Gripaut hot drink: detailed information

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GRIPOUT HOT DRINK (GRIPOUT HOT DRINK)

Composition:

Active substances: paracetamol, pheniramine maleate, phenylephrine hydrochloride, ascorbic acid;

1 sachet of 6 g contains: paracetamol 500 mg, pheniramine maleate 25 mg, phenylephrine hydrochloride 10 mg, ascorbic acid 200 mg;

Excipients: sucrose, sodium citrate, tartaric acid, aspartame (E 951), anhydrous citric acid, lemon essence, quinoline yellow dye (E 104).

Pharmaceutical form. Granules for oral solution.

Main physicochemical properties: free-flowing granular powder – a mixture of white, pale yellow and/or yellow granules of various sizes with lemon flavour and odour. Single red and/or orange granules may be present.

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

Pharmacological properties.

Pharmacodynamics.

Paracetamol exerts antipyretic, analgesic, and weak anti-inflammatory effects. It inhibits prostaglandin synthesis in the central nervous system (CNS) and blocks transmission of pain impulses.

Ascorbic acid enhances non-specific resistance of the body.

Pheniramine maleate is a histamine H1-receptor blocker that reduces vascular permeability and relieves lacrimation, as well as itching of eyes and nose.

Phenylephrine hydrochloride is an α-adrenomimetic agent that produces vasoconstrictive action, reduces swelling of nasal mucosa and paranasal sinuses.

Pharmacokinetics.

Paracetamol is well absorbed, penetrates the placental barrier, and passes in small amounts into breast milk. It is metabolized by the cytochrome P450 system, excreted by the kidneys, with a half-life of 1–4 hours. Duration of action is 3–4 hours.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is metabolized in the liver by the cytochrome P450 system, with a half-life of 16–18 hours; 70–83% is excreted by the kidneys.

The effect of phenylephrine hydrochloride begins rapidly and lasts approximately 20 minutes. It is metabolized in the liver or gastrointestinal tract and excreted by the kidneys.

Ascorbic acid is rapidly absorbed from the gastrointestinal tract, metabolized in the liver, and excreted by the kidneys.

Clinical characteristics.

Indications.

Symptomatic treatment of acute respiratory infections and influenza:

elevated body temperature;
headache;
nasal congestion;
runny nose;
muscle pain and malaise.

Contraindications.

Hypersensitivity to the components of the drug, severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, glutathione reductase deficiency, alcoholism, blood disorders, marked anemia, leukopenia, thrombosis, thrombophlebitis, conditions accompanied by increased excitation; sleep disturbances; severe arterial hypertension; organic cardiovascular diseases, rare hereditary conditions of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency in cases of severe arterial hypertension, decompensated heart failure, conduction disorders of the heart, bronchial asthma, severe atherosclerosis, predisposition to vascular spasm, ischemic heart disease, glaucoma (especially closed-angle), pheochromocytoma. Pregnancy and breastfeeding period.

The drug is contraindicated in elderly patients; in epilepsy, hyperthyroidism, acute pancreatitis, prostatic hypertrophy with urinary retention, bladder neck obstruction, pyloroduodenal obstruction, severe forms of diabetes mellitus. Do not use simultaneously with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs. Contraindicated in patients taking tricyclic antidepressants or beta-blockers, other sympathomimetics, appetite suppressants or stimulants, and amphetamine-like psychostimulants.

Interaction with other medicinal products and other forms of interaction.

The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine (this effect is negligible if cholestyramine is administered 1 hour apart).

Antacids and food reduce the absorption of paracetamol. The anticoagulant effect of warfarin and other coumarins may be enhanced when paracetamol is used concomitantly on a long-term, regular daily basis, increasing the risk of bleeding. Barbiturates reduce the antipyretic effect of paracetamol. Hepatotoxic drugs increase the likelihood of paracetamol accumulation and overdose.

Anticonvulsant drugs (including phenytoin, phenobarbital, barbiturates, carbamazepine, and antituberculosis agents – rifampicin, isoniazid), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concurrent use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of the drugs.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of hepatotoxicity. Paracetamol reduces the effectiveness of diuretics, may prolong the half-life of chloramphenicol; may induce hepatic metabolism of lamotrigine, thereby reducing its bioavailability and efficacy. Regular use of paracetamol together with zidovudine may lead to neutropenia and increased risk of liver damage. When probenecid is taken, the dose of paracetamol should be reduced, as probenecid affects paracetamol metabolism. Paracetamol may interfere with serum uric acid measurement by the phosphotungstic acid method. Paracetamol hepatotoxicity may be enhanced by prolonged or excessive alcohol consumption. Do not use concurrently with alcohol.

