Gripostad hot lemon

INSTRUCTION FOR MEDICAL USE|consumption| of the medicinal product GRIPOCITRON HOT LEMON (GRIPOCITRON HOT LEMON)

Composition:

Active substances: paracetamol; ascorbic acid (vit C); pheniramine; phenylephrine;

1 sachet contains|contains| 500 mg of paracetamol, 50 mg of ascorbic acid, 20 mg of pheniramine| maleate|, 10 mg of phenylephrine| hydrochloride|;

Excipients: sorbitol (E 420), anhydrous citric acid, sodium saccharin, lactose monohydrate, succinic acid, sodium citrate|, povidone, colloidal anhydrous silicon dioxide, tartrazine (E 102); "Lemon" flavor containing maltodextrin, gum arabic, citric acid.

Medicinal form. Powder for oral solution.

Main physico-chemical properties: contents of the sachet – a mixture of yellow and white granules and powder with a fruity odor.

Pharmacotherapeutic group. Other analgesics and antipyretics. Anilides. Paracetamol, combinations without psychotropic agents. ATC code N02BE51.

Pharmacological properties.

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

Ascorbic acid enhances the body's nonspecific resistance.

Pheniramine maleate is an H1-histamine 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, reducing swelling of the nasal mucosa and paranasal sinuses. Its effect begins rapidly and lasts approximately 20 minutes.

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 (T½) of 1–4 hours. Duration of action is 3–4 hours.

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

Pheniramine maleate is well absorbed from the gastrointestinal tract. It is metabolized in the liver by the cytochrome P450 system, with a half-life (T½) of 16–18 hours; 70–83% is excreted by the kidneys.

Phenylephrine hydrochloride is metabolized in the liver or gastrointestinal tract and excreted by the kidneys.

Clinical characteristics.

Indications. Symptomatic treatment of acute respiratory infections and influenza:

• elevated body temperature;
• headache;
• nasal congestion;
• rhinorrhea;
• 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; phenylketonuria; alcoholism; blood disorders; leukopenia; anemia; severe forms of arrhythmia, arterial hypertension, atherosclerosis, ischemic heart disease; hyperthyroidism; acute pancreatitis; prostate hypertrophy with urinary retention; bladder neck obstruction; pyloroduodenal obstruction; bronchial asthma; closed-angle glaucoma; pheochromocytoma; thrombosis; thrombophlebitis; diabetes mellitus; epilepsy; states of increased excitement; sleep disorders associated with treatment with tricyclic antidepressants, β-blockers, other sympathomimetics, appetite suppressants or stimulants, and amphetamine-like psychostimulants; concomitant therapy and within 2 weeks after administration of MAO inhibitors.

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 when used with cholestyramine (this effect is negligible if cholestyramine is administered 1 hour apart). Long-term use of paracetamol may enhance the anticoagulant effect of warfarin and other coumarin derivatives, increasing the risk of bleeding. This effect is not pronounced with occasional use of paracetamol. Barbiturates reduce the antipyretic effect of paracetamol. Hepatotoxic drugs increase the likelihood of paracetamol accumulation and overdose. The risk of paracetamol hepatotoxicity increases with drugs that induce hepatic microsomal enzymes (barbiturates; anticonvulsants – phenytoin, phenobarbital, carbamazepine; and antituberculosis agents – rifampicin, isoniazid). Paracetamol reduces the efficacy of diuretics, may prolong the T½ of chloramphenicol; may induce lamotrigine metabolism in the liver, thereby reducing its bioavailability and effectiveness. Regular concomitant use of paracetamol and 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 the determination of serum uric acid levels by the phosphotungstic acid method. Hepatotoxicity of paracetamol may be enhanced by prolonged or excessive alcohol consumption. Do not use concurrently with alcohol. 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").

Ascorbic acid, when taken orally, enhances iron absorption; increases blood levels of ethinylestradiol, penicillins, and tetracyclines; decreases blood levels of antipsychotic agents and phenothiazine derivatives; reduces the effectiveness of heparin and indirect anticoagulants; increases the risk of crystalluria during salicylate therapy and the risk of glaucoma during glucocorticoid therapy; high doses reduce the effectiveness of tricyclic antidepressants. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their concomitant use increases iron toxicity, especially in the myocardium, potentially leading to cardiac decompensation. Long-term use of high doses during disulfiram therapy inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taken with oral contraceptives, fruit or vegetable juices, or alkaline drinks.

Pheniramine enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents, and inhibits the action of anticoagulants. Concurrent use of pheniramine with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol may significantly increase its depressant effects.

Interaction of phenylephrine with MAO inhibitors causes a hypertensive effect; with tricyclic antidepressants (amitriptyline) – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – may lead to arrhythmias and infarction; with other sympathomimetics – increases the risk of adverse cardiovascular reactions and arterial hypertension; may reduce the effectiveness of β-blockers and other antihypertensive agents (reserpine, methyldopa, debrisoquin, 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.

Special precautions for use.

Do not exceed the recommended doses. If the condition does not improve within 5 days or is accompanied by high fever, chills lasting more than 3 days, rash, or prolonged headache, consult a physician, as these symptoms may indicate a more serious illness.

Due to the risk of severe liver damage in case of overdose, do not use simultaneously with other symptomatic cold and flu remedies (vasoconstrictors, paracetamol-containing products). Use with caution in patients with Raynaud's disease, arterial hypertension, heart disease, arrhythmia, bradycardia, thyroid disorders, liver or kidney disease, acute hepatitis, glaucoma, chronic pulmonary diseases, prostate hypertrophy (due to risk of urinary retention), elderly patients, increased blood coagulability, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The risk of hepatotoxicity is increased in patients with alcoholic liver disease or those who abuse alcohol.

