Pharmacological properties

Pharmacodynamics. an ibuprofen — derivative propionic acid, npvp which has analgeziruyushchy, anti-inflammatory and febrifugal activity. it is considered that therapeutic effects of medicine are caused by its inhibiting effect on enzyme tsog that leads to the significant decrease in synthesis of prostaglandins. these properties provide reduction of expressiveness of symptoms of inflammation, pain and fever.

Experimental data demonstrate that the ibuprofen can suppress competitively influence of low doses of acetylsalicylic acid / aspirin on aggregation of platelets when both medicines are appointed at the same time. Some pharmakodinamichesky researches show what at single dose of an ibuprofen in a dose of 400 mg for 8 h to or in 30 min. after intake of acetylsalicylic acid in shape with fast release of medicine (in a dose of 81 mg) influence of acetylsalicylic acid / aspirin on formation of thromboxane or aggregation of platelets decreased.

Though, it is impossible to exclude probability that regular prolonged use of an ibuprofen can reduce cardiotyre-tread effect of low doses of acetylsalicylic acid / aspirin. Clinically significant effects are improbable at irregular application of an ibuprofen (see INTERACTIONS).

Pharmacokinetics. The ibuprofen is quickly absorbed in a GIT, peak concentration in blood plasma are reached during 1–2 h after reception. T _½ — about 2 h

Ibuprofen is metabolized by

in a liver up to 2 inactive metabolites which are removed by kidneys together with not changed ibuprofen in pure form or in the form of conjugates. Renal excretion fast and full. The ibuprofen substantially contacts proteins of blood plasma.

Indication

Pseudorheumatism ankylosing a spondylitis, an osteoarthritis and other not rheumatoid (seronegative) arthropathies.

Not articulate rheumatic and periartikulyarny defeats, such as humeroscapular periarthritis (capsulitis), bursitis, tendinitis, is tendosinovit also by lower back pain; damages of soft tissues, for example stretchings and tension of sheaves.

For pain relief of moderate and average degree, such as pain at a dysmenorrhea, tooth and postoperative pain and also for symptomatic simplification of a headache, including migraine.

Use

Dose. side effects can be reduced if to apply a minimal effective dose during the short span necessary for control of symptoms (see special instructions).

Adult. The recommended dose of the medicine Brufenum makes 1200–1800 mg/days, it is applied in 2–3 receptions. To some patients there can be enough 600–1200 mg/days. Generally, the maximum daily dose should not exceed 2400 mg which apply in stages.

Patients of advanced age. There is an increased risk of emergence of serious consequences of side reactions at use of medicine for patients of advanced age. If it is necessary to apply NPVP, it is necessary to appoint the lowest effective dose during the shortest span. It is regularly necessary to carry out monitoring on presence at the patient of gastrointestinal bleeding during therapy of NPVP. It is individually necessary to select a dose in case of abnormal liver functions or kidneys.

Route of administration. For oral administration. For achievement of faster effect of medicine, it can be applied on an empty stomach. Patients who have gastrointestinal diseases should take the medicament at meal time.

Before application contents of 1 sachet should be dissolved in a glass of water. It is desirable to accept in time or after a meal.

temporary burning sensation in a mouth or a throat at use of the medicine Brufenum Can appear; be convinced that medicine is dissolved in enough water.

Children. Brufenum in this dosage form is contraindicated for application for children.

Contraindication

Known hypersensitivity to active ingredient or any of excipients.

Ibuprofen should not be applied to patients with OH, a small tortoiseshell or allergic reactions which arose after use of acetylsalicylic acid or other NPVP in the anamnesis.

Heavy heart failure (the IV functional class by criteria of the New York association of heart (NYHA).

Heavy liver failure.

Heavy renal failure (glomerular filtration of 30 ml/min.).

State, followed by the increased risk of bleedings or active bleeding.

Gastrointestinal bleeding or perforation as a result of the previous application of NPVP in the anamnesis.

