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

active substances - paracetamol - 0.5 g; ascorbic acid 0.15 g Excipients: hydroxypropylmethylcellulose (hypromellose), polyethylene glycol 6000 (macrogol 6000), corn starch, stearic acid

Description:

Tablets from white to white with yellowwith a shade of color, biconvex, elongated shape with rounded ends, with a risk on one side.

"Light marble" is allowed.

Pharmacotherapeutic group:Analgesic combined (analgesic non-narcotic remedy + vitamin)

ATX: & nbsp

N.02.B.E Anilides

N.02.B.E.51 Paracetamol in combination with other drugs, excluding psycholeptics

Pharmacodynamics:

Paracetamol has an analgesic and antipyretic effect. The drug blocks cyclooxygenase 1 and 2 mainly in the central nervous system (CNS), affecting the centers of pain and thermoregulation. In inflamed tissues cellular peroxidase neutralize the effect of paracetamol on the cyclo-oxygenase, which explains the almost complete absence of his anti-inflammatory effect. The drug does not adversely affect the water-salt exchange (sodium and water retention) and the mucous membrane of the gastrointestinal tract (GIT), due to the lack of influence on the synthesis of prostaglandins in peripheral tissues. The possibility of methaemoglobin formation is unlikely.

Ascorbic acid (vitamin C) is not formed in the human body, it comes only with food.

Physiological functions: is a cofactor of some reactions of hydroxylylation and amidation - transfers electrons to enzymes, providing them with a replacement equivalent. The participantsin the reactions of hydroxylproline and lysine residuescollagen with formation of hydroksiprolina and hydroxylysine (postranslyatsionnaya modification of collagen), oxidation of the side chains of lysine in proteins to form gidroksitrime- tillizina (during synthesis kartinita) oxidation of folic acid to folinic, metabolism of drugs in the liver microsomes and hydroxylation of dopamine to form norepinephrine.

Increases activity amidating enzymes involved in the processing of oxytocin, antidiuretic hormone and holitsistokinina. Participates in steroidogenesis in the adrenal glands.

The main role at the tissue level is participation in the synthesis of collagen, proteoglyteKanov et al. Organic components intercellular substance teeth, bone and endothelial capillaries.

Pharmacokinetics:

Paracetamol. Absorption is high. The time required to reach the maximum concentration (TC_mOh) - 0.5-2 hours; the maximum concentration (Cmax) is 5-20 μg / ml. Connection with plasma proteins - 15%. Penetrates through the blood-brain barrier (BBB). The volume of distribution varies from 0.8 to 1.36 l / kg body weight. Less than 1% of the dose of paracetamol taken by the lactating mother penetrates into breast milk.The therapeutically effective concentration of paracetamol in plasma is achieved when it is administered at a dose of 10-15 mg / kg. Metabolised in the liver in three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation with microsomal enzymes of the liver. In the latter case, toxic intermediate metabolites are formed, whichthe subsequently conjugated to glutathione, followed by 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 to glucuronides or sulfates.

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.

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.

Ascorbic acid. Connection with plasma proteins - 25%.

The concentration of ascorbic acid in the plasma is normally around 10-20 μg / ml. Easily penetrates into leukocytes, platelets, and then into all tissues; the greatest concentration is achieved in glandular organs, leukocytes, liver and lens of the eye; penetrates the placenta. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and in plasma. With deficient states, the concentration in leukocytes decreases later and more slowly and is considered as the best criterion for assessing the deficit than the concentration in the plasma.

Metabolised mainly in the liver in desoxyascorbic and then in oxaloacetic and ascorbate-2-sulfate.

It is excreted by the kidneys, through the intestines, with sweat, breast milk in unchanged form and in the form of metabolites.

At the appointment of high doses, the rate of excretion increases sharply. Smoking and the use of ethanol accelerate the destruction of ascorbic acid (conversion into inactive metabolites), sharply reducing the reserves in the body. It is in hemodialysis.