Ascorbic acid, when taken orally, enhances iron absorption, increases ethinylestradiol and penicillin, tetracycline levels, reduces blood levels of antipsychotic drugs and phenothiazine derivatives, and reduces the effect of heparin and indirect-acting anticoagulants. Concurrent use with salicylates increases the risk of crystalluria and the risk of glaucoma during glucocorticoid therapy; large doses reduce the effectiveness of tricyclic antidepressants.

Antidepressants, antiparkinsonian agents, antipsychotics, and phenothiazine derivatives increase the risk of urinary retention, dry mouth, and constipation. Glucocorticoids increase the risk of glaucoma development.

Absorption of ascorbic acid is reduced when taken concurrently with oral contraceptives, fruit or vegetable juices, or alkaline drinks. Ascorbic acid taken orally increases the absorption of penicillin and iron, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of crystalluria during salicylate therapy. Concurrent intake of ascorbic acid and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, potentially leading to circulatory decompensation. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their simultaneous use increases iron toxicity, particularly in the myocardium, which may lead to cardiac decompensation. Prolonged use of high doses in patients treated with disulfiram inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taken with oral contraceptives, fruit or vegetable juices, or alkaline drinks. High doses of the drug reduce the effectiveness of tricyclic antidepressants.

Concurrent use with alcohol may enhance drowsiness.

Due to the presence of pheniramine, the drug enhances the effects of central nervous system (CNS) depressants (hypnotics, anesthetics, barbiturates, tranquilizers, narcotic analgesics, and ethanol). Pheniramine may inhibit the action of anticoagulants and interact with progesterone, reserpine, and thiazide diuretics. Concurrent use of contraceptives may lead to reduced efficacy of the antihistamine component of the drug.

Phenylephrine, an ingredient in Grippaut Hot Drink, is incompatible with sympathomimetics and monoamine oxidase inhibitors (MAOIs) due to the risk of increased arterial pressure, negative effects on the cardiovascular system and CNS, and with tricyclic antidepressants (amitriptyline) – increasing the risk of cardiovascular adverse effects, with digoxin and cardiac glycosides – leading to arrhythmias and infarction, and with other sympathomimetics – increasing the risk of cardiovascular side reactions and hypertension. It may reduce the effectiveness of beta-blockers and other antihypertensive agents (reserpine, methyldopa, debrezoquine, guanethidine), increasing the risk of arterial hypertension and cardiovascular adverse reactions. Concurrent use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism. Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as this combination has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

Special precautions for use.

Do not exceed the recommended doses.

If symptoms do not improve within 5 days or are accompanied by high fever lasting more than 3 days, skin rashes, or persistent headache, consult a physician, as these may be signs of a more serious condition. Due to the risk of severe liver damage in case of overdose, this medicinal product should not be used simultaneously with other medicinal products for symptomatic treatment of cold and rhinitis (vasoconstrictors and medications containing paracetamol). Use with caution in patients with Raynaud's disease, arterial hypertension, heart disease, arrhythmia, bradycardia, thyroid disorders, liver and kidney diseases, acute hepatitis, glaucoma, chronic lung diseases, benign prostatic hyperplasia (due to the risk of urinary retention), elderly patients, those with increased blood coagulability, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The risk of hepatotoxicity is increased in patients with alcohol-induced liver damage and in those who abuse alcohol.

Use with caution in patients with impaired liver, gastrointestinal tract, or kidney function, with benign hyperbilirubinemia, urinary retention, severe cardiovascular diseases, diabetes mellitus, bronchial asthma, or productive cough. During prolonged treatment, monitoring of peripheral blood counts and liver function is required (once every 10 days).

In sensitive patients, even small doses may cause insomnia, dizziness, tachycardia, tremor, or cardiac arrhythmia. If any of the above symptoms occur, discontinue the medication.

Alcohol consumption is prohibited during treatment.

During treatment, avoid taking sedative drugs (especially barbiturates), as they may enhance the sedative effect of the antihistamine component of the drug (pheniramine maleate).

If the illness is caused by a bacterial infection, simultaneous treatment with antibiotics is recommended.

If hemolysis of erythrocytes or drug-induced hemolytic anemia occurs during treatment with Grippaut Goryachiy Napoy (Gripaust Hot Drink), discontinue the drug immediately.

The drug contains: phenylephrine, which may provoke angina attacks; sucrose, which is contraindicated in patients with fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency. If a patient has known sugar intolerance, consult a physician before taking this medication. Use with caution in patients with diabetes mellitus. May be harmful to teeth.

