Next tablet p / o, No. 10

• Headache (including migraine);

• toothache;

• algodismenorrhea (painful menstruation);

• neuralgia;

• myalgia;

• back pain;

• joint pain, pain syndrome in inflammatory and degenerative diseases of the musculoskeletal system;

• pain with bruises, sprains, dislocations, fractures;

• post-traumatic and postoperative pain syndrome;

• feverish conditions (including flu and colds).

The drug is used as a means of symptomatic therapy for febrile conditions, headache, muscle pain in acute respiratory diseases and influenza. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of application, does not affect the progression of the disease.

Inside, after eating.
1 tablet 3 times a day. The maximum daily dose is 3 tablets.
The duration of treatment is no more than 3 days as an antipyretic agent and no more than 5 days as an anesthetic.
Continuation of treatment with the drug is possible only after consulting a doctor.

Composition per tablet:
Active ingredients: ibuprofen - 400 mg, paracetamol - 200 mg.
Excipients:
core: calcium hydrogen phosphate - 80.0 mg, microcrystalline cellulose - 64.5 mg, croscarmellose sodium - 24.3 mg, hyprolose (hydroxypropyl cellulose) - 19.3 mg, talc - 12.1 mg, magnesium stearate - 7 , 3 mg, colloidal silicon dioxide (aerosil) - 2.5 mg;

• Hypersensitivity to the components of the drug, including other non-steroidal anti-inflammatory drugs (NSAIDs);

• erosive and ulcerative diseases of the gastrointestinal tract (in the acute phase), gastrointestinal bleeding;

• progressive kidney disease;

• severe renal failure (creatinine clearance (CC) less than 30 ml / min.);

• severe liver failure or active liver disease;

• bleeding disorders (hemophilia, prolonged bleeding time, bleeding tendency, hemorrhagic diathesis);

• cerebrovascular or other bleeding;

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, incl. history;

• chronic heart failure (NYHA functional class III-IV)

• condition after coronary artery bypass grafting;

• confirmed hyperkalemia;

• deficiency of glucose-6-phosphate dehydrogenase;

• pregnancy (III trimester);

• breastfeeding period;

• children under 18 years of age.

Precautions:
Chronic heart failure; viral hepatitis, alcoholic liver damage, hepatic and / or renal failure of moderate and mild severity, benign hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome), cirrhosis of the liver with portal hypertension, nephrotic syndrome; diabetes mellitus, peripheral arterial disease, gastric ulcer and duodenal ulcer (in history); gastritis, enteritis, colitis; bronchial asthma, bronchospasm; elderly age; pregnancy (I and II trimesters - use is possible only as directed by a doctor in cases where the potential benefit outweighs the possible risk).

Application during pregnancy and during breastfeeding:
If necessary, use the drug in the I and II trimester of pregnancy, you should be careful? - use is possible only as directed by a doctor in cases where the potential benefit outweighs the possible risk. The use of the drug in the III trimester of pregnancy is contraindicated.
During breastfeeding, if necessary, use the drug should stop breastfeeding.

Pharmacotherapeutic group:
combined analgesic agent (NSAIDs + non-narcotic analgesic agent)
ATC code: M01AE51
Pharmacological properties:
Pharmacodynamics:
Combined drug, has analgesic, anti-inflammatory and antipyretic effects.
Paracetamol is a non-narcotic analgesic that has antipyretic and analgesic effects due to the blockade of cyclooxygenase in the central nervous system and the effect on the centers of pain and thermoregulation.
Ibuprofen is a non-steroidal anti-inflammatory agent that has analgesic, anti-inflammatory and antipyretic effects associated with non-selective suppression of the activity of cyclooxygenase, which regulates the synthesis of prostaglandins.
The components of the drug affect both the central and peripheral mechanisms of pain syndrome formation. The targeted, complementary action of the two components has a quick therapeutic effect and a pronounced analgesic effect.

Pharmacokinetics:
Paracetamol
Absorption - high, the maximum concentration (Cmax) is 5 - 20 ?g / ml, the time to reach the maximum concentration (Tmax) - 0.5 - 2 hours; connection with plasma proteins - 15%. Penetrates the blood-brain barrier.
It is metabolized in the liver by glucuronidation, sulfation and hydroxylation, with the formation of both active and inactive metabolites. The isoenzyme of the cytochrome P450 CYP2E1 system takes part in the metabolism of paracetamol.
The half-life (T1 / 2) is 1 to 4 hours. It is mainly excreted by the kidneys in the form of metabolites - glucuronides and sulfates, 3% - unchanged.
Ibuprofen
Well absorbed from the gastrointestinal tract. The time to reach the maximum concentration (Tmax) when taken on an empty stomach is 45 minutes, when taken after eating - 1.5 - 2.5 hours. The connection with plasma proteins is 90%. The concentration of the drug in the synovial fluid exceeds the content in the plasma.
Undergoes presystemic and post-systemic metabolism in the liver. The isoenzyme of the cytochrome P450 CYP2C9 system is involved in the metabolism of ibuprofen.
It has a two-phase kinetics of excretion, T1 / 2 is 2 - 2.5 hours. It is excreted by the kidneys (not more than 1% unchanged) and, to a lesser extent, with bile.

