Ibuprofen b.braun

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN B. BRAUN (IBUPROFEN B. BRAUN)

Composition:

Active substance: ibuprofen;

1 ml of solution contains 4 mg of ibuprofen;

50 ml of solution contains 200 mg of ibuprofen.

Excipients: L-arginine, sodium chloride, sodium hydroxide 1M, hydrochloric acid 1M, water for injections.

Pharmaceutical form. Solution for infusion.

Main physico-chemical properties: clear, colorless to pale yellow solution, practically free from visible particles.

pH: 6.8–7.8.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01AE01.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that has demonstrated efficacy in standard experimental models of inflammation in animals, likely due to inhibition of prostaglandin synthesis. In humans, ibuprofen exerts antipyretic effects and reduces pain and inflammation-related swelling. Additionally, ibuprofen reversibly inhibits platelet aggregation induced by adenosine diphosphate (ADP) and collagen.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both are administered concomitantly. Some pharmacodynamic studies have shown that administration of a single 400 mg dose of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) resulted in reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty exists regarding the extrapolation of these findings to clinical settings, it is possible that regular, long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. Such a clinically significant effect is considered unlikely with occasional, intermittent use of ibuprofen (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Pharmacokinetics

Absorption

"Ibuprofen B. Braun" is administered intravenously; therefore, the absorption process does not occur, and the bioavailability of ibuprofen is 100%.

After intravenous administration, the maximum concentration of the S-enantiomer (active) and R-enantiomer is reached approximately 40 minutes after the start of infusion, with the recommended infusion duration of 30 minutes.

Distribution

The calculated volume of distribution ranges from 0.11 to 0.21 L/kg. Ibuprofen is highly bound to plasma proteins, primarily to albumin.

Metabolism

Ibuprofen is metabolized in the liver into two inactive metabolites, which, together with unchanged ibuprofen, are excreted by the kidneys either unchanged or as conjugates.

After oral administration, ibuprofen is rapidly absorbed partially in the stomach and more completely in the small intestine. Following hepatic metabolism (hydroxylation, carboxylation), pharmacologically inactive metabolites are completely eliminated predominantly via the kidneys (90%), and also through bile.

Elimination

Renal elimination occurs rapidly and completely. The elimination half-life is approximately 2 hours.

Linearity/Non-linearity

Ibuprofen exhibits linearity of the area under the plasma concentration-time curve (AUC) after single doses of ibuprofen (in the range of 200–800 mg).

Pharmacokinetic/Pharmacodynamic Relationship

There is a correlation between plasma levels of ibuprofen, its pharmacodynamic properties, and overall safety profile. The pharmacokinetics of ibuprofen are stereoselective following both intravenous and oral administration.

The mechanism of action and pharmacology following intravenous administration do not differ from those observed with oral administration of ibuprofen.

Special Patient Populations

Patients with Renal Impairment

In patients with mild renal insufficiency, increased levels of unbound (S)-ibuprofen, higher AUC values of (S)-ibuprofen, and an increased AUC (S/R) enantiomeric ratio were observed compared to healthy volunteers.

In patients with end-stage renal disease on dialysis, the mean free fraction of ibuprofen was approximately 3% compared to about 1% in healthy volunteers. Severe renal impairment may lead to accumulation of ibuprofen metabolites. The clinical significance of this effect is unknown. Metabolites can be removed by hemodialysis (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Patients with Hepatic Impairment

In patients with liver cirrhosis and moderate hepatic insufficiency (Child-Pugh score 6–10), receiving racemic ibuprofen, an average two-fold prolongation of elimination half-life was observed, and the AUC (S/R) enantiomeric ratio was significantly lower compared to healthy volunteers, indicating impaired metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Children

The pharmacokinetic properties of ibuprofen in children are similar to those in adults.

Clinical Characteristics

Indications
“Ibuprofen B. Braun” is indicated for use in children with a body weight of 20 kg and above and aged 6 years and older for short-term symptomatic treatment of acute moderate pain and short-term symptomatic treatment of fever, when intravenous administration is clinically justified and when other routes of administration are not feasible.

Contraindications

• Hypersensitivity to ibuprofen, to other NSAIDs, or to any of the excipients of the medicinal product.
• Bronchospasm, asthma, rhinitis, angioedema, or urticaria in medical history associated with the use of acetylsalicylic acid (ASA) or other NSAIDs.
• Conditions associated with increased bleeding tendency or active bleeding, such as severe coagulation disorders (e.g., thrombocytopenia).
• Active or recurrent peptic ulcer / gastrointestinal bleeding in medical history (two or more documented episodes of ulceration or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
• Cerebrovascular or other active bleeding.
• Severe hepatic or renal insufficiency.
• Severe heart failure (NYHA Class IV [New York Heart Association]).
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
• Third trimester of pregnancy (see section "Use in pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction

Other NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors and salicylates. Concomitant use of two or more NSAIDs increases the risk of gastrointestinal ulceration and bleeding due to synergistic effects. Therefore, simultaneous use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions for use").