Consult a physician before using the drug in the following cases:

in liver or kidney disease;
when taking warfarin or similar anticoagulants;
when taking analgesics daily for mild forms of arthritis;
in bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

The drug may affect laboratory test results for blood glucose, uric acid, creatinine, and inorganic phosphates. Fecal occult blood testing may yield false-negative results.

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, sepsis, malnutrition, or other sources of glutathione deficiency (e.g., chronic alcoholism) who were treated long-term with therapeutic doses of paracetamol or a combination of paracetamol and flucloxacillin. In suspected cases of HAGMA due to pyroglutamic acidosis, immediate discontinuation of paracetamol and careful 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. In patients with severe infections (sepsis), where glutathione levels are reduced, paracetamol use increases the risk of metabolic acidosis. Symptoms include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite—in such cases, seek immediate medical attention.

This medication should not be taken late in the day, as high doses of ascorbic acid may have a mild stimulating effect. Due to the stimulatory effect of ascorbic acid on corticosteroid hormone production, kidney function and blood pressure should be monitored.

Extreme caution is required when prescribing this medication to patients with disorders of iron metabolism (hemochromatosis, hemosiderosis, thalassemia) or a history of nephrolithiasis (risk of hyperoxaluria and oxalate deposition in the urinary tract after high-dose ascorbic acid intake).

Long-term use of high doses of ascorbic acid may accelerate its own metabolism, potentially leading to paradoxical hypovitaminosis after discontinuation. Do not use simultaneously with other products containing vitamin C. Absorption of ascorbic acid may be altered in cases of intestinal motility disorders, enteritis, or reduced gastric secretion.

The drug contains aspartame, a source of phenylalanine, which may be harmful to patients with phenylketonuria.

Patients with diabetes mellitus should be aware that the drug contains sucrose.

This medicinal product contains sodium citrate. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy or breastfeeding. The effect of the drug on fertility has not been specifically studied. Preclinical studies have not revealed any particular effect of paracetamol on fertility when used at therapeutic doses. Adequate studies on the reproductive toxicity of phenylephrine and pheniramine in animals have not been conducted.

Ability to affect reaction speed when driving or operating machinery.

During treatment, avoid driving, operating machinery, or engaging in other potentially hazardous activities, as the drug may cause drowsiness and other adverse reactions affecting the nervous system and vision.

Method of Administration and Dosage.

Dissolve the contents of the sachet in a glass of hot water (not boiling water) and drink. The medication may be repeated every 3–4 hours, but not more than 3 sachets per day. The maximum duration of use without medical consultation is 3 days; further use should be under a physician's recommendation.

Children.

Do not use in children under 14 years of age.

Overdose.

Paracetamol. Within the first 24 hours, symptoms may include pallor, nausea, vomiting, anorexia, and abdominal pain. After ingestion of large doses, disturbances in orientation, psychomotor agitation, dizziness, sleep disturbances, cardiac arrhythmias, pancreatitis, and hepatonecrosis may occur. The first sign of liver damage may be abdominal pain, which does not always manifest within the first 12–48 hours and may appear later, up to 4–6 days after drug administration. Liver injury typically develops within 72–96 hours after ingestion. Glucose metabolism disturbances and metabolic acidosis, as well as hemorrhages, may occur. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

In isolated cases, acute renal failure with tubular necrosis has been reported, which may occur even in the absence of severe liver injury, presenting as severe lumbar pain, hematuria, and proteinuria. Nephrotoxicity is possible: renal colic, interstitial nephritis, capillary necrosis.

Ingestion of 10 g or more of paracetamol by adults or more than 150 mg/kg body weight by children, especially with alcohol, may lead to hepatocellular necrosis, resulting in encephalopathy, hemorrhages, hypoglycemia, hepatic coma, and fatal outcome. In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may cause liver damage.

In case of overdose, immediate medical assistance is required. The patient must 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 administered within the first hour after overdose. Paracetamol blood concentration should be measured 4 hours or later after ingestion (earlier concentrations are not reliable). Treatment with N-acetylcysteine can be administered within 24 hours after paracetamol ingestion, but maximum efficacy is achieved when administered within the first 8 hours; after this, its effectiveness decreases sharply. If intravenous N-acetylcysteine is required, it should be administered according to the established dosage regimen. As an alternative, in the absence of vomiting and when far from a hospital, oral methionine may be used.

Phenylephrine. Symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmia, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension, and in severe cases, coma. To counteract hypertensive effects, an intravenous alpha-blocker may be used; for seizure management, diazepam may be administered.

