Ibumet

General characteristics. Structure:

Active ingredients: 400 mg of an ibuprofen, 325 mg of paracetamol.

Excipients: corn starch, povidone, sodium krakhmalglikolit (type A), magnesium stearate, talc, silicon dioxide colloid anhydrous, cellulose microcrystallic.

Structure of a cover of a tablet: gipromelloza, talc, macrogoal 1500, dye yellow-orange E 110, titanium dioxide, polysorbate 80, диметикон.

The non-steroidal anti-inflammatory drug possessing the antiinflammatory, febrifugal and anesthetizing action

Pharmacological properties:

Pharmacodynamics. The ibuprofen - non-steroidal anti-inflammatory drug, derivative fenilpropionovy acid, possesses the antiinflammatory, febrifugal and anesthetizing action, due to oppression of activity of TsOG - the main enzyme which is responsible for metabolism of arachidonic acid being the predecessor of prostaglandins which play a major role in a pathogeny of an inflammation, pain and fever. Analgetic action is caused as peripheral (indirectly, through decrease in synthesis of prostaglandins), and the central mechanism (inhibition of synthesis of prostaglandins in the central and peripheral nervous system). Suppresses aggregation of thrombocytes.

Paracetamol - the anesthetizing non-narcotic means, renders anesthetic, febrifugal and weak antiinflammatory action due to suppression of activity of TsOG, and decrease in production of prostaglandins; exerts preferential impact on the center of thermal control in a hypothalamus.

Pharmacokinetics. The ibuprofen after intake is quickly and almost completely absorbed from a GIT. The maximum concentration in blood after reception of tablets, coated, is defined in 1-2 hours. In synovial fluid the maximum concentration is reached 3 hours later after reception. The ibuprofen in a liver (90%) is metabolized. It is removed by kidneys (80% of the entered dose) as in not changed look (10%), and in the form of metabolites (70%). 20% are removed in the form of metabolites through intestines. Elimination half-life about 2-3 hours.

Paracetamol is quickly soaked up from a GIT, is preferential in a small bowel, after a single dose the maximum concentration in blood is reached in 10-60 minutes, then gradually decreases. Paracetamol is widely distributed in fabrics and liquids, except for fatty tissue and cerebrospinal fluid. Linkng with proteins makes less than 10%. It is metabolized preferential in a liver by linkng with a glucuronide, sulfate and oxidation with participation of oxidases of a liver and P450 cytochrome. At adults the most part of paracetamol contacts glucuronic acid, at children - sulphuric acid. These conjugated metabolites have no metabolic activity, do not contact proteins of plasma. Also at overdose there can be an accumulation of a hydroxylated metabolite to toxic action - N-acetyl-r-benzokhinonimina which is formed in a liver and kidneys under the influence of the mixed oxidases and in usual conditions is detoxified by linkng with glutathione.

The elimination half-life makes 1-3 hours and can increase at cirrhosis. The renal clearance of paracetamol makes 5%. It is removed in not changed look (about 5%) and in the form of glyukuronidny and sulphatic conjugates.

Indications to use:

1. Inflammatory and degenerative diseases of joints and a backbone (including rhematoid and rheumatic arthritis, the osteoarthrosis ankylosing a spondylarthrosis), a joint syndrome at an exacerbation of gout, psoriasis arthritis, tendinites, a bursitis.
2. Radiculitis, neuralgia, mialgiya.
3. Head and a dentagra, a pain syndrome at injuries, burns, inflammatory diseases of ENT organs, bodies of a small pelvis (an adnexitis, альгодисменорея).

Medicine is intended for symptomatic therapy - reduction of pain and an inflammation at the time of use (does not influence progressing of a disease).

Route of administration and doses:

Adult IBUMET usually appoint on a half or the whole tablet 2-3 times a day after food. The maximum daily dose - 3 tablets, an interval between receptions should not be less than 8 hours. It is not necessary to accept drug more than 5 days as anesthetic. At preservation of symptoms within more than 3 days or an aggravation of symptoms it is necessary to consult at the doctor. For reduction of risk of emergence of side effects it is recommended to accept drug after food, in a minimal effective dose and minimum possible course.