Acute or postponed earlier ulcer colitis, Crohn's disease, recurrent stomach ulcer or gastrointestinal bleeding (2 or more episodes of the confirmed ulceration or bleeding).

During the III trimester of pregnancy.

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Side effects

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Side reactions of an ibuprofen are similar to side reactions at application of others npvp.

from a GIT: side reactions from a GIT are observed most often.

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At reception of an ibuprofen it was reported about nausea, vomiting, diarrhea, a meteorism, a constipation, dyspepsia, an abdominal pain, a melena, a hematemesis, a stomacace, gastrointestinal bleeding and exacerbation of colitis and Crohn's disease (see CONTRAINDICATIONS). With a smaller frequency the gastritis, a duodenal ulcer and a gastric ulcer, gastrointestinal perforation was observed.

during reception of an ibuprofen the emergence of short-term burning sensation in a mouth or in a throat is possible

.

from the immune system: it was reported about reaction of hypersensitivity at application of an ibuprofen. Nonspecific allergic reactions and an anaphylaxis concern them; reactivity of airways, including OH, aggravation OH, a bronchospasm or dispnoe, and various skin manifestations, including rash of various type, an itch, urticaria, a purpura, a Quincke's disease and, very rare — a multiformny erythema, a bullous dermatosis (including Stephens's syndrome — Johnson, a toxic epidermal necrolysis).

Infection and invasion. Cases of aggravation of inflammation of skin, caused by an infection are described (for example, development of a necrotic fascitis) at application of NPVP. If at application of an ibuprofen symptoms of an infection arise or become aggravated, the patient should see a doctor immediately.

Damage of skin and hypodermic cellulose. In exceptional cases against the background of chicken pox there can be heavy skin infections and complications from soft tissues (see Infections and invasions).

from a cardiovascular system. Data of clinical trials demonstrate that application of an ibuprofen, especially in high doses (2400 mg a day) can increase several risk of emergence of the arterial trombotichesky phenomena (for example a myocardial infarction or a stroke) (see. Special INSTRUCTIONS).

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it is provided side reactions which can be connected with an ibuprofen, classified by frequency and the systems of bodies according to MedDRA Below.

side reactions are subdivided by

On frequency on: very frequent (≥1/10), frequent (≥1/100 to 1/10), infrequent (≥1/1,000 to 1/100), rare (≥1/10,000 to 1/1000), very rare (1/10,000), unknown frequency (it is impossible to determine by the available data).

from blood and lymphatic system: rare — a leukopenia, thrombocytopenia, aplastic anemia, a neutropenia, the Agranulocytosis, hemolytic anemia.

from mentality: infrequent — insomnia, anxiety disorders; rare — a depression, confusion of consciousness.

from nervous system: frequent — a headache, dizziness; infrequent — paresthesias, drowsiness; rare — an optic neuritis.

Infection and invasion: infrequent — rhinitis; rare — aseptic meningitis (see. Special INSTRUCTIONS).

from an organ of sight: infrequent — deterioration in sight; rare — toxic neuropathy of an optic nerve.

from an organ of hearing and a vestibular mechanism: infrequent — deterioration in hearing, vertigo, a ring in ears.

from a gepatobiliarny system: infrequent — hepatitis, jaundice, an abnormal liver function; very rare — a liver failure.

from skin and hypodermic cellulose: frequent — rash; infrequent — urticaria, an itch, purple, a Quincke's disease, reactions of photosensitivity; very rare — severe forms of skin reactions (for example a multiformny erythema, bullous reactions, including Stephens's syndrome — Johnson and a toxic epidermal necrolysis).

from an urinary system: infrequent — a toxic nephropathy in various forms, including tubulointerstitsialny nephrite, a nephrotic syndrome and a renal failure.

