Gripomed®

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

Composition:

Active substance: paracetamol;

1 ml of oral solution contains 30 mg of paracetamol;

Excipients: macrogol 6000; sucrose; sodium saccharin; potassium sorbate; citric acid monohydrate; flavoring agent "Caramel"; flavoring agent "Orange"; coloring agent "Caramel"; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical characteristics: slightly viscous solution ranging from light yellow to light brown in color with a caramel or caramel-citrus odor.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol.

ATC code N02BE01.

Pharmacological properties.

Pharmacodynamics.

Exerts analgesic, antipyretic, and weak anti-inflammatory effects. The mechanism of action is due to inhibition of prostaglandin synthesis and predominant influence on the thermoregulatory center in the hypothalamus.

Pharmacokinetics.

Paracetamol is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentration of paracetamol is reached within 30–60 minutes after administration. Paracetamol is mainly metabolized in the liver, forming inactive compounds with glucuronic acid and sulfates.

It is primarily excreted in the urine. 90% of the administered dose of paracetamol is eliminated by the kidneys within 24 hours, mainly as glucuronide and sulfate conjugates. Less than 5% is excreted unchanged. The half-life is approximately 2 hours.

Clinical characteristics.

Indications.

Symptomatic treatment of diseases accompanied by mild to moderate pain and/or elevated body temperature.

Contraindications.

Hypersensitivity to paracetamol or to other components of the drug.

Severe impairment of kidney and/or liver function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, severe anemia, leukopenia.

Interaction with other medicinal products and other types of interactions.

When taking maximum doses of paracetamol (4 g/day) for at least 4 days, there is a risk of enhanced effect of oral anticoagulants and an increased risk of bleeding. The INR (International Normalized Ratio) should be monitored at regular intervals. If necessary, the dose of the oral anticoagulant should be adjusted during paracetamol treatment.

The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsant drugs (including 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. Concurrent use of paracetamol with hepatotoxic agents increases the hepatotoxic effect of the drug. Concurrent use of high doses of paracetamol with isoniazid or rifampicin increases the risk of hepatotoxic syndrome.

Caution is advised when using paracetamol concomitantly with floxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions for use").

Paracetamol reduces the effectiveness of diuretics.

Do not use concurrently with alcohol.

High concentrations of paracetamol may interfere with laboratory test results for blood glucose measured by the oxidase-peroxidase method and for uric acid when using the phosphotungstic acid method.

Special precautions for use

Do not administer the drug to children together with other medicines containing paracetamol.

When treating with paracetamol at a dose of 60 mg/kg/day, concomitant use of another antipyretic is justified only if paracetamol is ineffective. Recommended doses should not be exceeded.

The product contains sucrose, which should be taken into account in patients with hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency. If symptoms of illness do not begin to improve within 3 days of treatment with the drug, or if the patient's condition worsens, medical advice must be sought.

In patients with severe infections such as sepsis, associated with reduced glutathione levels, the use of paracetamol increases the risk of 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 5-oxoprolinuria (pyroglutamic acidosis) have been reported in patients with severe conditions such as severe renal failure and sepsis, as well as in patients with inadequate nutrition 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 high anion gap metabolic acidosis due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring of the patient. Measurement of urinary 5-oxoproline levels may be helpful in identifying pyroglutamic acidosis as the underlying cause of high anion gap metabolic acidosis in patients with multiple risk factors.

Use with caution in patients with body weight below 50 kg, chronic malnutrition (low hepatic glutathione stores), dehydration, or mild to moderate hepatic impairment.

Treatment should be discontinued if acute viral hepatitis is diagnosed.

Use during pregnancy or breastfeeding

The drug is intended for use in pediatric practice.

A substantial amount of data in pregnant women does not indicate teratogenic effects or fetal/neonatal toxicity. Epidemiological studies on neurodevelopmental outcomes in children exposed to paracetamol in utero have shown inconclusive results. If clinically necessary, paracetamol may be used during pregnancy at the lowest effective dose, for the shortest duration, and with the lowest possible frequency.

Appropriate standard reproductive and developmental toxicity studies have not been conducted.

Effect on the ability to drive or operate machinery

The medicinal product is intended for use in pediatric practice.

Dosage and Administration

Grippomed® is intended for children with body weight from 4 to 32 kg (from 1 month to 12 years of age).

The single dose of paracetamol is 15 mg/kg of body weight. The daily dose of paracetamol should not exceed 60 mg/kg of body weight per day. The interval between doses should be at least 6 hours. In cases of severe renal impairment (creatinine clearance less than 10 mL/min), the interval between doses should be at least 8 hours.