At long (more than 5 days) reception control of peripheral blood and a functional condition of a liver and kidneys is necessary. See also subsections "Pregnancy and Lactation", "Children" and the section "Special instructions. Precautionary measures".

Features of use:

With care of IBUMET it is necessary to apply at patients at instructions in the anamnesis on the allergic reactions connected with reception of NPVS. See also subsections "Pregnancy and Lactation", "Children" and the sections "Route of Administration and Doses" and "Interaction with Other Medicines".

Elderly patients: the risk of development of side reactions, especially from a GIT (bleeding, perforation) at this category of patients is higher in this connection when using drug it is recommended to be careful.

Diseases of a respiratory organs: NPVS can cause a bronchospasm in the patients having bronchial asthma or allergic diseases.

Cardiovascular system: NPVS can cause a delay of liquid and hypostases in this connection the aggravation of symptoms of the patients having arterial hypertension and/or heart failure is possible. Data of some clinical trials allow to assume that long use of an ibuprofen, especially in high doses (2400 mg/day) can lead to small increase in risk of development of arterial thrombosis (for example, a myocardial infarction or a stroke). Use low (less than 1200 mg/day) ibuprofen doses, apparently, does not render such effect. At patients with uncontrollable hypertensia, heart failure, coronary heart disease, diseases of peripheral arteries or tserebrovasulyarny diseases it is necessary to use an ibuprofen only after careful assessment of potential risk. Also with care it is necessary to use drug at patients with risk factors of development of cardiovascular diseases (a lipidemia, a diabetes mellitus, smoking, etc.).

Digestive tract: NPVS can cause bleedings, ulcers and perforation of a GIT, including in the patients who did not have earlier instructions in the anamnesis on gastrointestinal diseases. The risk of emergence of these complications is higher at patients with the burdened anamnesis, use of high doses of NPVS, elderly patients in this connection in this group it is recommended to begin therapy with the minimum recommended dose. Also it is necessary to consider the possibility of use of such drugs as мизопростол or inhibitors of a proton pomp at this category of patients, and also the persons needing the accompanying use of low doses of salicylic acid or other drugs capable to increase risk of side effects from a GIT (corticosteroids, anticoagulants, inhibitors of the return serotonin reuptake and др). The patients having episodes of gastrointestinal bleedings in the anamnesis have to be informed on need to inform the attending physician on emergence of any unusual symptoms from a GIT, especially at the initial stage of therapy. At emergence of symptoms of a gastrointestinal ulcer or bleeding administration of drug should be stopped immediately. NPVS should be applied with care at patients with gastrointestinal diseases in the anamnesis (ulcer colitis, a disease Krone) in connection with risk of an aggravation of symptoms.

General diseases: at patients with a system lupus erythematosus and other diseases of the NPVS connecting fabric can increase risk of development of aseptic meningitis.

Dermatological disturbances: very seldom when using NPVS heavy reactions from integuments were noted, including with a fatal outcome (exfoliative dermatitis, Stephen-Johnson's syndrome, a toxic epidermal necrolysis). The risk of emergence of these disturbances is higher within the first month of reception of NPVS. In this regard, it is necessary to stop administration of drug in case of any enanthesis and mucous, and also any other signs of hypersensitivity.

Disturbances of functions of kidneys: the risk of development of complications is higher at patients at whom production of prostaglandins plays a compensatory role for maintenance of a renal blood-groove (a condition of dehydration, disturbance of functions of a liver and kidneys, heart failure, the expressed atherosclerosis, reception of diuretics, APF inhibitors, elderly patients).

In this regard at purpose of drug the following precautionary measures are recommended to patients from risk group:
• monitoring of functions of a liver and kidneys at purpose of drug to elderly patients, patients with arterial hypertension and a diabetes mellitus within the first week of reception at purpose of drug more than 1 week;
• blood serum creatinine control 48-72 hours later after the beginning of administration of drug at patients with chronic heart failure and a chronic renal failure at a glomerular filtration rate less than 60 ml/min.