Pheniramine. Anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, intestinal atony. CNS depression leads to respiratory and cardiovascular system dysfunction (bradycardia, arterial hypotension, collapse). Symptoms due to mutual potentiation of the anticholinergic effect of pheniramine and the sympathomimetic effect of phenylephrine include drowsiness, which may progress to agitation (especially in children) or CNS depression, visual disturbances, skin rash, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disturbances, and bradycardia. There is no specific antidote for antihistamine overdose. Standard emergency care should be provided, including administration of activated charcoal, a saline laxative, and standard supportive measures for the cardiopulmonary system. CNS stimulants are contraindicated; vasoconstrictors may be used to treat arterial hypotension.

Ascorbic acid. Symptoms include nausea, vomiting, or diarrhea (which resolve after discontinuation); abdominal bloating and pain, itching, skin rashes, and increased excitability. Doses exceeding 3000 mg may cause temporary osmotic diarrhea and gastrointestinal disturbances, disturbances in zinc and copper metabolism, myocardial dystrophy; prolonged high-dose use may lead to suppression of the pancreatic islet apparatus function and glucosuria. Overdose may result in changes in renal excretion of ascorbic and uric acids during acetylation of urine, leading to precipitation of oxalate stones.

Treatment is symptomatic: gastric lavage should be performed within the first 6 hours; within the first 8 hours, oral methionine or intravenous cysteamine or N-acetylcysteine should be administered.

Adverse Reactions

Skin and its appendages: increased sweating, rash, pruritus, dermatitis, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin and mucous membrane rashes (usually generalized erythematous eruptions, urticaria), angioedema (Quincke's edema).

Immune system: in isolated cases – anaphylactic shock, angioneurotic edema.

Nervous system: drowsiness, general weakness, nervousness, headache, dizziness, psychomotor agitation and disorientation, restlessness, fear, irritability, hallucinations, sleep disturbances, paresthesia, insomnia, confusion, depressive states, tremor, epileptic seizures, dyskinesia; in individual cases – coma, sensations of tingling and heaviness in limbs, tinnitus, behavioral changes.

Eye disorders: visual disturbances and accommodation disorders, increased intraocular pressure, mydriasis, dry eyes, eye pain, burning sensation in eyes, blurred vision, photophobia, acute angle-closure glaucoma.

Gastrointestinal tract: nausea, vomiting, dry mouth, epigastric discomfort and pain, hypersalivation, decreased appetite, increased liver enzyme activity, heartburn, diarrhea, constipation, flatulence, anorexia, aphthae, hemorrhages, mucosal irritation.

Hepatobiliary system: liver function abnormalities, hypertransaminasemia (usually without jaundice), hepatonecrosis (with high-dose use).

Blood and lymphatic system: anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding. With prolonged use at high doses – aplastic anemia, pancytopenia, which may lead to nosebleeds and/or gum bleeding, bruising, agranulocytosis, neutropenia, leukopenia, thrombocytopenia.

Renal and urinary system: with high-dose use – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), urinary disturbances (especially in patients with prostate hyperplasia), crystalluria, formation of urate and oxalate kidney stones and urinary tract stones, dysuria, renal colic, renal failure.

Cardiovascular system: arterial hypertension, tachycardia or reflex bradycardia, dyspnea, chest pain, arrhythmia, palpitations, angina attacks.

Endocrine system: hypoglycemia up to hypoglycemic coma, hyperglycemia, glucosuria.

Metabolic changes: disturbances in zinc and copper metabolism; metabolic acidosis with high anion gap of unknown frequency.

Respiratory system: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Other: general weakness, malaise.

Adverse reactions possibly related to the presence of ascorbic acid in the medicinal product

Renal and urinary system: glomerular kidney apparatus damage, crystalluria, renal failure.

Skin: eczema.

Endocrine system: impaired glycogen synthesis up to the development of diabetes mellitus.

Cardiovascular system: myocardial dystrophy.

Hematopoietic system: thrombocytosis, hyperprothrombinemia, thrombus formation, erythrocytopenia, neutrophilic leukocytosis.

Nervous system: sleep disturbances, hot sensations, increased fatigue.

Metabolism: disturbances in zinc and copper metabolism, metabolic acidosis with high anion gap (HAGMA)*.

Unlike second-generation antihistamines, pheniramine use is not associated with QT interval prolongation or cardiac arrhythmia.

*Reported in the post-marketing period during concomitant use of paracetamol with flucloxacillin, usually in the presence of risk factors.

Description of selected adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed during paracetamol use in patients with risk factors (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Shelf life. 2 years.

Storage conditions.

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

Packaging. 6 g per sachet. 10 sachets per cardboard box.

Supply category. Over-the-counter (without prescription).

Manufacturer.

