Paracetamol - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Non-narcotic analgesic. Has analgesic and antipyretic effect. It blocks cyclooxygenase I and cyclooxygenase II predominantly in the central nervous system, affecting pain cycles and thermoregulation.In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on cyclooxygenase, which explains the almost complete absence of anti-inflammatory effect. The absence of a blocking effect on the synthesis of prostaglandins in peripheral tissues causes the absence of negative influence on water-salt metabolism (sodium and water retention) and gastrointestinal tract mucosa (GIT).

Pharmacokinetics:

- suction: quickly absorbed from the digestive tract. Absorption is high. The maximum concentration (5-20 μg / ml) is achieved after 0.5-2 hours. The therapeutically effective concentration of paracetamol in plasma is achieved when it is applied at a dose of 10-15 mg / kg.

- distribution: communication with plasma proteins - 15%. Penetrates through the blood-brain barrier. Less than 1% of the accepted, mother-feeding dose, paracetamol penetrates into breast milk.

- metabolism: metabolized in the liver in three main ways: conjugation with glucuronic acid, conjugation with sulfuric acid, oxidation with microsomal enzymes of the liver. In the latter case, toxic intermediate metabolites are formed, which are subsequently conjugated to glutathione,and then with cysteine and mercapturic acid. The main isoenzymes of cytochrome P450 for this pathway of metabolism are, isoenzyme CYP2E1 (predominantly), CYP1A2 and CYP3A4 (a secondary role). With a deficiency of glutathione, these metabolites can cause damage and necrosis of hepatocytes.

Additional the metabolic pathways are hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated to glucuronic or sulfuric acid. In adults, glucuronation predominates, in newborns (including premature infants) and small children, sulfation. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (in t.ch. toxic) activity.

- excretion: is displayed kidneys in the form of metabolites, mainly conjugates, only 3% unchanged. In elderly patients paracetamol clearance decreases and the half-life period increases.

Indications:Pain syndrome (of mild and moderate severity): arthralgia, myalgia, neuralgia, dental, headache, migraine pain, algodismenorea.

The raised temperature of a body at "cold" and other infectious-inflammatory diseases.

Contraindications:Hypersensitivity to the components of the drug, children under 6 years (for this dosage form). Pronounced impairment of liver or kidney function.

Carefully:Renal and hepatic insufficiency, benign hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor syndrome), viral hepatitis, alcoholic liver damage, alcoholism, pregnancy, lactation, elderly age, deficiency of glucose-6-phosphate dehydrogenase.

Pregnancy and lactation:

The use of the drug during pregnancy and breastfeeding is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Dosing and Administration:

Inside, drinking a glass of water, 1-2 hours after taking, food (reception immediately after meals leads to a delay in the onset of action).

Adults and adolescents older than 12 years (body weight over 40 kg) single dose - 500 mg; the maximum single dose - 1 g. The frequency of admission - up to 4 times a day. The maximum daily dose is 4 g. In patients with impaired liver or kidney function, with Gilbert syndrome, in elderly patients the daily dose should be reduced and the interval between doses should be increased.

Children from 6 to 12 years old (body weight up to 40 kg) single dose - 250-500 mg, at the rate of 15 mg / kg body weight (possibly pre-grinding tablets).

Multiplicity of admission - 4 times a day; the interval between each intake is not less than 4 hours. The maximum daily dose for children from 6 to 12 years is 1-2 g.

The maximum duration of treatment without consulting a doctor is 3 days (when taken as an antipyretic drug) and 5 days (as analgesic).

Side effects:

From the skin: skin rash, skin rash and mucous membranes (usually erythematous or urticaria), Quincke's edema, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

From the digestive system: nausea, epigastric pain, increased activity of "liver" enzymes, usually without the development of jaundice, hepatonecrosis (dose-dependent effect).

From the central and peripheral nervous system (usually developed with high doses): dizziness, psychomotor agitation, disorientation in time and space.

From the endocrine system: hypoglycemia, up to hypoglycemic coma.

From the hematopoiesis: thrombocytopenia, leukopenia, agranulocytosis, sulfogemaglobinemia, hemolytic anemia (especially for patients with deficiency of glucose-6-phosphate dehydrogenase). With prolonged use in large doses - neutropenia, aplastic anemia, pancytopenia.

Co the side of the urinary system (when taking large doses): nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, about this doctor.

Overdose:

Symptom: during the first 24 hours after ingestion, pallor of the skin, nausea, vomiting, anorexia, abdominal pain, impaired glucose metabolism, metabolic acidosis. Symptoms of liver dysfunction may appear 12-48 hours after an overdose. In severe overdose - liver failure with progressive encephalopathy, coma, death; acute renal failure with tubular necrosis (including in the absence of severe liver damage); arrhythmia; pancreatitis.Hepatotoxic effect in adults, manifested when taking 10 g or more.

Treatment: introduction of donators SH-groups and precursors of glutathione-methionine synthesis 8-9 hours after an overdose and N-acetylcysteine after 12 hours. The need for additional therapeutic measures (further introduction of methionine, intravenous administration N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration.

Interaction:

Reduces the effectiveness of uricosuric medicines.

The concomitant use of paracetamol in high doses increases the effect of anticoagulant drugs (a decrease in the synthesis of procoagulant factors in the liver). Inductors of microsomal liver enzymes (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) and hepatotoxic agents increase the production of hydroxylated active metabolites, which makes it possible to develop severe intoxication even with a slight overdose.

Long-term use of barbiturates reduces the effectiveness of paracetamol.

Ethanol promotes the development of acute pancreatitis.

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

Long-term combined use of paracetamol and other non-steroidal anti-inflammatory drugs increases the risk of developing an "analgesic" Nephropathy and renal papillary necrosis, the onset of the terminal stage of renal failure.

Simultaneous long-term use of paracetamol in high doses and salicylates increases the risk of developing kidney or bladder cancer.

Diflunisal increases the plasma concentration of paracetamol by 50% - the risk of developing hepatotoxicity.

Myelotoxic agents increase the manifestation of hematotoxicity of the drug.

Special instructions:

With the ongoing febrile syndrome in the background of the use of paracetamol more than 3 days, and pain syndrome for more than 5 days, consultation of the doctor is required.

To avoid toxic damage to the liver paracetamol Do not combine with the reception of alcoholic beverages. The risk of developing liver damage increases in patients with alcoholic hepatosis.

During long-term treatment, monitoring of the peripheral blood pattern and the functional state of the liver is necessary.

Distorts the indicators of laboratory studies in quantitative determination of glucose and uric acid in the plasma.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care should be taken when managing vehicles, mechanisms, and occupations requiring concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 500 mg.

Packaging:

10 tablets are placed in a contour mesh package made of a polyvinylchloride film and aluminum foil.

1 or 2 contour mesh packs together with instructions for use are put in a pack of cardboard.

300 contour cell packs with an equal number of instructions for use are placed in a corrugated box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:Without recipe

Registration number:P N002697 / 01

Date of registration:15.05.2009

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Information update date: & nbsp07.10.2015

Illustrated instructions

Instructions

Paracetamol (Paracetamol)