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

Pharmacodynamics:Paracetamol is an analgesic and antipyretic. It blocks cyclooxygenase COX1 and COG2 mainly in the central nervous system (CNS), affecting the centers of pain and thermoregulation. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on cyclooxygenase (COX), which explains the almost complete absence of anti-inflammatory effect.The absence of influence on the synthesis of prostaglandins in peripheral tissues causes the absence of a negative influence on the water-salt metabolism (sodium and water retention) and the mucous membrane of the gastrointestinal tract.

Pharmacokinetics:

Absorption is high, the time to reach the maximum concentration (TCmah) in the plasma - 0.5-2 h; the maximum concentration (Сmах) in plasma - 5-20 mkg / ml. Connection with plasma proteins - 15%. Penetrates through the blood-brain barrier. Less than 1% of the dose of paracetamol taken by the lactating mother penetrates into breast milk.

Metabolised 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 to 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 ways of metabolism are hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol,which are subsequently conjugated with glucuronic or sulfuric acid.

In adults, glucuronation predominates, in newborns (including prematurity) and small children, sulfation. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity.

The half-life (T1 / 2) is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% in unchanged form. In elderly patients the clearance of the drug decreases and T1 / 2 increases.

Indications:

Increased temperature against the background of infectious diseases; pain syndrome (mild and moderate manifestations): arthralgia, myalgia, neuralgia, migraine, dental and headache, aphidismenorea.

Contraindications:

- hypersensitivity to paracetamol or any other ingredient in the drug;

- severe dysfunction of the liver or kidney;

- children's age till 6 years.

Carefully:

Use with caution in benign hyperbilirubinemia (including Gilbert's syndrome), viral hepatitis, alcohol damage of the liver, deficiency of glucose-6-phosphate dehydrogenase, alcoholism, pregnancy,during lactation. The drug should not be taken concurrently with other paracetamol-containing drugs.

Pregnancy and lactation:

Paracetamol penetrates the placental barrier. Paracetamol is excreted in breast milk: the content in milk is 0.04-0.23% of the dose taken by the mother.

If it is necessary to use paracetamol during pregnancy and lactation(breastfeeding) should carefully weigh the expected benefit of therapy for mother and potential risk to the fetus or child.

Dosing and Administration:

Adults, including the elderly and children over 12 years of age:

For 0.5-1 g, 1-2 hours after eating with a lot of liquid, after 4-6 hours, the maximum daily dose to 4 grams per day.

Children over 6 years of age:

For 250-500 mg in 4-6 hours up to 4 times a day, at the rate of 50 mg per kg of body weight.

The interval between receptions should be at least 4 hours. Do not take more than 8 tablets within 24 hours.

Do not exceed the indicated dose. If you have taken a dose exceeding the recommended dose, seek medical help, even if you are feeling well. Overdose of paracetamol can cause hepatic insufficiency. Peparat is not recommended more than five days as an anesthetic and more than three days as an antipyretic without the appointment and supervision of a doctor. An increase in the daily dose of the drug or the duration of treatment is possible only under the supervision of a physician.

Side effects:

In recommended doses, the drug is usually well tolerated. There may be an allergic reaction in the form of rashes on the skin, itching, swelling of Quincke; disorders of the blood system (anemia, thrombocytopenia, methemoglobinemia, agranulocytosis). With prolonged use in high doses, the likelihood of impaired liver and kidney function, as well as the hematopoietic system, increases. If unusual symptoms occur consult a doctor.

Overdose:

Symptoms: during the first 24 hours after administration - pallor of the skin, nausea, vomiting, anorexia, abdominal pain; metabolic disorder of glucose acidosis. Symptoms of liver dysfunction may appear 12-48 h after 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 is manifested when taking 10 g or more.

Treatment: introduction of donators SH-groups and precursors of glutathione synthesis -methionine for 8-9 hours after an overdose and acetylcysteine - for 8 hours.

The need for dAdditional therapeutic measures (further introduction of methionine, intravenous injection of acetylcysteine) is determined in depending on the concentration of paracetamol in the blood, as well as on the time that has passed after its reception.

Interaction:Reduces the effectiveness of uricosuric drugs.

The concomitant use of paracetamol in high doses "increases the effect of anticoagulants (a decrease in the synthesis of procoagulant factors in the liver).

Inductors of microsomal enzymes in the liver (phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), ethanol and hepatotoxic agents increase the production of hydroxylated active metabolites, which allows the development of 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 liver enzymes (including cimetidine) reduce the risk of hepatotoxic effects.

Long-term sharing of paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing "analgesic" nephropathy and renal papillary necrosis, the onset of the terminal stage of kidney 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 drugs increase the manifestation of hematotoxicity of the drug.

Special instructions:

Before admission, consult a doctor if:

- You have a serious liver or kidney disease;

- You take drugs against nausea and vomiting (metoclopramide, domperidone), as well as drugs that lower the concentration of cholesterol in the blood (inhibitors of hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA reductase);

- You take anticoagulants and you need painkillers daily for a long time.

TO AVOID THE TOXIC LESION OF THE LIVER PARACETAMOL DO NOT CONSTITUTE WITH THE RECEPTION OF ALCOHOLIC BEVERAGES, AND ALSO TO TAKE PERSONS STRONG TO THE CHRONIC CONSUMPTION OF ALCOHOL.

In time of long-term treatment is necessary to monitor the picture of peripheral blood and the functional state of the liver.

Effect on the ability to drive transp. cf. and fur:There is no data on the effect on the ability to drive a car and perform work that requires a high rate of psychomotor reactions.

Form release / dosage:Tablets 500 mg.

Packaging:For 10 tablets in a planar cell package. For 20 or 30 tablets in a jar of polymer materials. Each jar or 1, 2, 3, 5 or 10 contour mesh packages together with instructions for use in the pack. A polymer-free can is supplied with a glue instruction for use and placed in a group package.

For 10 tablets in a contour non-cellular package of paper with a polymer coating. Contour non-cellular packages with instructions for use are placed directly in the group package.

Storage conditions:

Keep in a dry place, protected from light and 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:LS-001331

Date of registration:27.09.2011

The owner of the registration certificate:PHARMACY 36.6, CJSC PHARMACY 36.6, CJSC Russia

Manufacturer: & nbsp

MEGA PHARM, CJSC Russia

VEROPHARM SA Russia

Information update date: & nbsp03.10.2015

Illustrated instructions

Instructions

Paracetamol (Paracetamol)