Piaron rapid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PIARON RAPID (PIARON® RAPID)

Composition:

Active substance: paracetamol (paracetamol);

One effervescent tablet contains 500 mg of paracetamol;

Excipients: sorbitol (E 420), sodium bicarbonate, povidone, sodium lauryl sulfate, dimethicone, anhydrous citric acid, anhydrous sodium carbonate, aspartame (E 951).

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white or almost white, round tablets with bevelled edges, smooth on both sides.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol.

ATC code N02B E01.

Pharmacological Properties

Pharmacodynamics. Paracetamol is an analgesic and antipyretic (pain-relieving and fever-reducing agent). Its mechanism of action is associated with selective inhibition of prostaglandin synthesis.

Pharmacokinetics. Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. Maximum plasma concentration is reached within 30–60 minutes, and the plasma half-life ranges from 1 to 4 hours.

Paracetamol is relatively uniformly distributed in most body fluids and exhibits variable protein binding. It is primarily excreted by the kidneys in the form of conjugated metabolites.

Clinical Characteristics

Indications. For the treatment of conditions accompanied by pain and fever, such as headache, including migraine and tension headache, toothache, back pain, rheumatic and muscular pain, dysmenorrhea, sore throat, as well as for relief of fever and pain symptoms associated with cold and flu.

Contraindications. Hypersensitivity to paracetamol or to any of the other components of the medicinal product, severe hepatic or renal function impairment, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, Gilbert's syndrome, marked anemia, leukopenia.

Children under 10 years of age.

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 with cholestyramine. The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced if paracetamol is used concomitantly over a prolonged period. Occasional use has no significant effect. Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (particularly phenytoin, barbiturates, carbamazepine), which stimulate the activity of hepatic microsomal enzymes, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of the drugs. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Caution is advised when paracetamol is used 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 Warnings and Precautions for Use").

Paracetamol reduces the effectiveness of diuretics. Do not use concomitantly with alcohol.

Probenecid reduces paracetamol clearance by half by blocking its conjugation with glucuronic acid; therefore, in case of combined therapy with probenecid, the dose of paracetamol should be reduced.

Paracetamol should be used with caution together with chloramphenicol due to prolonged elimination half-life and increased toxicity of the latter.

Special precautions for use

The medicinal product contains paracetamol; therefore, it should not be used together with other medicinal products containing paracetamol, such as those used for fever reduction, pain relief, cold and flu symptoms, or insomnia. Concurrent use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may require liver transplantation or result in death.

Consult a physician before using the product in the following cases:

• Patients diagnosed with impaired liver or kidney function or disease;
• Patients requiring daily analgesic use for mild forms of arthritis;
• Patients taking warfarin or similar anticoagulant agents.

It should be noted that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol.

Cases of impaired liver function or liver failure have been reported in patients with reduced glutathione levels, such as those with severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis.

In patients with reduced glutathione levels, the use of paracetamol increases the risk of developing metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe conditions such as severe renal failure and sepsis, or in patients with malnutrition or other sources 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 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.

If symptoms persist or headache becomes persistent, consult a physician. Prolonged use without medical supervision may be hazardous.

The medicinal product should be used only when clearly necessary. Do not exceed the recommended doses.

Keep the product out of sight and reach of children.

Excipients. This medicinal product contains sodium in the amount of 428.74 mg per tablet. Caution is advised for patients on a sodium-restricted diet.

This medicinal product contains sorbitol. If the patient has known sugar intolerance, they should consult a physician before taking this medicinal product.

This medicinal product contains aspartame, a derivative of phenylalanine, which poses a risk for patients with phenylketonuria.

Use during pregnancy or breastfeeding

The use of this medicinal product during pregnancy or breastfeeding should only be considered if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Pregnancy. As with other medicinal products, consult a physician before using paracetamol during pregnancy. Extensive data from pregnant women do not indicate any malformative or fetal/neonatal toxicity. Epidemiological studies on neurodevelopmental outcomes in children exposed to paracetamol in utero have yielded inconclusive results. Paracetamol may be used during pregnancy if clinically necessary, but it should be administered at the lowest effective dose, for the shortest possible duration, and with the least possible frequency.

Breastfeeding period. Paracetamol is excreted in breast milk, but in clinically insignificant amounts when used at recommended doses. Available published data do not contraindicate the use of this product during breastfeeding.