Side effects:
Side effects are listed with an indication of the frequency of occurrence in accordance with the WHO classification: very often (with a frequency of more than 1/10), often (with a frequency of at least 1/100, but less than 1/10), infrequently (with a frequency of at least 1/1000, but less than 1/100), rarely (with a frequency of not less than 1/10000, but less than 1/1000), very rarely (with a frequency of less than 1/10000, including single messages), the frequency is unknown (cannot be set according to available data).
From the nervous system: infrequently - headache, dizziness, sleep disturbances, anxiety, hallucinations, confusion, rarely aseptic meningitis, very rarely - depression.
From the side of the cardiovascular system: often - peripheral edema, very rarely - tachycardia, increased blood pressure, heart failure.
From the respiratory system: very rarely - shortness of breath, bronchospasm.
From the gastrointestinal tract: often - abdominal pain, nausea, vomiting, heartburn, loss of appetite, diarrhea, flatulence, erosive and ulcerative lesions of the gastrointestinal tract; infrequently - constipation, ulceration of the gingival mucosa, aphthous stomatitis, pancreatitis, gastrointestinal bleeding. Sense organs: very rarely - hearing impairment, ringing or tinnitus, visual impairment, blurred vision or diplopia, frequency unknown - dry and irritated eyes.
From the urinary system: very rarely - acute renal failure, nephrotic syndrome, cystitis; frequency unknown - polyuria. Allergic reactions: infrequently - skin rash, pruritus, allergic rhinitis, angioedema; very rarely - exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).
From the side of hematopoiesis: very rarely - anemia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis, leukopenia, eosinophilia.
On the part of the skin and subcutaneous tissues: often - hyperhidrosis.
With prolonged use in high doses - hepatotoxic and nephrotoxic effects (hepatitis, interstitial nephritis and papillary necrosis); hemolytic anemia, aplastic anemia, methemoglobinemia, pancytopenia.
If you experience side effects, you should consult a doctor.

Overdose:
Symptoms: abdominal pain, nausea, vomiting, agitation or lethargy, drowsiness, confusion, tachycardia, arrhythmia, acute renal failure, metabolic acidosis, increased urination, pyrexia, headache, tremors or muscle twitching; an increase in the activity of 'hepatic' transaminases, an increase in prothrombin time. If you suspect an overdose, you should immediately seek medical help.
Treatment: gastric lavage, followed by the appointment of activated carbon; alkaline drinking, forced diuresis, symptomatic therapy, the introduction of donors of sulfhydryl groups (acetylcysteine) and precursors of glutathione synthesis (methionine).

Interaction with other drugs:
Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which makes it possible to develop severe intoxication in case of overdose.
Inhibitors of microsomal oxidation (including cimetidine) reduce the risk of hepatotoxic effects.
Myelotoxic drugs increase the manifestations of the drug's hematotoxicity.
Cyclosporine and gold preparations increase the nephrotoxicity of the drug.
The combination of ibuprofen with ethanol, glucocorticosteroids increases the risk of erosive and ulcerative lesions of the gastrointestinal tract.
The simultaneous use of paracetamol with ethanol increases the risk of acute pancreatitis.
Paracetamol and ibuprofen increase the effect of indirect anticoagulants and reduce the effectiveness of uricosuric drugs.
Long-term use of barbiturates reduces the effectiveness of paracetamol.
Diflunisal increases the plasma concentration of paracetamol by 50%, which increases the risk of developing hepatotoxicity.
Ibuprofen reduces the hypotensive activity of vasodilators, natriuretic and diuretic - furosemide and hydrochlorothiazide.
Antacids and cholestyramine reduce the absorption of ibuprofen.
Caffeine increases the analgesic effect of ibuprofen.
Ibuprofen enhances the effect of oral hypoglycemic agents and insulin.
Ibuprofen increases the concentration of digoxin, lithium and methotrexate in the blood.
When administered simultaneously with acetylsalicylic acid, ibuprofen reduces its anti-inflammatory and antiplatelet effect.
Cefamandol, cephaperazone, cefotetan, valproic acid, plicamycin increase the incidence of hypoprothrombinemia.

Special instructions:
Simultaneous use of the drug with other drugs containing paracetamol and / or non-steroidal anti-inflammatory drugs should be avoided.
With simultaneous use with indirect anticoagulants, it is necessary to control hemostasis indicators.
When using the drug for more than 5 - 7 days, the peripheral blood parameters and the functional state of the liver should be monitored.
Paracetamol distorts the results of laboratory tests of the content of glucose and uric acid in the blood plasma.
When symptoms of NSAID gastropathy appear (nausea, vomiting, abdominal pain, heartburn, loss of appetite, flatulence, discomfort in the epigastric region), careful monitoring is shown, including esophagogastroduodenoscopy, blood test with determination of hemoglobin and hematocrit, fecal occult blood test.
If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.
During the period of treatment, it is not recommended to take alcoholic beverages.

Influence on the ability to drive vehicles, mechanisms:
While taking the drug, patients should refrain from all types of activities that require increased attention, quick mental and motor reactions.