Nurofen Long - instructions for use, dose, side effects, contraindications

Composition:One tablet, film-coated, contains: active ingredients: ibuprofen 200 mg and paracetamol 500 mg; Excipients: croscarmellose sodium 30 mg, microcrystalline cellulose 120 mg, silicon dioxide colloid 3 mg, magnesium stearate 5 mg, stearic acid 4 mg.
Shell composition: white film shell 13 mg (polyvinyl alcohol 40%, titanium dioxide 25%, macrogol 20.2%, talc 14.8%), film shell with a pearlescent effect of 7 mg (polyvinyl alcohol 47%, talc 27%, macrogol 13.3% pearlescent pigment based on mica 10% (titanium dioxide 28%, potassium aluminosilicate (E555) 72%), polysorbate 2.7%).

Description:Tablets are capsular biconvex, covered with a film coat from white to almost white with a pearlescent effect. On one side, the symbol

Pharmacotherapeutic group:Analgesic combined (NSAIDs + analgesic non-narcotic remedy).

ATX: & nbsp

M.01.A.E.51 Ibuprofen in combination with other drugs

Pharmacodynamics:Combined drug, the effect of which is due to its constituent components. It has a directed action against pain (anesthetic), antipyretic and anti-inflammatory action. Ibuprofen and paracetamol differ in the mechanism and location of action. As a result of their mutually reinforcing effect, a more pronounced decrease in pain sensitivity and an increase in antipyretic activity is achieved than individually.
Ibuprofen - a derivative of propionic acid from the group of non-steroidal anti-inflammatory drugs (NSAIDs), has an anti-inflammatory, anti-edema, analgesic and antipyretic effect. The mechanism of action of ibuprofen is due to the inhibition of the synthesis of prostaglandins - mediators of pain,inflammation and hyperthermic reaction, by indiscriminately inhibiting the activity of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). An analgesic effect of ibuprofen is provided by its inhibitory action at the peripheral level. The antipyretic effect of ibuprofen is associated with a central inhibition of the synthesis of prostaglandins in the hypothalamus. Ibuprofen inhibits the migration of leukocytes to the focus of inflammation. Besides, ibuprofen reversibly inhibits the aggregation of platelets.
Paracetamol - analgesic non-narcotic agent, has analgesic, antipyretic and weak anti-inflammatory effect. Non-selectively blocks COX-2, mainly in the central nervous system. Paracetamol can also stimulate the activity of descending serotonin pathways, which leads to the arrest of transmission of a pain impulse in the spinal cord. At the peripheral level paracetamol has a slightly expressed 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 pill anesthetic effect is noted on average 15 minutes after taking the drug, a clinically significant analgesic effect is achieved 40 minutes after taking the drug and remains for 8 hours. After taking two tablets, the analgesic effect is noted on average 18 minutes after taking the drug, a clinically significant analgesic effect is achieved 45 minutes after taking the drug and is maintained for 9 hours.

Pharmacokinetics:Ibuprofen: absorption is high, quickly and almost completely absorbed from the gastrointestinal tract (GIT). Connection with blood plasma proteins - 90%. Slowly penetrates into the joint cavity, is retained in the synovial fluid, creating in it greater concentrations than in the blood plasma. Detected in the blood plasma after 5 minutes after taking the drug on an empty stomach, the maximum concentration (C_max) in the blood plasma is achieved in 1-2 hours. Simultaneous reception with food can reduce the concentration of ibuprofen in the blood plasma and increase the time to reach the maximum concentration (T_max). The degree of absorption of ibuprofen is not dependent on food intake.It is metabolized in the liver. After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into an active S-form. The half-life (T_1/2) - 2 hours. It is excreted by the kidneys mainly in the form of metabolites (in unchanged form not more than 1%) and, to a lesser extent, with bile in the form of metabolites. In elderly people, there were no significant differences in the pharmacokinetic profile of ibuprofen compared to younger people. There is evidence that ibuprofen was found in breast milk in insignificant concentrations.
Paracetamol: absorption is high, rapidly absorbed from the digestive tract. The association with blood plasma proteins is insignificant when taken at therapeutic doses; slightly increases with an overdose. Found in plasma 5 minutes after administration of the drug on an empty stomach, Cmax in plasma attained in 30-40 minutes after administration. Simultaneous treatment with food may reduce the concentration of paracetamol in plasma and increase T_max. The degree of absorption of paracetamol does not depend on the intake of food. It is metabolized in the liver and excreted predominantly in the form of glucuronides and sulfated conjugates to form a glutathione conjugate (about 10%). It is excreted by the kidneys.In the form of unchanged paracetamol, less than 5% of the dose taken is excreted. The half-life (T_1/2) - 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, can accumulate in case of an overdose of paracetamol and cause damage to liver tissue. In elderly people, there were no significant differences in the pharmacokinetic profile of paracetamol compared to younger people. Bioavailability and pharmacokinetic indices of ibuprofen and paracetamol taken in the composition of this combined preparation do not change with single or repeated use.