Also with care drug should be used at patients with the broken function of a liver or kidneys, directly after carrying out surgical interventions, at instructions in the anamnesis on the allergic reactions connected with reception of NPVS, removal of polyps of a mucous membrane of a nasal cavity. At long (more than 5 days) administration of drug control of peripheral blood and a functional condition of a liver and kidneys is necessary. At emergence of signs of disturbance of functions of kidneys (the back pain, reduction of daily volume of urine, hypostases) or a liver (pain in hypochondrium, jaundice, urine discoloration) administration of drug should stop and see the attending physician immediately. In order to avoid a possible hepatotoxic action of drug it is recommended to abstain from alcohol intake during treatment.

Alcohol. In order to avoid a possible hepatotoxic action of IBUMETA it is recommended to abstain from alcohol intake during treatment.

Influence on ability of control of vehicles and other difficult mechanisms. When using ИБУМЕТа the patient is recommended to abstain from occupations potentially dangerous types of activity, requiring special attention and speed of psychomotor reactions.

Side effects:

Side below-mentioned reactions are classified by bodies, systems and frequency of emergence, and the most widespread are specified the first. Classification of frequency of emergence of side reactions: very often (> 1/10); often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), it is rare (> 1/10000 and <1/1000), is very rare (<1/10000, including single messages). For each frequency in group side reactions are located in ascending order of gravity.

System of blood and lymphatic system: very seldom - disturbance of a hemogenesis (an agranulocytosis, anemia, aplastic anemia, hemolitic anemia, a leukopenia, a neutropenia, a pancytopenia, thrombocytopenia).

Immune system: very seldom - hypersensitivity reactions (nonspecific allergic reactions and an anaphylaxis).

Mental disorders: very seldom - confusion of consciousness, a depression, a hallucination.

Nervous system: infrequently - a headache and dizziness; very seldom - paresthesia, an optic neuritis, drowsiness; aseptic meningitis.

Organ of sight: very seldom - vision disorders.

Acoustic organ and vestibular mechanism: very seldom - a sonitus and dizziness. Cardiovascular system: very seldom - hypostases, hypertensia, heart failure.

Respiratory system and bodies of a thorax: very seldom - asthma, weighting of a course of asthma, a bronchospasm, диспноэ.

Alimentary system: often - abdominal pains, diarrhea, dyspepsia, nausea, discomfort in a stomach,  vomiting;  infrequently  -  the meteorism,  a lock,    stomach ulcer,  perforation  or gastrointestinal bleeding with melena symptoms, a hematemesis, sometimes fatal, is more often at elderly, a stomacace, an exacerbation of ulcer colitis and disease Krone, gastritis, pancreatitis.

Gepatobiliarny system: very seldom - an abnormal liver function, hepatitis, jaundice, an acute liver failure, a liver necrosis, injury of a liver (at paracetamol overdose).

Skin and hypodermic fatty tissue: infrequently - rash of various types, including an itch and urticaria, a Quincke's edema and a face edema. Very seldom - a hyperhidrosis, a purpura, a photosensitization, exfoliative dermatitis, a multiformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis.

Kidneys and urinary system: very seldom - nephrotoxicity in various forms, including intersticial nephrite, a nephrotic syndrome, an acute and chronic renal failure.

General disturbances: very seldom - fatigue and an indisposition.

Researches: often - increase in ALT and gamma глутамилтрансферазы, disturbance of tests of function of a liver, increase in creatinine and urea; infrequently - increase in ACT, ShchF and KFK, decrease in hemoglobin, increase in quantity of thrombocytes.

First signs of disturbance of a hemogenesis: fever, pharyngalgia, superficial ulcers of a mouth, grippopodobny symptoms, exhaustion, inexplicable bleedings and bruises, nasal bleeding.

Reactions of hypersensitivity were shown by a face edema, language and a throat, диспноэ, tachycardia, hypotension, a Quincke's edema, an acute anaphylaxis.

The isolated cases of aseptic meningitis at patients with autoimmune disorders (such as system lupus erythematosus and general diseases of connecting fabric) at treatment by an ibuprofen which were followed by symptoms are registered: stiff neck, headache, nausea, vomiting, fever or disorientation.

Interaction with other medicines:

This drug (as well as any other drugs containing paracetamol) is contraindicated in combination with other drugs containing paracetamol in connection with the increased risk of serious side effects (see the section "Side effect").