Table 1 provides dosage recommendations based on the child's age and body weight:

Table 1

* Before administering the medication, the child must be weighed to prevent overdose and avoid toxic effects of the drug.

The dosing pipette is marked with graduations corresponding to the required dose of the medication in milliliters, depending on the child's body weight.

Grippomed® can be used undiluted or diluted in a small amount of liquid (e.g. water, milk, fruit juice).

Fill the dosing pipette according to the required dose of the medication, depending on the child's body weight.

• From 4 to 16 kg: use the dosing pipette.

For example: from 4 to 5 kg: fill the dosing pipette up to the 2 mL mark; from 14 to 16 kg: fill the dosing pipette up to the 5 mL mark, then fill again up to the 2 mL mark. If necessary, the dose may be repeated after 6 hours.

• From 16 to 32 kg: use the dosing pipette.

Fill the dosing pipette the necessary number of times to obtain the required dose of medication per administration. If necessary, the dose may be repeated after 6 hours.

If pain or fever persists or worsens within 3 days from the start of treatment with the medication, the appropriateness of continuing therapy should be reassessed.

Children.

The medication should be administered to children with body weight from 4 to 32 kg (aged from 1 month to 12 years).

Overdose.

To avoid overdose, check that other medications the patient is taking do not contain paracetamol.

There is a risk of severe poisoning in elderly individuals, young children, patients with liver impairment, chronic alcoholism, or chronic malnutrition. This may lead to fatal outcomes.

In children weighing less than 37 kg, the total daily dose of paracetamol should not exceed 80 mg/kg/day.

In children weighing from 38 kg to 50 kg, the total daily dose of paracetamol should not exceed 3 g/day.

In adults and children weighing more than 50 kg, the total daily dose of paracetamol should not exceed 4 g/day.

A single dose of 10 g in adults or 150 mg/kg body weight in children may cause hepatocellular insufficiency, impaired glucose metabolism, metabolic acidosis, hemorrhages, hypoglycemia, encephalopathy, coma, and fatal outcome. In such cases, levels of liver transaminases, lactate dehydrogenase, and bilirubin increase, and prothrombin levels decrease within 12–48 hours. 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 pancreatitis have also been reported. With prolonged use of high doses, blood-forming organs may develop aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. High-dose intake may cause central nervous system disturbances – dizziness, psychomotor agitation, and disorientation; urinary system – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis); digestive system – hepatonecrosis. In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione system deficiency, e.g. due to malnutrition, AIDS, fasting, cystic fibrosis, cachexia), administration of 5 g or more of paracetamol may lead to liver damage. Liver injury may become apparent 12–48 hours after overdose. In case of overdose, the patient should be immediately hospitalized, even if early symptoms of overdose are absent. Symptoms of overdose appear within the first 24 hours: nausea, vomiting, loss of appetite, pallor, abdominal pain. These symptoms may not reflect the severity of overdose or risk of organ damage. Emergency measures:

− immediate hospitalization;

− determination of paracetamol plasma concentration;

− gastric lavage;

− administration of the antidote N-acetylcysteine intravenously or oral methionine within the first 10 hours;

− symptomatic therapy.

Adverse Reactions.

Very rare:

Allergic reactions: anaphylaxis, anaphylactic shock, angioedema, erythema, urticaria, pruritus, skin and mucous membrane rashes, multiform exudative erythema, toxic epidermal necrolysis;

Hematological disorders: anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, thrombocytopenia, leukopenia and neutropenia, bruising or bleeding;

Respiratory system: bronchospasm in patients sensitive to aspirin and other NSAIDs;

Gastrointestinal system: nausea, epigastric pain, impaired liver function, increased liver enzyme activity (usually without development of jaundice), hepatonecrosis (dose-dependent effect);

Metabolism and nutrition: metabolic acidosis with high anion gap (frequency unknown);

Endocrine system: hypoglycemia, up to hypoglycemic coma.

Occasionally possible malaise and decreased blood pressure, renal colic.

If any adverse reactions occur, discontinue use of the medication immediately and consult a physician without delay.

Description of individual adverse reactions.

Metabolic acidosis with high anion gap. Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors taking paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Shelf life after first opening — 3 months.

Do not use after the expiry date.

Storage conditions.

Keep out of reach of children.

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

Packaging.

100 ml in polymer bottles No. 1, with a dosing pipette, in a cardboard box.

100 ml in glass bottles No. 1, with a dosing pipette, in a cardboard box.

Availability. Over-the-counter.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and site of operations.

1 Gordienkivska Street, Kharkiv, Kharkiv Oblast, 61010, Ukraine.