General violations and changes in the injection site: frequent — indisposition/fatigue; rare — hypostasis.

from the immune system: infrequent — hypersensitivity; rare — anaphylactic reaction.

from a cardiovascular system: very rare — heart failure, a myocardial infarction (see. Special INSTRUCTIONS).

from the vascular system: very rare — AG.

from a respiratory system: infrequent — OH, a bronchospasm, dispnoe.

from digestive system: frequent — dyspepsia, diarrhea, nausea, vomiting, an abdominal pain, a meteorism, a lock, a melena, a hematemesis, gastrointestinal bleeding; infrequent — gastritis, a duodenal ulcer, stomach ulcer, a stomacace, gastrointestinal perforation; very rare — pancreatitis; unknown frequency — colitis and Crohn's disease.

Special instructions

General cautions. undesirable effects can be minimized, applying the lowest effective dose during the shortest span to control of symptoms (see application and gastrointestinal, cardiovascular risks is lower).

As well as at application of other NPVP, reception of an ibuprofen can mask infection symptoms.

At prolonged use of any anesthetics of medicines the developing of a headache which it is not necessary to treat the raised medicament doses is possible

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At simultaneous application of NPVP with alcohol side effects which belong to active agent, in particular, the touching GITs or central nervous system can amplify.

Drug contains sucrose. It should be considered to patients with diabetes. Patients with rare hereditary intolerance of fructose, violation of absorption of glucose galactose or insufficiency of invertase-isomaltase should not use this drug.

Each sachet of medicine contains sodium. It should be considered to patients who need to limit the sodium use.

Patients of advanced age. At patients of advanced age the frequency of development of side reactions at application of NPVP is higher, especially gastrointestinal bleeding and perforation which can be lethal.

Gastrointestinal bleeding, ulceration and perforation. NPVP should be applied with care to patients with a round ulcer and other gastrointestinal diseases in the anamnesis as their state can worsen (see CONTRAINDICATIONS).

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At application of all NPVP it was reported about development of gastrointestinal bleeding, ulcer or perforation during any span during treatment. These side reactions can have a lethal outcome and arise with or without the menacing symptoms or cases of serious gastrointestinal violations in the anamnesis.

Risk of developing gastrointestinal bleeding, ulcer or perforation is higher than

at increase in a dose of an ibuprofen at patients with an ulcer in the anamnesis, especially at a complication bleeding or perforation, and at patients of advanced age. Such patients have to begin treatment with the lowest available dose.

Should consider the possibility of co-administration to such patients of protective medicines (for example a mizoprostol or inhibitors of a proton pomp), as well as to patients who at the same time accept acetylsalicylic acid in a low dose or other medicines increasing risk of damage of a GIT (see INTERACTIONS).

Should avoid application of an ibuprofen along with other NPVP, including selection TsOG-2 inhibitors, because of the increased risk of developing of an ulcer or bleeding (see INTERACTIONS).

Patients, especially advanced age with gastrointestinal diseases in the anamnesis have to report about any unusual abdominal symptoms (in particular about gastrointestinal bleeding), especially at the initial stages of treatment.

should appoint by

With care an ibuprofen to patients who receive the accompanying treatment by medicines which can increase risk of developing an ulcer or bleeding, for example oral corticosteroids, anticoagulants, such as warfarin, selective serotonin reuptake inhibitors or antiagregantny medicines, in particular acetylsalicylic acid (see INTERACTIONS).

in case of development of gastrointestinal bleeding or an ulcer in the patient accepting an ibuprofen, medicine it is necessary to cancel.

Respiratory violations. With care should appoint an ibuprofen patients who suffer OH, chronic rhinitis, allergic diseases or which have them in the anamnesis as it was reported that the ibuprofen can cause a bronchospasm, urticaria or a Quincke's disease in such patients.

Dysfunction of heart, kidneys and liver. With care it is necessary to apply NPVP to patients with renal failures, a liver or heart as it can lead to deterioration in function of kidneys.

