Gripositron hot orange

INSTRUCTIONS FOR MEDICAL USE|consumption| of the medicinal product GRIPOCITRON HOT ORANGE (GRIPOCITRON HOT ORANGE)

Composition:

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

One 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, Yellow FCF (E 110); orange flavouring containing maltodextrin, gum arabic, ascorbic acid, alpha-tocopherol, sulfur dioxide (E 220).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: contents of the sachet – a mixture of pinkish-orange and white granules and powder with a fruity odour.

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. Duration of action is 3–4 hours.

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 effects, reducing swelling of the nasal mucosa and paranasal sinuses. Its action begins rapidly and lasts approximately 20 minutes.

Pharmacokinetics. Paracetamol is well absorbed, crosses the placental barrier, and passes into breast milk to a minor extent. It is metabolized by the cytochrome P450 system, excreted by the kidneys, and has a half-life (T½) of 1–4 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 via the cytochrome P450 system, has a half-life (T½) of 16–18 hours, and 70–83% is excreted by the kidneys.

Phenylephrine hydrochloride is metabolized either 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;
• 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; 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 excitation; sleep disorders associated with treatment using tricyclic antidepressants, β-blockers, other sympathomimetics, appetite-suppressing or appetite-enhancing agents, 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 potentiate 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 half-life (T½) of chloramphenicol; may induce lamotrigine metabolism in the liver, 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 taken, 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. Hepatotoxicity of paracetamol may be enhanced by prolonged or excessive alcohol consumption. Do not use concurrently with alcohol. Caution is advised 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 enhances iron absorption when taken orally; increases blood levels of ethinylestradiol, penicillins, and tetracyclines; reduces blood levels of antipsychotic drugs 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; large doses reduce the efficacy 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. Prolonged intake of large doses during disulfiram treatment inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taken with oral contraceptives, fruit or vegetable juices, and alkaline beverages.

Pheniramine potentiates the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, antiparkinsonian agents, and inhibits the action of anticoagulants. Concomitant use of pheniramine with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol may significantly enhance 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 adverse cardiovascular reactions. Concomitant 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, skin rashes, 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 medications intended for symptomatic treatment of cold and rhinitis (vasoconstrictors, paracetamol-containing products). Use with caution in patients with Raynaud's disease, arterial hypertension, heart disease, arrhythmias, 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 medication in cases of liver or kidney disease; when taking warfarin or similar anticoagulants; when using analgesics daily for mild forms of arthritis; or in patients with bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

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

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 careful monitoring of the patient’s condition. Measurement of 5-oxoproline levels in urine may be helpful in identifying pyroglutamic acidosis as the primary 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 in the evening, 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 iron metabolism disorders (hemochromatosis, hemosiderosis, thalassemia) and in those 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 this medication simultaneously with other vitamin C-containing products. Absorption of ascorbic acid may be altered in cases of intestinal motility disorders, enteritis, or reduced gastric secretion.

The medication contains phenylephrine, which may provoke angina attacks.

Yellow FCF (E 110) may cause allergic reactions.

Sulfur dioxide (E 221) may rarely cause hypersensitivity reactions and bronchospasm.

If a patient has known intolerance to certain sugars, 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 medication is contraindicated during pregnancy or 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 medication may cause drowsiness and other adverse effects on the nervous system and visual organs, driving or operating complex machinery is not recommended during treatment.

Dosage and Administration.

For oral use in adults and children aged 12 years and older: take 1 sachet every 3–4 hours, but no 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.

Paracetamol overdose: Within the first 24 hours, symptoms may include pallor, nausea, vomiting, anorexia, and abdominal pain. Following 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 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, even in the absence of severe liver damage. Symptoms include 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, 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)), ingestion of 5 g or more of paracetamol may lead to liver damage.

Ascorbic acid overdose: Nausea, vomiting, or diarrhea (resolving after discontinuation); abdominal distension and pain, itching, skin rashes, and increased excitability may occur. 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.

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

Phenylephrine overdose: 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 may occur.

Treatment.

In case of paracetamol overdose, prompt medical attention 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 administered within the first hour after overdose. Paracetamol blood concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). N-acetylcysteine can be administered within 24 hours after paracetamol ingestion, but maximum efficacy occurs when administered within the first 8 hours; after this, its effectiveness decreases sharply. If intravenous administration of N-acetylcysteine is required, it should be given according to the established dosing schedule. Alternatively, in remote locations far from hospitals and in the absence of 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, a saline laxative, and standard supportive measures for cardiovascular and respiratory systems. Stimulants must not be used; vasopressors may be used to treat arterial hypotension.

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

Side effects.

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

Immune system-related: hypersensitivity reactions, including anaphylaxis, angioneurotic edema.

Nervous system-related: headache, dizziness, tremor, psychomotor agitation and disorientation, restlessness, nervous excitement, fear, irritability, sleep disturbances, insomnia, drowsiness, confusion, hallucinations, depressive states, paresthesia, tinnitus; in individual cases – coma, seizures, dyskinesia, behavioral changes.

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

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

Metabolism and nutrition-related: metabolic acidosis with a high anion gap.

Cases of metabolic acidosis with a 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 system-related: nausea, vomiting, heartburn, dry mouth, epigastric discomfort and pain, constipation, diarrhea, flatulence, anorexia, aphthae, hypersalivation, hemorrhage, mucosal irritation.

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

Endocrine system-related: hypoglycemia, up to hypoglycemic coma.

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

Renal and urinary system-related: nephrotoxicity, interstitial nephritis, capillary necrosis, dysuria, urinary retention and difficulty urinating, renal colic, renal failure.

Cardiovascular system-related: 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 arrhythmias.

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 per sachet; 10 sachets per cardboard box;

4 g per sachet; 5 paired sachets per cardboard box.

Prescription status. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and location of business operations. 22 Shevchenko Street, Kharkiv, Kharkiv Region, Ukraine, 61013.