Nurofen Intensive, 200 mg+500 mg 12 pcs

A combination drug, the action of which is due to its constituent components. It has a directed effect against pain (analgesic), antipyretic and anti-inflammatory effects. Ibuprofen and paracetamol differ in mechanism and site of action. As a result of their mutually reinforcing action a more pronounced reduction of pain sensitivity and increased antipyretic effect is achieved than separately.

Ibuprofen is a derivative of propionic acid from the group of non-steroidal anti-inflammatory drugs (NSAIDs), has anti-inflammatory, anti-edema, analgesic and antipyretic effect. Mechanism of action of ibuprofen is due to inhibition of prostaglandin synthesis – mediators of pain, inflammation and hyperthermia by non-selective inhibition of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) activity.

The analgesic effect of ibuprofen is provided by its inhibitory effect at the peripheral level. Antipyretic effect of ibuprofen is associated with central inhibition of prostaglandin synthesis in hypothalamus. Ibuprofen inhibits migration of leukocytes to the center of inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation.

Paracetamol is an analgesic non-narcotic, has analgesic, antipyretic and mild 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 results in knocking out the transmission of the pain impulse in the spinal cord. At peripheral level paracetamol has a weak effect on COX-1 and COX-2.

The drug has a more rapid therapeutic effect and more pronounced analgesic effect than ibuprofen and paracetamol separately. After taking one tablet of the drug the analgesic effect is noted on average after 15 minutes, clinically significant analgesic effect is achieved after 40 minutes and lasts for 8 hours. After taking two tablets of the preparation analgesic effect is noted on the average in 18 minutes, clinically significant analgesic effect is achieved within 45 minutes and lasts for 9 hours.

Pharmacokinetics

Ibuprofen: absorption is high, quickly and almost completely absorbed from the gastrointestinal tract (GIT). The binding to blood plasma proteins is 90%. Slowly penetrates into the joint cavity, lingers in synovial fluid, creating higher concentrations in it than in blood plasma. It is detected in blood plasma 5 minutes after the drug intake on an empty stomach; maximum concentration (C_max) in blood plasma is reached after 1-2 hours.

Concomitant administration with food may decrease the plasma concentration of ibuprofen and increase the time to reach maximum concentration (T_max). The degree of absorption of ibuprofen is independent of 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 half-life (T_1/2) is 2 hours.

Extracted by kidneys mainly as metabolites (unchanged not more than 1 %) and, to a lesser extent, in bile as metabolites. There were no significant differences in the pharmacokinetic profile of ibuprofen in elderly people compared to younger people. There is evidence that ibuprofen was detected in breast milk in insignificant concentrations.

Paracetamol: Absorption is high, quickly absorbed from the gastrointestinal tract. Binding to plasma proteins is insignificant when administered in therapeutic doses; slightly increased in overdose. Detectable in blood plasma 5 minutes after the drug intake on an empty stomach; C_max in blood plasma is reached 30-40 minutes after intake. Concomitant intake with food may decrease the plasma concentration of paracetamol and increase T_max. The degree of absorption of paracetamol is independent of food intake.

Metabolized in the liver and excreted mainly as glucuronides and sulfated conjugates with the formation of glutathione conjugates (about 10%). It is excreted by the kidneys.

Less than 5% of the dose taken is excreted as unchanged paracetamol. The elimination half-life (T_1/2) is 3 hours. 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, may accumulate in paracetamol overdose and cause liver tissue damage.

In the elderly there were no significant differences in the pharmacokinetic profile of paracetamol 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 multiple administration.

Indications

Back pain, joint pain, muscle and rheumatic pain, neuralgia, headache, migraine, 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.

Active ingredient

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.

The composition of the shell:

White film coating 13 mg (polyvinyl alcohol 40%, titanium dioxide 25%, macrogol 20.2%, talc 14.8%), pearlescent film coating 7 mg (polyvinyl alcohol 47%, Talc 27%, macrogol 13.3%, pearlescent pigment on the basis of mica 10% (titanium dioxide 28%, potassium aluminosilicate (E555) 72%), polysorbate 2.7%).

How to take, the dosage

Read the instructions carefully before taking this medicine.

To be taken orally, before or 2-3 hours after meals. For short-term use only.

Take 1 tablet up to 3 times a day with water. The interval between each dose should be at least 6 hours.

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

The maximum daily dose: 6 tablets (corresponding to 1200 mg of ibuprofen, 3000 mg of paracetamol).

The duration of treatment is recommended for no more than 3 days. If symptoms persist or worsen when taking the drug for 2-3 days, it is necessary to stop treatment and see a doctor.

Interaction

Paracetamol

– Antiemetics: decrease the rate of absorption of paracetamol when used simultaneously with metoclopramide or domperidone.

– Anticoagulants: prolonged use of drugs containing paracetamol may increase the effect of anticoagulants, particularly warfarin, and increase the risk of bleeding.

– Colestiramine: decrease the rate of absorption of paracetamol when used simultaneously with colestiramine.

