Gripcytron forte

INSTRUCTIONS FOR MEDICAL USE of the medicinal product GRIPOCITRON FORTE (GRIPOCITRON FORTE)

Composition:

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

1 sachet contains paracetamol 650 mg, ascorbic acid 50 mg, pheniramine maleate 20 mg, phenylephrine hydrochloride 10 mg;

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.

Pharmaceutical form. Powder for oral solution.

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

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

Pharmacological Properties.

Pharmacodynamics.

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

Ascorbic acid enhances the body's non-specific resistance.

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

Phenylephrine hydrochloride is an α-adrenomimetic agent with 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 in small amounts. 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 T½ of 16–18 hours; 70–83% is excreted by the kidneys.

The action of phenylephrine hydrochloride begins rapidly and lasts approximately 20 minutes. It 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;
• 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; epilepsy; states of increased excitation; sleep disorders associated with treatment with tricyclic antidepressants, β-blockers, other sympathomimetics, appetite suppressants or stimulants, and amphetamine-like psychostimulants; concomitant therapy with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after their discontinuation.

Interaction with other medicinal products and other types of interactions. The absorption rate of paracetamol may be increased when used with metoclopramide and domperidone, and decreased 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 half-life (T½) 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 used, the dose of paracetamol should be reduced, as probenecid affects paracetamol metabolism. Paracetamol may interfere with serum uric acid measurements using 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").

Interaction of phenylephrine with MAO inhibitors causes a hypertensive effect; with tricyclic antidepressants (e.g., 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 cardiovascular side reactions and 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, methysergide) may increase the risk of ergotism.

Ascorbic acid, when taken orally, enhances iron absorption; 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; high doses reduce the efficacy of tricyclic antidepressants. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their simultaneous use increases iron toxicity, especially in the myocardium, potentially leading to cardiac decompensation. Prolonged 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 beverages.

Pheniramine enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents; it may inhibit the action of anticoagulants. Concurrent use of pheniramine with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol may significantly enhance its central nervous system depressant effects.

Special precautions for use.

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

Due to the risk of severe liver damage in overdose, do not use simultaneously with other medications 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), diabetes mellitus, elderly individuals, increased blood coagulability, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The risk of hepatotoxicity is increased in individuals with alcoholic liver disease or those who abuse alcohol.

Consult a physician before using the drug in case of liver or kidney disease; concurrent use of warfarin or similar anticoagulants; daily use of analgesics for mild forms of arthritis; bronchopulmonary diseases (asthma, emphysema, chronic bronchitis).

The drug may affect laboratory test results for blood levels of 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) (symptoms include deep, rapid, or labored breathing, nausea, vomiting, loss of appetite) due to 5-oxoproline acidosis have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other causes of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or in combination with flucloxacillin. If HAGMA due to 5-oxoproline acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with close monitoring of the patient. Measurement of 5-oxoproline levels in urine may be useful in identifying 5-oxoproline acidosis as the underlying cause of HAGMA in patients with multiple risk factors. In such cases, seek immediate medical attention.

This medication is not recommended at the end of the day, as high doses of ascorbic acid 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.

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 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 vitamin deficiency after discontinuation. Do not use 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 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 of the medicinal product). 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 shown no 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. Since the drug may cause drowsiness and other adverse reactions affecting the nervous system and visual organs, driving or operating complex machinery is not recommended during treatment.

Dosage and Administration.

Take orally. For adults and children aged 14 years and older, administer 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 – 5 days.

Children. The drug is contraindicated in children under 14 years of age.

Overdose.

In paracetamol overdose, pallor of the skin, nausea, vomiting, anorexia, and abdominal pain may appear within the first 24 hours. When large doses are taken, 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 occurs within 72–96 hours after ingestion. Glucose metabolism disturbances and metabolic acidosis, as well as 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, which may occur even in the absence of severe liver damage, and is manifested by 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 that induce liver enzymes; chronic alcohol abuse; glutathione deficiency due to malnutrition, cystic fibrosis, HIV infection, fasting, cachexia), ingestion of 5 g or more of paracetamol may lead to liver damage.

In ascorbic acid overdose, nausea, vomiting, or diarrhea (which resolve after discontinuation) may occur; also bloating and abdominal pain, pruritus, skin rashes, and increased excitability. Doses exceeding 3000 mg may cause transient osmotic diarrhea and gastrointestinal disturbances, disturbances in zinc and copper metabolism, myocardial dystrophy; with prolonged use in high doses, suppression of the insular apparatus of the pancreas 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 calculi.

In pheniramine overdose, anticholinergic-like symptoms occur: mydriasis, photophobia, dryness of skin and mucous membranes, hyperthermia, intestinal atony. CNS depression leads to impaired respiratory and cardiovascular system function (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 rashes, persistent headache, nervousness, insomnia, hyperreflexia, irritability, circulatory disturbances, bradycardia.

In phenylephrine overdose, symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmias, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension; in severe cases – coma.

Treatment. In paracetamol overdose, prompt medical attention 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 unreliable). 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 dosing schedule. Alternatively, in the absence of vomiting and when medical care is distant, oral methionine may be used.

In 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 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 cardiopulmonary function. Stimulants must not be used; vasopressors may be used to treat arterial hypotension.

In 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, anxiety, nervousness, irritability, fear, insomnia, drowsiness, confusion, hallucinations, psychomotor agitation, disorientation, depression, paresthesia, tinnitus, and 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 high anion gap (frequency unknown).

Cases of metabolic acidosis with high anion gap, resulting from 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-related: nausea, vomiting, heartburn, dry mouth, abdominal discomfort and pain, constipation, diarrhea, flatulence, anorexia, aphthae, hypersalivation, hemorrhages, 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), bruising or bleeding, thrombocytopenia, neutropenia, agranulocytosis, leukopenia, pancytopenia.

Renal and urinary system-related: nephrotoxicity, interstitial nephritis, capillary necrosis, dysuria, urinary retention and difficulty in urination, 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, the use of pheniramine 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, 10 sachets per box.

Availability. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and location of business activity. 22 Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.