Usual concomitant use of similar anesthetics of medicines increases further this risk.

to Patients with a renal failure, a liver or heart it is necessary to apply the lowest effective dose during the shortest span and also to control function of kidneys, especially at patients at long-term treatment (see CONTRAINDICATIONS).

Cardiovascular and cerebrovascular effects. Patients should appoint an ibuprofen with care with heart failure in the anamnesis or AG as it was reported about hypostasis as a result of application of an ibuprofen. Clinical trials demonstrate that purpose of an ibuprofen, especially in a high dose (2400 mg/days) can be followed by insignificant increase in risk of arterial trombotichesky events (for example a myocardial infarction or a stroke). In general, epidemiological researches do not give the chance to predict existence of communication between reception of an ibuprofen in a low dose (that is ≤1200 mg a day) and the increased risk of arterial trombotichesky events.

to Patients with the uncontrollable AG, stagnant heart failure (the II-III functional class by criteria of NYHA) diagnosed by an ischemic heart disease, a disease of peripheral arteries and/or cerebrovascular diseases should appoint by

an ibuprofen after the careful analysis of a situation and also it is necessary to avoid application of high doses of an ibuprofen (2400 mg/days).

Careful analysis of a situation it is also necessary for

before long therapy by an ibuprofen of patients with risk factors of developing cardiovascular diseases (such as AG, lipidemia, diabetes, smoking), especially in case of need reception of high doses of an ibuprofen (2400 mg/days).

Dermatological effects. Very seldom at application of NPVP it was reported about development of serious skin reactions some of which can be lethal, including exfoliative dermatitis, Stephens's syndrome — Johnson and a toxic epidermal necrolysis. The greatest risk of development of these reactions at patients exists in an initiation of treatment. In most cases reaction begins within the first month of therapy. Reception of an ibuprofen should be stopped at the first appearance of rash on skin, injury of a mucous membrane or any other signs of hypersensitivity.

In exceptional cases on against the background of chicken pox serious infectious complications from skin and soft tissues can arise. Today NPVP role in deterioration in these infections is not defined. Thus, it is recommended to avoid application of an ibuprofen in case of chicken pox.

Effects from kidneys. With care it is necessary to begin treatment with an ibuprofen of patients with considerable dehydration. There is a risk of a renal failure, especially at children, teenagers and elderly patients with dehydration. As well as at application of other NPVP, long reception of an ibuprofen can lead to papillary necrosis of kidneys and other pathological changes in kidneys. Toxic impact on kidneys was also observed at patients at whom renal prostaglandins played a compensatory role in maintenance of perfusion of kidneys. Purpose of NPVP to such patients can cause dose-dependent reduction of formation of prostaglandins and, again, reduction of a kidney blood-groove that can lead to a renal failure.

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To group of high risk of development of such reaction possess patients with a renal failure, heart failure, an abnormal liver function which accept diuretics and APF inhibitors and also patients of advanced age. The termination of reception of NPVP usually is followed by restoration of the state preceding treatment.

Hematologic effects. An ibuprofen, it is similar to other NPVP, can suppress aggregation of platelets and extend a bleeding time at healthy volunteers.

Aseptic meningitis. Seldom at patients at treatment the ibuprofen observed aseptic meningitis. In spite of the fact that probably aseptic meningitis is observed at patients with a system lupus erythematosus and the related diseases of connective tissue, was reported about cases of aseptic meningitis at the patients who do not have these chronic diseases.

Use during pregnancy or feeding by a breast.

Fertility. Use of an ibuprofen can worsen female fertility and is not recommended to application to the women planning pregnancy. At women who have problems with ability to become pregnant or who undergo inspection concerning infertility it is necessary to consider need of the termination of reception of an ibuprofen.

