Paracetamol-C-Hemofarm (Tablets) Instructions for Use

Marketing Authorization Holder

Hemofarm, A.D. (Serbia)

ATC Code

N02BE51 (Paracetamol in combination with other drugs, excluding psycholeptics)

Active Substances

Ascorbic acid (Rec.INN registered by WHO)

Paracetamol (Rec.INN registered by WHO)

Dosage Form

Paracetamol-C-Hemofarm

Effervescent tablets 330 mg+200 mg: 10, 20, or 40 pcs.

Dosage Form, Packaging, and Composition

Effervescent tablets from white to white with a yellowish tint, round, flat-cylindrical, with a bevel on both sides.

Excipients: sodium bicarbonate, sodium carbonate, citric acid, lactose monohydrate, docusate sodium, sodium saccharin, sodium benzoate, povidone.

10 pcs. – plastic tubes (1) – cardboard packs.
10 pcs. – plastic tubes (2) – cardboard packs.
20 pcs. – plastic tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Analgesic-antipyretic

Pharmacotherapeutic Group

Non-narcotic analgesic agent (non-narcotic analgesic + vitamin)

Pharmacological Action

Paracetamol-C-Hemofarm is a combination of paracetamol and ascorbic acid (vitamin C).

Paracetamol is a non-narcotic analgesic, the mechanism of action is associated with inhibition of prostaglandin synthesis and a predominant effect on the thermoregulation center in the hypothalamus.

Ascorbic acid (vitamin C) plays an important role in the regulation of redox processes, carbohydrate metabolism, blood clotting, and tissue regeneration; it is involved in the synthesis of glucocorticosteroids, collagen, and procollagen; it normalizes capillary permeability. The ability to increase the body’s resistance is particularly important, which is probably associated with the antioxidant property of ascorbic acid and stimulation of the immune system.

Pharmacokinetics

Paracetamol is characterized by high absorption, T_max – 0.5-2 h; C_max – 5-20 µg/ml. Plasma protein binding – 15%. Penetrates the blood-brain barrier. Less than 1% of the paracetamol dose taken by a nursing mother penetrates into breast milk. Therapeutically effective plasma concentration of paracetamol is achieved when administered at a dose of 10-15 mg/kg. Metabolized in the liver (90-95%): 80% undergoes conjugation reactions with glucuronic acid and sulfates to form inactive metabolites; 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form already inactive metabolites. With glutathione deficiency, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The isoenzyme CYP2E1 is also involved in the metabolism of the drug. T_1/2 – 1-4 h. Excreted by the kidneys as metabolites, mainly conjugates, only 3% unchanged. In elderly patients, the clearance of the drug decreases and T_1/2 increases.

Ascorbic acid is absorbed in the gastrointestinal tract, mainly in the jejunum. With an increase in dose to 200 mg, up to 140 mg (70%) is absorbed; with a further increase in dose, absorption decreases (50-20%). Plasma protein binding – 25%. Gastrointestinal diseases (gastric and duodenal ulcers, constipation or diarrhea, helminthic invasion, giardiasis), consumption of fresh fruit and vegetable juices, and alkaline drinks reduce the absorption of ascorbate in the intestine.

The normal plasma concentration of ascorbic acid is approximately 10-20 µg/ml, body stores are about 1.5 g when taking daily recommended doses and 2.5 g when taking 200 mg/day. T_max after oral administration is 4 h.

It easily penetrates into leukocytes, platelets, and then into all tissues; the highest concentration is achieved in glandular organs, leukocytes, liver, and the lens of the eye; it is deposited in the posterior lobe of the pituitary gland, adrenal cortex, ocular epithelium, interstitial cells of the seminal glands, ovaries, liver, spleen, pancreas, lungs, kidneys, intestinal wall, heart, muscles, thyroid gland; it crosses the placenta. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and plasma. In deficient states, the concentration in leukocytes decreases later and more slowly and is considered a better criterion for assessing deficiency than plasma concentration. It is metabolized mainly in the liver to dehydroascorbic acid and then to oxaloacetic and diketogulonic acids.

It is excreted by the kidneys, through the intestines, with sweat, and breast milk as unchanged ascorbate and metabolites.

When high doses are prescribed, the excretion rate increases sharply. Smoking and ethanol consumption accelerate the destruction of ascorbic acid (conversion to inactive metabolites), sharply reducing body stores. It is removed by hemodialysis.

Indications

• Mild to moderate pain syndrome (headache, neuralgia, myalgia, arthralgia, dysmenorrhea, toothache);
• For reducing elevated body temperature in infectious and inflammatory diseases (including colds) and influenza.

ICD codes

Dosage Regimen

The effervescent tablet of Paracetamol-C-Hemofarm is completely dissolved in a glass of water, and the resulting solution is drunk immediately. It is better to take the medicine between meals.

Unless otherwise instructed by a doctor, the following dosages should be observed when using the drug.

For adults and adolescents over 14 years old, the drug is prescribed 1-2 tablets 1-3 times/day. The maximum daily dose of paracetamol is 4 g (12 effervescent tablets).

For younger school-age children (6-9 years old), the drug is prescribed 1/2 tablet 1-3 times/day. The maximum single dose is 1 tablet, the maximum daily dose is 3 tablets.

For children 9-12 years old – 1 tablet 1-3 times/day. The maximum single dose is 2 tablets, the maximum daily dose is 6 tablets.

The interval between doses should be at least 4 hours. The maximum duration of treatment for children is 3 days. The maximum duration of treatment for adults is no more than 5 days when prescribed as an analgesic and no more than 3 days as an antipyretic.

