Astrocitron

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASTRACITRONE (ASTRACITRONE)

Composition:

Active substances: 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 monohydrate; glucose monohydrate; sodium citrate; colloidal silicon dioxide anhydrous; "Quinoline yellow" colouring (E104); "Lemon" flavour, or "Orange" flavour, or "Raspberry" flavour.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white or almost white powder with a fruity odour.

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 lacrimation, as well as itching of the 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 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 via 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 aching.

Contraindications.

Hypersensitivity to the active substances or to other components of the medicinal product; 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 disturbances associated with treatment with tricyclic antidepressants, β-blockers, other sympathomimetics, appetite suppressants or stimulants, and amphetamine-like psychostimulants; concomitant use during and within 2 weeks after treatment with monoamine oxidase inhibitors (MAOIs).

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 taken 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 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 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 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 side effects. 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, 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; 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. Long-term use of high doses during disulfiram treatment 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; 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 CNS depressant effects.

Paracetamol should be used with caution 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 lasting more than 3 days, rash, 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, do not use simultaneously with other cold and flu remedies (vasoconstrictors and medicinal products containing paracetamol). 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 lung 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 alcoholic liver disease or those who abuse alcohol.

The product contains: phenylephrine, which may provoke angina attacks; and sucrose, which is contraindicated in patients with fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency. If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicine. Use with caution in diabetic patients. May be harmful to teeth.

Consult a physician before use in cases 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 glucose, uric acid, creatinine, and inorganic phosphates. Fecal occult blood testing may yield false-negative results.

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, immediate medical attention is required.

It is not recommended to take this medicine late in the day, as high doses of ascorbic acid have a mild stimulatory 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 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 deficiency 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.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic acid) accumulation have been reported in patients with severe underlying conditions such as severe renal failure 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 careful monitoring of the patient’s condition. 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.

Excipients.

Glucose. If a patient has known intolerance to certain sugars, medical advice should be sought before using this medicinal product.

Quinoline Yellow (E104). May cause allergic reactions.

Use during pregnancy or breastfeeding.

This medicinal product is contraindicated during pregnancy or breastfeeding. The effect of the drug on fertility has not been specifically studied. Preclinical studies have not shown 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.

Effect on ability to drive or operate machinery.

Since this medicinal product 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

The medicinal product is intended for use in adults and children aged 14 years and older.

The contents of the sachet should be dissolved in a glass of hot water (not boiling water) and taken orally. The dose may be repeated every 3–4 hours, but not more than 3 sachets per day.

Maximum duration of treatment is 5 days.

Children

The drug is contraindicated 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, 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 appear within the first 12–48 hours but may develop 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, 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, manifesting 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 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 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 measurements 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 remote settings without vomiting, oral methionine may be used.

Phenylephrine: 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. To counteract hypertensive effects, intravenous alpha-receptor 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 respiratory and cardiovascular system dysfunction (bradycardia, arterial hypotension, collapse). Symptoms caused by mutual potentiation of the parasympatholytic effect of pheniramine and the 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 cardiorespiratory function. CNS stimulants are contraindicated; 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 pancreatic islet function and glucosuria are possible. Overdose may lead to changes in renal excretion of ascorbic and uric acids during urine acidification, resulting in precipitation of oxalate stones.

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.

Side effects

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

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

Nervous system disorders: headache, dizziness, tremor, anxiety, nervousness, irritability, fear, insomnia, drowsiness, 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 nonsteroidal anti-inflammatory drugs.

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 system 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.

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

Metabolism and nutrition disorders: metabolic acidosis with high anion gap, frequency category: "unknown" (cannot be estimated based on 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 were administered 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, pheniramine use is not associated with QT interval prolongation or cardiac arrhythmia.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

20 g in sachets.

10 sachets of lemon-flavored powder in a cardboard box.

10 sachets of orange-flavored powder in a cardboard box.

10 sachets of raspberry-flavored powder in a cardboard box.

Availability category. Over-the-counter.

Manufacturer.

LLC "ASTRAFARM", Ukraine.

Manufacturer's address and location of business activity.

6, Kyivska St., Vyshneve, Buchanskyi district, Kyiv region, 08132, Ukraine.