Fervex^® for children (Powder) Instructions for Use

Marketing Authorization Holder

UPSA, SAS (France)

Contact Information

BRISTOL-MYERS SQUIBB (USA)

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)

Pheniramine (Rec.INN registered by WHO)

Dosage Form

Fervex® for children

Powder for oral solution 280 mg+10 mg+100 mg/1 sachet: sachet 3 g 8 pcs.

Dosage Form, Packaging, and Composition

Powder for oral solution light pink in color with inclusions of white and dark pink.

Excipients: mannitol – 2.26 g, citric acid – 0.03 g, povidone K30 – 0.006 g, magnesium citrate – 0.242 g, acesulfame potassium – 0.036 g, raspberry flavor* – 0.036 g.

3 g – sachets made of paper/Al/polyethylene (8) – cardboard boxes.

* composition of raspberry flavor: maltodextrin, E1450 modified corn starch, E129 Allura Red AC dye, E133 Brilliant Blue FCF dye, E110 Sunset Yellow FCF dye, Permastabil 505528 RI, Raspberry 054428 A (ethyl acetate, isoamyl acetate, acetic acid, benzyl alcohol, triacetin, vanillin, p-hydroxy-benzylacetone), sodium chloride and/or sodium sulfate.

Clinical-Pharmacological Group

Drug for symptomatic therapy of acute respiratory diseases

Pharmacotherapeutic Group

Analgesics; other analgesics and antipyretics; anilides

Pharmacological Action

Fervex^® for children is a combined drug that contains Paracetamol, Pheniramine Maleate, and ascorbic acid.

Paracetamol is a non-steroidal anti-inflammatory drug that blocks cyclooxygenase, predominantly in the CNS, affecting the centers of pain and thermoregulation; it has an analgesic and antipyretic effect. Paracetamol has analgesic and antipyretic effects.

Pheniramine Maleate is a histamine H₁-receptor blocker. It constricts the vessels of the nose, eliminates swelling and hyperemia of the nasal mucosa, nasopharynx, and paranasal sinuses.

Ascorbic acid participates in the regulation of redox processes, reduces vascular permeability, and increases the body’s resistance.

Pharmacokinetics

Paracetamol

The absorption of paracetamol is complete and rapid. Peak plasma concentration is reached 30-60 minutes after administration. The distribution of paracetamol in tissues is rapid. Comparable drug concentrations are achieved in blood, saliva, and plasma. Plasma protein binding is low, 10-25%. It penetrates the blood-brain barrier.

Metabolism occurs in the liver, 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 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 drug’s metabolism. T_1/2 is 1-4 hours. It is excreted by the kidneys as metabolites, mainly conjugates. Less than 5% is excreted unchanged. T_1/2 is about 2 hours.

Pheniramine Maleate

It is well absorbed in the digestive tract. T_1/2 from blood plasma is from 1 to 1.5 hours. It is excreted from the body mainly by the kidneys.

Ascorbic acid

It is well absorbed in the digestive tract. T_max after oral administration is 4 hours. It is metabolized mainly in the liver. It is excreted by the kidneys, through the intestines, with sweat in unchanged form and as metabolites.

Indications

For children aged 6 to 15 years for the short-term treatment of conditions accompanied by

• Increased body temperature, runny nose with “cold” illnesses;
• Rhinitis and rhinopharyngitis of infectious-inflammatory and allergic nature.

ICD codes

Dosage Regimen

The drug is taken orally. Before use, the contents of the sachet should be dissolved in a glass (200 ml) of warm water.

Depending on the child’s age, the drug is used in the following doses

• children from 6 to 10 years – 1 sachet 2 times/day;
• children from 10 to 12 years – 1 sachet 3 times/day;
• children from 12 to 15 years – 1 sachet 4 times/day.

The interval between doses of the drug is at least 4 hours. The duration of treatment is no more than 3 days.

Adverse Reactions

The drug is well tolerated at recommended doses.

Possible dry mouth, nausea, vomiting, abdominal pain, urination disorder, constipation, allergic reactions (skin rash, itching, urticaria, angioedema), drowsiness, accommodation disorder, anemia, leukopenia, agranulocytosis, thrombocytopenia.