Consult a physician before using the drug in case of liver or kidney disease; when taking warfarin or similar anticoagulants; daily use of analgesics for mild forms of arthritis; or 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 5-oxoproline (pyroglutamic) acidosis have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or in cases of malnutrition and other causes of glutathione deficiency (e.g., chronic alcoholism), who were treated with therapeutic doses of paracetamol over a prolonged period or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with close monitoring of the patient. 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. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. If these symptoms occur, seek immediate medical attention.

It is not recommended to take this medication late in the day, as high doses of ascorbic acid may have a mild stimulatory effect. Due to the stimulatory effect of ascorbic acid on corticosteroid hormone production, monitoring of kidney function and blood pressure is required.

Use with particular caution in patients with disorders of iron metabolism (hemochromatosis, hemosiderosis, thalassemia) and in those with a history of nephrolithiasis (risk of hyperoxaluria and oxalate precipitation 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 this medication 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 product contains phenylephrine, which may provoke angina attacks.

Tartrazine (E 102) may cause allergic reactions.

If a patient has known sugar intolerance, consult a physician before taking this medication.

This medicinal product contains 1.26 mmol (or 28.9 mg)/dose of sodium (1 sachet). Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding. The drug is contraindicated during pregnancy and breastfeeding. The effect of the drug on fertility has not been specifically studied. It is known that preclinical studies have not revealed any specific 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. Since the drug may cause drowsiness and other adverse reactions affecting the nervous system and vision, driving vehicles or operating complex machinery is not recommended during treatment.

Method of Administration and Dosage

For oral use in adults and children aged 12 years and older: take 1 sachet every 3–4 hours, but not more than 3 sachets per day. Before use, dissolve the contents of 1 sachet in a glass of boiled hot water (not boiling water) and take while warm.

Maximum duration of use without medical consultation – 3 days.

Children. The drug is contraindicated in children under 12 years of age.

Overdose. In case of paracetamol overdose, within the first 24 hours, symptoms such as pallor, nausea, vomiting, anorexia, and abdominal pain may appear. 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 drug intake. Glucose metabolism disturbances and metabolic acidosis, hemorrhages may also 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, 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.

Administration of 10 g or more of paracetamol in adults, especially with alcohol, or more than 150 mg/kg body weight in children, 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)), administration of 5 g or more of paracetamol may lead to liver damage.

In case of overdose of ascorbic acid, nausea, vomiting, or diarrhea (which resolve after discontinuation) may occur; abdominal distension and pain, pruritus, skin rashes, and increased excitability may also develop. 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 pancreatic islet function and glucosuria are possible. Overdose may lead to changes in renal excretion of ascorbic and uric acids during acetylation of urine, resulting in precipitation of oxalate stones.

In case of pheniramine overdose, anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, intestinal atony. CNS depression leads to impaired function of the respiratory and cardiovascular systems (bradycardia, arterial hypotension, collapse). Symptoms due to mutual potentiation of the parasympatholytic effect of pheniramine and sympathomimetic effect of phenylephrine: drowsiness, which may be followed by agitation (especially in children) or CNS depression, visual disturbances, rashes, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disturbances, bradycardia.

In case of phenylephrine overdose, hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, disturbances in consciousness, arrhythmia, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension may occur; in severe cases – coma.

Treatment. In case of paracetamol overdose, prompt medical attention is required. The patient should 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 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). N-acetylcysteine can be administered within 24 hours after paracetamol ingestion, but maximum efficacy is achieved when administered within the first 8 hours, after which its effectiveness rapidly declines. If intravenous administration of N-acetylcysteine is required, it should be given according to the established dosing schedule. Alternatively, in remote locations without vomiting, oral methionine may be used.

In case of ascorbic acid overdose, gastric lavage should be performed within the first 6 hours, and within the first 8 hours, oral methionine or intravenous cysteamine or N-acetylcysteine should be administered.

In case of pheniramine overdose, there is no specific antidote. Standard emergency measures should be provided, including administration of activated charcoal, saline laxative, and standard supportive measures for the cardiopulmonary system. Stimulants must not be used; vasopressors may be used to treat arterial hypotension.

In case of phenylephrine overdose, α-receptor blockers may be administered intravenously to counteract hypertensive effects; diazepam may be used to control seizures.

Adverse Reactions

Skin disorders: rash (usually generalized, erythematous), pruritus, dermatitis, urticaria, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, angioneurotic edema.

Nervous system disorders: headache, dizziness, tremor, psychomotor agitation and disorientation, restlessness, nervousness, fear, irritability, sleep disturbances, insomnia, somnolence, confusion, hallucinations, depressive states, paresthesia, tinnitus, and in isolated cases – coma, seizures, dyskinesia, behavioral changes.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

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

Metabolism and nutrition disorders: 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.

Gastrointestinal disorders: nausea, vomiting, heartburn, dry mouth, epigastric discomfort and pain, constipation, diarrhea, flatulence, anorexia, aphthae, hypersalivation, hemorrhage, mucosal irritation.

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

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

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

Renal and urinary disorders: nephrotoxicity, interstitial nephritis, papillary necrosis, dysuria, urinary retention and difficulty in micturition, renal colic, renal failure.

Cardiovascular disorders: arterial hypertension, tachycardia, bradycardia, arrhythmia, dyspnea, chest pain, angina attacks.

Other: general weakness, malaise.

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

Shelf life: 3 years.

Storage conditions: Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging: 4 g in sachets, pack of 5, pack of 10 in a box.

Availability: Over-the-counter.

Manufacturer: LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business: 22 Shevchenko Street, Kharkiv, Kharkiv region, 61013, Ukraine.