Gripeks hotaktiv

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

Composition:

Active substances: 1 sachet contains 650 mg of paracetamol, 10 mg of phenylephrine hydrochloride, 50 mg of ascorbic acid;

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

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: powder from white to pale yellow in color with a citrus odor. 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-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 exerts a vasoconstrictor effect, helping to reduce edema 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 total peripheral vascular resistance, and raises arterial pressure.

Ascorbic acid is an essential vitamin added to the formulation to compensate for vitamin C depletion that may occur at the onset of viral infection. Ascorbic acid actively participates in the body's redox reactions. It stimulates tissue respiration, oxidative phosphorylation in the liver, activates proteolytic and microsomal enzymes, and promotes the conversion of folic acid into folinic acid. Ascorbic acid is necessary 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 activation, 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 liver or kidney function disorders, acute hepatitis, severe arterial hypertension, severe cardiovascular diseases including conduction disorders, pronounced atherosclerosis, severe form 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, prostate hyperplasia with difficult urination, 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.

Consult a physician regarding the possibility of using the drug in patients with impaired kidney or liver function.

Overdose risk exists in patients with non-cirrhotic alcoholic liver disease. Avoid alcohol consumption during treatment.

Consider that in patients with alcoholic liver damage, the risk of hepatotoxic effect of paracetamol increases; 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.

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

Use of the drug in fasting individuals may increase the risk of liver damage.

Use with caution in individuals predisposed to increased blood pressure and in patients with bronchial asthma. Avoid concomitant use with other medications intended for symptomatic treatment of cold and flu, vasoconstrictive agents for rhinitis treatment, and medications containing paracetamol.

Use with caution in elderly patients, patients with difficult urination, and patients with Raynaud's disease (which may manifest as pain in fingers and toes in response to cold or stress). Do not exceed recommended doses. Phenylephrine contained in the drug may provoke angina attacks.

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

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

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

In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, the risk of developing metabolic acidosis increases during paracetamol administration. 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 over a prolonged period or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and careful monitoring of the patient's condition are recommended. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the primary cause of HAGMA in patients with multiple risk factors.

Do not exceed the specified doses.

If headache becomes persistent, consult a physician.

If symptoms of illness do not begin to resolve within 3 days of treatment or, conversely, the patient's condition worsens, medical advice should be sought.

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 regimen.

Barbiturates reduce the antipyretic effect of paracetamol.

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

Concomitant use of high doses of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Concomitant use of paracetamol with hepatotoxic agents increases the toxic effects of the drugs on the liver.

Paracetamol reduces the effectiveness of diuretics. Do not use concomitantly with alcohol.

Paracetamol should be used with caution concomitantly with flucloxacillin, as co-administration 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 causes a hypertensive effect; with tricyclic antidepressants (e.g., amitriptyline) – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – leads to arrhythmia or myocardial infarction. Phenylephrine combined with other sympathomimetics increases the risk of cardiovascular adverse reactions. 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. Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

Ascorbic acid enhances the absorption of penicillin and iron when taken orally, 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 development.

Absorption of vitamin C is reduced when used concomitantly with oral contraceptives, fruit or vegetable juices, and alkaline drinks. Concurrent intake of vitamin C and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, which may lead to circulatory decompensation. Vitamin C should be taken only 2 hours after deferoxamine injection. Prolonged intake of large 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 neuroleptics – phenothiazine derivatives, amphetamine tubular reabsorption, impair renal excretion of mexiletine, and affect vitamin B12 resorption. Ascorbic acid promotes intestinal absorption of aluminum when taken orally, which should be considered during concomitant treatment with antacids containing aluminum.

Special precautions.

Use during pregnancy or breastfeeding.

The use of the drug during these periods is contraindicated.

Ability to affect reaction speed when driving or operating machinery.

During treatment with this medicinal product, driving vehicles or operating machinery requiring increased concentration of attention should be avoided.

Method of Administration and Dosage.

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

Adults and children aged 12 years and older: The single dose is 1 sachet. If necessary, the dose may be repeated every 4–6 hours. Do not exceed 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.

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 dizziness, psychomotor agitation, and disorientation from the central nervous system; urinary system disorders – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Overdose is usually caused by paracetamol and manifests as pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, increased activity of liver transaminases, and prolonged 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, death. Acute kidney injury 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 of paracetamol. 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 that induce liver enzymes; regular consumption of excessive amounts of ethanol; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)).

Overdose caused by 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 increased blood pressure. In severe cases, impaired consciousness, hallucinations, seizures, and arrhythmias may occur.

Overdose caused by ascorbic acid may manifest as nausea, vomiting, bloating and abdominal pain, itching, skin rash, and increased excitability. High doses of ascorbic acid (over 3000 mg) may cause temporary osmotic diarrhea and gastrointestinal disturbances, disturbances in zinc and copper metabolism, glucosuria, crystalluria, and kidney stone formation.

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

Symptoms may be limited to nausea and vomiting, or may not reflect the severity of the overdose or risk of organ damage. Treatment with activated charcoal should be considered if an excessive dose of paracetamol was ingested within 1 hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but the maximum protective effect is achieved 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 dosage regimen. In the absence of vomiting, oral methionine may be used as an appropriate 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 mucous membrane 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, sedation, depression, hallucinations, anxiety, tinnitus, vertigo, general weakness, dizziness, excitement; impaired concentration the following day, especially with insufficient sleep after taking the drug.

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 disturbances.

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) – urinary disturbances, 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 selected 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 for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 5, 7, 8, or 10 sachets in a cardboard pack.

Availability. Over-the-counter.

Manufacturer.

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

Manufacturer's location and address of business activity.

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

Applicant.

Unilab, LP / Unilab, LP.

Applicant's and/or applicant's representative's address.

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