This drug (as well as any other drugs containing an ibuprofen and NPVS), is contraindicated in combination with:
• acetylsalicylic acid, except low doses of acetylsalicylic acid (it is not higher than 75 mg in day) as it can increase risk of side reactions (see the section "Side effect");
• other NPVS, including the selection inhibitors of cyclooxygenase 2 types since increase in risk of side effects is possible (see the section "Side effect").
This drug (as well as any other drugs containing paracetamol), it is necessary to use with care in combination with:
• chloramphenicol: concentration in chloramphenicol plasma increases;
• holestiraminy: paracetamol absorption speed decreases. If the maximum anesthesia is required, холестирамин it is necessary to accept not earlier than in an hour after reception ИБУМЕТа.
• Metoclopramidum and domperidony: paracetamol absorption increases. It is necessary to avoid joint reception of these drugs.
• warfarin: the effect of warfarin and other coumarins can amplify at prolonged regular use of paracetamol with increase in risk of bleeding. Single use has no significant effect.

This drug (as well as any other drugs containing an ibuprofen and NPVS) should be applied with care in combination with:
• anticoagulants: NPVS can strengthen effect of anticoagulants, for example warfarin.
• anti-hypertensive: NPVS can reduce effects of these drugs.
• dezagregant and selective serotonin reuptake inhibitors (SSRI): the risk of gastrointestinal bleedings increases.
• acetylsalicylic acid: experimental data demonstrate that the ibuprofen can inhibit action of low doses of acetylsalicylic acid on aggregation of thrombocytes at simultaneous use. Nevertheless, limitation yielded and uncertainty of extrapolation of results of a research in conditions of clinical practice results in impossibility to draw a conclusion for regular use of an ibuprofen. The clinical importance of this effect for single use of drug is considered improbable.
• cardiac glycosides: NPVS can cause a decompensation of heart failure, decrease in SKF and increase in level in plasma of cardiac glycosides.
• cyclosporine: the risk of nephrotoxicity increases.
• corticosteroids: the risk of gastrointestinal bleeding or ulcer increases.
• diuretics: the diuretic effect decreases. Diuretics can increase risk of nephrotoxicity of NPVS.
• lithium: lithium elimination decreases.
• methotrexate: elimination of a methotrexate decreases.
• mifepristone: NPVS should not be used within 8-12 days after mifepristone reception as NPVS can reduce effect of mifepristone.
• antibiotics of group of a hinolon: researches on animals showed that NPVS can increase risk of the spasms connected using antibiotics, derivatives of a hinolon. At the patients accepting NPVS and hinolona the risk of development of spasms can increase.
• takrolimusy: increase in risk of nephrotoxicity is possible.
• zidovudine: the risk of hematologic toxicity increases. Cases of increase in risk of a hemarthrosis and a hematoma at HIV (+) the patients with hemophilia receiving at the same time treatment by a zidovudine and an ibuprofen are registered.

The risk of development of undesirable reactions from kidneys increases at joint purpose of an ibuprofen with the drugs exerting impact on renin-angiotensin-aldosteronovuyu system.

Contraindications:

1. The increased individual sensitivity to drug components.
2. Existence in the anamnesis of reactions of hypersensitivity (a bronchospasm, urticaria, asthma, rhinitis, rash and other allergic symptoms) at use of acetylsalicylic acid or other NPVS.
3. Acute stomach ulcer or intestines; gastrointestinal bleeding or perforation, and also patients with these diseases in the anamnesis including connected with reception of non-steroidal anti-inflammatory drugs (NPVS).
4. Diseases of system of blood, defects of a coagulative hemostasis.
5. Damage of an optic nerve.
6. A renal failure at reduction in the rate of glomerular filtering less than 30 ml/min.
7. Diseases of a liver or kidneys.
8. The expressed heart failure (the III-IV class on NYHA).
9. Combined use with other NPVS, including TsOG-2 inhibitors and acetylsalicylic acid more than 75 mg/days - increases risk of development of side reactions.
10. Combined use about paracetamol - the containing drugs - increases risk of development of side reactions.
11. Genetically caused absence glyukozo-6-fosfatdegidrogenazy;
12. Pregnancy.
13. Lactation.
14. Age up to 18 years.