Paracetamol falsely increases Continuous Blood Sugar Monitoring (CGM) readings compared to glucose meter readings. This applies to patients using CGM devices that do or do not contain an automatic insulin pump, i.e., those with type I diabetes.

Caution should be exercised when concomitant use of paracetamol and flucloxacillin is associated with an increased risk of high anion difference metabolic acidosis, especially in patients with a risk factor for glutathione deficiency (including patients with severe renal impairment, sepsis, eating disorders and chronic alcoholism).

The careful monitoring is recommended to detect signs of acid-base imbalance, namely metabolic acidosis with a high anion difference, including determination of 5-oxoproline in the urine.

Ibuprofen

The concomitant use of ibuprofen with the following medicinal products should be avoided:

– Acetylsalicylic acid: except in low doses of acetylsalicylic acid (no more than 75 mg per day) prescribed by a physician, because co-administration may increase the risk of side effects. Co-administration of ibuprofen reduces anti-inflammatory and antiplatelet effects of acetylsalicylic acid (the incidence of acute coronary failure may increase in patients receiving low doses of acetylsalicylic acid as antiplatelet agents after starting ibuprofen administration).

– Other NSAIDs, particularly selective COX-2 inhibitors: concomitant use of two or more drugs from the NSAID group should be avoided because of possible increased risk of side effects.

Cautiously use concomitantly with the following drugs:

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

– Antihypertensives (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 (e.g., in patients with dehydration or elderly patients with impaired renal function), simultaneous administration of ACE inhibitors or angiotensin II antagonists and cyclooxygenase inhibitors may lead to worsening of renal function, including 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 administered with caution, especially in the elderly. It is necessary to prevent dehydration in patients and to consider monitoring renal function after initiation of such combined treatment and periodically thereafter. Diuretics and ACE inhibitors may increase nephrotoxicity of NSAIDs.

– Glucocorticosteroids: increased risk of GI ulcers and gastrointestinal bleeding.

– Antiaggregants and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.

– Cardiac glycosides: concomitant administration of NSAIDs and cardiac glycosides may worsen heart failure, decrease glomerular filtration rate, and increase plasma concentrations of cardiac glycosides.

Lithium drugs: there is data on the likelihood of increased plasma lithium concentrations with NSAIDs.

– Methotrexate: there is data on the likelihood of increased plasma concentrations of methotrexate with NSAIDs.

Cyclosporine: there is an increased risk of nephrotoxicity when concomitant administration of NSAIDs and cyclosporine.

– Mifepristone: NSAIDs should not be started earlier than 8-12 days after taking mifepristone, because NSAIDs may reduce the effectiveness of mifepristone.

– Tacrolimus: simultaneous administration of NSAIDs and tacrolimus may increase the risk of nephrotoxicity.

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

– Quinolone antibiotics: patients co-treated with NSAIDs and quinolone antibiotics may have an increased risk of seizures.

– Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

– Caffeine increases the analgesic effect.

Special Instructions

It is recommended that the drug be taken in as short a course as possible and in the lowest effective dose necessary to relieve symptoms.

In patients with acute bronchial asthma or allergic disease, and 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.

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

It is not recommended to take ethanol during treatment.

Patients with renal insufficiency should consult a physician before using the drug, since there is a risk of impairment of renal function.

Patients with hypertension, including a history of hypertension and/or chronic heart failure, should consult a physician before using the drug, as the drug may cause fluid retention, increased blood pressure, and edema.

Patients with uncontrolled blood pressure, NYHA class II-III congestive heart failure, coronary heart disease, peripheral artery disease and/or cerebrovascular disease should only be prescribed ibuprofen after careful assessment of the benefit/risk ratio, 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 severe suppurative complications of infectious and inflammatory skin and subcutaneous fat diseases (e.g., necrotizing fasciitis). In this regard, it is recommended to avoid using the drug in case of chicken pox.

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

Do not take with any other drugs containing paracetamol. If this happens, it is necessary to seek medical attention urgently, even if you feel satisfactory, as it may lead to an overdose.

Impact on ability to drive, operate machinery

The drug does not affect the ability to drive or operate machinery, as well as other potentially dangerous activities requiring increased concentration and quick psychomotor reactions, if the recommended dosing regimen and timing of administration are observed.

Contraindications

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

– Simultaneous use of other drugs containing paracetamol.

– Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other NSAIDs (including a history).

– Erosive-ulcer disease of the gastrointestinal tract (including gastric and duodenal ulcer, Crohn’s disease, ulcerative colitis) or ulcer bleeding in the active phase or in the anamnesis (two or more confirmed episodes of peptic ulcer disease or ulcer bleeding).

– Bleeding or gastrointestinal ulcer perforation in a history triggered by the use of NSAIDs.

– Severe heart failure (NYHA class IV – New York Heart Association classification).

– Severe hepatic insufficiency or active liver disease.

