Paracetamol

General characteristics. Structure:

International and chemical names: paracetamol; N-(4-hydroxyphenyl) acetamide; main physical and chemical properties: transparent viscous liquid of pink color with sweet taste and a characteristic smell of raspberry; structure: 5 ml of syrup contain 120 mg of paracetamol;
excipients: propylene glycol, glycerin, alcohol of ethyl 96%, sorbitol, methylparahydroxybenzoate, пропилпарагидроксибензоат, fragrance food Malines, понсо 4R, the water purified.

Pharmacological properties:

Pharmacodynamics. Possesses analgetichesky, febrifugal and weak antiinflammatory action. The mechanism of action is connected with inhibition of synthesis of prostaglandins and influence on the center of thermal control in a hypothalamus.

Pharmacokinetics. After intake paracetamol is quickly soaked up from a GIT, is preferential in a small bowel, generally by passive transport. After a single dose in a dose of 500 mg the maximum concentration in a blood plasma is reached in 10-60 min. and makes about 6 mkg/ml, then gradually decreases and in 6 h makes 11-12 mkg/ml. It is well distributed in fabrics and generally in fluid mediums of an organism, except for fatty tissue and cerebrospinal fluid. Linkng with proteins makes less than 10% and slightly increases at increase in a dose. Sulphatic and glyukuronidny metabolites do not contact proteins of plasma even in rather high concentration. Paracetamol is metabolized preferential in a liver by conjugation with glucuronides, conjugation with sulfate and oxidations with the participation of the mixed oxidases of a liver and P450 cytochrome. The hydroxylated metabolite with negative action - N-acetyl-r-benzokhinonimin which is formed in very small amounts in a liver and kidneys under the influence of the mixed oxidases and is usually detoxified by linkng with glutathione can collect at overdose of paracetamol and cause damages of fabrics. At adults the most part of paracetamol contacts glucuronic acid and in smaller quantity - sulphuric acid. These conjugated metabolites have no biological activity. At premature children, newborns and on the first year of life the sulphatic metabolite prevails. The elimination half-life makes 1 - 3 h. At patients with cirrhosis the elimination half-life is slightly more. The renal clearance of paracetamol makes 5%. Drug is removed with urine mainly in the form of glyukuronidny and sulphatic conjugates. Less than 5% are removed in the form of not changed paracetamol.

Indications to use:

Pain syndrome of small and medium intensity of various genesis (head and tooth pains, neuralgia, muscle pain; pain at a teething; at injuries; burns; pharyngitis, rheumatic pains). Fever at  infectious and inflammatory diseases.

Route of administration and doses:

Drug is appointed inside. The single dose for children aged from 6 months till 1 year – on 60 – 120 mg of paracetamol (1/2 - 1 teaspoon of syrup), from 1 year to 3 years – on 120 – 180 mg of paracetamol (1 - 1,5 teaspoon of syrup), from 3 to 6 years – on 180 – 240 mg of paracetamol (1,5 - 2 teaspoons of syrup), from 6 to 12 years - on 240 – 360 mg of paracetamol (2 - 3 teaspoons of syrup), is more senior than 12 years – on 360 – 600 mg of paracetamol (3 - 5 teaspoons of syrup). Frequency rate of reception – 3-4 times a day with an interval between each reception not less than 4 h. The maximum duration of treatment – 3 days.

Features of use:

With care apply to treatment of patients with abnormal liver functions and kidneys, with a high-quality hyperbilirubinemia. Long reception of anticonvulsant drugs causes increase in activity of liver enzymes that increases intensity of effect of "the first passing" through a liver, extends clearance of drug. It can interfere with achievement of therapeutic level of concentration of paracetamol in blood. At prolonged use of drug control of a picture of peripheral blood and a functional condition of a liver is necessary.

Side effects:

There can be nausea, pains in epigastriums; allergic reactions (skin rash, itch, small tortoiseshell, Quincke's edema). Such by-effects as hemolitic anemia, a Werlhof's disease, a methemoglobinemia, an agranulocytosis are possible. At prolonged use in the doses exceeding therapeutic, perhaps hepatotoxic action.

Interaction with other medicines:

At patients who accepted Phenytoinum, rifampicin, barbiturates and tricyclic antidepressants increase in an elimination half-life of paracetamol and increase in risk of a hepatotoxic action is possible. Increases effect of indirect anticoagulants. Increases toxicity of levomycetinum.

Contraindications:

Hypersensitivity to paracetamol and other components of drug, the expressed disturbances of functions of a liver and kidneys, deficit glyukozo-6-fosfatdegidrogenazy, blood diseases (the expressed anemia, a leukopenia), children's age up to 6 months. Inborn hyperbilirubinemias (Gilbert's syndrome, Cudgel Johnson, Rotor).

Overdose:

At reception of syrup in the doses exceeding recommended the following by-effects are possible: hemolitic anemia, Werlhof's disease; methemoglobinemia, agranulocytosis, hepatotoxic action. In this case the gastric lavage, whenever possible early introduction of an antidote – Acetylcysteinum is necessary.

Storage conditions:

To store in the unavailable to children, protected from light place at a temperature not above 25 °C.

After opening of a bottle a drug period of validity – 30 days at a temperature of 20-25 °C.

Period of validity - 3 years.

Issue conditions:

Without recipe

Packaging:

On 50 ml or 100 ml in a bottle glass, on 1 bottle in a pack; on 50 ml or 100 ml in a bottle polymeric, on 1 bottle in a pack; on 100 ml in bank glass or polymeric, after 1 bank in a pack.