Pregnancy and lactation. At pregnancy and during breastfeeding (lactation) it is not recommended to apply IBUMET. In need of inclusion in time of a lactation it is necessary to resolve an issue of transfer into artificial feeding. IBUMET can exert impact on female fertility in this connection its reception is not recommended to the patients who are going to become pregnant. At the women having problems with conception of IBUMET it has to be cancelled.

Children. It is not recommended for use for children aged up to 18 years.

Overdose:

Paracetamol. Reception of 10 g of paracetamol (it is equivalent to 35 tablets) or more can lead at adults to damage of a liver. Intake of 5 g of paracetamol (it is equivalent to 16 tablets) or more can lead to injury of a liver, in the presence at the patient of one or more risk factors:
• Prolonged treatment by carbamazepine, phenobarbital, Phenytoinum, Primidonum, rifampicin, a St. John's Wort or other drugs which induce liver enzymes.
• Regular alcohol intake over safe doses.
• Deficit of glutathione that can be observed at frustration of a feeding behavior,
• Mucoviscidosis, HIV infection, starvation, cachexia.

Symptoms: Symptoms of overdose of paracetamol in the first 24 hours include pallor, nausea, vomiting, anorexia and an abdominal pain. Injury of a liver can become obvious during from 12 to 48 hours after intake when functional indicators of a liver change. Disturbance of metabolism of glucose and a metabolic acidosis can develop. At a serious poisoning the liver failure can progress in encephalopathy, bleeding, a hypoglycemia, wet brain and to lead to death. The acute renal failure with an acute necrosis of tubules which is shown a back pain, a hamaturia and a proteinuria can develop even in the absence of severe damage of a liver. Also disturbances of a heart rhythm and development of pancreatitis are registered.

Treatment: The overdose of paracetamol demands rendering immediate medical care even in the absence of symptoms during the early period. The overdose can be shown only by nausea or vomiting and not to correspond to weight of poisoning or risk of damage of bodies. At treatment it is necessary to be guided by the local established principles of therapy. Reception of absorbent carbon is obligatory within 1 hour after paracetamol reception inside. Plasma concentration of paracetamol need to be estimated in 4 hours or later after administration of drug (more earlier definition of concentration is unreliable).

Treatment by means of N-Acetylcysteinum can be used within 24 hours after paracetamol reception, however, the maximum protective effect develops at reception of N-Acetylcysteinum within 8 hours after paracetamol reception. Efficiency of antidotal action after this time sharply decreases. In the absence of vomiting methionine use orally is possible as an alternative at impossibility of introduction of Acetylcysteinum. Maintaining patients with severe damage of a liver in terms more than 24 watch after reception of paracetamol has to be carried out according to local practice.

Ibuprofen. Symptoms: At most of the patients who accepted clinically significant quantity of NPVS nausea, vomiting, pain develop in epigastriums, is more rare — a diarrhea. Perhaps also emergence of a sonitus, headache and gastrointestinal bleeding. In more hard cases, development of toxicity in the relation of the central nervous system, the shown drowsiness, sometimes excitement and a disorientation or a coma is possible. Sometimes spasms develop. In hard cases development of a metabolic acidosis, the lengthening of prothrombin time / MNO which is possibly connected with influence on the circulating blood-coagulation factors is possible. The acute renal failure and damage of a liver can arise, especially in the presence of dehydration. At the patients having bronchial asthma development of an aggravation is possible.

Treatment: Treatment has to be symptomatic and supporting and includes maintenance of passability of respiratory tracts and monitoring cordial and the vital functions before stabilization of a state. Peroral administration of absorbent carbon within 1 hour after reception of potentially toxic dose is recommended.

Storage conditions:

To store in the place protected from light at a temperature not above 25 °C in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

Coated tablets of 325 mg / 400 mg in a blister strip packaging No. 10×1, No. 10×2 and in banks No. 10, No. 20 in packaging No. 1. Together with a leaf insert blister strip packagings (one or two) or one bank are located in a pack from a cardboard.