With long-term use in doses exceeding the recommended ones, hepatotoxic and nephrotoxic effects, hemolytic anemia, aplastic anemia, methemoglobinemia, pancytopenia are possible.

If adverse reactions occur, the patient should stop taking the drug and consult a doctor.

Contraindications

• Hypersensitivity to any component of the drug;
• Severe liver dysfunction;
• Severe renal dysfunction;
• Blood diseases;
• Glucose-6-phosphate dehydrogenase deficiency;
• I and III trimesters of pregnancy;
• Lactation period;
• Age under 6 years;
• Phenylketonuria;
• Sucrase/isomaltase deficiency;
• Fructose intolerance, glucose-galactose malabsorption.

With caution benign hyperbilirubinemias (including Gilbert’s syndrome), in case of impaired liver or kidney function, in diabetes mellitus, II trimester of pregnancy.

Use in Pregnancy and Lactation

The use of the drug is contraindicated in the I and III trimesters of pregnancy. The drug should be used with caution in the II trimester of pregnancy.

The use of the drug during lactation is contraindicated.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe liver dysfunction.

With caution the drug should be used in case of impaired liver function, in Gilbert’s syndrome.

Use in Renal Impairment

The use of the drug is contraindicated in severe renal dysfunction.

With caution the drug should be used in case of impaired renal function.

Pediatric Use

The use of the drug is contraindicated in children under 6 years of age.

Special Precautions

Fervex^® for children should not be used simultaneously with other drugs containing Paracetamol.

If the drug is used for more than a week, monitoring of the functional state of the liver and peripheral blood picture is necessary.

Paracetamol distorts the results of laboratory tests of plasma glucose and uric acid levels.

In the absence of a therapeutic effect (increased body temperature persists for more than 3 days and pain syndrome for more than 5 days), a doctor’s consultation is required.

Effect on ability to drive vehicles and machinery

Considering the possibility of such adverse reactions as drowsiness, accommodation disorder, one should refrain from driving vehicles and working with machinery.

Overdose

Symptoms signs of acute paracetamol poisoning are anorexia, nausea, vomiting, epigastric pain, sweating, pale skin, drowsiness. After 1-2 days, signs of liver damage appear. In severe cases, liver failure, hepatonecrosis, encephalopathy, and coma develop.

Treatment if symptoms of poisoning appear, stop using the drug and immediately consult a doctor. Gastric lavage, intake of enterosorbents (activated charcoal, hydrolytic lignin), intravenous administration of the antidote acetylcysteine, and intake of methionine are recommended.

Drug Interactions

Fervex^® for children, due to the pheniramine maleate it contains, enhances the effect of sedative drugs, and when used together with antipsychotic agents (phenothiazine derivatives), the risk of developing adverse effects of the drug (urinary retention, dry mouth, constipation) increases.

The possibility of enhanced central atropine-like effects should be considered when used in combination with other substances possessing anticholinergic properties (other antihistamines, imipramine group antidepressants, phenothiazine neuroleptics, anticholinergic antiparkinsonian agents, atropine-like antispasmodic agents, disopyramide).

When using the drug together with barbiturates, tricyclic antidepressants, anticonvulsants (phenytoin), flumecinol, phenylbutazone, rifampicin, and ethanol, the risk of hepatotoxic action significantly increases (due to the paracetamol contained).

When used simultaneously with salicylates, the risk of nephrotoxic action increases.

When used simultaneously with chloramphenicol, the toxicity of the latter increases.

Paracetamol, contained in the drug, enhances the effect of indirect anticoagulants and reduces the effectiveness of uricosuric drugs.

Caution should be exercised when using paracetamol simultaneously with inducers of liver microsomal enzymes (e.g., ethanol, barbiturates, isoniazid, rifampicin, carbamazepine, zidovudine, anticoagulants, amoxicillin + clavulanic acid, phenylbutazone, tricyclic antidepressants) due to an increased risk of hepatotoxic action.

Myelotoxic drugs enhance the manifestations of the hematotoxicity of paracetamol, metoclopramide enhances its absorption.

Storage Conditions

The drug should be stored out of the reach of children at a temperature from 15°C (59°F) to 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use the drug after the expiration date printed on the packaging.

Dispensing Status

The drug is available without a prescription.

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.