Acetylsalicylic acid (ASA). Concomitant use of ibuprofen and acetylsalicylic acid (ASA) is generally not recommended due to the potential for increased adverse reactions. Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose ASA on platelet aggregation when administered concomitantly. Although uncertainty exists regarding the extrapolation of these data to clinical settings, it is possible that regular, prolonged use of ibuprofen may reduce the cardioprotective effect of low-dose ASA. A clinically significant effect is considered unlikely with occasional use of ibuprofen (see section "Pharmacodynamics").

Lithium. Concomitant use of ibuprofen with lithium preparations may increase serum lithium levels.
Serum lithium levels should be monitored.

Cardiac glycosides (digoxin). NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides. Monitoring of serum digoxin levels is recommended.

Pentoxifylline. In patients receiving ibuprofen in combination with pentoxifylline, the risk of bleeding is increased; therefore, bleeding time should be monitored.

Phenytoin. Serum phenytoin levels may increase during concomitant treatment with ibuprofen, increasing the risk of toxicity.

Antihypertensive agents (diuretics, ACE inhibitors, beta-blockers, and angiotensin II antagonists). Diuretics and angiotensin-converting enzyme (ACE) inhibitors may enhance the nephrotoxicity of nonsteroidal anti-inflammatory drugs. NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents, including ACE inhibitors and beta-blockers. In patients with renal impairment (e.g., dehydrated patients or elderly patients with impaired renal function), concomitant use of ACE inhibitors or angiotensin II antagonists with drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should be instructed to maintain adequate fluid intake. Renal function should be monitored at the start of concomitant therapy and periodically thereafter.

Concomitant use of ibuprofen and ACE inhibitors may lead to hyperkalemia.

Potassium-sparing diuretics. Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (monitoring of serum potassium levels is recommended).

Captopril. Experimental studies indicate that ibuprofen counteracts the sodium-excreting effect of captopril.

Corticosteroids. When used concomitantly with ibuprofen, the risk of gastrointestinal ulceration or bleeding is increased (see section "Special precautions for use").

Antiplatelet agents (e.g., clopidogrel and ticlopidine) and selective serotonin reuptake inhibitors (SSRIs). Concomitant use with ibuprofen increases the risk of gastrointestinal bleeding (see section "Special precautions for use"). NSAIDs should not be combined with ticlopidine due to the risk of additive effects on platelet inhibition.

Metotrexate at doses of 15 mg/week or higher. NSAIDs inhibit tubular secretion of methotrexate and may cause metabolic interactions leading to reduced methotrexate clearance. Administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate concentrations and enhance its toxic effects. Therefore, concomitant use of NSAIDs and high-dose methotrexate should be avoided. Potential interaction risk should also be considered during low-dose methotrexate therapy, especially in patients with impaired renal function. Renal function should be monitored during combination therapy.

Low-dose methotrexate — less than 15 mg/week. Ibuprofen increases methotrexate levels. When used in combination with low-dose methotrexate, blood parameters should be closely monitored, especially during the first weeks of concomitant use. Enhanced monitoring is also necessary in case of worsening renal function, even mild, and in elderly patients. Renal function should be monitored to prevent possible reduction in methotrexate clearance.

Cyclosporine. The risk of cyclosporine-induced nephrotoxicity is increased when used concomitantly with certain nonsteroidal anti-inflammatory drugs. This effect cannot be excluded when cyclosporine is used concomitantly with ibuprofen.

Anticoagulants. NSAIDs may potentiate the effects of anticoagulants such as warfarin (see section "Special precautions for use"). In case of concomitant therapy, coagulation status should be monitored.

Sulfonylureas. NSAIDs may enhance the hypoglycemic effect of sulfonylureas. Blood glucose levels should be monitored during concomitant therapy.

Tacrolimus. Concomitant use with ibuprofen increases the risk of nephrotoxicity.

Zidovudine. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia who concomitantly use zidovudine and ibuprofen. An increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs is known. Blood analysis is recommended 1–2 weeks after initiation of concomitant therapy.

Probenecid and sulfinpyrazone. Medicinal products containing probenecid or sulfinpyrazone may slow down the elimination of ibuprofen.

Quinolone antibiotics. Animal studies indicate that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones may have an increased risk of developing seizures.

CYP2C9 inhibitors. Concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) showed an approximately 80–100% increase in the effect of S(+)-ibuprofen. Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are used with voriconazole or fluconazole.