Indications:Back pain, joint pain, muscle and rheumatic pain, neuralgia, headache, migraine, toothache, painful menstruation, sore throat, febrile condition, 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 separately.

Contraindications:- Hypersensitivity to ibuprofen, paracetamol or to other components of the drug.
- Simultaneous reception of other medications containing paracetamol.
- Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses, and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis).
- Erosive and ulcerative diseases of the gastrointestinal tract (including peptic ulcer of stomach and duodenum, Crohn's disease, ulcerative colitis) or ulcerative bleeding in the active phase or in the anamnesis (two or more confirmed episodes of peptic ulcer or ulcer bleeding).
- Bleeding or perforation of the gastrointestinal ulcer in an anamnesis, provoked by the use of NSAIDs.
- Severe hepatic insufficiency or liver disease in the active phase.
- Renal failure of severe severity (creatinine clearance <30 ml / min), confirmed hyperkalemia.
Decompensated heart failure; period after aortocoronary bypass surgery.
- Cerebrovascular or other bleeding.
- Pregnancy (III trimester).
- Children under 12 years.
- Hemophilia and other disorders of blood clotting (including hypocoagulation), hemorrhagic diathesis.

Carefully:In the presence of conditions specified in this section, before using the drug should consult a doctor.
Simultaneous reception of other NSAIDs, a history of a single episode of peptic ulcer or gastric ulcer bleeding; gastritis, enteritis, colitis, the presence of Helicobacter pylori infection, ulcerative colitis; A bronchial asthma or allergic diseases in a stage of an exacerbation or in the anamnesis - development of a bronchospasm is possible; systemic lupus erythematosus or mixed connective tissue disease (Sharpe's syndrome) - increased risk of aseptic meningitis; renal failure, including during dehydration (creatinine clearance less than 30-60 ml / min); nephrotic syndrome; liver failure; frequent use of alcohol; arterial hypertension and / or heart failure, cerebrovascular disease; simultaneous use of drugs that may increase the risk of ulcers or bleeding, in particular,oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline) or antiplatelet agents (including acetylsalicylic acid, clopidogrel); pregnancy I-II trimester, the period of breastfeeding; elderly age; cirrhosis of the liver with portal hypertension, hyperbilirubinemia; blood diseases of unclear etiology (leukopenia and anemia), hyperlipidemia, diabetes mellitus, peripheral arterial disease.

Pregnancy and lactation:Data on the use of the drug during pregnancy are absent. Contraindicated use of the drug in the III trimester of pregnancy. NSAIDs can delay the onset and prolong delivery, and also increase bleeding in both the mother and the baby. To date, there has been no adverse effect of paracetamol in the recommended doses on the fetus. If possible, the use of the drug in I and II trimesters of pregnancy should be avoided. If you need to use the drug in I and II trimesters and during labor, you should carefully weigh the expected benefit of therapy for the mother and the potential risk to the fetus or child. Ibuprofen and its metabolites in small amounts (0.0008% of the dose taken by the mother) penetrate into breast milk, there is no evidence of negative consequences for the health of the infant. Paracetamol excreted in breast milk; however, it has no clinically significant effect.

