Brufen syrup 100 mg/5 ml bottle of 100 ml

Instructions Brufen syrup 100 mg/5 ml bottle 100 ml

Composition

active ingredient: ibuprofen;

5 ml of syrup contains 100 mg of ibuprofen;

excipients: methyl parahydroxybenzoate (E 218); propyl parahydroxybenzoate (E 216); citric acid, monohydrate; glycerol; sorbitol solution, non-crystallizing (E 420); sucrose; sodium benzoate (E 211); orange yellow (E 110); orange flavor (D717 BBA); polysorbates; agar; purified water.

Dosage form

Syrup.

Main physicochemical properties: syrupy orange suspension with an orange odor.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.

Pharmacological properties

Pharmacodynamics.

Ibuprofen is a propionic acid derivative, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic properties. In addition, ibuprofen reversibly inhibits platelet aggregation. The therapeutic effect of the drug is believed to be due to inhibition of the cyclooxygenase enzyme, which leads to a marked reduction in prostaglandin synthesis. These properties provide relief from symptoms of inflammation, pain and fever.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid/aspirin on platelet aggregation when both drugs are administered concomitantly. Some pharmacodynamic studies have shown that a single dose of ibuprofen 400 mg administered 8 hours before or 30 minutes after immediate-release acetylsalicylic acid/aspirin (81 mg) reduced the effect of acetylsalicylic acid/aspirin on thromboxane formation or platelet aggregation.

Although there are uncertainties regarding the extrapolation of the obtained data to the clinical situation, the possibility cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid/aspirin. Clinically significant effects are unlikely with irregular use of ibuprofen.

Pharmacokinetics.

Ibuprofen is rapidly absorbed after oral administration. Peak plasma concentrations are reached approximately 45 minutes after administration in the fasting state.

Taking the same dose of the drug after a meal showed that absorption occurs more slowly with peak plasma concentrations after 1.5-3 hours. The plasma half-life is 2 hours. Ibuprofen is metabolized in the liver to form two inactive metabolites, which, together with unchanged ibuprofen, are excreted by the kidneys in unchanged form or as conjugates.

Elimination is rapid, with plasma concentrations showing no evidence of accumulation. 44% of the ibuprofen dose is excreted in the urine as two pharmacologically inactive metabolites and 20% as unchanged drug.

Indication

Short-term treatment of fever and pain in children.

Contraindication

Known hypersensitivity to the active substance or to any other component of the drug.

History of hypersensitivity reactions (such as bronchial asthma, rhinitis, angioedema or urticaria) in response to the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).

Increased bleeding tendency or active bleeding.

Active or history of recurrent peptic ulcer disease or gastrointestinal bleeding (2 or more episodes of confirmed ulceration or bleeding).

History of gastrointestinal bleeding or perforation associated with NSAID use.

Severe heart failure (IV functional class according to the New York Heart Association (NYHA) criteria).

Severe liver failure.

Severe renal failure (glomerular filtration rate <30 ml/min).

Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).

Third trimester of pregnancy.

Cerebrovascular or other bleeding.

Disorders of hematopoiesis or blood clotting.

Hereditary fructose intolerance.

Interaction with other medicinal products and other types of interactions

Caution should be exercised when using any of the following drugs simultaneously with ibuprofen, as interactions have been reported in some patients.

Diuretics, ACE inhibitors, beta-blockers and angiotensin II receptor antagonists. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Diuretics may increase the risk of nephrotoxicity associated with NSAIDs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function), the concomitant use of ACE inhibitors, beta-blockers or angiotensin II receptor antagonists with cyclooxygenase inhibitors may lead to additional deterioration of renal function, including the possibility of acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, especially in elderly patients.

Cardiac glycosides: NSAIDs may worsen cardiac decompensation, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides (e.g., digoxin). Monitoring of serum glycoside levels is recommended.

Lithium. Concomitant use of ibuprofen and lithium preparations leads to increased levels of the latter in the blood plasma.

Methotrexate: NSAIDs may inhibit the tubular secretion of methotrexate and reduce the clearance of methotrexate and increase the risk of toxicity.

Moclobemide increases the effect of ibuprofen;

Cyclosporine increases the risk of renal damage from NSAIDs. This effect cannot be excluded for the combination of cyclosporine and ibuprofen.

Mifepristone: A reduction in the efficacy of the medicinal product could theoretically occur due to the antiprostaglandin properties of NSAIDs, in particular acetylsalicylic acid. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not alter the effects of mifepristone or prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical abortion.