FDS Limited.

Manufacturer's address and place of business.

Plot No. B-8, MIDC, Industrial Area, Waluj, 431 136, Dist. Aurangabad, India.

INSTRUCTIONS

for medical use of the medicinal product

GRIPOUT HOT DRINK

(GRIPOUT HOT DRINK)

Composition:

Active substances: paracetamol, pheniramine maleate, phenylephrine hydrochloride, ascorbic acid;

One 6 g sachet contains: paracetamol 500 mg, pheniramine maleate 25 mg, phenylephrine hydrochloride 10 mg, ascorbic acid 200 mg;

Excipients: sucrose, sodium citrate, tartaric acid, aspartame (E 951), anhydrous citric acid, lemon essence, quinoline yellow dye (E 104).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: granulated free-flowing powder – a mixture of white, pale yellow and/or yellow granules of different sizes with lemon flavour and odour. Single red and/or orange granules may be present.

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

Pharmacological properties.

Pharmacodynamics.

Paracetamol exerts antipyretic, analgesic, and weak anti-inflammatory effects. It inhibits prostaglandin synthesis in the central nervous system (CNS) and blocks transmission of pain impulses.

Ascorbic acid enhances non-specific resistance of the body.

Pheniramine maleate is a histamine H1-receptor blocker that reduces vascular permeability and relieves lacrimation, as well as itching of the eyes and nose.

Phenylephrine hydrochloride is an α-adrenomimetic agent that produces vasoconstrictive action, reducing swelling of the nasal mucosa and paranasal sinuses.

Pharmacokinetics.

Paracetamol is well absorbed, penetrates the placental barrier, and passes into breast milk to a minor extent. It is metabolized by the cytochrome P450 system, excreted by the kidneys, with a half-life of 1–4 hours. Duration of action is 3–4 hours.

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is metabolized in the liver by the cytochrome P450 system, has a half-life of 16–18 hours, and 70–83% is excreted by the kidneys.

The effect of phenylephrine hydrochloride begins rapidly and lasts approximately 20 minutes. It is metabolized in the liver or gastrointestinal tract and excreted by the kidneys.

Ascorbic acid is rapidly absorbed from the gastrointestinal tract, metabolized in the liver, and excreted by the kidneys.

Clinical characteristics.

Indications.

Symptomatic treatment of acute respiratory infections and influenza:

elevated body temperature;
headache;
nasal congestion;
runny nose;
muscle pain and aching.

Contraindications.

Hypersensitivity to the components of the drug, severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, glutathione reductase deficiency, alcoholism, blood disorders, severe anemia, leukopenia, thrombosis, thrombophlebitis, conditions accompanied by pronounced excitation; sleep disturbances; severe arterial hypertension; organic cardiovascular diseases, rare hereditary conditions of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency in cases of severe arterial hypertension, decompensated heart failure, conduction disorders, bronchial asthma, severe atherosclerosis, tendency to vascular spasm, ischemic heart disease, glaucoma (especially closed-angle), pheochromocytoma. Pregnancy and breastfeeding period.

The drug is contraindicated in elderly patients; in epilepsy, hyperthyroidism, acute pancreatitis, prostatic hypertrophy with urinary retention, bladder neck obstruction, pyloroduodenal obstruction, severe forms of diabetes mellitus. Do not use concurrently with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs. Contraindicated in patients taking tricyclic antidepressants or beta-blockers, other sympathomimetics, appetite suppressants or stimulants, and amphetamine-like psychostimulants.

Interaction with other medicinal products and other forms of interactions.

The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine (this effect is negligible if cholestyramine is administered 1 hour apart).

Antacids and food reduce the absorption of paracetamol. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged, regular daily use of paracetamol, increasing the risk of bleeding. Barbiturates reduce the antipyretic effect of paracetamol. Hepatotoxic drugs increase the likelihood of paracetamol accumulation and overdose.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of hepatotoxicity. Paracetamol reduces the effectiveness of diuretics, may prolong the half-life of chloramphenicol; may induce hepatic metabolism of lamotrigine, thereby reducing its bioavailability and efficacy. Regular concomitant use of paracetamol and zidovudine may lead to neutropenia and increased risk of liver damage. When probenecid is administered, the dose of paracetamol should be reduced, as probenecid affects paracetamol metabolism. Paracetamol may interfere with serum uric acid determination by the phosphotungstic acid method. Paracetamol hepatotoxicity may be enhanced by prolonged or excessive alcohol consumption. Do not use concurrently with alcohol.

