Nurofen Intensive pain relief pills 200mg+500mg, 12pcs

Composition

One film-coated tablet contains:

active ingredients:

ibuprofen 200 mg and paracetamol 500 mg;

excipients:

croscarmellose sodium 30 mg,

microcrystalline cellulose 120 mg,

colloidal silicon dioxide 3 mg,

magnesium stearate 5 mg,

stearic acid 4 mg.

Shell composition:

white film cover 13 mg (polyvinyl alcohol 40%, titanium dioxide 25%, macrogol 20,2%, talc 14,8%), membranous sheath, pearl effect 7 mg (polyvinyl alcohol 47%, talc 27%, macrogol of 13.3%, pearlescent pigment based on mica 10% (titanium dioxide 28%, potassium aluminosilicate (E 555) 72%), Polysorbate 2,7%).

Pharmacological action

A combined drug, the action of which is due to the components included in its composition. It has a directed action against pain (analgesic), antipyretic and anti-inflammatory effect. Ibuprofen and paracetamol differ in their mechanism and place of action. As a result of their mutually reinforcing action, a more pronounced decrease in pain sensitivity and an increase in antipyretic effect are achieved than separately.

Ibuprofen-a propionic acid derivative from the group of nonsteroidal anti-inflammatory drugs (NSAIDs), has anti-inflammatory, decongestant, analgesic and antipyretic effects. The mechanism of action of ibuprofen is due to the inhibition of prostaglandin synthesis-mediators of pain, inflammation, and hyperthermia-by selectively inhibiting the activity of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The analgesic effect of ibuprofen is provided by its inhibitory effect at the peripheral level. The antipyretic effect of ibuprofen is associated with central inhibition of prostaglandin synthesis in the hypothalamus. Ibuprofen inhibits the migration of white blood cells to the site of inflammation. In addition, ibuprofen reversibly suppresses platelet aggregation.

Paracetamol is an analgesic non-narcotic drug that has analgesic, antipyretic and weak anti-inflammatory effects. It indiscriminately blocks COX-2, mainly in the central nervous system. Paracetamol can also stimulate the activity of the descending serotonin pathways, which leads to stopping the transmission of pain impulses in the spinal cord. At the peripheral level, paracetamol has a weak effect on COX-1 and COX-2. The drug has a faster therapeutic effect and a more pronounced analgesic effect than ibuprofen and paracetamol separately. After taking one tablet of the drug, the analgesic effect is observed on average in 15 minutes, a clinically significant analgesic effect is achieved in 40 minutes and persists for 8 hours. After taking two tablets of the drug, the analgesic effect is observed in an average of 18 minutes, a clinically significant analgesic effect is achieved in 45 minutes and persists for 9 hours.

Pharmacokinetics

of Ibuprofen: absorption is high, rapidly and almost completely absorbed from the gastrointestinal tract (GIT). Binding to plasma proteins is 90%. Slowly penetrates the joint cavity, lingers in the synovial fluid, creating higher concentrations in it than in the blood plasma. It is detected in the blood plasma 5 minutes after taking the drug on an empty stomach, the maximum concentration (cmax) in the blood plasma is reached in 1-2 hours. Concomitant use with food may reduce the concentration of ibuprofen in the blood plasma and increase the time to reach the maximum concentration (tmax). The degree of absorption of ibuprofen does not depend on food intake. It is metabolized in the liver. After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into the active S-form. The elimination half-life (T_1/2) is 2 hours. It is excreted by the kidneys mainly in the form of metabolites (no more than 1% unchanged) and, to a lesser extent, with bile in the form of metabolites. There were no significant differences in the pharmacokinetic profile of ibuprofen in older people compared to younger people. There is evidence that ibuprofen has been detected in breast milk in low concentrations.

Paracetamol: high absorption, rapidly absorbed from the gastrointestinal tract. The association with plasma proteins is insignificant when taken in therapeutic doses; slightly increases with overdose. It is detected in the blood plasma 5 minutes after taking the drug on an empty stomach, with_max in the blood plasma reached in 30-40 minutes after ingestion. Concomitant use with food may reduce the concentration of paracetamol in the blood plasma and increase T_max. The degree of absorption of paracetamol does not depend on food intake. It is metabolized in the liver and is mainly excreted in the form of glucuronides and sulfated conjugates with the formation of glutathione conjugates (about 10%). It is excreted by the kidneys.

