihypertensive drugs, sympathomimetics, appetite suppressants or stimulants; amphetamine-like psychostimulants. Pregnancy and breastfeeding. Not to be used in children under 12 years of age. Epilepsy, increased excitability, sleep disorders. Bronchial asthma.

Interaction with other medicinal products and other forms of interaction.

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, including phenytoin; carbamazepine, barbiturates, rifampicin, alcohol, and isoniazid may enhance the hepatotoxicity of paracetamol;
• metoclopramide and domperidone increase, while cholestyramine, antacids, and food reduce the absorption of paracetamol;
• salicylamide prolongs the elimination period of paracetamol;
• 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 concomitant use enhances the anticoagulant effect of coumarins (e.g., warfarin), increasing the risk of bleeding. Occasional use has no significant effect.

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

Concomitant use with flucloxacillin may lead to 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 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 with 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 its absorption.

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

There are no data on enhanced sedative effects when used at therapeutic doses. However, concomitant use of sedatives should be avoided during treatment. Concomitant use with alcohol or central nervous system depressants in sensitive patients may cause additional reduction in alertness and ability to perform tasks.

Use of phenylephrine hydrochloride with MAO inhibitors (including moclobemide), indomethacin, and bromocriptine may cause severe arterial hypertension; with tricyclic antidepressants (amitriptyline) increases the risk of cardiovascular adverse effects; may reduce the effectiveness of β-blockers and other antihypertensive agents (debrisoquin, guanethidine, reserpine, methyldopa), increasing the risk of arterial hypertension and cardiovascular side effects; with sympathomimetic amines, digoxin, and cardiac glycosides increases the risk of arrhythmias and myocardial infarction. Rauwolfia alkaloids reduce the therapeutic effect of phenylephrine hydrochloride; α-adrenergic blockers (phentolamine), phenothiazines, furosemide, and other diuretics counteract vasoconstriction. Concomitant use of phenylephrine with ganglionic blockers, adrenergic blockers, 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 drugs containing paracetamol, as this may result in paracetamol overdose. In case of overdose, seek immediate medical advice 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 doctor if symptoms persist, worsen, or last longer than 3 days, or if headache becomes persistent.

Patients with liver disease (increased risk of hepatotoxic effects of paracetamol), kidney disease, patients taking warfarin or similar anticoagulant drugs, and those taking analgesics daily for mild forms of arthritis should consult a doctor before using this medicinal product.

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. Seek immediate medical attention 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 poor nutrition 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.

Exercise caution when prescribing the drug to patients with Raynaud's disease. The medicinal product may affect laboratory test results 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 insufficiency (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 exacerbate seizure attacks (see section "Contraindications").

Phenylephrine may provoke an attack of angina pectoris.

Antihistamines suppress skin allergy tests; therefore, administration of the medicinal product must be discontinued at least 3 days before testing (elimination period). The colorant tartrazine (E 102) may cause allergic reactions.

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

Helpex® Anticold NEO contains sucrose; therefore, patients with diagnosed intolerance to certain sugars should consult their doctor before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy

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

Breastfeeding

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

Fertility

There are no data on the effect of the 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).

Dosage and Administration.

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 treatment duration should not exceed 5 days.

Maximum duration of use without prior medical consultation – 3 days.

Children.

Do not use in children under 12 years of age.

Overdose.

Hepatic injury is possible 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.

Within the first 24 hours after paracetamol overdose, symptoms may develop, including 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 accompanied by liver function abnormalities 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 manifest as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver injury. Ingestion of 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 inducing liver enzymes; alcoholism; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may lead to liver injury.

After ingestion of large doses, disturbances in orientation may occur due to central nervous system effects.

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 suspected overdose, the patient should be taken to 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 risk of organ damage. Gastric lavage should be performed within the first hours after suspected overdose. Activated charcoal may be beneficial 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). Intravenous administration of N-acetylcysteine should be initiated within 24 hours after paracetamol ingestion according to current guidelines. Maximum antidote efficacy is achieved within 8 hours after paracetamol ingestion; beyond this time, antidote effectiveness decreases sharply.

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

Symptoms of levocetirizine dihydrochloride 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.

Overdose of phenylephrine manifests with cardiovascular 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 used.

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 rotary eye movements), mydriasis, increased intraocular pressure.

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

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

Cardiac 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 disorders: spasm of urethral channels and vesical sphincters, dysuria, enuresis, urinary retention, difficulty in urination, 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 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 for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

If any adverse reactions occur, discontinue use of the medicinal product and consult a physician.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should 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 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 box.

Supply category. Over-the-counter.

Manufacturer. Alpex Pharma SA.

Manufacturer's address and location of operations.

Via Cantonale, 6805 Mezzovico-Vira, Switzerland.