Dosing and Administration:Read the instructions carefully before taking the drug.
For oral administration. Only for short-term use.
Adults and children over 12 years of age: 1 tablet up to 3 times a day, with water. The interval between doses of the drug should be at least 6 hours.
The maximum single dose: 2 tablets (corresponding to 400 mg of ibuprofen, 1000 mg of paracetamol).
The maximum daily intake for adults: 6 tablets (corresponding to 1200 mg of ibuprofen, 3000 mg of paracetamol).
The maximum daily dose for children 12-18 years: 4 tablets (corresponding to 800 mg of ibuprofen, 2000 mg of paracetamol).
The duration of treatment is not more than 3 days. If the symptoms persist or worsen during 2-3 days, stop treatment and consult a doctor.

Side effects:The risk of side effects can be minimized if you take the drug with a short course, at the lowest effective dose needed to eliminate the symptoms.
In elderly people, there is an increased incidence of adverse reactions when NSAIDs are used, especially gastrointestinal bleeding and perforations, in some cases fatal. Side effects are predominantly dose-dependent. In particular, the risk of developing gastrointestinal bleeding depends on the range of doses and duration of treatment.
Estimated incidence of adverse reactions is based on the following criteria: very frequent (≥ 1/10), frequent (≥ 1/100 to <1/10), infrequent (from ≥ 1/1000 to <1/100), rare from ≥ 1/10 000 to <1/1000), very rare (≤ 1/10 000), the frequency is unknown (there is no data on frequency estimation).
Violations from 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 oral cavity, flu-like symptoms, severe weakness, nosebleeds and subcutaneous hemorrhages, bleeding and bruising of unknown origin.
Immune system disorders:
Infrequent: hypersensitivity reactions - nonspecific allergic reactions and anaphylactic reactions, respiratory tract reactions (bronchial asthma, including its aggravation, bronchospasm, dyspnea, dyspnea), skin reactions (itching, urticaria, purpura, Quincke's edema, less exfoliative and bullous dermatoses, including toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, erythema multiforme), allergic rhinitis, eosinophilia.
Very rare: severe hypersensitivity reactions (nonspecific allergic reactions and anaphylactic reactions), including edema of the face, tongue and larynx, dyspnea, tachycardia, lowering of blood pressure (BP) (anaphylaxis, Quincke's edema or severe anaphylactic shock).
Impaired nervous system:
Infrequent: headache.
Very rare: aseptic meningitis. In patients with autoimmune disorders such as systemic lupus erythematosus, mixed connective tissue disease, single cases of aseptic meningitis symptoms were observed during treatment with ibuprofen: stiff neck stiffness, headache, nausea, vomiting, fever and disorientation, confusion, depression, hallucinations.
Disorders from the cardiovascular system:
The frequency is unknown: heart failure, peripheral edema, with prolonged use increased risk of thrombotic complications (eg, myocardial infarction), increased blood pressure.
Disturbances from the respiratory system, chest and mediastinal organs:
The frequency is unknown: bronchial asthma, including its aggravation, bronchospasm, dyspnea.
Disorders from 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.
The frequency is unknown: exacerbation of colitis and Crohn's disease.
Disorders from the liver and bile ducts:
Very rare: violations of the liver (especially with prolonged use), increased activity of "liver" transaminases, hepatitis and jaundice.
Disorders from the kidneys and urinary tract:
Very rare: acute renal failure (compensated and decompensated), especially with prolonged use, in combination with increased urea concentration in the blood plasma and the appearance of edema, papillary necrosis, hematuria and proteinuria, nephritic syndrome, nephrotic syndrome, interstitial nephritis, cystitis.
Disturbances from the skin and subcutaneous tissues:
Frequent: hyperhidrosis (increased sweating).
Laboratory indicators:
Frequent: increased levels of alanine aminotransferase, gamma-glutamyltranspeptidase, elevated plasma concentrations of creatinine and urea, liver function indicators beyond normal.
Infrequent: increased levels of aspartate aminotransferase, alkaline phosphatase, creatinine phosphokinase, lowering hemoglobin, increasing platelet levels.
If side effects occur, stop taking the medication 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. Damage to the liver can occur 12-48 hours after admission,therefore it is necessary to see a doctor even if there are no symptoms. Possible disturbance of glucose metabolism and metabolic acidosis. 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 pain in the lower back, hematuria and proteinuria) can develop even in the absence of severe liver damage. There are reports of heart rhythm disturbances and pancreatitis.
Treatment: immediate treatment is necessary in case of an overdose of paracetamol. Despite the lack of significant early symptoms, patients should be rushed to the hospital for immediate medical examination. Symptoms can be limited by nausea or vomiting and do not correspond to the severity of the overdose or the risk of organ damage. Damage to the liver can occur 12-48 hours after paracetamol enters the interior, so you need to see a doctor even if you have no symptoms. Treatment with activated charcoal should be considered if an excessive dose was taken less than 1 hour ago.The concentration of paracetamol in plasma should be measured after 4 hours or more after administration (earlier concentrations are unreliable). Treatment with N-acetylcysteine can be performed up to 24 hours after taking paracetamol, 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 in accordance with the established scheme of use. Outside the hospital, if there is no vomiting, you can apply methionine inside. Patients who have been treated with serious hepatic dysfunction 24 hours after taking the drug, should be referred to a specialist for poisoning.
Additional information about specific patient groups
The increased risk of liver damage with paracetamol overdose is most likely in:
- Patients receiving long-term treatment with enzyme-inducing agents (such as, carbamazepine, phenobarbitone, phenytoin, primidon, rifampicin and St. John's wort pitted);
- patients who consume alcohol in quantities higher than those recommended;
- Patients with glutathione depletion (eg, patients with eating disorders, cystic fibrosis, HIV infection, cachexia, starvation).
Ibuprofen
In children, overdose symptoms may occur after taking a dose exceeding 400 mg / kg body weight. In adults, the dose-dependent effect of an overdose is less pronounced. The half-life of the drug with an overdose is 1.5-3 hours.
Symptoms: nausea, vomiting, pain in the epigastric region or, more rarely, diarrhea, tinnitus, headache and gastrointestinal bleeding. In more severe cases, there are manifestations of the central nervous system: drowsiness, rarely - excitation, convulsions, disorientation, coma. In cases of severe poisoning, metabolic acidosis and an increase in prothrombin time, renal failure, damage to liver tissue, lowering blood pressure, respiratory depression and cyanosis may develop. Patients with bronchial asthma may exacerbate this disease.
Treatment: symptomatic, with mandatory provision of airway patency, monitoring of ECG and basic indicators of vital activity, up to the normalization of the patient's condition.Recommended oral administration of activated carbon or gastric lavage within 1 hour after taking a potentially toxic dose of ibuprofen. If ibuprofen already absorbed, alkaline drink may be prescribed to excrete the acid derivative of ibuprofen by the kidneys, forced diuresis. Frequent or prolonged seizures should be stopped with intravenous diazepam or lorazepam. When bronchial asthma worsens, the use of bronchodilators is recommended.