– Severe renal insufficiency (creatinine clearance
< 30 ml/min), confirmed hyperkalemia.

– Decompensated heart failure; period after coronary artery bypass grafting.

– Cerebrovascular or other bleeding.

– Pregnancy (III trimester).

– Age under 18 years of age.

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

– Genetic absence of glucose-6-phosphate dehydrogenase.

With caution

In the presence of the conditions listed in this section, a physician should be consulted before using the drug.

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

Side effects

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

The elderly have an increased incidence of adverse reactions with NSAIDs, especially gastrointestinal bleeding and perforations, in some cases fatal.

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

The following adverse reactions have been reported with short-term administration of ibuprofen at doses of 1200 mg/day, paracetamol at 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 was evaluated 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 < 1/1000), very rare (≤ 1/10 000), frequency unknown (no data on frequency evaluation).

Disorders of the blood and lymphatic system:

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

Disorders of the immune system:

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

Very rare: severe hypersensitivity reactions, including swelling of the face, tongue and throat, shortness of breath, tachycardia, decreased blood pressure (anaphylaxis, Quincke’s edema 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, single cases of symptoms of aseptic meningitis have been observed during treatment with ibuprofen: stiffness of occipital muscles, headache, nausea, vomiting, fever and disorientation, confusion, depression, hallucinations.

Disorders of the cardiovascular system:

Frequency unknown: heart failure, peripheral edema, increased risk of thrombotic complications (e.g., myocardial infarction) with prolonged use, increased blood pressure.

Disorders of the respiratory system, thorax and mediastinum:

Frequency unknown: bronchial asthma, including its exacerbation, bronchospasm, dyspnea.

Gastrointestinal disorders:

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.

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

Hepatic and biliary tract disorders:

Very rare: liver dysfunction (especially with long-term use), increased activity of “hepatic” transaminases, hepatitis and jaundice.

Renal and urinary tract disorders:

Very rare: Acute renal failure (compensated and decompensated), especially with long-term use, combined with an increase in plasma urea concentration 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: 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 findings:

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

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

If side effects occur, discontinue the drug and see a physician.

Overdose

Paracetamol

Symptoms: symptoms of paracetamol overdose during the first 24 hours: pale skin, nausea, vomiting, anorexia and abdominal pain. Damage to the liver may appear 12-48 hours after ingestion, so it is necessary to consult a doctor even in the absence of symptoms. Impaired glucose metabolism and metabolic acidosis are possible.

In severe poisoning, liver failure may progress with complications such as encephalopathy, hemorrhage, hypoglycemia, cerebral edema and death. Acute renal failure with acute tubular necrosis (defined by lumbar pain, hematuria, and proteinuria) may develop even in the absence of severe liver damage. There have been reports of abnormal heart rhythm and pancreatitis.

Treatment: immediate treatment of paracetamol overdose is necessary. Despite the lack of significant early symptoms, patients should be rushed to the hospital for immediate medical evaluation. Symptoms may be limited to nausea or vomiting and not consistent with the severity of the overdose or risk of organ damage. Treatment with activated charcoal should be considered if the overdose was taken less than 1 hour ago. Plasma concentrations of paracetamol should be measured 4 hours or more after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine can be given up to 24 hours after paracetamol administration, but the maximum protective effect is achieved about 8 hours after taking the drug.

The effectiveness of the antidote gradually decreases after this time. If necessary, N-acetylcysteine is administered intravenously according to the established regimen. Outside the hospital, if there is no vomiting, methionine may be administered orally. Patients presenting with severe hepatic dysfunction 24 hours after taking the drug should be referred to a poison specialist.

Further information about special patient groups

An increased risk of liver damage from paracetamol overdose is most likely in:

Patients receiving long-term treatment with enzyme-inducing drugs (such as, carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, and St. John’s wort);

– Patients who drink alcohol in amounts higher than recommended;

Patients with glutathione depletion (e.g., patients with eating disorders, cystic fibrosis, HIV infection, cachexia, starvation).

Ibuprofen

In adults, the dose-dependent effect has no clear threshold. The half-life of the drug in overdose is 1.5-3 hours.

Symptoms: nausea, vomiting, epigastric pain or, less frequently, diarrhea, tinnitus, headache and gastrointestinal bleeding. In more severe cases, there are manifestations of the central nervous system: somnolence, rarely – agitation, seizures, 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 may develop. In patients with bronchial asthma, exacerbation of this disease is possible.

The treatment: symptomatic, with mandatory provision of airway patency, ECG monitoring and basic vital signs until the patient’s condition normalizes. Oral administration of activated charcoal or gastric lavage within 1 hour after taking a potentially toxic dose of ibuprofen is recommended.

If ibuprofen is already absorbed, alkaline drinking may be prescribed in order to eliminate the acidic derivative of ibuprofen by the kidneys, forced diuresis. Frequent or prolonged seizures should be controlled with intravenous diazepam or lorazepam. In worsening bronchial asthma the use of bronchodilators is recommended.

Similarities