Indications:

Paracetamol EXTRATAB is used as:

- antipyretic agents for infectious and inflammatory diseases (ARVI, including influenza);

- anesthetic for mild to moderate pain syndrome (headache, toothache) of non-inflammatory origin, with neuralgia, pain in muscles and joints, algodismenore.

Contraindications:

Severe diseases of the kidneys, liver, including renal and / or hepatic insufficiency, deficiency of glucose-6-phosphate dehydrogenase; eraozivno-ulcerative lesions of the gastrointestinal tract (in the phase of exacerbation), gastrointestinal bleeding; children's age till 6 years; pregnancy (I-III trimesters), lactation period.

Carefully:

Erosive-ulcerative lesions of the gastrointestinal tract (in the anamnesis), congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor).

Diseases of the blood (thrombocytopenia, leukopenia, agranulocytosis), sideroblastic anemia, thalassemia.

Hemochromatosis, hyperoxaluria, urolithiasis.

Bronchial asthma. Alcoholism.

Pregnancy and lactation:Data on the efficacy and safety studies of the combination of paracetamol and ascorbic acid in pregnant and lactating women are not available. Thus, it is not possible to assess the possible correlation of risk and benefit possible, in connection with which the use of the drug in these categories of patients is not recommended.

Dosing and Administration:

Adults and children over 12 years of age (with a body weight of more than 50 kg) take inside 1 tablet 3-4 times a day with an interval between doses 4-8 hours. Children from 6 to 12 years - 1/2 tablets, the maximum daily dose - 2 tablets. The maximum duration of treatment for children is 3 days.

The maximum duration of treatment for adults - no more than 5 days with an appointment as an anesthetic and no more than 3 days - as an antipyretic.

Side effects:

Paracetamol.

From the digestive system: rarely - nausea, very rarely - vomiting, diarrhea, epigastric pain, jaundice, pancreatitis and increased activity of "liver" enzymes. Allergic reactions: rarely - skin rash, skin itching, hives, angioedema, edema).

From the organs of hematopoiesis and lymphatic system: Very rarely - anemia, leukopenia.

Other: weakness.

Ascorbic acid.

Allergic reactions: skin rash, skin hyperemia.

Laboratory indicators: thrombocytosis, hyperprothrombinemia, erythropenia, neutrinorofilny leukocytosis, hypokalemia, glucosuria.

Overdose:

Symptoms (due to paracetamol): during the first 24 hours after administration - pallor of the skin, nausea, vomiting; anorexia, abdominal pain; disturbance of 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 turbulent necrosis (including in the absence of severe liver damage); arrhythmia, pancreatitis. Hepatotoxic effect in adults is manifested when taking 10 g or more. Rarely, liver failure develops at a lightning speed and can be complicated by renal insufficiency (tubular necrosis).

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

The need for additional therapeutic measures (further introduction of methionine, intravenous injection of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after admission.

Symptoms (due to ascorbic acid): diarrhea, nausea, irritation of the mucous membrane of the gastrointestinal tract, flatulence, abdominal pain of a spastic nature, frequent urination, nephrolithiasis, insomnia, irritability, hypoglycemia.

Treatment: symptomatic, forced diuresis.

Interaction:

When concomitantly taking other medicines with Paracetamol EXTRATAB should consult a doctor.

Paracetamol reduces the effectiveness of uricosuric drugs.

For prolonged and regular use paracetamol potentiates the effects of warfarin and other coumarin derivatives and increases the risk of bleeding. Simultaneous reception of colestyramine leads to a decrease in paracetamol absorption (and weakening of paracetamol effects).

Metoclopramide and domperidone increase the absorption of paracetamol. Simultaneous use of paracetamol and non-steroidal anti-inflammatory drugs (metamizol sodium, acetylsalicylic acid, ibuprofen etc.) increases the risk of developing "analgesic" nephropathy and renal papillary necrosis, the terminal stage of renal failure. Simultaneous use of paracetamol and chloramphenicol may be accompanied by an increase in T1 / 2chloramphenicol up to 5 times.