Corticosteroids: Ibuprofen should be administered with caution in combination with corticosteroids due to a possible increased risk of adverse reactions, especially from the gastrointestinal tract (gastrointestinal ulcers or bleeding, see sections "Contraindications", "Special instructions for use").

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4).

Acetylsalicylic acid. It is not recommended to use ibuprofen simultaneously with acetylsalicylic acid/aspirin, as well as with other drugs containing NSAIDs, including selective cyclooxygenase-2 inhibitors, due to an increased likelihood of adverse reactions. Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid/aspirin on platelet aggregation when used simultaneously. However, despite the uncertainty regarding the possibility of extrapolating these data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid/aspirin. There are no clinically significant effects with irregular administration of ibuprofen (see section "Pharmacodynamics").

Sulfonylureas: NSAIDs may potentiate the effects of sulfonylureas. Hypoglycemia has been reported rarely in patients taking sulfonylureas when ibuprofen is administered. Blood glucose monitoring is recommended in cases of concomitant use.

Zidovudine. NSAIDs increase the risk of hematological toxicity when used concomitantly with zidovudine. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia when ibuprofen is prescribed with zidovudine. Hematological monitoring is recommended 1 to 2 weeks after initiation of treatment.

Other NSAIDs, including salicylates and selective COX-2 inhibitors. The simultaneous use of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to the development of a synergistic effect. Therefore, the simultaneous use of ibuprofen with other NSAIDs should be avoided (see section "Special instructions").

Aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides.

Cholestyramine: Concomitant use of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical significance of this interaction is unknown.

Tacrolimus: Increased risk of nephrotoxicity when the two drugs are used simultaneously.

Antiplatelet agents and selective serotonin reuptake inhibitors increase the risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").

Herbal extracts. Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.

Quinolone antibiotics: Animal data suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones concurrently are at increased risk of seizures.

CYP2C9 inhibitors. Co-administration of ibuprofen with CYP2C9 inhibitors may increase the exposure of ibuprofen (a CYP2C9 substrate). In one study, voriconazole and fluconazole (CYP2C9 inhibitors) were shown to increase the exposure of S(+) ibuprofen by approximately 80-100%. A reduction in the ibuprofen dose should be considered when co-administered with CYP2C9 inhibitors, especially when high doses of ibuprofen are administered to patients taking voriconazole or fluconazole.

Application features

General warnings

Undesirable effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section “Dosage and administration” and effects on the gastrointestinal tract and cardiovascular system described below).

Ibuprofen may temporarily inhibit platelet function (platelet aggregation).

With prolonged use of any painkillers, a headache may occur, which should not be treated with increased doses of this medication.

In the case of simultaneous consumption of alcohol while taking NSAIDs, the risk of undesirable effects caused by the action of the active substance may increase, especially from the gastrointestinal tract or central nervous system.

Elderly patients

Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

Cardiovascular and cerebrovascular disorders

Caution should be exercised (consult your doctor or pharmacist) before starting treatment in patients with a history of hypertension and/or heart failure, as fluid retention and edema have been reported with the use of NSAIDs.

NSAIDs may reduce the effects of diuretics and other antihypertensive drugs (see section "Interaction with other medicinal products and other types of interactions").

Clinical trial data suggest that ibuprofen, especially at high doses (2400 mg/day), may slightly increase the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). In general, epidemiological studies suggest that low-dose ibuprofen (e.g. ≤1200 mg/day) does not increase the risk of arterial thrombotic events. Ibuprofen should be used with particular caution in patients with uncontrolled hypertension, congestive heart failure (NYHA functional class II-III), established coronary heart disease, peripheral arterial disease and/or cerebrovascular disease, and high doses of ibuprofen (2400 mg/day) should be avoided. Long-term treatment of patients with risk factors for cardiovascular disorders (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be approached with great caution, especially if there is a need to use high doses (2400 mg per day) of ibuprofen.

Cases of Kounis syndrome have been reported in patients treated with ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with narrowing of the coronary arteries, potentially leading to myocardial infarction.

Gastrointestinal bleeding, ulceration and perforation

Gastrointestinal bleeding, perforation or ulceration, which can be fatal, has been reported with all NSAIDs at any time during treatment. These events have occurred regardless of the presence of warning symptoms or a previous history of serious gastrointestinal events.

