Astrocytron extra

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASTRACITRON EXTRA

Composition:

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

1 sachet contains 500 mg of paracetamol, 10 mg of phenylephrine hydrochloride, 20 mg of pheniramine maleate, 50 mg of ascorbic acid;
Excipients: citric acid; sodium citrate; colloidal anhydrous silicon dioxide; sucrose (saccharose); saccharin; orange flavor (a mixture of flavoring substances, maltodextrin, glucose, acacia gum (gum arabic) (E414), pectin (E440)); colorant "Sunset Yellow" (E110).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: pale orange-pink powder with an orange 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 transmission of pain impulses.

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

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

Ascorbic acid enhances non-specific resistance of the body.

Pharmacokinetics.

Paracetamol is well absorbed, penetrates the placental barrier, and passes slightly 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, 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 (rhinorrhea),
• 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 using monoamine oxidase inhibitors (MAOIs).

Interaction with other medicinal products and other forms 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). With prolonged use of paracetamol, the anticoagulant effect of warfarin and other coumarin derivatives may be enhanced, 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 when taken with drugs that induce hepatic microsomal enzymes (barbiturates; anticonvulsants – phenytoin, phenobarbital, carbamazepine; and antituberculosis agents – rifampicin, isoniazid). Paracetamol: reduces the effectiveness of diuretics, may prolong the half-elimination period of chloramphenicol; may induce lamotrigine metabolism in the liver, 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 the determination of 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.

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 cardiovascular adverse 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 effects. Concurrent use of phenylephrine with ergot alkaloids (ergotamine and 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 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 treatment inhibits the disulfiram-alcohol reaction. Absorption of ascorbic acid is reduced when taking 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 increase its CNS depressant effects.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap as a result of 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, chills lasting more than 3 days, rash, 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, do not use simultaneously with other cold and flu symptomatic treatments (vasoconstrictors, paracetamol-containing products). Use with caution in patients with Raynaud's disease, arterial hypertension, heart disorders, arrhythmias, bradycardia, thyroid disorders, liver or kidney disease, acute hepatitis, glaucoma, chronic pulmonary diseases, prostate hyperplasia (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 individuals with alcohol-related liver damage or those who abuse alcohol.

The product contains: phenylephrine, which may provoke angina attacks; sucrose and saccharin, which are contraindicated in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency. If a patient has known sugar intolerance, 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 use if you have: liver or kidney disease; are taking warfarin or similar anticoagulants; take analgesics daily for mild forms of arthritis; or have bronchopulmonary disorders (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.

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.

It is not recommended to take this medication late in 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 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 vitamin C 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.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic acid) accumulation have been reported in patients with severe conditions such as severe renal insufficiency or sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with therapeutic doses of paracetamol over a prolonged period or with a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic 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 helpful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Use with caution, as the product contains the colorant Sunset Yellow (E 110), which may cause allergic reactions.

The medicinal product Astracitron Extra contains sodium citrate; therefore, patients on a sodium-controlled diet should use this product with caution.

Use during pregnancy or breastfeeding.

The product is contraindicated during pregnancy and breastfeeding. The effect of the drug on fertility has not been specifically studied. 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 or operating complex machinery during treatment is not recommended.

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.

Maximum duration of use – 5 days.

Children.

The drug is contraindicated 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, 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 appear within the first 12–48 hours and may develop later, up to 4–6 days after drug administration. Liver injury typically occurs within 72–96 hours after 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, 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; chronic 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, prompt medical assistance is required. The patient should be immediately taken to 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 unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol intake, 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 remote settings without vomiting, oral methionine may be used.

Phenylephrine: symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, disturbances in consciousness, arrhythmias, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension; in severe cases – coma. To counteract hypertensive effects, intravenous alpha-blockers may be used; for seizures – diazepam.

Pheniramine: 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 sympathomimetic effect of phenylephrine: drowsiness, which may progress to agitation (especially in children) or CNS depression, visual disturbances, 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, saline laxative, and standard supportive measures for 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 rash, 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 pancreatic islet function and glucosuria. Overdose may alter renal excretion of ascorbic and uric acids during acetylation of urine, leading to precipitation of oxalate calculi.

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 subcutaneous tissue disorders: rash, pruritus, dermatitis, urticaria, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.

Immune system disorders: hypersensitivity reactions, including anaphylactic shock and angioneurotic edema.

Nervous system disorders: headache, dizziness, tremor, restlessness, nervousness, irritability, feeling of fear, insomnia, somnolence, confusion, hallucinations, psychomotor agitation, disorientation, depression, paresthesia, tinnitus, in individual cases – coma, seizures, dyskinesia, behavioral changes.

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

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

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

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

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

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

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

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

Metabolism and nutrition disorders: metabolic acidosis with high anion gap with frequency "unknown" (cannot be estimated from available data).

Description of selected adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap as a consequence 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.

Other: general weakness, malaise.

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

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

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. Sachets of 5 g. 10 or 30 sachets per cardboard box.

Availability category. Over-the-counter.

Manufacturer. ASTRAFARM LLC, Ukraine.

Manufacturer's address and location of business activity. 6, Kyivska St., Vyshneve, Bucha district, Kyiv region, 08132, Ukraine.