In the form of unchanged paracetamol, less than 5% of the dose is excreted. The elimination half-life (T_1/2) is 3 hours. The hydroxylated metabolite N-acetyl-p-benzoquinonimine, which is formed in small amounts in the liver and kidneys under the influence of mixed oxidases and is usually detoxified by binding to glutathione, can accumulate with an overdose of paracetamol and cause liver tissue damage. There were no significant differences in the pharmacokinetic profile of paracetamol in older people compared to younger people. The bioavailability and pharmacokinetic parameters of ibuprofen and paracetamol taken as part of this combination drug do not change with both single and repeated use.

Indications

Back pain, joint pain, muscle and rheumatic pains, neuralgia, headache, migraines, toothache, painful menstruation, sore throat, fever, cold and flu symptoms.

The drug is especially indicated for the symptomatic treatment of pain requiring a more pronounced analgesic effect than ibuprofen or paracetamol alone.

Contraindications

* Hypersensitivity to ibuprofen, paracetamol or other components of the drug.

* Concomitant use of other medications containing paracetamol.

* Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis).

·  Erosive and ulcerative diseases of the gastrointestinal tract (including peptic ulcer of the stomach and duodenum, Crohn’s disease, ulcerative colitis) active or history of ulcerative bleeding (two or more confirmed episodes of peptic ulcer disease or ulcerative bleeding).

* A history of bleeding or perforation of a gastrointestinal ulcer caused by NSAID use.

·  Severe heart failure (NYHA Class IV-New York Heart Association Classification).

·  Severe liver failure or active liver disease.

·  Severe renal insufficiency (creatinine clearance

* Decompensated heart failure; the period after coronary artery bypass grafting.

* Cerebrovascular or other bleeding.

* Pregnancy (third trimester).

·  Under 18 years of age.

· Hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diathesis.

* Genetic absence of glucose-6-phosphate dehydrogenase.

With caution

If you have the conditions described in this section, you should consult a doctor before using the drug.

Concomitant use of other NSAIDs, a history of a single episode of gastric ulcer or ulcerative bleeding of the gastrointestinal tract; gastritis, enteritis, colitis, Helicobacter pylori infection, ulcerative colitis; bronchial asthma or allergic diseases in the acute stage or in the anamnesis – possible development of bronchospasm; systemic lupus erythematosus or mixed connective tissue disease (Sharp’s syndrome) – increased risk of aseptic meningitis; chickenpox smallpox; renal failure, including dehydration (creatinine clearance less than 30-60 ml/min); nephrotic syndrome; liver failure; frequent alcohol consumption; arterial hypertension and/or heart failure, cerebrovascular diseases; concomitant use of medications that may increase the risk of ulceration or bleeding, in particular, oral glucocorticosteroids (including prednisone), anticoagulants (including warfarin) serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline) or antiplatelet agents (including acetylsalicylic acid, clopidogrel); pregnancy I-II trimester, breast-feeding period; elderly age; cirrhosis of the liver with portal hypertension, hyperbilirubinemia; blood diseases of unknown etiology (leukopenia and anemia), hyperlipidemia, diabetes mellitus diabetes, peripheral artery diseases.

Side effects

The risk of side effects can be minimized by taking the drug in a short course, at the minimum effective dose necessary to eliminate symptoms.

In the elderly, there is an increased frequency of adverse reactions associated with NSAID use, especially gastrointestinal bleeding and perforation, in some cases with a fatal outcome.

Side effects are mostly dose-dependent. In particular, the risk of gastrointestinal bleeding depends on the dose range and duration of treatment.

The following adverse reactions were observed with short-term use of ibuprofen in doses of 1200 mg / day, paracetamol in doses of 3000 mg / day (6 tablets). In the treatment of chronic conditions and with prolonged use, other side effects may occur.

The frequency of adverse reactions is estimated based on the following criteria: very frequent (≥ 1/10), frequent (≥ 1/100 to < 1/10), infrequent (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to

Disorders of the blood and lymphatic system:

Very rare: hematopoietic disorders (anemia, leukopenia, aplastic anemia, hemolytic anemia, thrombocytopenia, pancytopenia, agranulocytosis). The first symptoms of such disorders are fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, severe weakness, nosebleeds and subcutaneous hemorrhages, bleeding and bruising of unknown origin.