Ability to influence the speed of reactions when driving or operating machinery. No effect.

Method of Administration and Dosage

This medicinal product is intended for oral use only. Before administration, the tablet must be dissolved in at least half a glass of water.

Adults and children aged 16 years and older. 1–2 tablets up to 4 times daily as needed.

Children aged 10 to 15 years. 1 tablet up to 4 times daily.

Paracetamol should not be given to children for more than 3 days without consulting a physician.

The interval between doses should be at least 4 hours. Do not exceed 4 tablets (2000 mg) within 24 hours.

Children. Use is not recommended in children under 10 years of age.

Overdose

Hepatic damage is possible in adults who have ingested 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. In patients with risk factors such as: long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs that induce liver enzymes; chronic alcohol abuse; glutathione system depletion (due to gastrointestinal disorders, cystic fibrosis, HIV infection, malnutrition, cachexia) — liver damage may occur after ingestion of 5 g or more of paracetamol.

Paracetamol overdose may lead to liver failure, which may require liver transplantation or result in death. Clinical signs of liver damage after paracetamol overdose usually appear within 24–48 hours after ingestion and peak at 4–6 days.

There is an increased risk of paracetamol poisoning, particularly in elderly patients, children, patients with liver disease, chronic alcoholism, and in cases of chronic malnutrition.

Symptoms of overdose within the first 24 hours: pallor, nausea, vomiting, loss of appetite, and abdominal pain; however, overdose may also be asymptomatic.

Overdose of a single dose of paracetamol in adults and children may cause reversible or irreversible necrosis of liver cells, leading to disturbances in glucose metabolism, metabolic acidosis, hepatocellular failure, encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Elevated levels of liver transaminases (alanine aminotransferase, aspartate aminotransferase), lactate dehydrogenase, bilirubin, and prothrombin time may occur 12–48 hours after ingestion. Liver damage is likely in adults who have taken more than the recommended amount of paracetamol. It is believed that an increased amount of a paracetamol metabolite (normally neutralized by glutathione at therapeutic doses) irreversibly binds to liver tissue.

Acute renal failure with acute tubular necrosis may manifest as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and acute pancreatitis have also been reported, usually accompanied by liver function disturbances and hepatotoxicity.

With prolonged use of the drug in high doses, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. High doses may also cause dizziness, psychomotor agitation, and disorientation from the central nervous system; from the urinary system — nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage.

Risk factors for paracetamol overdose include:

• Long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, and other drugs inducing liver enzyme synthesis;
• Chronic alcohol abuse;
• Reduced glutathione levels, e.g., due to nutritional disorders, fasting, body exhaustion, cystic fibrosis, HIV.

In case of overdose, immediate medical attention is required. Treatment for overdose or even suspected overdose must be initiated immediately by hospitalizing the patient, even if early symptoms are absent, as liver damage may not develop immediately. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable).

Treatment with activated charcoal may be beneficial if an excessive dose of paracetamol (>150 mg/kg) was ingested within 1 hour. Treatment with N-acetylcysteine or methionine should be considered. Symptomatic treatment is also necessary.

Symptoms of sodium bicarbonate overdose. High doses of sodium bicarbonate may cause gastrointestinal disturbances, including belching and nausea, and may also lead to hypernatremia; therefore, electrolyte balance should be monitored and appropriate treatment provided to patients.

Adverse Reactions

The following terms were used to define the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); not known (frequency cannot be estimated from the available data).

Blood and lymphatic system disorders: very rare — thrombocytopenia, agranulocytosis; not known — anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding.

Immune system disorders: very rare — anaphylaxis, hypersensitivity reactions including skin rash, angioneurotic edema, multiform exudative erythema, Stevens–Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome); not known — pruritus.

Respiratory, thoracic and mediastinal disorders: very rare — bronchospasm (in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs).

Hepatobiliary disorders: very rare — liver function abnormalities; not known — increased liver enzyme activity, usually without development of jaundice.

Gastrointestinal disorders: not known — nausea, epigastric pain.

Endocrine system disorders: not known — hypoglycemia, up to hypoglycemic coma.

Metabolism and nutrition disorders: not known — metabolic acidosis with high anion gap.

Description of selected adverse reactions

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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine registration is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and 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 at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 4 tablets in a multilayer strip. 4 strips in a cardboard pack.

Pharmaceutical supply category. Over-the-counter.

Manufacturer. KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business activity. Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India / Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India