Mifepristone. If NSAIDs are used 8–12 days after mifepristone intake, they may reduce its effect.

Alcohol. Ibuprofen use should be avoided in individuals who regularly consume alcohol (14–20 or more drinks per week) due to an increased risk of significant gastrointestinal adverse effects, including bleeding.

Aminoglycosides. NSAIDs may reduce the excretion of aminoglycosides and increase their toxicity. Strict monitoring of serum aminoglycoside levels is recommended during concomitant use with ibuprofen.

Herbal extracts. Ginkgo biloba increases the risk of bleeding when used with NSAIDs.

Special precautions

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary (see section "Adverse reactions").

Concomitant use of "Ibuprofen B. Braun" with NSAIDs, including selective COX-2 inhibitors (coxibs), should be avoided.

Gastrointestinal risks. Cases of gastrointestinal bleeding, perforation, and ulcers, sometimes fatal, have been reported with NSAID therapy at any stage of treatment, with or without warning symptoms, regardless of whether the patient has a history of gastrointestinal complications.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses and in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should initiate treatment with the lowest available dose. For these patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid (ASA) or other drugs increasing gastrointestinal risk, consideration should be given to co-therapy with protective agents (e.g., misoprostol or proton pump inhibitors) (see below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, particularly elderly individuals, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during initial treatment phases.

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

If gastrointestinal bleeding or ulceration occurs in patients taking "Ibuprofen B. Braun", treatment should be discontinued (see section "Contraindications").

NSAIDs should be administered with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated (see section "Adverse reactions").

Cardiovascular and cerebrovascular effects. Particular caution is required in patients with a history of hypertension and/or mild to moderate heart failure, as fluid retention, hypertension, and edema have been reported with NSAID therapy. Clinical trial data indicate that ibuprofen use, particularly at high doses (2400 mg daily), slightly increases the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological data suggest that low-dose ibuprofen (e.g., ≤ 1200 mg daily) does not significantly increase the risk of arterial thrombotic complications.

Patients with uncontrolled hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful clinical assessment. High doses of the drug should be avoided.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome presents with cardiovascular symptoms due to coronary artery spasm caused by an allergic or hypersensitivity reaction, potentially leading to myocardial infarction.

Careful consideration should also be given before initiating long-term treatment in patients with cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus).

Severe skin adverse reactions. Serious skin adverse reactions have been reported with ibuprofen use, including exfoliative dermatitis, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions").

Most such reactions occur within the first month of treatment. If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative therapy considered (if necessary).

Hepatic or renal impairment, dehydration. Ibuprofen should be used with caution in patients with a history of hepatic or renal dysfunction, especially when concomitantly treated with diuretics, as prostaglandin inhibition may lead to fluid retention and impaired renal function. These patients should receive the lowest possible dose of ibuprofen, and renal function should be monitored regularly.

There is a risk of renal failure in dehydrated children and adolescents.

In cases of dehydration, adequate fluid intake should be ensured. Particular caution is required in treating patients with dehydration, for example due to diarrhea, as dehydration may precipitate renal failure.

Regular use of analgesics, especially in combination with different pain-relieving substances, may lead to kidney damage with a risk of renal failure (analgesic nephropathy). This risk is increased in elderly patients and in patients with renal impairment, heart failure, hepatic dysfunction, and those taking diuretics or ACE inhibitors. After discontinuation of NSAID therapy, the patient's condition usually improves.

Like other NSAIDs, ibuprofen may cause mild, transient increases in some liver function parameters, as well as significant elevations in transaminase levels. If marked increases in these parameters occur, treatment should be discontinued (see section "Contraindications").

Anaphylactic reactions. During intravenous infusion, careful monitoring of the patient is recommended as standard practice, especially at the beginning of the infusion, to detect any anaphylactic reaction caused by the active or excipient substances.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) occur. At the first signs of a hypersensitivity reaction after administration of "Ibuprofen B. Braun", therapy must be discontinued and symptomatic treatment initiated by specialists according to the symptoms present.

Respiratory disorders. Ibuprofen should be used with caution in patients with bronchial asthma, chronic rhinitis, or active or past allergic diseases, as NSAIDs have been reported to cause bronchospasm, urticaria, or angioedema in such patients.

Hematological reactions. Ibuprofen may transiently inhibit platelet function (platelet aggregation), prolonging bleeding time and increasing the risk of hemorrhage.

Ibuprofen should be used with caution in patients taking ASA for antiplatelet aggregation (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacodynamics").

Close monitoring is recommended in patients with coagulation disorders or increased bleeding risk (e.g., postoperative patients), especially when the drug is used immediately after major surgery.

