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

Pharmacodynamics:Has analgesic, antipyretic and weak anti-inflammatory effect. The drug blocks, cyclooxygenase I and II, mainly in the central nervous system, affecting the centers of pain 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 determines the absence of a negative effect on water-salt metabolism (sodium and water retention) and gastrointestinal mucosa (GI tract).

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 dose of paracetamol taken by the lactating mother 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 metabolic pathways include 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 (including toxic) activity.

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

Indications:

Paracetamol is used to relieve headache, migraine, toothache, sore throat, back pain, muscle pain, painful menstruation.

Paracetamol is also used for symptomatic treatment of febrile syndrome (as an antipyretic agent); at an elevated body temperature against the background of "catarrhal" diseases and influenza.

The drug is designed to reduce pain at the time of application and the progression of the disease is not affected.

Contraindications:

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

- severe hepatic impairment or decompensated liver disease in the acute stage;

- pregnancy (I and III trimesters) and lactation;

- children's age till 6 years.

Carefully:

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

Pregnancy and lactation:

During pregnancy and during breastfeeding, use only at recommended doses after consultation with a doctor.

Paracetamol penetrates into breast milk in a small amount.

Dosing and Administration:

Inside.

Adults (including seniors):

1-2 tablets (0.5-1 g) up to 4 times a day, if necessary. The maximum single dose is 2 tablets (1 g). The maximum daily dose is 8 tablets (4 g). The interval between receptions is not less than 4 hours.

Children

The dose is calculated based on the body weight of the child: the maximum single dose is 15 mg / kg body weight, the maximum daily dose is 60 mg / kg body weight.

Children (6-9 years):

½ tablets (250 mg) up to 4 times a day, if necessary. The maximum single dose - ½ tablets (250 mg). The maximum daily dose is 2 tablets (1 g). The interval between receptions is not less than 4 hours.

Children (9-12 years):

1 tablet (500 mg) up to 4 times a day, if necessary. The maximum single dose is 1 tablet (500 mg). The maximum daily dose is 4 tablets (2 g). The interval between receptions is not less than 4 hours.

In adults, the drug is not recommended for more than 5 days as an anesthetic and for more than 3 days as an antipyretic agent without prescribing and seeing a doctor.

In children, the drug is not recommended for more than 3 days without prescribing and monitoring the doctor.

Do not exceed the indicated dose. If the recommended dose is exceeded, consult a doctor immediately, even if you are feeling well, as there is a risk of delayed severe liver damage.

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. The following side effects were revealed spontaneously during the post-marketing use of the drug.

Side effects are classified according to organ systems and frequency. The frequency of side effects is defined as follows: very often (greater than or equal to 1/10), often (greater than or equal to 1/100 and less than 1/10), infrequently (greater than or equal to 1/1000 and less than 1/100), rarely greater than or equal to 1/10 000 and less than 1/1000) and very rarely (greater than or equal to 1/100 000 and less than 1/10 000).

Allergic reactions:

Very rarely - in the form of rashes on the skin, itching, angioedema, Stevens-Johnson syndrome, anaphylaxis;

On the part of the hematopoiesis system:

Very rarely - thrombocytopenia, methemoglobinemia, hemolytic anemia;

From the respiratory system:

Very rarely - bronchospasm (in patients with hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs);

From the hepatobiliary system:

Very rarely - a violation of the liver.

With prolonged use in high doses, the likelihood of impaired liver and kidney function (renal colic, nonspecific bacteriuria, interstitial nephritis, papillary necrosis) increases, a blood picture check is necessary.

If any of these side effects occur, stop taking the medication and consult a doctor immediately.

Overdose:

Symptoms: during the first 24 hours after an overdose - nausea, vomiting, stomach pain, sweating, pale skin, anorexia. After 1-2 days, signs of liver damage are determined (soreness in the liver, increased activity of "liver" enzymes). It is possible to develop a violation of carbohydrate metabolism and metabolic acidosis. In adult patients, liver damage develops after taking more than 10 g of paracetamol. In the presence of factors that affect the toxicity of paracetamol for the liver (see the section "Interaction with other drugs", "Special instructions"), liver damage is possible after taking 5 or more grams of paracetamol.