Immune system disorders:

Infrequent: hypersensitivity reactions-non-specific allergic reactions and anaphylactic reactions, skin reactions (pruritus, urticaria), allergic rhinitis, eosinophilia.

Very rare: severe hypersensitivity reactions, including swelling of the face, tongue and larynx, shortness of breath, tachycardia, low blood pressure (anaphylaxis, angioedema or severe anaphylactic shock).

Nervous system disorders:

Infrequent: headache.

Very rare: aseptic meningitis. In patients with autoimmune disorders, such as systemic lupus erythematosus, mixed connective tissue disease, during treatment with ibuprofen, isolated cases of symptoms of aseptic meningitis were observed: rigidity of the occipital muscles, headache, nausea, vomiting, fever and disorientation, confusion, depression, hallucinations.

Disorders of the cardiovascular system:

Frequency unknown: heart failure, peripheral edema, long-term use increases the risk of thrombotic complications (for example, myocardial infarction), increased blood pressure.

Respiratory, thoracic and mediastinal disorders:

Frequency unknown: bronchial asthma, including its exacerbation, bronchospasm, shortness of breath.

Disorders of the gastrointestinal tract:

Infrequent: abdominal pain, nausea, dyspepsia (including heartburn, bloating).

Rare: diarrhea, flatulence, constipation, vomiting.

Very rare: peptic ulcer, perforation or gastrointestinal bleeding, melena, bloody vomiting, in some cases fatal, especially in elderly patients, ulcerative stomatitis, gastritis.

Frequency unknown: exacerbation of colitis and Crohn’s disease.

Liver and biliary tract disorders:

Very rare: impaired liver function (especially with prolonged use), increased activity of “liver” transaminases, hepatitis and jaundice.

Kidney and urinary tract disorders:

Very rare: acute renal failure (compensated and decompensated), especially with prolonged use, in combination with increased urea concentration in blood plasma and the appearance of edema, papillary necrosis, hematuria and proteinuria, nephritic syndrome, nephrotic syndrome, interstitial nephritis, cystitis.

Skin and subcutaneous tissue disorders:

Frequent: hyperhidrosis (increased sweating).

Infrequent ones: Skin rash and acute generalized exanthematous pustulosis.

Very rare: Exfoliative and bullous dermatoses, including toxic epidermal necrolysis (Lyell’s syndrome), Stevens-Johnson syndrome, erythema multiforme.

Laboratory parameters:

Frequent: increased levels of alanine aminotransferase, gamma-glutamyltranspeptidase, increased plasma concentrations of creatinine and urea, liver function indicators beyond normal.

Infrequent: increased levels of aspartate aminotransferase, alkaline phosphatase, creatinine phosphokinase, decreased hemoglobin, increased platelet levels.

If side effects occur, you should stop taking the drug and consult a doctor.

Interaction

Paracetamol

· Antiemetics: reduced absorption rate of paracetamol when used concomitantly with metoclopramide or domperidone.

·  Anticoagulants: long-term use of drugs containing paracetamol may increase the effect of anticoagulants, in particular warfarin, and increase the risk of bleeding.

* Colestyramine: reduced absorption rate of paracetamol when co-administered with colestyramine.

Paracetamol falsely increases the performance of the continuous blood sugar monitoring system (CGM) compared to the performance of a glucose meter. This applies to patients using CGM devices that contain or do not contain an automatic insulin pump, i. e. those with type I diabetes.

Caution should be exercised when concomitantly using paracetamol and flucloxacillin, which is associated with an increased risk of developing metabolic acidosis with a high anionic difference, especially in patients with a risk factor for developing glutathione deficiency (including patients with severe renal insufficiency, sepsis, malnutrition and chronic alcoholism). Careful monitoring is recommended to detect signs of acid-base imbalance, namely metabolic acidosis with a high anionic difference, including the determination of 5-oxoproline in the urine.

Ibuprofen

Concomitant use of ibuprofen with the following medications should be avoided:

* Acetylsalicylic acid: with the exception of low doses of acetylsalicylic acid (no more than 75 mg per day) prescribed by a doctor, since co-use may increase the risk of side effects. When used concomitantly, ibuprofen reduces the anti-inflammatory and antiplatelet effects of acetylsalicylic acid (it is possible to increase the incidence of acute coronary insufficiency in patients receiving small doses of acetylsalicylic acid as an antiplatelet agent after starting ibuprofen).