Pregnancy. Suppression of synthesis of prostaglandins can negatively influence pregnancy and/or development of an embryo/fruit. The data obtained from epidemiological researches indicate the increased risk of an abortion and developing of malformations of heart and a gastroshizis after use of inhibitor of synthesis of prostaglandins in the early stages of pregnancy. It is considered that this risk increases depending on a dose and duration of treatment. In the course of the researches on animals it was revealed that use of inhibitor of synthesis of prostaglandins leads to increase pre- and post-implantation losses and to death of an embryo/fruit. Besides, it was reported about increase in quantity of cases of various malformations, including cardiovascular, at the animals receiving inhibitor of synthesis of prostaglandins in the period of an organogenesis.

During I and II trimester of pregnancy an ibuprofen should be accepted only on condition of obvious need. At application of an ibuprofen by women who plan pregnancy or during I or II trimester of pregnancy the dose has to be as low as possible, and treatment duration — is how vomozhno shorter.

During the III trimester of pregnancy all inhibitors of synthesis of prostaglandins can influence a fruit, causing:

• cardio-pulmonary toxicity (with premature closing of an arterial channel and pulmonary hypertensia)
• renal failure, can develop in a renal failure with oligogidramniony.

inhibitors of synthesis of prostaglandins at mother and the newborn can give

at the end of pregnancy to:

• to possible lengthening of a bleeding time,
• to oppression of reductions of a uterus that can lead to a delay or lengthening of childbirth.

So, the ibuprofen is contraindicated during the III trimester of pregnancy.

Childbirth and delivery. It is not recommended to accept an ibuprofen during childbirth and deliveries.

Beginning of childbirth can be postponed in time, and their duration to be extended together with increase in tendency to bleedings of mother and the child.

Feeding by a breast. The available limited researches show that the ibuprofen is allocated in breast milk in very low concentration. The ibuprofen is not recommended to be applied to women during feeding by a breast.

Children. Brufenum in this dosage form is contraindicated for application to children.

Ability to influence speed of response at control of vehicles or other mechanisms. Reception of an ibuprofen can influence the speed of response of patients. It should be meant, being engaged in the activity demanding the increased concentration of attention, for example at control of vehicles or work with other mechanisms. It concerns substantially a combination with alcohol.

Interaction

Should be careful at simultaneous application with the below-mentioned medicines because of the possible medicinal interaction noted at some patients.

Antihypertensive medicines, β-blockers and diuretics. NPVP can reduce effect of antihypertensive medicines, such as APF inhibitors, antagonists of receptors of angiotensin II, β-blockers and diuretics. Diuretics can increase risk of nephrotoxicity of NPVP also.

Cardiac glycosides. NPVP can cause exacerbation of heart failure, reduction in the rate of glomerular filtration and increase in level of cardiac glycosides in blood plasma.

Holestiramin. Co-administration of an ibuprofen and holestiramin can reduce absorption of an ibuprofen in a GIT. However the clinical value of it is unknown.

Lities. NPVP can reduce lithium removal.

Methotrexate. NPVP can suppress canalicular secretion of a methotrexate and reduce clearance of a methotrexate.

Cyclosporine. Increase in risk of nephrotoxicity at application with NPVP.

Mifepristone. Reduction of efficiency of medicine can theoretically happen because of the NPVP antiprostaglandinovy properties. Limited data give the chance to assume that simultaneous application of NPVP in day of use of prostaglandin does not change effect of mifepristone or prostaglandin to maturing of a neck of the uterus or contractility of a uterus and does not reduce clinical performance of medicamentous termination of pregnancy.

Other NPVP, including selection TsOG-2 inhibitors. It is necessary to avoid co-administration with other NPVP, including TsOG-2 inhibitors, because of risk of development of additive effect (cm SPECIAL INSTRUCTIONS).

Acetylsalicylic acid. As well as when prescribing other medicines containing NPVP, the concomitant use of an ibuprofen and acetylsalicylic acid usually is not recommended because of risk of increase in side reactions.

Experimental data demonstrate that the ibuprofen can suppress competitively effect of low doses of acetylsalicylic acid on aggregation of platelets at co-administration.