Inductors of microsomal liver enzymes (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which causes the possibility of severe intoxication even with small overdoses.

Salicylamide increases T1 / 2 paracetamol, which leads to the accumulation of paracetamol and, accordingly, increased formation of its toxic metabolites.

Simultaneous use of paracetamol and ethanol can enhance hepatotoxicity of paracetamol, as well as promote the development of acute pancreatitis. Diflunisal increases the plasma concentration of paracetamol by 50% - the risk of developing hepatotoxicity.

Do not use other medicines containing paracetamol, as well as other non-narcotic analgesics.

Simultaneous the use of other medicines should be agreed with the doctor.

Ascorbic acid increases the concentration of benzylpenicillin and tetracyclines in the blood; in a dose of 1 g / day increases the bioavailability of ethinyl estradiol (incl.which is part of oral contraceptives); improves intestinal absorption of drugs Fe (converts trivalent iron into bivalent iron); can increase excretion of iron with simultaneous application with deferoxamine; reduces the effectiveness of heparin and indirect anticoagulants.

Acetylsalicylic acid oral contraceptives, fresh juices and alkaline drink reduce the absorption and absorption of ascorbic acid.

With simultaneous use with acetylsalicylic acid, urinary excretion of ascorbic acid increases and the excretion of acetylsalicylic acid decreases.

Acetylsalicylic acid reduces the absorption of ascorbic acid by about 30%.

Ascorbic acid increases the risk of developing crystalluria in the treatment of short-acting salicylates and sulfonamides, slows the excretion of acids by the kidneys, increases the excretion of drugs that have an alkaline reaction (including alkaloids), and reduces the concentration of oral contraceptives in the blood.

Drugs of quinoline series, СаСl₂, salicylates, GCS with long-term use deplete the stores of ascorbic acid.

With simultaneous application ascorbic acid reduces the chronotropic effect of isoprenaline.

With prolonged use or use in high doses ascorbic acid can interfere with the interaction of disulfiram and ethanol; in high doses increases the excretion of mexiletine by the kidneys.

Baentrants and primidon increase the excretion of ascorbic acid in the urine. Ascorbic acid reduces the therapeutic effect of antipsychotic drugs (neuroleptics) - phenothiazine derivatives, tubular reabsorption of amphetamine and tricyclic antidepressants.

Special instructions:

Do not exceed recommended doses of Paracetamol EXTRATAB. With hyperthermia, lasting more than 3 days, and pain syndrome for more than 5 days, a doctor's consultation is required.

After 5 days of using the drug Paracetamol EXTRATAB it is necessary to monitor the picture of peripheral blood and the functional state of the liver.

Paracetamol distorts the results of laboratory studies in quantifying the concentration of glucose and uric acid in the plasma. To avoid toxic damage to the liver paracetamol do not follow sochethaw with the reception of drinks containing, alcohol, and also to people who are prone to alcohol abuse.

There is evidence that frequent use of drugs containing paracetamol, leads to a weighting of the symptoms of bronchial asthma. Simultaneous use of other drugs should be agreed with the doctor.

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

There is no data on the effect of Paracetamol EXTRATAB on the ability to drive vehicles and other technical means.

Form release / dosage:Tablets 500 mg + 150 mg.

Packaging:

By 5, 6, 7, 10, 12, 15 tablets in contour cell packaging from polyvinyl chloride film and foil aluminum printed varnished.

By 1, 2, 3, 4 or 5 contiguous cells Packages together with the use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:Without recipe

Registration number:LSR-004857/10

Date of registration:28.05.2010

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp27.09.2015

Illustrated instructions

Instructions

Paracetamol EXTRATAB (Paracetamol EXTRATAB)