Gripeks hotaktiv max

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GRIPEX HOTACTIVE MAX (GRIPEX® HOTACTIVE MAX)

Composition:

Active substances: 1 sachet contains paracetamol 1000 mg, phenylephrine hydrochloride 12.2 mg, ascorbic acid 100 mg;

Excipients: sucrose, citric acid, sodium citrate, potassium acesulfame (E 950), aspartame (E 951), quinoline yellow (E 104), lemon flavoring 875928, lemon flavoring 87А069, lemon flavoring 875060, lemon flavoring 501.476 АР0504.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: Powder from white to pale yellow with a characteristic citrus odor and taste. Small lumps of powder may be present.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol combinations without psychotropic agents. ATC code N02BE51.

Pharmacological properties.

The drug has analgesic, antipyretic, and vasoconstrictor activities.

Paracetamol is an analgesic and antipyretic. The mechanism of action of paracetamol is due to inhibition of prostaglandin synthesis and other mediators of pain and inflammation, predominantly in the central nervous system.

Phenylephrine hydrochloride is an α-adrenomimetic agent that produces vasoconstriction, helping to reduce swelling of the mucous membranes of the upper respiratory tract and nasal sinuses, decrease rhinorrhea and lacrimation, and normalize nasal breathing. It causes constriction of arterioles, increases systemic peripheral vascular resistance, and elevates arterial blood pressure.

Ascorbic acid is an essential vitamin added to the formulation to compensate for vitamin C loss that may occur at the onset of viral infection.

Ascorbic acid actively participates in the body's redox reactions. It stimulates tissue respiration and oxidative phosphorylation in the liver, activates proteolytic and microsomal enzymes, and promotes the conversion of folic acid into folinic acid. Ascorbic acid is required for the synthesis of steroid hormones and procollagen. It regulates vascular wall permeability and blood coagulation, supports regenerative processes, and influences the formation of connective tissues. Ascorbic acid enhances immune system activity, replenishes the increased demand for vitamin C during influenza and colds, and strengthens the body's defense mechanisms.

Clinical characteristics.

Indications.

Symptomatic treatment of cold and influenza (headache, muscle and joint pain, fever, lacrimation, runny nose, nasal congestion).

Contraindications.

Hypersensitivity to any component of the drug, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, severe impairment of liver or kidney function, acute hepatitis, severe arterial hypertension, severe cardiovascular diseases including conduction disorders, pronounced atherosclerosis, severe forms of ischemic heart disease, states of increased excitation, sleep disorders, epilepsy, blood disorders, Gilbert's syndrome, leukopenia, anemia, thrombosis, thrombophlebitis, hyperthyroidism, severe forms of diabetes mellitus, acute pancreatitis, alcoholism, closed-angle glaucoma, benign prostatic hyperplasia with urinary retention, concomitant use with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of MAOIs, contraindicated in patients taking tricyclic antidepressants, β-blockers or other antihypertensive drugs, appetite suppressants or stimulants, and amphetamine-like psychostimulants. Phenylketonuria. Age under 12 years.

Special precautions.

Patients with impaired renal or hepatic function should consult a physician regarding the possibility of using the drug.

Risk of overdose exists in patients with non-cirrhotic alcoholic liver disease. Alcohol consumption should be avoided during treatment.

Administration to individuals who are fasting may increase the risk of liver damage.

The drug should not be taken for more than 3 days. If symptoms do not begin to improve within 3 days of treatment or if the condition worsens, medical advice must be sought.

The drug should be used with caution in patients predisposed to elevated blood pressure and in those with bronchial asthma. Concomitant use with other medications intended for symptomatic treatment of cold and flu, vasoconstrictive agents for rhinitis treatment, and medications containing paracetamol should be avoided.

Use with caution in elderly patients, in patients with urinary retention, and in those with Raynaud's disease (which may manifest as pain in fingers and toes in response to cold or stress). Recommended doses must not be exceeded.

Phenylephrine contained in the drug may provoke angina attacks.

If the drug is used long-term as directed by a physician, monitoring of liver function and peripheral blood parameters is necessary.

