Paracetamol

General characteristics. Structure:

Active ingredient: 50 mg, 100 mg, 250 mg or 500 mg of paracetamol.

Excipients (basis): fat firm (витепсол W35) – before receiving suppository weighing 1,25 g or 2,25 g.

Pharmacological properties:

Pharmacodynamics. Non-narcotic analgesic, blocks cyclooxygenase 1 and cyclooxygenase 2 preferential in the central nervous system, influencing the centers of pain and thermal control. In the inflamed fabrics cellular peroxidases neutralize influence of paracetamol on cyclooxygenase that explains almost total absence of antiinflammatory effect.

Lack of the blocking influence on synthesis of prostaglandin in peripheral fabrics causes absence at it negative influence on a water salt metabolism (a delay of ions of sodium and water) and a mucous membrane of digestive tract. 

Pharmacokinetics. Absorption - high, time of achievement of the maximum concentration of drug in plasma – 0,5-2 h; the maximum concentration of drug in plasma (Cmax) - 5-20 mkg/ml. Communication with proteins of plasma – 15%. Gets through a blood-brain barrier. Less than 1% from the accepted nursing mother of a dose of paracetamol get into breast milk.

It is metabolized in a liver on three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation by microsomal enzymes of a liver. In the latter case toxic intermediate metabolites which conjugate afterwards with glutathione, and then with cysteine and mercapturic acid are formed. The main isoenzymes of P450 cytochrome for this way of metabolism are CYP2E1 isoenzyme (preferential), CYP1A2 and CYP3A4 (supporting role). At deficit of glutathione these metabolites can cause damage and a necrosis of hepatocytes.

Additional ways of metabolism are a hydroxylation to 3-hydroxy-paracetamol and a metoksilirovaniye to a 3-metoksiparatsetamol which conjugate afterwards with glucuronides or sulfates. At adults the glyukuronirovaniye, at newborns (including premature) and small children - sulphation prevails. The conjugated paracetamol metabolites (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity. An elimination half-life of drug (T½) – 1 - 4 h. Only 3% in not changed look are removed by kidneys in the form of metabolites, preferential conjugates. At elderly patients the clearance of drug decreases and T½ increases.

Indications to use:

In quality:

- an antipyretic at acute respiratory diseases, including flu, the children's infections, postvaccinal reactions and other states which are followed by fervescence;

- an anesthetic at a pain syndrome of weak and moderate intensity, including head and a dentagra, muscle pains, neuralgia, альгодисменорея.

At children from 1 to 3 months the single dose of drug, for decrease in temperature and after vaccination is possible, use of drug according to all indications is possible only on doctor's orders.

Route of administration and doses:

Rektalno. After spontaneous bowel emptying or a cleansing enema, suppository is exempted from a blister strip packaging and entered into a rectum. The dose of drug is calculated depending on age and body weight, according to the table.

The single dose for children makes 10-15 mg of body weight of the child 2-3 times a day, in 4-6 hours. The maximum daily dose of paracetamol should not exceed 60 mg/kg of body weight of the child.

Age	Weight	Single dose
		mg	suppository
6-12 months	8-10 kg	96-120 mg	1 suppository on 100 mg
1-3 years	10-15 kg	120-180 mg	1-2 suppositories on 100 mg
3-5 years	15-20 kg	180-240 mg	2 suppositories on 100 mg
5-10 years	15-20 kg	240-336 mg	1 suppository on 250 mg + 1 suppository on 50 mg or 100 mg
10-12 years	28-40 kg	336-480 mg	1 suppository on 250 mg + 1 suppository on 50 mg or 100 mg – 2 suppositories on 250 mg

The adult - on 500 mg of 1 - 4 time a day; the maximum single dose - 1 g; the maximum daily dose - 4 g. Duration of a course of treatment: 3 days as febrifugal and up to 5 days, as anesthetic. Extension of a course if necessary after consultation with the doctor.

Features of use:

At the proceeding feverish syndrome against the background of paracetamol use    more than 3 days and a pain syndrome more than 5 days, consultation of the doctor is required.

It is necessary to avoid simultaneous use of paracetamol with other paratsetamolsoderzhashchy drugs as it can cause drug overdose. The risk of development of injuries of a liver increases at patients with an alcoholic liver disease.

Distorts indicators of laboratory researches at quantitative definition of glucose and uric acid in plasma. During prolonged treatment control of a picture of peripheral blood and a functional condition of a liver is necessary. The concomitant use with ethanol is not recommended.

Side effects:

Nausea, vomiting, abdominal pains.

Allergic reactions (a skin itch, rash on skin and mucous membranes, a small tortoiseshell, a Quincke's edema).

From bodies of a hemopoiesis – anemia, hemolitic anemia, aplastic anemia, a methemoglobinemia, a pancytopenia, a leukopenia, an agranulocytosis, thrombocytopenia.

At prolonged use in high doses - hepatotoxic and nephrotoxic (intersticial nephrite, a papillary necrosis) action, hemolitic anemia, aplastic anemia, a methemoglobinemia, a pancytopenia.

Interaction with other medicines:

Reduces efficiency of the uricosuric medicines (M). The accompanying use of paracetamol in high doses increases effect of anticoagulating HP (decrease in synthesis of procoagulant factors in a liver).

Inductors of a microsomal oxidation in a liver (Phenytoinum, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), ethanol and hepatotoxic HP increase products of hydroxylated active metabolites that causes a possibility of development of heavy intoxications even at small overdose. Prolonged use of barbiturates reduces efficiency of paracetamol.

Ethanol promotes development of acute pancreatitis. Inhibitors of a microsomal oxidation (including Cimetidinum) reduce risk of a hepatotoxic action.

Long sharing of paracetamol and other non-steroidal anti-inflammatory drugs increases risk of development of an "analgetic" nephropathy and renal papillary necrosis, approach of an end-stage of a renal failure.

Simultaneous long purpose of paracetamol in high doses and salicylates increases risk of development of cancer of kidney or bladder.

Diflunisal increases plasma concentration of paracetamol for 50% - risk of development of a hepatotoxic. Miyelotoksichny HP strengthen manifestations of a gematotoksichnost of drug.

Contraindications:

Individual hypersensitivity to drug components, the expressed abnormal liver functions and kidneys, genetic absence glyukozo-6-fosfatdegidrogenazy, age less than 6 months.

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 proyavltsya at reception of 10 g and more.

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

Storage conditions:

In the dry, protected from light place at a temperature not above 20 °C. In the place, unavailable to children. A period of validity - 2 years. Not to use after the expiry date specified on packaging

Issue conditions:

Without recipe

Packaging:

Suppositories rectal 50, 100, 250, 500 mg. Suppositories on 5 pieces place in a blister strip packaging. Two planimetric packagings together with the application instruction place in a pack from a cardboard.