Interaction:Paracetamol
- Antiemetics: decrease in the rate of absorption of paracetamol when used concomitantly with metoclopramide or domperidone.
- Anticoagulants: long-term use of drugs containing paracetamol, can enhance the effect of anticoagulants, in particular, warfarin and increase the risk of bleeding.
- Kolestyramin: decrease in the rate of absorption of paracetamol when used simultaneously with colestyramine.
Ibuprofen
It should be avoided simultaneous use of ibuprofen with the following medicines:
- Acetylsalicylic acid: with the exception of low doses of acetylsalicylic acid (not more than 75 mg per day),prescribed by the doctor, since joint application may increase the risk of side effects. With simultaneous application ibuprofen reduces the anti-inflammatory and antiplatelet effect of acetylsalicylic acid (it is possible to increase the incidence of acute coronary insufficiency in patients receiving small doses of acetylsalicylic acid as antiplatelet agent after the onset of ibuprofen administration).
- Other NSAIDs, in particular selective COX-2 inhibitors: simultaneous use of two or more drugs from the NSAID group should be avoided because of the possible increase in the risk of side effects.
Use with caution simultaneously with the following medicines:
- Anticoagulants and thrombolytic drugs: NSAIDs can enhance the effect of anticoagulants, in particular, warfarin and thrombolytic drugs.
- Antihypertensives (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of the drugs of these groups. In some patients with impaired renal function (for example,in patients with dehydration or in elderly patients with impaired renal function) simultaneous administration of ACE inhibitors or angiotensin II antagonists and cyclooxygenase inhibiting agents can lead to impaired 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 joint use of the above-mentioned drugs should be administered with caution, especially in the elderly. It is necessary to prevent dehydration in patients, and also to consider the possibility of monitoring renal function after the beginning of such combined treatment and periodically - in the future. Diuretics and ACE inhibitors can increase the nephrotoxicity of NSAIDs.
- Glucocorticosteroids: increased risk of gastrointestinal ulcers and gastrointestinal bleeding.
- Antiaggregants and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.
- Cardiac glycosides: simultaneous administration of NSAIDs and cardiac glycosides may lead to worsening of heart failure,decrease the glomerular filtration rate and increase the concentration of cardiac glycosides in blood plasma.
- Lithium preparations: there are data on the probability of an increase in the concentration of lithium in blood plasma against the background of NSAIDs.
- Methotrexate: There are data on the probability of an increase in the concentration of methotrexate in the blood plasma against the background of NSAIDs.
- Cyclosporin: an increased risk of nephrotoxicity while concomitant administration of NSAIDs and cyclosporine.
- Mifepristone: NSAIDs should be started no earlier than 8-12 days after taking mifepristone, because NSAIDs may reduce the effectiveness of mifepristone.
- Tacrolimus: with simultaneous administration of NSAIDs and tacrolimus, an increased risk of nephrotoxicity may occur.
- Zidovudine: simultaneous use of NSAIDs and zidovudine may lead to an increase in hematotoxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia who received co-treatment with zidovudine and ibuprofen.
- Antibiotics of the quinolone series: patients receiving collaborative care NSAIDs and quinolone antibiotics series, may increase the risk of seizures.
- Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.
- Caffeine strengthens the analgesic effect.