However, despite ambiguities concerning a possibility of extrapolation of these data on a clinical situation, cannot exclude probability that regular prolonged use of an ibuprofen can reduce cardiotyre-tread effect of low doses of acetylsalicylic acid. There are no clinically significant effects at irregular reception of an ibuprofen (see the Pharmacodynamics);

Corticosteroids. Increase in risk of developing of a gastrointestinal ulcer or bleeding when assigning with NPVP.

Anticoagulants. NPVP can enhance effects of anticoagulants, such as warfarin.

Hinolonovy antibiotics. The data obtained on animals specify that NPVP can increase risk of appearance of the spasms connected with reception of hinolonovy antibiotics. The patients accepting at the same time NPVP and hinolona have the increased risk of developing spasms.

Sulfonilmochevin's

. NPVP can enhance effects of medicines of sulphonylurea. It was seldom reported about development of a hypoglycemia in the patients accepting sulphonylurea when assigning an ibuprofen.

Antiagregantny medicines and selective serotonin reuptake inhibitors (for example klopidogrel and tiklopidin). Increase in risk of gastrointestinal bleeding at reception with NPVP.

Takrolimus. Increase in risk of nephrotoxicity when assigning NPVP to patients who accept takrolimus is possible.

Zidovudin. NPVP increase risk of hematologic toxicity at reception along with a zidovudine. There are proofs of increase in risk of developing a hemarthrosis and hematomas at the HIV-positive patients having hemophilia when assigning an ibuprofen against the background of reception of a zidovudine.

Aminoglycosides. NPVP can reduce removal of aminoglycosides.

Extracts of plants. The ginkgo of a bilob can enhance the risk of bleedings connected with NPVP.

CYP Inhibitors 2C9. Co-administration of an ibuprofen with CYP inhibitors 2C9 can increase exposure of an ibuprofen (CYP substrate 2C9). During one research it was shown that vorikonazol and flukonazol (CYP inhibitors 2C9) increased exposure of S (+) - an ibuprofen approximately for 80–100%. It is necessary to consider an ibuprofen dose decline at co-administration with CYP inhibitors 2C9, especially when assigning high doses of an ibuprofen to the patients accepting vorikonazol or flukonazol.

Overdose

Toxicity. signs and symptoms of toxicity usually it was not observed at application of doses lower than 100 mg/kg. however the supporting measures in certain cases can be required. at children the symptoms of toxicity were observed after administration of medicament in a dose of 400 mg/kg and more.

Symptoms. At most of patients the symptoms of overdose develop during 4–6 h after reception of a large number of an ibuprofen.

Most frequent symptoms of overdose include

: nausea, vomiting, abdominal pain, slackness and drowsiness. Manifestations from central nervous system: a headache, a ring in ears, dizziness, spasms and a loss of consciousness. It was seldom reported about a nystagmus, a metabolic acidosis, a hypothermia, symptoms from kidneys, gastrointestinal bleeding, a coma, an apnoea and oppression of central nervous system and a respiratory system. It was reported about cardiovascular toxicity, including development of arterial hypotension, bradycardia and tachycardia.

In cases of considerable overdose the development of a renal failure and injury of a liver is possible

. The considerable overdose is usually well transferred if other medicaments were not taken.

Treatment

Is not present specific antidote at overdose of an ibuprofen. If the accepted amount of medicine exceeds 400 mg/kg, it is recommended during 1 h after reception to carry out washing/gastric emptying with the subsequent symptomatic treatment. Treatment has to include ensuring passability of airways and monitoring of warm function and key indicators of activity before normalization of a condition of the patient. For obtaining the most relevant information it is necessary to address to local poison control center.

Storage conditions

Out of children's reach at a temperature not above 25 °C.

Brufen Compendium — UABFN180063

Full information on medicament is provided to

in the Instruction for medical use of BRUFENUM medicine (BRUFEN) of 23.01.2017