Ascorbic acid, when taken orally, enhances iron absorption, increases ethinylestradiol and penicillin, tetracycline levels, reduces blood levels of antipsychotic drugs and phenothiazine derivatives, reduces the effect of heparin and indirect anticoagulants. Concurrent use with salicylates increases the risk of crystalluria and glaucoma during glucocorticoid therapy; large doses reduce the effectiveness of tricyclic antidepressants.

Antidepressants, antiparkinsonian and antipsychotic drugs, phenothiazine derivatives increase the risk of urinary retention, dry mouth, constipation. Glucocorticosteroids increase the risk of glaucoma development.

Absorption of ascorbic acid is reduced when used concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks. Orally administered ascorbic acid increases the absorption of penicillin and iron, reduces the effectiveness of heparin and indirect anticoagulants, increases the risk of crystalluria during salicylate therapy. Concurrent intake of ascorbic acid and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, which may lead to circulatory decompensation. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their concomitant use increases iron toxicity, particularly in the myocardium, potentially leading to cardiac decompensation. Prolonged intake of large doses in patients treated with disulfiram inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taking oral contraceptives, consuming fruit or vegetable juices, or alkaline drinks. High doses of the drug reduce the effectiveness of tricyclic antidepressants.

Concurrent use with alcohol may enhance drowsiness.

Due to the presence of pheniramine, the drug enhances the effects of central nervous system (CNS) depressants (hypnotics, anesthetics, barbiturates, tranquilizers, narcotic analgesics, as well as ethanol). Pheniramine may reduce the effect of anticoagulants and interact with progesterone, reserpine, and thiazide diuretics. Concurrent use of contraceptives may lead to reduced efficacy of the antihistamine component of the drug.

Phenylephrine, an ingredient of the product Gripaut Hot Drink, is incompatible with sympathomimetics and monoamine oxidase inhibitors (MAOIs) due to the risk of increased arterial pressure, negative effects on the cardiovascular system and CNS. Interaction with tricyclic antidepressants (amitriptyline) increases the risk of cardiovascular side effects; with digoxin and cardiac glycosides – may lead to arrhythmias and infarction; with other sympathomimetics – increases the risk of cardiovascular side reactions and hypertension; may reduce the effectiveness of beta-blockers and other antihypertensive agents (reserpine, methyldopa, debrisoquin, guanethidine), increasing the risk of arterial hypertension and cardiovascular side effects. Concurrent use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism. Caution is required when using paracetamol concomitantly with flucloxacillin, as this combination has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

Special precautions for use.

Do not exceed the recommended doses.

If symptoms do not improve within 5 days or are accompanied by high fever, fever lasting more than 3 days, skin rashes, or persistent headache, consult a physician, as these manifestations may indicate a more serious illness. Due to the risk of severe liver damage in case of overdose, this medicinal product should not be used concurrently with other medicinal products for symptomatic treatment of cold and rhinitis (vasoconstrictors and drugs containing paracetamol). Use with caution in patients with Raynaud's disease, arterial hypertension, heart disorders, arrhythmia, bradycardia, thyroid disorders, liver and kidney diseases, acute hepatitis, glaucoma, chronic lung diseases, prostate hypertrophy (due to the risk of urinary retention), elderly patients, patients with increased blood coagulability, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The risk of hepatotoxicity is increased in patients with alcohol-induced liver damage and in those who abuse alcohol.

Use with caution in patients with impaired liver, gastrointestinal tract, or kidney function, benign hyperbilirubinemia, urinary retention, severe cardiovascular disorders, diabetes mellitus, bronchial asthma, or productive cough. During prolonged treatment, monitoring of peripheral blood and liver function is required (once every 10 days).

In sensitive patients, even small doses may cause insomnia, dizziness, tachycardia, tremor, or cardiac arrhythmia. If any of the above symptoms occur, discontinue the drug immediately.

Alcohol consumption is contraindicated during treatment with this drug.

During treatment, avoid using sedative drugs (especially barbiturates), as they may enhance the sedative effect of the antihistamine component of the drug (pheniramine maleate).

If the illness is caused by a bacterial infection, concomitant antibiotic therapy is recommended.

If hemolysis of erythrocytes or drug-induced hemolytic anemia occurs during treatment with Gripaut Hot Drink, the drug must be discontinued immediately.

The drug contains: phenylephrine, which may provoke angina attacks; sucrose, which is contraindicated in patients with fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency. Patients with known sugar intolerance should consult a physician before taking this medicinal product. Use with caution in patients with diabetes mellitus. May be harmful to teeth.