Do not use in patients with rare hereditary conditions of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Prior to use, patients taking warfarin or similar anticoagulant agents should consult a physician.

Note that in patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased; the drug may affect laboratory test results for blood glucose and uric acid levels.

Patients who take analgesics daily for mild forms of arthritis should consult a physician.

The medicinal product contains aspartame—a phenylalanine derivative—which poses a risk for patients with phenylketonuria.

In patients with severe infections such as sepsis, associated with reduced glutathione levels, 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 therapeutic doses of paracetamol over a prolonged period or with a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and close patient monitoring are recommended. Measurement of 5-oxoproline levels in urine may be helpful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

If symptoms do not resolve, medical advice should be sought.

If headache becomes persistent, medical advice should be sought.

Keep the drug out of sight and reach of children.

Interaction with other medicinal products and other forms of interaction.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased with cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced, increasing the risk of bleeding, during long-term regular daily use of paracetamol. These interactions are not clinically significant when paracetamol is used short-term according to the recommended dosage regimen.

Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effects of paracetamol due to increased formation of hepatotoxic metabolites.

Concomitant use of paracetamol with hepatotoxic agents increases the risk of liver toxicity. Simultaneous use of high doses of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics. Do not use concomitantly with alcohol.

Paracetamol should be used with caution concomitantly with flucloxacillin, as this combination has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

Interaction of phenylephrine with monoamine oxidase inhibitors (MAOIs) causes a hypertensive effect; with tricyclic antidepressants (e.g., amitriptyline), it increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides, it may lead to arrhythmias or myocardial infarction. Phenylephrine combined with other sympathomimetics increases the risk of cardiovascular side effects. Phenylephrine may reduce the effectiveness of β-blockers and other antihypertensive drugs (reserpine, methyldopa, etc.), increasing the risk of hypertension and other cardiovascular adverse effects. α-adrenergic blockers (phentolamine), phenothiazines, furosemide, and other diuretics counteract vasoconstriction. Rauwolfia alkaloids reduce the therapeutic effect of phenylephrine hydrochloride.

Ascorbic acid, when taken orally, enhances the absorption of penicillin and iron, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of crystalluria during salicylate therapy. Antidepressants, antiparkinsonian and antipsychotic drugs, phenothiazine derivatives increase the risk of urinary retention, dry mouth, and constipation. Glucocorticoids increase the risk of glaucoma.

Absorption of vitamin C is reduced when taken concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks. 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. Prolonged intake of high doses by patients treated with disulfiram inhibits the disulfiram-alcohol reaction. High doses of the drug reduce the effectiveness of tricyclic antidepressants. High doses of the drug reduce the effectiveness of phenothiazine-derived neuroleptics, decrease tubular reabsorption of amphetamine, interfere with renal excretion of mexiletine, and affect vitamin B12 resorption. Orally administered ascorbic acid enhances intestinal absorption of aluminum, which should be considered when treating concomitantly with aluminum-containing antacids.

Pregnancy and lactation.
(If applicable, this section would normally follow, but it was not included in the provided text.)

Special precautions.

Use during pregnancy or breastfeeding.

The use of the drug during these periods is contraindicated.

Ability to affect reaction rate when driving vehicles or operating machinery.

During treatment with this drug, driving vehicles or operating machinery requiring increased attention is not recommended.

Dosage and Administration.

Empty the contents of 1 sachet into a cup and pour in hot water. Stir until completely dissolved. Take while warm.

The single dose of paracetamol is 10–15 mg/kg body weight; the maximum daily dose is 60 mg/kg body weight. Do not take more than 4 doses within 24 hours.

Adults and children aged 12 years and older: 1 sachet. The dose may be repeated every 4–6 hours if necessary. Do not take more than 4 sachets per day.

The interval between doses should be at least 4 hours.

The treatment course should not exceed 3–5 days. The duration of treatment is determined by a physician.

The maximum duration of use in children without medical consultation is 3 days.

Do not exceed the recommended dose.