In case of renal and/or hepatic impairment, the daily dose is reduced by decreasing the single dose and/or frequency of administration.

Adverse Reactions

Allergic reactions: skin rash, itching, urticaria, angioedema.

From the digestive system: nausea, epigastric pain.

From the hematopoietic system: anemia, thrombocytopenia, agranulocytosis.

With long-term use in large doses – hepatotoxic effect, irritation of the gastrointestinal mucosa, nephrotoxic effect (renal colic, glucosuria, aseptic pyuria, interstitial nephritis, papillary necrosis), hyperprothrombinemia, hemolytic anemia, aplastic anemia, methemoglobinemia, pancytopenia.

Very rarely, decreased blood pressure, dyspnea occur.

Long-term use of large doses of vitamin C may lead to the formation of oxalate stones in the kidneys.

Contraindications

• Bronchospasm;
• Rhinitis;
• Urticaria provoked by taking acetylsalicylic acid or other NSAIDs (including in history);
• Severe renal failure (creatinine clearance (CrCl) less than 30 ml/min);
• Acute liver disease or severe hepatic failure in the exacerbation phase;
• Condition after coronary artery bypass surgery, confirmed hyperkalemia;
• Gastrointestinal bleeding;
• Inflammatory bowel diseases;
• Erosive and ulcerative changes of the gastric and duodenal mucosa in the exacerbation phase;
• Portal hypertension;
• Pregnancy (I and III trimesters);
• Lactation period;
• Glucose-6-phosphate dehydrogenase deficiency;
• Children under 6 years of age;
• Hypersensitivity to the components of the drug.

With caution: erosive and ulcerative lesions of the gastrointestinal tract (in history), presence of Helicobacter pylori; mild to moderate hepatic failure, renal failure (creatinine clearance (CrCl) more than 30 ml/min but less than 60 ml/min); coronary artery disease, chronic heart failure; cerebrovascular diseases; blood diseases (thrombocytopenia, leukopenia, agranulocytosis), constitutional hyperbilirubinemia (Gilbert’s syndrome), congenital hyperbilirubinemias (Dubin-Johnson syndrome and Rotor syndrome), dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, severe somatic diseases, long-term use of NSAIDs, simultaneous use of oral corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), smoking, alcoholism, elderly age.

Use in Pregnancy and Lactation

Contraindicated during pregnancy (I and III trimesters) and during lactation.

Use in Hepatic Impairment

In case of hepatic impairment, the daily dose is reduced by decreasing the single dose and/or frequency of administration.

With caution: mild to moderate hepatic failure.

Use in Renal Impairment

In case of renal impairment, the daily dose is reduced by decreasing the single dose and/or frequency of administration.

With caution: renal failure (creatinine clearance (CrCl) more than 30 ml/min but less than 60 ml/min).

Pediatric Use

For younger school-age children (6-9 years old), the drug is prescribed 1/2 tablet 1-3 times/day. The maximum single dose is 1 tablet, the maximum daily dose is 3 tablets.

For children 9-12 years old – 1 tablet 1-3 times/day. The maximum single dose is 2 tablets, the maximum daily dose is 6 tablets.

The interval between doses should be at least 4 hours. The maximum duration of treatment for children is 3 days.

Contraindicated

• Children under 6 years of age.

Special Precautions

Simultaneous use with other medicines should be agreed with a doctor.

After 5 days of using the drug, monitoring of the peripheral blood picture and functional state of the liver is necessary.

To avoid toxic liver damage, Paracetamol should not be combined with the intake of alcoholic beverages, nor should it be taken by persons prone to chronic alcohol consumption.

There is evidence that frequent use of drugs containing Paracetamol leads to worsening of bronchial asthma symptoms.

Overdose

Symptoms (caused by paracetamol): pallor of the skin, decreased appetite, nausea, vomiting; hepatonecrosis (the severity of necrosis due to intoxication directly depends on the degree of overdose). Toxic effects in adults are possible after taking more than 10-15 g of paracetamol: increased activity of liver transaminases, increased prothrombin time (12-48 hours after intake); the full clinical picture of liver damage appears after 1-6 days. Rarely, liver failure develops rapidly and may be complicated by renal failure (tubular necrosis).

Treatment: gastric lavage, intake of activated charcoal, administration of SH-group donors and precursors of glutathione synthesis – methionine – 8-9 hours after overdose and N-acetylcysteine – after 12 hours.

The need for additional therapeutic measures (further administration of methionine, intravenous administration of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after its intake.

Drug Interactions

Stimulators of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants, estrogen-containing contraceptives) increase the production of hydroxylated active metabolites, which may lead to the development of severe intoxications even with small overdoses.

Ethanol contributes to the development of acute pancreatitis.

Inhibitors of microsomal oxidation (cimetidine) reduce the risk of hepatotoxic action.

Reduces the effectiveness of uricosuric drugs.

Enhances the effect of drugs that depress the central nervous system, ethanol.

With delayed gastric emptying (propantheline bromide), a delayed onset of paracetamol action may occur.

With accelerated gastric emptying (metoclopramide), the drug begins to act faster.

The toxicity of chloramphenicol is enhanced.

Exercise caution with prolonged use of paracetamol and simultaneous therapy with oral drugs that inhibit blood clotting.

Storage Conditions

Store in a place inaccessible to children, dry, protected from light, at a temperature from 15°C (59°F) to 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is approved for use as an over-the-counter product.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.