Consult a physician before using the drug in the following cases:

in liver or kidney disorders;
when taking warfarin or similar anticoagulants;
when taking analgesics daily for mild forms of arthritis;
in bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

The drug may affect laboratory test results for blood glucose, uric acid, creatinine, and inorganic phosphate levels. Occult blood in stool may yield a false-negative result.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe conditions such as severe renal insufficiency, sepsis, malnutrition, or other sources of glutathione deficiency (e.g., chronic alcoholism) who were treated long-term with therapeutic doses of paracetamol or a combination of paracetamol and flucloxacillin. In suspected cases of HAGMA due to pyroglutamic acidosis, immediate discontinuation of paracetamol and close monitoring of the patient are recommended. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors. In patients with severe infections (sepsis), where glutathione levels are reduced, the use of paracetamol increases the risk of metabolic acidosis. Symptoms include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. In such cases, seek immediate medical attention.

This drug is not recommended at the end of the day, as high doses of ascorbic acid may exert a mild stimulating effect. Due to the stimulatory effect of ascorbic acid on corticosteroid hormone production, kidney function and arterial blood pressure should be monitored.

Use with particular caution in patients with disorders of iron metabolism (hemochromatosis, hemosiderosis, thalassemia) and in patients with a history of nephrolithiasis (risk of hyperoxaluria and oxalate deposition in the urinary tract after high-dose ascorbic acid intake).

Prolonged use of high doses of ascorbic acid may accelerate its own metabolism, potentially leading to paradoxical hypovitaminosis after discontinuation. Do not use concurrently with other vitamin C-containing products. Absorption of ascorbic acid may be altered in intestinal motility disorders, enteritis, or reduced gastric secretion.

The product contains aspartame, a source of phenylalanine, which may be harmful to patients with phenylketonuria.

Patients with diabetes mellitus should be aware that the medicinal product contains sucrose.

This medicinal product contains sodium citrate. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Method of Administration and Dosage.

Dissolve the contents of the sachet in a glass of hot water (not boiling water) and drink. The medication may be taken every 3–4 hours, but no more than 3 sachets per day. The maximum duration of use without medical consultation is 3 days; further use should be under a physician's recommendation.

Children.

Do not use in children under 14 years of age.

Overdose.

Paracetamol. Within the first 24 hours, symptoms include pallor, nausea, vomiting, anorexia, and abdominal pain. After ingestion of large doses, disorientation, psychomotor agitation, dizziness, sleep disturbances, cardiac arrhythmias, pancreatitis, and hepatonecrosis may occur. The first sign of liver damage may be abdominal pain, which does not always manifest within the first 12–48 hours and may appear later, up to 4–6 days after drug administration. Liver injury typically develops within 72–96 hours after intake. Glucose metabolism disturbances and metabolic acidosis, as well as hemorrhages, may occur. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

In isolated cases, acute renal failure with tubular necrosis has been reported, which may occur even in the absence of severe liver damage, presenting as severe lumbar pain, hematuria, and proteinuria. Nephrotoxicity is possible: renal colic, interstitial nephritis, capillary necrosis.

Ingestion of 10 g or more of paracetamol by adults or more than 150 mg/kg body weight by children, especially when combined with alcohol, may lead to hepatocellular necrosis, resulting in encephalopathy, hemorrhages, hypoglycemia, hepatic coma, and fatal outcome. In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione deficiency (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may lead to liver damage.

In case of overdose, prompt medical assistance is required. The patient should be immediately hospitalized, 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 the risk of organ damage. Activated charcoal should be administered within the first hour after overdose. Paracetamol blood concentration should be measured 4 hours or later after ingestion (earlier concentrations are not reliable). Treatment with N-acetylcysteine can be administered within 24 hours after paracetamol intake, but maximum efficacy is achieved when administered within the first 8 hours; after this time, its effectiveness decreases sharply. If intravenous N-acetylcysteine is required, it should be administered according to the established dosing schedule. Alternatively, in the absence of vomiting and when far from a hospital, oral methionine may be used.

Phenylephrine. Symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmia, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension, and, in severe cases, coma. To counteract hypertensive effects, intravenous alpha-receptor blockers may be used; for seizure control, diazepam may be administered.

Pheniramine. Anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, intestinal atony. CNS depression leads to respiratory and cardiovascular system dysfunction (bradycardia, arterial hypotension, collapse). Symptoms caused by mutual potentiation of the anticholinergic effect of pheniramine and the sympathomimetic effect of phenylephrine: drowsiness, which may progress to agitation (especially in children) or CNS depression, visual disturbances, skin rash, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disturbances, bradycardia. There is no specific antidote for antihistamine overdose. Standard emergency care should be provided, including administration of activated charcoal, a saline laxative, and standard supportive measures for the cardiovascular and respiratory systems. CNS stimulants must not be used; vasoconstrictors may be used to treat arterial hypotension.

