Piaron

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

Composition:

Active substance: paracetamol;

1 tablet contains 500 mg of paracetamol;

Excipients: microcrystalline cellulose, sodium croscarmellose, magnesium stearate,
povidone K 90, talc, Opadry 31G58920 white*.

*Opadry 31G58920 white: hypromellose, lactose monohydrate, titanium dioxide (E 171), polyethylene glycol, talc.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: coated tablets, white in color, capsule-shaped, with "P500" embossed on one side and a break line on the other.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol.

ATC code N02BE01.

Pharmacological properties.

Pharmacodynamics.

Piaron tablets contain paracetamol – an analgesic and antipyretic (pain-relieving and fever-reducing agent). The effect is based on inhibition of prostaglandin synthesis in the central nervous system.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract and distributed into most body tissues. Plasma protein binding of paracetamol is minimal when administered at therapeutic doses.

Paracetamol is primarily metabolized in the liver and excreted in the urine as metabolites. The mean elimination half-life of paracetamol in plasma following oral administration is approximately 2.3 hours.

Clinical characteristics.

Indications.

Short-term treatment of headache, toothache, muscle pain, menstrual pain, moderate pain associated with osteoarthritis, and symptoms of fever and pain due to colds and flu.

Contraindications.

Hypersensitivity to the components of the drug, severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, Gilbert's syndrome, marked anemia, leukopenia. Age under 6 years.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine. The anticoagulant effect of warfarin and other coumarins (with increased risk of bleeding) may be enhanced during prolonged concomitant use of paracetamol. Occasional use of the drug does not have a significant effect.

Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as concomitant administration 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 for use").

Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate microsomal liver enzyme activity, 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 potential of the drugs.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Paracetamol reduces the effectiveness of diuretics.

Do not use concomitantly with alcohol.

Special precautions for use.

The medicine contains paracetamol; therefore, it should not be used together with other medicines containing paracetamol and used, for example, to reduce fever, treat pain, flu or cold symptoms, or insomnia. Concurrent use with other paracetamol-containing medicines may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in fatal outcome.

In patients with liver or kidney disease, consult a physician before using this medicine.

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

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

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 and careful monitoring are recommended. 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.

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.

If symptoms persist, consult a physician. Prolonged use without medical supervision may be dangerous.

The medicine should be used only when clearly necessary.

Keep the medicine out of the sight and reach of children.

The medicine contains lactose. If you have been diagnosed with an intolerance to certain sugars, consult your physician before taking this medicine.

Use during pregnancy or breastfeeding.

Pregnancy.

As with the use of any other medicinal product, consult your physician before taking paracetamol during pregnancy.

Extensive data from pregnant women do not indicate any teratogenic 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 lowest possible frequency.

Breastfeeding.

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 the medicine during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

No effect.

Method of Administration and Dosage.

The medication is intended for oral use.

Do not exceed the recommended dose. The lowest effective dose required to achieve the treatment goal should be used.

Adults and children aged 12 years and older: 1–2 tablets up to 4 times daily (every 4–6 hours) as needed.

The interval between doses should be at least 4 hours.

Do not take more than 8 tablets (4000 mg) within 24 hours.

Children (6–11 years of age): ½–1 tablet up to 4 times daily (every 4–6 hours) as needed.

The maximum duration of use in children without medical consultation is 3 days.

Do not take more than 4 doses within 24 hours.

The interval between doses should be at least 4 hours.

Children.

Not recommended for children under 6 years of age.

Overdose.

Paracetamol overdose may cause liver failure, which could necessitate liver transplantation or result in death. Clinical experience shows that signs of liver damage following paracetamol overdose typically 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, or 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.

Paracetamol overdose, whether in adults or children, even after a single ingestion, may cause reversible or irreversible necrosis of liver cells, leading to impaired glucose metabolism, metabolic acidosis, hepatocellular failure, encephalopathy, hemorrhage, hypoglycemia, coma, and potentially death. Concurrently, elevated levels of liver transaminases (AST, ALT), lactate dehydrogenase, bilirubin, and prolonged prothrombin time may occur 12–48 hours after ingestion. Liver damage is likely in adults who have ingested more than the recommended amount of paracetamol. It is believed that an increased amount of the paracetamol metabolite (normally neutralized by glutathione when standard doses are used) binds irreversibly to liver tissues.

Acute renal failure with acute tubular necrosis may present with severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and acute pancreatitis have also been reported, typically accompanied by liver function abnormalities 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-dose intake may also cause central nervous system effects such as dizziness, psychomotor agitation, and disorientation; urinary system effects may include 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 that induce liver enzyme synthesis;
• Chronic alcohol abuse;
• Reduced glutathione levels, for example, due to nutritional disorders, fasting, cachexia, cystic fibrosis, or HIV.

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

Activated charcoal should be considered if a paracetamol dose exceeding 150 mg/kg was ingested within 1 hour. Treatment with N-acetylcysteine or methionine should also be considered. Symptomatic treatment is also necessary.

Side effects.

Blood and lymphatic system disorders: (rare: < 1/10000) – thrombocytopenia.

Immune system disorders: (rare: < 1/10000) – anaphylaxis, skin hypersensitivity reactions including rash, angioedema, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Respiratory, thoracic and mediastinal disorders: (rare: < 1/10000) – bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary disorders: (rare: < 1/10000) – liver function abnormalities.

Metabolism and nutrition disorders: (not known: cannot be estimated based on available data) – metabolic acidosis with a high anion gap.

Additionally, the following adverse reactions may occur after administration of products containing paracetamol: skin itching, erythema multiforme, nausea, epigastric pain, hypoglycemia up to hypoglycemic coma, agranulocytosis, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding, increased liver enzyme activity, usually without development of jaundice.

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 as a consequence of low glutathione levels in these patients.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives are encouraged to report any suspected adverse reactions or lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister; 1 or 2 blisters in a cardboard box.

Release category.

Over-the-counter.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's location and address of its business premises.

54 Skryabina Street, Sumy, Sumy region, 40020, Ukraine.

or

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's location and address of its business premises.

Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India.

or

Manufacturer.

LLC "GLEDFARM LTD".

Manufacturer's location and address of its business premises.

54 Davydovskoho Hryhorii Street, Sumy, Sumy region, 40020, Ukraine.