Paracetamol

General characteristics. Structure:

Active ingredient: 500 mg of paracetamol.

Excipients: potato starch, povidone (povidone middlemolecular), stearic acid.

The Analgeziruyushchy drug possessing analgeziruyushchy, febrifugal and weak antiinflammatory action.

Pharmacological properties:

Pharmacodynamics. Paracetamol possesses anesthetic and febrifugal action. Drug blocks cyclooxygenase I and II preferential in the central nervous system, influencing the centers of pain and thermal control. In inflammatory fabrics cellular peroxidases neutralize influence of paracetamol on cyclooxygenase that explains almost total absence of antiinflammatory effect. Drug does not make negative impact on a water salt metabolism (a delay of sodium and water) and mucous digestive tract owing to lack of influence on synthesis of prostaglandins in peripheral fabrics.

Pharmacokinetics. After intake paracetamol is quickly absorbed from a GIT, is preferential in a small bowel, generally by passive transport. After a single dose in a dose of 500 mg of Cmax in a blood plasma it 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 widely 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 overdose. 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 a glucuronide, 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-p-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 be heated at overdose of paracetamol and cause damages of fabrics.

At adults the most part of paracetamol contacts glucuronic acid and to a lesser extent - sulphuric acid. These conjugated metabolites have no biological activity. At premature children, newborns and on the first year of life the sulphatic metabolite prevails.

T1/2 makes 1-3 h. Patients with cirrhosis have T1/2 slightly more. The renal clearance of paracetamol makes 5%.

It 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 weak and moderate intensity of various genesis (including headache, migraine, dentagra, neuralgia, mialgiya, альгодисменорея; pain at injuries, burns). Fever at infectious and inflammatory diseases.

Route of administration and doses:

Inside at adults and teenagers with body weight more than 60 kg apply in a single dose 500 mg, frequency rate of reception - to 4 times/days. The maximum duration of treatment - 5-7 days.

Maximum doses: one-time - 1 g, daily - 4 g.

Single doses for intake for children at the age of 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg/kg. Single doses at rectal use for children at the age of 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.

Frequency rate of use - 4 times/days with an interval not less than 4 h. The maximum duration of treatment - 3 days.

Maximum dose: 4 single doses a day.

Features of use:

With care apply at patients with abnormal liver functions and kidneys, with a high-quality hyperbilirubinemia, and also at patients of advanced age.

At prolonged use of paracetamol control of a picture of peripheral blood and a functional condition of a liver is necessary.

It is applied to treatment of a syndrome of premenstrual tension in a combination with pamabrom (diuretic, derivative xanthine) and mepiraminy (a blocker histamine H1 receptors).

Paracetamol gets through a placental barrier. So far the negative impact of paracetamol on a fruit at the person is noted.

Paracetamol is emitted with breast milk: content in milk makes 0.04-0.23% of the dose accepted by mother.

In need of use of paracetamol at pregnancy and in the period of a lactation (breastfeeding) it is necessary to weigh carefully expected advantage of therapy for mother and potential risk for a fruit or the child.

In pilot studies embriotoksichesky, teratogenic and mutagen effect of paracetamol is not established.

Side effects:

From the alimentary system: seldom - the dispeptic phenomena, at prolonged use in high doses - a hepatotoxic action.

From system of a hemopoiesis: seldom - thrombocytopenia, a leukopenia, a pancytopenia, a neutropenia, an agranulocytosis.

Allergic reactions: seldom - skin rash, an itch, a small tortoiseshell.

Interaction with other medicines:

At simultaneous use with the inductors of microsomal enzymes of a liver, means possessing a hepatotoxic action there is a risk of strengthening of a hepatotoxic action of paracetamol.

At simultaneous use with anticoagulants perhaps small or moderately expressed increase in a prothrombin time.

At simultaneous use with anticholinergics paracetamol absorption reduction is possible.

At simultaneous use with oral contraceptives removal of paracetamol from an organism accelerates and reduction of its analgetic action is possible.

At simultaneous use with uricosuric means their efficiency decreases.

At simultaneous use of absorbent carbon bioavailability of paracetamol decreases.

At simultaneous use with diazepam reduction of excretion of diazepam is possible.

There are messages on a possibility of strengthening of miyelodepressivny effect of a zidovudine at simultaneous use with paracetamol. The case of crushing toxic damage of a liver is described.

Cases of manifestations of toxic effect of paracetamol at simultaneous use with an isoniazid are described.

At simultaneous use with carbamazepine, Phenytoinum, phenobarbital, Primidonum efficiency of paracetamol decreases that is caused by increase in his metabolism (processes of a glyukuronization and oxidation) and removal from an organism. Hepatotoxic cases at simultaneous use of paracetamol and phenobarbital are described.

At use of Colestyraminum during the period less than 1 h after reception of paracetamol reduction of absorption of the last is possible.

At simultaneous use with lamotridzhiny removal of a lamotridzhin from an organism moderately increases.

At simultaneous use with Metoclopramidum increase in absorption of paracetamol and increase in its concentration in a blood plasma is possible.

At simultaneous use with probenetsidy reduction of clearance of paracetamol is possible; with rifampicin, Sulfinpyrazonum - increase in clearance of paracetamol owing to increase in his metabolism in a liver is possible.

At simultaneous use with ethinylestradiol absorption of paracetamol from intestines increases.

Contraindications:

Alcoholism, hypersensitivity to paracetamol, children's age up to 6 years.

Overdose:

Symptoms: during the first 24 h after reception — pallor of integuments, nausea, vomiting, anorexia, abdominal pain; glucose metabolism disturbance, metabolic acidosis. Symptoms of an abnormal liver function can appear in 12-48 h after overdose. At heavy overdose — a liver failure with the progressing encephalopathy, a coma, death; an acute renal failure with a tubular necrosis (including in the absence of severe damage of a liver); arrhythmia, pancreatitis. The hepatotoxic effect at adults is shown at reception of 10 g and more.

Treatment: introduction of donators of SH-group and predecessors of synthesis of glutathione — methionine in 8-9 h after overdose and N-Acetylcysteinum — during 8 h. Need for holding additional therapeutic actions (further administration of methionine, intravenous administration of N-Acetylcysteinum) is defined depending on concentration of paracetamol in blood, and also from time which passed after its reception.

Storage conditions:

To store in dry, protected from light and the place, unavailable to children, at a temperature not above 30 °C.

Issue conditions:

Without recipe

Packaging:

10 pieces - packagings bezjyacheykovy planimetric. 10 pieces - planimetric strip packagings (2) - packs cardboard. 20 pieces - banks polymeric (1) - packs cardboard.