Composition, form of production and packaging
? Tablets from white to white with a yellowish tint of color, biconvex, oblong, with rounded ends, with a risk on one side, allowed "light marble."
1 tab.
paracetamol 500 mg
ascorbic acid 150 mg
Excipients: hypromellose, polyethylene glycol, corn starch, stearic acid.
5 pieces. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
5 pieces. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
5 pieces. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
5 pieces. - Cellular outline packaging (aluminum / PVC) (4) - cardboard packs.
5 pieces. - Cellular outline packaging (aluminum / PVC) (5) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (4) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (5) - cardboard packs.
12 pcs. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
12 pcs. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
12 pcs. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
12 pcs. - Cellular outline packaging (aluminum / PVC) (4) - cardboard packs.
12 pcs. - Cellular outline packaging (aluminum / PVC) (5) - cardboard packs.
15 pcs. - Cellular outline packaging (aluminum / PVC) (1) - cardboard packs.
15 pcs. - Cellular outline packaging (aluminum / PVC) (2) - cardboard packs.
15 pcs. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
15 pcs. - Cellular outline packaging (aluminum / PVC) (4) - cardboard packs.
15 pcs. - Cellular outline packaging (aluminum / PVC) (5) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Combined analgesic preparation
Paracetamol has an analgesic and antipyretic effect. It 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 lack of anti-inflammatory effect. The drug has no negative effect on water-salt metabolism (sodium and water retention) and gastrointestinal mucosa, due to the absence 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 hydroxylation and amidation reactions - transfers electrons to enzymes, providing them with a replacement equivalent.Participates in the reactions of hydroxylation of proline and lysine residues of procollagen with the formation of hydroxyproline and hydroxylisin (poststranslational modification of collagen), the oxidation of side chains of lysine in proteins with the formation of hydroxytrimethyllysine (during synthesis of the picture), the oxidation of folic acid to folinic, the metabolism of drugs in liver microsomes and hydroxylation dopamine with the formation of norepinephrine. Increases the activity of amidating enzymes involved in the processing of oxytocin, ADH and holitsistokinina. 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 the teeth, bones and endothelium of the capillaries.
PHARMACOKINETICS
Paracetamol
Absorption is high. T mах - 0.5-2 h; With mах - 5-20 mkg / ml. Binding to plasma proteins - 15%. Penetrates through the BBB. V d 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, 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 the 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
Binding to plasma proteins - 25%.
The concentration of ascorbic acid in the plasma is normally around 10-20 Ојg / 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 placental barrier. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and in plasma. With deficit conditions, 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.
When administered in high doses, the rate of excretion increases dramatically. Smoking and consumption of ethanol accelerate the destruction of ascorbic acid (conversion into inactive metabolites), drastically reducing stocks in the body. It is in hemodialysis.
INDICATIONS
- as an antipyretic agent for infectious and inflammatory diseases (ARVI, including influenza);
- as an anesthetic for mild to moderate pain syndrome (headache, toothache) of non-inflammatory origin, with neuralgia, pain in muscles and joints, algodismenore.
DOSING MODE
Adults and children over 12 years of age (with a body weight of more than 50 kg) take 1 tablet inside. 3-4 times / day with an interval between doses 4-8 hours.
Children from 6 to 12 years - 1/2 tablets, the maximum daily dose - 2 tab.
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 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, skin itching, hives, angioedema.
On the part of the system of hematopoiesis and lymphatic system: very rarely - anemia, leukopenia.
Other: weakness.
Ascorbic acid
Allergic reactions: skin rash, skin hyperemia.
Laboratory indices: thrombocytosis, hyperprothrombinemia, erythropenia, neutrophilic leukocytosis, hypokalemia, glucosuria.
CONTRAINDICATIONS
- severe kidney disease;
- severe liver disease;
renal and / or hepatic insufficiency;
- deficiency of glucose-6-phosphate dehydrogenase;
- erosive and ulcerative lesions of the gastrointestinal tract in the phase of exacerbation;
- gastrointestinal bleeding;
- children's age till 6 years;
- Pregnancy;
lactation period (breastfeeding).
With caution: erosive and ulcerative lesions of the gastrointestinal tract (in the anamnesis), congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor); blood diseases (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, and therefore the use of the drug in these categories of patients is not recommended.
APPLICATION FOR CHILDREN
Contraindication: children under 6 years.
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.
In order to avoid toxic damage to the liver, paracetamol should not be combined with the intake of alcohol-containing beverages, as well as 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.
Impact on the ability to drive vehicles and manage mechanisms
There is no data on the effect of 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; 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: the introduction of donors of SH-groups and precursors of the synthesis of glutathione - methionine - for 8-9 hours after overdose and acetylcysteine ​​- for 8 hours. The need for additional therapeutic measures (further introduction of methionine, iv injection of acetylcysteine) is determined in dependence from the concentration of paracetamol in the blood, as well as from the time passed after taking.
Ascorbic acid
Symptoms: 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.
DRUG INTERACTION
When concomitantly taking other medicines with the drug Paracetamol EXTRATAB should consult a doctor.
Paracetamol reduces the effectiveness of uricosuric drugs.
With 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 NSAIDs (including metamizole sodium, acetylsalicylic acid, ibuprofen) 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 T 1/2 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 allows the development of severe intoxication even with small overdoses.
Salicylamide increases T 1/2 of paracetamol, which leads to the accumulation of paracetamol and, accordingly, the 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 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 (also included in oral contraceptives); improves absorption in the intestine of iron preparations (converts trivalent iron into bivalent); 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 quinoline series, calcium chloride, salicylates, GCS with long-term use depletes the stores of ascorbic acid.
With simultaneous use of ascorbic acid reduces the chronotropic effect of isoprenaline.
With prolonged use or high-dose application, ascorbic acid may interfere with the interaction of disulfiram and ethanol; in high doses increases the excretion of mexiletine by the kidneys.
Barbiturates 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.
TERMS OF RELEASE FROM PHARMACY
The drug is approved for use as a means of OTC.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 2 years.