Do not take together with other medicinal products containing paracetamol.

Children.

Contraindicated in children under 12 years of age.

Overdose.

The risk of overdose is increased in patients with liver disease.

With prolonged use at high doses: aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. High doses may cause central nervous system effects such as dizziness, psychomotor agitation, and disorientation; urinary system disorders such as nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Overdose is usually caused by paracetamol and manifests as pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated liver transaminase activity, and increased prothrombin index. In case of overdose, increased sweating, psychomotor agitation or central nervous system depression, drowsiness, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures may occur. Liver damage may appear 12–48 hours after overdose.

Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress and lead to toxic encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, coma, and in some cases, fatal outcome. Acute kidney dysfunction with acute tubular necrosis may present as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported. Liver damage is possible in adults who have taken 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. 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 consumption of excessive amounts of ethanol; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)).

Overdose due to phenylephrine may cause increased sweating, psychomotor agitation or central nervous system depression, headache, pallor, dizziness, insomnia, cardiac arrhythmias, tachycardia, reflex bradycardia, extrasystoles, tremor, hyperreflexia, nausea, vomiting, irritability, restlessness, and elevated blood pressure. In severe cases, impaired consciousness, hallucinations, seizures, and arrhythmias may occur.

Overdose due to ascorbic acid may manifest as nausea, vomiting, abdominal distension and pain, itching, skin rash, and increased excitability. High doses of ascorbic acid (over 3000 mg) may cause transient osmotic diarrhea, gastrointestinal disturbances, zinc and copper metabolism disorders, glucosuria, crystalluria, and kidney stone formation.

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

Symptoms may be limited to nausea and vomiting, or may not reflect the severity of overdose or risk of organ damage. 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 more after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but the maximum protective effect occurs when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, intravenous N-acetylcysteine should be administered according to the established dosing regimen. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside the hospital.

Adverse reactions.

The following adverse effects may occur.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, anaphylactic shock.

Skin and subcutaneous tissue disorders: allergic dermatitis, pruritus, skin and mucosal rashes (usually erythematous, urticaria), angioneurotic edema, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), purpura, hemorrhages.

Nervous system disorders: headache, tremor, paresthesia, fear, anxiety, nervous excitement, irritability, confusion, sleep disturbances, insomnia, somnolence, sedative state, depression, hallucinations, anxiety, tinnitus, vertigo, general weakness, dizziness, excitement; impaired concentration the following day, especially with insufficient sleep duration after drug administration.

Gastrointestinal disorders: nausea, vomiting, epigastric discomfort and pain, heartburn, decreased appetite, constipation, diarrhea, flatulence, dry mouth, oral mucosal ulcers, hypersalivation, hemorrhages.

Hepatobiliary disorders: increased liver enzyme activity, usually without development of jaundice, hepatonecrosis (dose-dependent effect), liver function impairment.

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

Eye disorders: mydriasis, visual and accommodation disturbances, increased intraocular pressure.

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

Renal and urinary disorders: (with high-dose use) – impaired urinary excretion, nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), oliguria, aseptic pyuria.

Cardiac disorders: increased blood pressure, chest pain, palpitations, sinus tachycardia, dyspnea, edema, reflex bradycardia.

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

Metabolism and nutrition disorders: frequency unknown (cannot be estimated from available data) – metabolic acidosis with high anion gap.

The drug may have a slight laxative effect.

Description of individual adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap as a result 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.

Shelf life. 3 years.

Storage conditions. Store in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 5 or 8 sachets per cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

TOV US Farmatsiya / US Pharmacia Sp. z o.o.

Manufacturer's address and place of business.

ul. Ziebicka 40, 50-507 Wroclaw, Poland / ul. Ziebicka 40, 50-507 Wroclaw, Poland.

Marketing Authorization Holder.

Unilab, LP.

Address of the Marketing Authorization Holder and/or its representative.

966 Hungerford Drive, Suite ZB, Rockville, MD 20850, USA /
966 Hungerford Drive, Suite ZB, Rockville, MD 20850, USA.