* Other NSAIDs, in particular selective COX-2 inhibitors: concomitant use of two or more NSAID drugs should be avoided due to the possible increased risk of side effects.

Use with caution at the same time as the following medications::

·  Anticoagulants and thrombolytics: NSAIDs may increase the effect of anticoagulants, particularly warfarin and thrombolytics.

·  Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of drugs in these groups. In some patients with impaired renal function (for example, in patients with dehydration or in elderly patients with impaired renal function), the simultaneous use of ACE inhibitors or angiotensin II antagonists and cyclooxygenase inhibitors may lead to deterioration of renal function, including the development of acute renal failure (usually reversible). These interactions should be considered in patients taking coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. In this regard, the combined use of the above drugs should be prescribed with caution, especially in the elderly. Patients should be prevented from becoming dehydrated, and renal function monitoring should be considered after starting this combination treatment and periodically thereafter. Diuretics and ACE inhibitors may increase the nephrotoxicity of NSAIDs.

* Glucocorticosteroids: increased risk of gastrointestinal ulcers and gastrointestinal bleeding.

·  Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.

* Cardiac glycosides: concomitant use of NSAIDs and cardiac glycosides may worsen heart failure, reduce glomerular filtration rate, and increase the concentration of cardiac glycosides in blood plasma.

* Lithium preparations: there is evidence of the likelihood of an increase in the concentration of lithium in the blood plasma with the use of NSAIDs.

·  Methotrexate: There is evidence for the likelihood of an increase in the concentration of methotrexate in blood plasma against the background of NSAID use.

* Cyclosporine: increased risk of nephrotoxicity with concomitant NSAIDs and cyclosporine.

* Mifepristone: NSAIDs should be started no earlier than 8-12 days after taking mifepristone, as NSAIDs may reduce the effectiveness of mifepristone.

·  Tacrolimus: concomitant use of NSAIDs and tacrolimus may increase the risk of nephrotoxicity.

* Zidovudine: concomitant use of NSAIDs and zidovudine may lead to increased hematotoxicity. There is evidence of an increased risk of hemarthrosis and hematomas in HIV-positive patients with hemophilia treated with zidovudine and ibuprofen.

·  Quinolone-type antibiotics: patients receiving concomitant treatment with NSAIDs and quinolone antibiotics may have an increased risk of seizures.

* Myelotoxic drugs increase the manifestations of hematotoxicity of the drug.

* Caffeine enhances the analgesic effect.

How to take, course of use and dosage

Please read the instructions carefully before taking the drug.

For oral use, before or 2-3 hours after a meal. Only for short-term use.

Take 1 tablet up to three times a day with water. The interval between doses of the drug should be at least 6 hours.

Maximum single dose: 2 tablets (corresponds to 400 mg of ibuprofen,1000 mg of paracetamol).

Maximum daily dose: 6 tablets (corresponds to 1200 mg of ibuprofen,3000 mg of paracetamol).

The recommended duration of treatment is no more than 3 days. If symptoms persist or worsen after taking the drug for 2-3 days, you should stop treatment and consult a doctor.

Overdose

Paracetamol

Symptoms: symptoms of paracetamol overdose during the first 24 hours: pallor of the skin, nausea, vomiting, anorexia, and abdominal pain. Liver damage can occur 12-48 hours after ingestion, so you should consult a doctor even if there are no symptoms. Glucose metabolism disorders and metabolic acidosis may occur. With severe poisoning, liver failure can progress with complications such as encephalopathy, hemorrhage, hypoglycemia, brain edema, and death. Acute renal failure with acute tubular necrosis (defined by low back pain, hematuria, and proteinuria) can develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Treatment: Immediate treatment is required for an overdose of paracetamol. Despite the lack of significant early symptoms, patients should be rushed to the hospital for immediate medical examination. Symptoms may be limited to nausea or vomiting and may not correspond

to the severity of the overdose or the risk of organ damage. Treatment with activated charcoal should be considered if the excessive dose was taken less than 1 hour ago. The plasma concentration of paracetamol should be measured 4 hours or more after use (earlier concentrations are unreliable). Treatment with N-acetylcysteine can be carried out up to 24 hours after taking paracetamol, but the maximum protective effect is achieved after about 8 hours after taking the drug. The effectiveness of the antidote gradually decreases after this time. If necessary, N-acetylcysteine is administered intravenously in accordance with the established scheme of use. Outside the hospital, if there is no vomiting, you can apply methionine inside. Patients who report serious hepatic dysfunction 24 hours after taking the drug should be referred to a poison control specialist.