In severe cases of overdose, as a result of liver failure, encephalopathy (impaired brain function), bleeding, hypoglycemia, cerebral edema can occur, up to a lethal outcome.It is possible to develop acute renal failure with acute tubular necrosis, the characteristic signs of which are pain in the lumbar region, hematuria (blood or erythrocyte admixture in the urine), proteinuria (high protein in the urine), with severe liver damage may be absent. There were cases of heart rhythm disturbances, pancreatitis.

Treatment: If you suspect an overdose, even if the first symptoms are not pronounced, stop using the drug and seek medical help immediately. Within 1 hour after an overdose it is recommended to wash the stomach and receive enterosorbents (Activated carbon, polyphepan). It is necessary to determine the level of paracetamol in the blood plasma, but not earlier than 4 hours after an overdose (earlier results are not reliable). Introduction of acetylcysteine within 24 hours after an overdose. The maximum protective effect is achieved within the first 8 hours after an overdose, with time the effectiveness of the antidote drops sharply. If necessary, enter acetylcysteine intravenously. If there is no vomiting before the patient enters the hospital, methionine may be used.The need for additional therapeutic measures (further introduction of methionine, iv injection of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration. Treatment of patients with severe impairment of liver function 24 hours after taking paracetamol should be done in conjunction with specialists from the toxicology center or specialized department of liver diseases.

Interaction:

Long-term combined use of paracetamol and non-steroidal anti-inflammatory drugs increases the risk of developing "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.

With regular intake for a long time, the drug enhances the effect of indirect anticoagulants (warfarin and other coumarins), which increases the risk of bleeding. Episodic intake of a single dose of the drug has no significant effect on the effect of indirect anticoagulants.

Diflunisal increases the plasma concentration of paracetamol by 50%, which increases the risk of hepatotoxicity.

Barbiturates, carbamazepine, phenytoin, primidon, ethanol, rifampicin, zidovudine, flumecinol, phenylbutazone, preparations of St. John's wort, tricyclic antidepressants and other inducers of microsomal oxidation increase the production of hydroxylated active metabolites, causing the possibility of developing severe liver damage with small overdoses of paracetamol (5 g or more). Inhibitors of microsomal liver enzymes (cimetidine) reduce the risk of hepatotoxic effects.

Under the influence of paracetamol, the time of chloramphenicol elimination is increased by 5 times. Simultaneous reception of paracetamol and alcoholic beverages increases the risk of developing liver damage and acute pancreatitis.

Metoclopramide and domperidone increase, and colestramine reduces the rate of absorption of paracetamol. The drug may reduce the effectiveness of uricosuric drugs.

Special instructions:

Before taking the drug Paracetamol you should consult your doctor if you are taking any of the drugs listed in the "Interactions with Other Drugs" section.

If there is no improvement in the condition when the drug is taken or the headache becomes permanent, it is necessary to consult a doctor.

Deficiency of glutathione due to eating disorders, cystic fibrosis, HIV infection, starvation, exhaustion causes the possibility of developing severe liver damage with small overdoses of paracetamol (5 g or more). The drug should not be taken concurrently with other paracetamol-containing drugs.

When analyzing the determination of uric acid and blood glucose levels, the doctor should be informed of the drug.

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.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and other mechanisms during treatment with the drug, taking into account the possible development of side effects.

Form release / dosage:

Tablets 500 mg.

Packaging:

For 20 or 30 tablets in cans of polymer complete with lids or cans of polyethylene terephthalate with the means of corking.

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

Each jar, 1 or 2 contour mesh packages together with the instruction for use is placed in a pack of cardboard.

For 10 tablets in a contour non-cellular package of paper with a polymer coating.

It is allowed to pack 30 or 40 cans without a bundle with an equal number of instructions for use in group packaging (for hospitals).

300 or 500 contiguous cell-free packages or contiguous cell packs with an equal number of instructions for use are placed in a group package (for hospitals).

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

5 years. Do not use after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:LP-004374

Date of registration:12.07.2017

Expiration Date:12.07.2022

The owner of the registration certificate:IVANOVSKAYA Pharmaceutical Factory, OAO IVANOVSKAYA Pharmaceutical Factory, OAO Russia

Manufacturer: & nbsp

IVANOVSKAYA Pharmaceutical Factory, OAO Russia

Information update date: & nbsp03.10.2017

Illustrated instructions

Instructions

Paracetamol (Paracetamol)