In patients with a history of ulcer, especially if complicated by bleeding or perforation (see section 4.3), and in elderly patients, increasing doses of NSAIDs increases the risk of gastrointestinal bleeding, ulceration or perforation. Treatment of these patients should be initiated at the lowest available dose.

For such patients, as well as for patients who require concomitant therapy with low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal complications, the use of combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered (see section "Interaction with other medicinal products and other types of interactions").

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be advised to report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.

Ibuprofen should be prescribed with caution to patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

In patients with gastrointestinal bleeding or ulceration, ibuprofen treatment should be discontinued.

NSAIDs should be prescribed with caution to patients with a history of peptic ulcers and other gastrointestinal diseases, such as ulcerative colitis and Crohn's disease, due to the possible exacerbation of these diseases (see section "Adverse reactions").

Use with caution in patients with coagulation disorders.

Renal manifestations

Continuous use of analgesics, especially when using multiple pain-relieving agents at the same time, can lead to irreversible kidney damage with the risk of renal failure (analgesic nephropathy). This risk may be increased by physical exertion accompanied by salt loss and dehydration. It should therefore be avoided.

Caution should be exercised when prescribing the drug to patients with arterial hypertension and/or cardiac disorders due to possible deterioration of renal function (see sections "Adverse reactions" and "Contraindications")

Renal tubular acidosis and hypokalemia may develop after acute overdose and in patients taking high doses of ibuprofen for a long period (usually longer than 4 weeks), including doses exceeding the recommended daily dose.

Long-term use of ibuprofen, as with other NSAIDs, has been associated with renal papillary necrosis and other pathological changes in renal function. Renal toxicity has been reported in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. The use of NSAIDs in these patients may result in a dose-dependent decrease in prostaglandin formation and, as a secondary effect, in renal blood flow, which may rapidly lead to renal decompensation. Patients with impaired renal function, cardiac decompensation, hepatic dysfunction, the elderly, and those taking diuretics and ACE inhibitors are at greatest risk of such reactions. Discontinuation of NSAID treatment is usually accompanied by recovery from pre-treatment conditions.

Respiratory tract manifestations

Ibuprofen should be prescribed with caution to patients with bronchial asthma, chronic rhinitis, allergic diseases, including a history of them, since cases of bronchospasm, urticaria or angioedema caused by the use of NSAIDs have been reported in such patients.

Dermatological manifestations

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs) including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug-induced eosinophilia with systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with ibuprofen (see section 4.8). The majority of these reactions occurred within the first month of treatment. If signs and symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In exceptional cases, serious infectious complications of the skin and soft tissues can be caused by chickenpox.

At this stage, the effect of NSAIDs on the exacerbation of these infections cannot be ruled out. In this regard, it is recommended to avoid the use of ibuprofen in patients with chickenpox.

SLE and mixed connective tissue diseases

Caution should be exercised when prescribing the drug to patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases. There is an increased risk of aseptic meningitis (see section "Adverse reactions").

Impaired heart, kidney and liver function

Particular caution should be exercised when treating patients with impaired cardiac, hepatic, or renal function, as the use of NSAIDs may lead to deterioration of renal function.

Regular concomitant use of analgesics may increase this risk. Patients with impaired cardiac, hepatic or renal function should be treated with the lowest effective dose for the shortest possible period and should have their clinical and laboratory parameters monitored periodically, especially during long-term treatment (see section 4.3).

Hematological effects

Like other NSAIDs, ibuprofen may inhibit platelet aggregation and has shown evidence of prolonged bleeding in healthy volunteers. Therefore, patients with coagulation disorders or patients receiving anticoagulant treatment should be closely monitored.

Aseptic meningitis

In rare cases, symptoms of aseptic meningitis have been observed in patients receiving ibuprofen.

Although this is more likely to occur in patients with systemic lupus erythematosus and associated connective tissue diseases, it has also been observed in patients without evidence of chronic diseases (see section 4.8).

Ibuprofen may mask the symptoms of infection (fever, pain, and swelling).

The use of Brufen®, as with any inhibitor of prostaglandin synthesis and cyclooxygenase, is contraindicated in women attempting to conceive (see section “Use during pregnancy or lactation”). Brufen® should be discontinued in women who have fertility problems or who are undergoing fertility testing.

