Paracetamol Extratab tablets with vit. C 500 + 150mg, No. 10

• As an antipyretic agent for infectious and inflammatory diseases (ARVI, including influenza);

• as an anesthetic for mild and moderate pain syndrome (headache, toothache) of non-inflammatory origin, for neuralgia, pain in muscles and joints, algodismenorrhea.

Adults and children over 12 years old (weighing more than 50 kg) should be taken orally 1 tab. 3-4 times / day with an interval between doses of 4-8 hours.

Children from 6 to 12 years old - 1/2 tab., The maximum daily dose - 2 tab. The maximum duration of treatment for children is 3 days.

The maximum duration of treatment for adults is no more than 5 days when prescribed as an anesthetic and no more than 3 days as an antipyretic.

Tablets from white to white with a yellowish tinge, biconvex, oblong, with rounded ends, with a risk on one side, 'slight marbling' is allowed.

1 tab.

paracetamol 500 mg

ascorbic acid 150 mg

Excipients: hydroxypropyl methylcellulose (hypromellose), polyethylene glycol 6000 (macrogol 6000), corn starch, stearic acid.

• Severe kidney disease;

• severe liver disease;

• renal and / or hepatic impairment;

• deficiency of glucose-6-phosphate dehydrogenase;

• erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; gastrointestinal bleeding;

• children under 6 years of age;

• pregnancy;

• lactation period (breastfeeding).

• With care: erosive and ulcerative lesions of the gastrointestinal tract (in history), congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes); blood diseases (thrombocytopenia, leukopenia, agranulocytosis), sideroblastic anemia, thalassemia; hemochromatosis, hyperoxaluria, urolithiasis; bronchial asthma; alcoholism.

pharmachologic effect

Combined analgesic drug

Paracetamol has analgesic and antipyretic effects. Blocks COX-1 and COX-2 mainly in the central nervous system, affecting the centers of pain and thermoregulation. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on COX, which explains the almost complete absence of its anti-inflammatory effect. The drug does not have a negative effect on water-salt metabolism (sodium and water retention) and the gastrointestinal mucosa, due to the lack of effect on the synthesis of prostaglandins in peripheral tissues. Methemoglobin 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 hydroxylation and amidation reactions - transfers electrons to enzymes, supplying them with a reducing equivalent. Participates in the reactions of hydroxylation of proline and lysine residues of procollagen with the formation of hydroxyproline and hydroxylysine (post-translational modification of collagen), oxidation of lysine side chains in proteins with the formation of hydroxytrimethyllysine (in the process of kartytite synthesis), oxidation of folic acid to folinic acid, metabolism and drugs in liver microsomes dopamine to form norepinephrine. Increases the activity of amidating enzymes involved in the processing of oxytocin, ADH and cholcystokinin. Participates in steroidogenesis in the adrenal glands.The main role at the tissue level is participation in the synthesis of collagen, proteoglycans and other organic components of the intercellular substance of teeth, bones and capillary endothelium.

Pharmacokinetics

Paracetamol

Absorption is high. Tmax - 0.5-2 h; Cmax - 5-20 ?g / ml. Plasma protein binding - 15%. Penetrates the BBB. Vd varies from 0.8 to 1.36 l / kg of body weight. Less than 1% of the dose of paracetamol taken by a nursing mother passes 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. It is metabolized in the liver by three main pathways: conjugation with glucuronides, conjugation with sulfates, oxidation by microsomal liver enzymes. In the latter case, toxic intermediate metabolites are formed, which are subsequently conjugated with glutathione, and then with cysteine ??and mercapturic acid. The main isoenzymes of cytochrome P450 for this metabolic pathway are the isoenzyme CYP2E1 (mainly), CYP1A2 and CYP3A4 (minor role).

When glutathione is deficient, these metabolites can cause damage and necrosis of hepatocytes. Additional metabolic pathways are hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated to glucuronides or sulfates. In adults, glucuronidation predominates, in newborns (including premature babies) and small children - sulfation. Conjugated paracetamol metabolites (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% unchanged. In elderly patients, the clearance of the drug decreases and T1 / 2 increases

Vitamin C

Plasma protein binding - 25%. The concentration of ascorbic acid in plasma is normally approximately 10-20 ?g / ml. Easily penetrates into leukocytes, platelets, and then into all tissues; the highest concentration is achieved in the glandular organs, leukocytes, liver and lens of the eye; penetrates the placental barrier. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and plasma. In states of deficiency, the concentration in leukocytes decreases later and more slowly and is considered as a better criterion for assessing deficiency than plasma concentration. It is metabolized mainly in the liver to deoxyascorbic acid and then to oxaloacetic acid 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.When administered in high doses, the rate of elimination increases dramatically. Smoking and ethanol consumption accelerate the breakdown of ascorbic acid (conversion into inactive metabolites), dramatically reducing body stores. It is excreted during hemodialysis.