Special instructions:It is recommended to take the drug as short a course as possible and at the minimum effective dose necessary to eliminate symptoms.
In patients with bronchial asthma or allergic disease in the acute stage, as well as in patients with an anamnesis of bronchial asthma / allergic disease, the drug can provoke bronchospasm. The use of the drug in patients with systemic lupus erythematosus or a mixed disease of connective tissue is associated with an increased risk of developing aseptic meningitis.
During long-term treatment, control of the peripheral blood picture and the functional state of the liver and kidneys is necessary. When symptoms of gastropathy appear, careful monitoring including esophagogastroduodenoscopy, a general blood test (determination of hemoglobin), and analysis of feces for latent blood are shown. If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the test.
During the period of treatment, ethanol is not recommended.
Patients with renal insufficiency should consult with a doctor before using the drug, since there is a risk of impairment of the functional state of the kidneys.
Patients with hypertension, including anamnesis and / or chronic heart failure, should consult with a doctor before using the drug, because the drug can cause fluid retention, increased blood pressure and swelling.
Information for women planning pregnancy: these drugs suppress cyclooxygenase and prostaglandin synthesis, affect ovulation, disrupting female reproductive function (reversible after withdrawal of treatment).

Effect on the ability to drive transp. cf. and fur:If the recommended dosage regimen and timing of application is observed, the drug does not affect the ability to drive vehicles and mechanisms, as well as to engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 200 mg + 500 mg.

Packaging:By 4, 5, 6, 8, 10 or 12 tablets in the blister (PVC / PVDC / aluminum).For 1 or 2 blisters together with instructions for use in a cardboard bundle.

Storage conditions:Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life:3 years.
Do not use the drug with expired shelf life.

Terms of leave from pharmacies:Without recipe

Registration number:LP-003836

Date of registration:14.09.2016

Expiration Date:14.09.2021

The owner of the registration certificate:Rekitt Benckiser Helsar International Ltd.Rekitt Benckiser Helsar International Ltd. United Kingdom

Manufacturer: & nbsp

RECKITT BENCKISER HEALTHCARE (UK), Limited United Kingdom

Representation: & nbspRekitt Benckiser Halskar LLCRekitt Benckiser Halskar LLC

Information update date: & nbsp2016-10-11

Illustrated instructions

Instructions

Nurofen® Long (Nurofen® long)