Allergic reactions

Caution should be exercised when prescribing ibuprofen to patients who have had hypersensitivity or allergic reactions to other substances, such as other analgesics, antipyretics, nonsteroidal anti-inflammatory drugs, as they are at increased risk of developing hypersensitivity reactions when using ibuprofen.

Caution should be exercised when prescribing ibuprofen to patients with bronchial hyperactivity (asthma), hay fever, nasal polyps or chronic obstructive airways disease or previous episodes of angioedema, due to an increased risk of allergic reactions in such patients. The latter may manifest as asthma attacks (so-called analgesic asthma), angioedema or urticaria.

Masking the symptoms of underlying infections

As with other NSAIDs, ibuprofen may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment and thereby complicate the course of the infectious disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or for the relief of pain in an infectious disease, monitoring of the disease is recommended. In the context of outpatient treatment, the patient should consult a doctor if symptoms persist or worsen.

Information on excipients

The drug contains sucrose and sorbitol. Therefore, it should not be prescribed to patients with rare hereditary conditions of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency. These factors should also be taken into account when treating patients with diabetes mellitus. The drug may be harmful to the teeth.

The drug contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

The medicine contains orange-yellow dye (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding

Impact on ability to get pregnant

There is evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis impair female fertility by affecting ovulation. This process is reversible upon discontinuation of treatment.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/fetal development. Epidemiological studies have shown an increased risk of miscarriage, cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors has been associated with an increase in pre- and post-implantation losses and embryo/fetal lethality. In addition, there was an increased incidence of various malformations, including cardiovascular malformations, in animals treated with a prostaglandin synthesis inhibitor during organogenesis.

From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This pathology may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus after treatment in the second trimester of pregnancy, which in most cases disappeared after discontinuation of treatment. Therefore, ibuprofen should not be prescribed in the first and second trimesters of pregnancy unless clearly necessary. If ibuprofen is prescribed to women planning a pregnancy or during the first or second trimester of pregnancy, the lowest possible dose should be used for the shortest possible period of time.

It may be appropriate to monitor antenatally for oligohydramnios and narrowing of the ductus arteriosus after exposure to ibuprofen for several days, starting from the 20th week of gestation. The use of ibuprofen-containing medicinal products should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.

The use of any prostaglandin inhibitors in the third trimester of pregnancy may affect the fetus, causing:

development of cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);

renal dysfunction (see above).

At the end of pregnancy, prostaglandin synthesis inhibitors can affect the condition of the mother and child:

possible prolongation of bleeding time, anti-aggregation effect, which can occur even at very low doses;

suppression of uterine contractility, which may be accompanied by delayed and prolonged labor.

Therefore, the use of ibuprofen in the third trimester of pregnancy is contraindicated (see section "Contraindications").

Childbirth

Ibuprofen is not recommended for use during labor. It may delay or prolong labor, as well as prolong bleeding time in both mother and baby.

Use during breastfeeding

In a limited number of studies, ibuprofen has been detected in breast milk at very low concentrations. Ibuprofen is not recommended for use in breastfeeding women.

Ability to influence reaction speed when driving vehicles or other mechanisms

Taking ibuprofen may affect the reaction speed of patients, as cephalalgia, drowsiness, dizziness, fatigue and visual disturbances may occur. This should be borne in mind when engaging in activities that require increased concentration, such as driving or operating other mechanisms. This is especially true when taking ibuprofen and alcohol simultaneously.

Method of administration and doses

Doses

For oral administration and short-term use only.

Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special warnings and precautions for use").

The dose of ibuprofen depends on the patient's age and body weight. The maximum single dose for adolescents should not exceed 400 mg of ibuprofen.

A single dose exceeding 400 mg does not provide a better analgesic effect. The interval between doses should be at least 4 hours.

The total dose for adolescents should not exceed 1200 mg of ibuprofen in 24 hours.

Adolescents (ages 12 and older)

200–400 mg (10–20 ml) as a single dose or 3–4 times daily.

For children, the daily dose is 20 mg/kg per day, which should be divided into 3–4 doses, as described in the table below (the data in the table are given as an example for children with a body weight of 7 kg to 30 kg, but are not limited to them).

To correctly calculate the daily dose of the drug, it is assumed that 1 ml of syrup per 1 kg of the child's body weight is equivalent to 20 mg of ibuprofen (for example, for a child weighing 9 kg, 9 ml of syrup is used per day, which is equivalent to 180 mg of ibuprofen). To calculate a single dose, the daily dose should be divided into 3–4 doses.