Additional information about special patient groups

Increased risk of liver damage in case of overdose with paracetamol the most likely to have:

· patients receiving long-term treatment with enzyme-inducing drugs (such as carbamazepine, phenobarbital, phenytoin, primidon, rifampicin, and Hypericum perforatum);

· patients who consume alcohol in higher quantities recommended;

in patients with depletion of glutathione (for example, patients with eating disorders, cystic fibrosis, HIV infection, cachexia, starving).

Ibuprofen

In adults, the dose-dependent effect does not have a clear threshold. The half-life of the drug in case of overdose is 1.5-3 hours.

Symptoms: nausea, vomiting, epigastric pain or, less commonly, diarrhea, tinnitus, headache, and gastrointestinal bleeding. In more severe cases, there are manifestations of the central nervous system: drowsiness, rarely-agitation, convulsions, disorientation, coma. In cases of severe poisoning, metabolic acidosis and increased prothrombin time, renal failure, liver tissue damage, decreased blood pressure, respiratory depression and cyanosis can develop. Patients with bronchial asthma may have an exacerbation of this disease.

Treatment: symptomatic, with mandatory provision of airway patency, monitoring of ECG and basic vital signs until the patient’s condition normalizes. Oral use of activated charcoal or gastric lavage within 1 hour of taking a potentially toxic dose of ibuprofen is recommended. If ibuprofen has already been absorbed, an alkaline drink may be prescribed to remove the acidic ibuprofen derivative by the kidneys, forced diuresis. Frequent or prolonged seizures should be stopped by intravenous use of diazepam or lorazepam. In case of worsening of bronchial asthma, the use of bronchodilators is recommended.

Description

Special instructions

It is recommended to take the drug in the shortest possible course and in the minimum effective dose necessary to eliminate symptoms.

In patients with acute bronchial asthma or allergic disease, as well as in patients with a history of bronchial asthma/allergic disease, the drug may provoke bronchospasm.

The use of the drug in patients with systemic lupus erythematosus or mixed connective tissue disease is associated with an increased risk of aseptic meningitis.

During long-term treatment, it is necessary to monitor the picture of peripheral blood and the functional state of the liver and kidneys. When symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, a general blood test (determination of hemoglobin), and a fecal occult blood test. If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

During the treatment period, it is not recommended to take ethanol.

Patients with renal insufficiency should consult a doctor before using the drug, as there is a risk of deterioration of the functional state of the kidneys.

Patients with hypertension, including in the anamnesis and / or chronic heart failure, should consult a doctor before using the drug, since the drug can cause fluid retention, increased blood pressure and edema.

Patients with uncontrolled blood pressure, NYHA class II-III congestive heart failure, coronary artery disease, peripheral artery disease, and/or cerebrovascular disease should only be prescribed ibuprofen after careful benefit/risk assessment, and high doses of ibuprofen (≥2400 mg/day) should be avoided.

The use of NSAIDs in patients with chickenpox may be associated with an increased risk of developing severe purulent complications of infectious and inflammatory diseases of the skin and subcutaneous fat (for example, necrotizing fasciitis). In this regard, it is recommended to avoid using the drug for chickenpox.

Information for women planning pregnancy: these drugs inhibit cyclooxygenase and prostaglandin synthesis, affect ovulation, impair female reproductive function (reversible after discontinuation of treatment).

Do not take with any other medications containing paracetamol. If this happens, you should immediately seek medical attention, even if you feel well, as this can lead to an overdose.

Influence on the ability to drive vehicles and mechanisms

If the recommended dosage regimen and time of use are observed, the drug does not affect the ability to drive vehicles and mechanisms, as well as to engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets. 6 or 12 tablets in a blister (PVC). /PVDC/aluminum).1 blister along with the instructions for use in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

: Ibuprofen, Paracetamol

Dosage form

Tablets

Purpose

For adults, Children as prescribed by a doctor, Children over 12 years of age

Indications

Sprains and sprains, From Neuritis, Colds, From Migraines, From arthrosis and arthritis, From osteochondrosis, Flu