Side effect

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, pruritus, urticaria, angioedema. From the hematopoietic and lymphatic system: very rarely - anemia, leukopenia. Others: weakness. Ascorbic acid Allergic reactions: skin rash, flushing of the skin. Laboratory indicators: thrombocytosis, hyperprothrombinemia, erythropenia, neutrophilic leukocytosis, hypokalemia, glucosuria.

Application during pregnancy and lactation

There are no data on studies of the efficacy and safety of the combination of paracetamol and ascorbic acid in pregnant and lactating women. Thus, it is not possible to assess the possible ratio of risk and benefit, and therefore it is not recommended to use the drug in these categories of patients.

Application in children

Contraindication: children under 6 years of age.

special instructions

Do not exceed the recommended doses of the drug 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 laboratory tests when quantifying plasma glucose and uric acid concentrations. To avoid toxic damage to the liver, paracetamol should not be combined with drinks containing alcohol, and should not be taken by persons prone to alcohol abuse. There is evidence that the frequent use of drugs containing paracetamol leads to an aggravation of the symptoms of bronchial asthma.Concomitant use of other drugs should be agreed with your doctor.

Influence on the ability to drive vehicles and use mechanisms

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

Overdose

Paracetamol

Symptoms: during the first 24 hours after administration - pallor of the skin, nausea, vomiting; anorexia, abdominal pain; violation 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 turbular necrosis (including in the absence of severe liver damage); arrhythmia, pancreatitis. The hepatotoxic effect in adults is manifested when taking 10 g or more. Rarely, liver failure develops lightning fast and can be complicated by renal failure (tubular necrosis).

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

Vitamin C

Symptoms: diarrhea, nausea, irritation of the gastrointestinal mucosa, flatulence, abdominal pain of a spastic nature, frequent urination, nephrolithiasis, insomnia, irritability, hypoglycemia.

Treatment: symptomatic, forced diuresis.

Drug interactions

If you are taking other medicines at the same time with Paracetamol EXTRATAB, you should consult your doctor.

Paracetamol reduces the effectiveness of uricosuric drugs. With prolonged and regular use, paracetamol potentiates the action of warfarin and other coumarin derivatives and increases the risk of bleeding.

The simultaneous administration of cholestyramine leads to a decrease in the absorption of paracetamol (and a weakening of the effects of paracetamol). Metoclopramide and domperidone increase the absorption of paracetamol.

The simultaneous use of paracetamol and NSAIDs (including metamizole sodium, acetylsalicylic acid, ibuprofen) increases the risk of developing 'analgesic' nephropathy and renal papillary necrosis, end-stage renal failure.

The simultaneous use of paracetamol and chloramphenicol can be accompanied by an increase in T1 / 2 of chloramphenicol up to 5 times. Inducers of microsomal liver enzymes (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which makes it possible to develop severe intoxications even with small overdoses.

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

The simultaneous use of paracetamol and ethanol can increase the hepatotoxicity of paracetamol, as well as contribute to the development of acute pancreatitis.

Diflunisal increases the plasma concentration of paracetamol by 50% - the risk of developing hepatotoxicity. You should not simultaneously use other medicines containing paracetamol, as well as other non-narcotic analgesics.

The simultaneous use of other medicines should be agreed with your doctor.

Ascorbic acid increases the concentration of benzylpenicillin and tetracyclines in the blood; at a dose of 1 g / day increases the bioavailability of ethinylestradiol (including that included in oral contraceptives); improves the absorption of iron preparations in the intestine (converts trivalent iron to bivalent); may increase the excretion of iron when used concomitantly with deferoxamine; reduces the effectiveness of heparin and indirect anticoagulants.

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

With simultaneous use with acetylsalicylic acid, the excretion of ascorbic acid in the urine 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 crystalluria during treatment with short-acting salicylates and sulfonamides, slows down the excretion of acids by the kidneys, increases the excretion of drugs with an alkaline reaction (including alkaloids), and reduces the concentration of oral contraceptives in the blood.

Medicines of the quinoline series, calcium chloride, salicylates, GCS, with prolonged use, deplete the reserves of ascorbic acid.

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

With long-term 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.

Barbiturates and primidone 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.