Brufen®, syrup 20 mg/ml, is not recommended for use in children weighing less than 7 kg.

The syrup can be used using the measuring syringe included in the package with the drug.

The drug can be used on an empty stomach - to quickly achieve the effect of the drug. Patients suffering from gastrointestinal diseases should take the drug with meals.

There are no specific recommendations on whether the drug should be taken with food.

The drug can be used for no more than 3 days without consulting a doctor.

Children under 6 months of age: If symptoms worsen or persist for more than 24 hours after starting treatment, you should consult a doctor immediately.

If symptoms persist for more than 3 days after the start of treatment or worsen in children aged 6 months and older and adolescents, a doctor should be consulted.

Patients with renal impairment

Patients with mild to moderate renal impairment should be treated with the lowest possible dose for the shortest duration necessary to control symptoms and renal function should be monitored (for patients with severe renal impairment, see section 4.3).

Patients with hepatic impairment (see section "Pharmacological properties")

In patients with mild to moderate hepatic impairment, the lowest possible dose should be used for the shortest duration necessary to control symptoms, and liver function should be monitored. Brufen® is contraindicated in patients with severe hepatic impairment (for patients with severe hepatic impairment, see section "Contraindications").

Children.

Used for children weighing from 7 kg.

Overdose

Toxicity

Signs of toxicity in children or adults have not usually been observed at doses below 100 mg/kg. However, supportive measures may be necessary in some cases. Signs of toxicity in children have been observed after doses of 400 mg/kg and above. In adults, the dose-dependent effect is less pronounced. The half-life in overdose is 1.5 to 3 hours.

Symptoms

In most patients, symptoms of ibuprofen overdose appear within 4 to 6 hours after taking the drug.

The most common symptoms of overdose include nausea, vomiting, abdominal pain, lethargy, and drowsiness.

Central nervous system (CNS) manifestations include headache, tinnitus, dizziness, seizures, and loss of consciousness.

Cardiovascular toxicity has been reported, including hypotension, bradycardia and tachycardia. In case of significant overdose, renal and hepatic damage may occur. Significant overdose is usually well tolerated if no other drugs are used. In severe poisoning, metabolic acidosis and an increase in prothrombin time/international normalized ratio (INR) may occur, probably due to interaction with circulating clotting factors. Prolonged use at doses higher than recommended may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and general weakness (see sections 4.4 and 4.8).

Treatment

There is no specific antidote for ibuprofen overdose. Patients should be treated symptomatically. Activated charcoal should be considered within one hour of ingestion of a potentially toxic amount. Serum electrolytes should be corrected if necessary. If the amount ingested exceeds 400 mg/kg, gastric lavage/emptying is recommended within one hour of ingestion, followed by symptomatic treatment. Treatment should include maintaining a patent airway and monitoring cardiac function and vital signs until the patient is stable. For the most up-to-date information, contact your local poison control center.

Side effects

The most common adverse reactions are gastrointestinal disorders. There is a risk of peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported after taking the drug (see section "Special warnings and precautions for use").

Gastritis has been reported less frequently.

When taking the drug, a temporary burning sensation in the mouth or throat may occur.

;Hypersensitivity

Hypersensitivity reactions have been observed with NSAIDs. They are represented by: non-specific allergic reactions and anaphylactic reactions, respiratory system reactivity including bronchial asthma, exacerbation of bronchial asthma, bronchospasm or dyspnoea, or mixed skin lesions including rash of various types, pruritus, urticaria, purpura, angioedema and, in extremely rare cases, erythema multiforme and bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis).

;Infections and invasions

Cases of exacerbation of skin inflammation caused by infection (e.g. development of necrotizing fasciitis) have been described during the use of NSAIDs. If signs of infection appear or worsen during the use of ibuprofen, the patient should immediately consult a doctor.

;Skin and subcutaneous tissue damage

In exceptional cases, severe skin infections and soft tissue complications may occur in association with chickenpox (see also “Infections and Invasions” and the “Special Precautions for Use” section).

;Cardiovascular system disorders

Clinical trial data suggest that the use of ibuprofen, especially at high doses (2400 mg per day), may slightly increase the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section "Special warnings and precautions for use").

The following adverse reactions, which may be associated with ibuprofen, are listed below, classified by frequency and system organ class according to MedRA. The following frequency groups are distinguished: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/100 to <1/10), rare (≥1/100 to <1/10