Ascorbic acid. Symptoms include nausea, vomiting, or diarrhea (which resolve after discontinuation); bloating and abdominal pain, itching, skin rashes, increased excitability. Doses exceeding 3000 mg may cause temporary osmotic diarrhea and gastrointestinal disturbances, disturbances in zinc and copper metabolism, myocardial dystrophy. With prolonged use in high doses, suppression of the pancreatic islet apparatus function and glucosuria are possible. Overdose may lead to altered renal excretion of ascorbic and uric acids during acetylation of urine, resulting in precipitation of oxalate calculi.

Treatment is symptomatic: gastric lavage should be performed within the first 6 hours, and oral methionine or intravenous cysteamine or N-acetylcysteine should be administered within the first 8 hours.

Adverse Reactions

Skin and appendages: Increased sweating, rash, pruritus, dermatitis, urticaria, erythema multiforme exudativum, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin and mucous membrane rashes (usually generalized erythematous eruptions, urticaria), angioedema (Quincke's edema).

Immune system disorders: In isolated cases – anaphylactic shock, angioneurotic edema.

Nervous system disorders: Drowsiness, general weakness, nervousness, headache, dizziness, psychomotor agitation and disorientation, restlessness, fear, irritability, hallucinations, sleep disturbances, paresthesia, insomnia, confusion, depressive states, tremor, epileptic seizures, dyskinesia; in individual cases – coma, sensations of tingling and heaviness in the extremities, tinnitus, behavioral changes.

Eye disorders: Visual disturbances and accommodation disorders, increased intraocular pressure, mydriasis, dry eyes, eye pain, burning sensation in the eyes, blurred vision, photophobia, acute angle-closure glaucoma.

Gastrointestinal disorders: Nausea, vomiting, dry mouth, epigastric discomfort and pain, hypersalivation, decreased appetite, increased liver enzyme activity, heartburn, diarrhea, constipation, flatulence, anorexia, aphthae, hemorrhages, mucosal irritation.

Hepatobiliary disorders: Liver function abnormalities, hypertransaminasemia (usually without jaundice), hepatonecrosis (with high-dose use).

Blood and lymphatic system disorders: Anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding. With prolonged use at high doses – aplastic anemia, pancytopenia which may lead to nosebleeds and/or gum bleeding, bruising, agranulocytosis, neutropenia, leukopenia, thrombocytopenia.

Renal and urinary system disorders: With high-dose use – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), urinary disturbances, especially in patients with prostate hyperplasia, crystalluria, formation of urate and oxalate kidney stones and urinary tract calculi, dysuria, renal colic, renal failure.

Cardiovascular system disorders: Arterial hypertension, tachycardia or reflex bradycardia, dyspnea, chest pain, arrhythmia, palpitations, angina attacks.

Endocrine system disorders: Hypoglycemia up to hypoglycemic coma, hyperglycemia, glucosuria.

Metabolic changes: Disturbances in zinc and copper metabolism; metabolic acidosis with high anion gap of unknown frequency.

Respiratory system disorders: Bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Other: General weakness, malaise.

Adverse reactions possibly related to the presence of ascorbic acid in the medicinal product

Renal and urinary system disorders: Glomerular apparatus kidney damage, crystalluria, renal failure.

Skin disorders: Eczema.

Endocrine system disorders: Disturbances in glycogen synthesis up to the development of diabetes mellitus.

Cardiovascular system disorders: Myocardial dystrophy.

Hematopoietic system disorders: Thrombocytosis, hyperprothrombinemia, thrombus formation, erythrocytopenia, neutrophilic leukocytosis.

Nervous system disorders: Sleep disturbances, sensation of warmth, increased fatigue.

Metabolism and nutrition disorders: Disturbances in zinc and copper metabolism, metabolic acidosis with high anion gap (HAGMA)*.

Unlike second-generation antihistamines, pheniramine use is not associated with QT interval prolongation or cardiac arrhythmia.

*Reported in the post-marketing period with concomitant use of paracetamol and flucloxacillin, usually in the presence of risk factors.

Description of selected adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed during paracetamol use in patients with risk factors (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Shelf life. 2 years.

Storage conditions.

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

Packaging. 6 g per sachet. 10 sachets per cardboard box.

Dispensing category. Over-the-counter.

Manufacturer.

Everest Generics Life Sciences Limited.

Manufacturer's address and place of business.

Plot No: S-8, S-9, S-13/PI & S-14/PI TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Yedcherla (M), Mahbubnagar, Telangana, IH-509301, India.