With prolonged use of ibuprofen, liver and kidney function tests and blood counts should be monitored regularly.

Ibuprofen should only be used after careful benefit-risk assessment in patients with inherited porphyrin metabolism disorders (e.g., acute intermittent porphyria).

The risk of adverse effects related to the active substance, particularly gastrointestinal or central nervous system effects, is increased when NSAIDs are used concomitantly with alcohol.

Ibuprofen should be used with caution in patients with certain conditions that may worsen:

• patients with allergic reactions to other substances — due to an increased risk of hypersensitivity reactions with this medicinal product;
• patients with hay fever, nasal polyps, or chronic obstructive respiratory diseases — due to an increased risk of allergic reactions, which may manifest as asthma attacks (so-called analgesic-induced asthma), Quincke's edema, or urticaria.

Aseptic meningitis. Cases of aseptic meningitis have been reported with ibuprofen use in patients with systemic lupus erythematosus (SLE). Although this is more likely in patients with SLE and related connective tissue disorders, aseptic meningitis has also occurred in some patients without underlying chronic disease. This should be considered when prescribing ibuprofen (see section "Adverse reactions").

Ophthalmological effects. With oral ibuprofen use, cases of blurred vision or visual disturbances, scotomata, and color vision disturbances have been reported. If a patient develops these symptoms, ibuprofen use should be discontinued and the patient referred for ophthalmological examination, including assessment of central visual field and color perception.

Other reactions. Long-term use of analgesics may cause headache, which should not be treated with increased doses of the drug.

"Ibuprofen B. Braun" should be avoided in cases of varicella (chickenpox), as in rare cases varicella may lead to serious skin and soft tissue infections. The role of NSAIDs in exacerbating these infections cannot currently be excluded.

Masking symptoms of underlying infections. "Ibuprofen B. Braun" may mask symptoms of infection, potentially leading to delayed treatment and worsening of the disease. Such symptom masking has been observed in bacterial pneumonia and bacterial complications of varicella. When "Ibuprofen B. Braun" is prescribed to reduce fever or relieve pain associated with infection, monitoring of the infection's course is recommended. The patient should consult a physician if symptoms persist or worsen.

Effects on laboratory test parameters:

• bleeding time (may be prolonged up to 1 day after discontinuation of therapy);
• blood glucose concentration (may decrease);
• creatinine clearance (may decrease);
• hematocrit or hemoglobin levels (may decrease);
• blood urea nitrogen, serum creatinine, and potassium levels (may increase);
• liver function tests: increased transaminase levels.

Sodium content warning

The medicinal product "Ibuprofen B. Braun" contains 179 mg of sodium per 50 ml vial, equivalent to 9% of the WHO recommended maximum daily intake of 2 g sodium for adults.

Use during pregnancy or breastfeeding

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

From the 20th week of gestation, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, cases of arterial duct constriction have been reported after second-trimester treatment, which mostly resolve after stopping therapy. Therefore, ibuprofen should not be used during the first and second trimesters of pregnancy except when strictly necessary. If ibuprofen is prescribed to women attempting to conceive or during the first and second trimesters, the dose should be as low as possible and treatment duration as short as possible.

Although intravenous ibuprofen is indicated for a maximum of 3 days of treatment, the need for prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of exposure starting from the 20th week of pregnancy. If oligohydramnios or arterial duct constriction is detected, ibuprofen use should be discontinued.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors:

• may affect the fetus by:
  • cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
  • impaired renal function (see above).
• may affect the mother at the end of pregnancy and the newborn by:
  • prolonged bleeding time and anti-aggregatory effect, which may occur even at very low doses;
  • inhibition of uterine contractions, leading to delayed or prolonged labor.

Ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding

Ibuprofen and its metabolites may pass into breast milk in low concentrations. No harmful effects on infants are currently known, so interruption of breastfeeding is generally not required for short-term, low-dose treatment. However, interruption of breastfeeding is recommended when doses exceeding 1200 mg daily are used, due to ibuprofen's ability to inhibit prostaglandin synthesis in newborns.

Fertility

According to some data, medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. This effect is reversible upon discontinuation of treatment.

Ability to influence reaction speed when driving or operating machinery

A single dose or short-term use of ibuprofen does not require special precautions. However, adverse reactions such as fatigue and dizziness may impair reaction time, potentially reducing the ability to drive or operate machinery. This is particularly relevant when the drug is used concomitantly with alcohol.

Method of Administration and Dosage

Dosage

The lowest effective dose should be used for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use"). This may minimize the risk of adverse reactions.

The medicinal product should be used only when oral administration is not appropriate. Patients should be switched to oral therapy as soon as possible.

This medicinal product is indicated for use for the shortest possible duration. Treatment should not exceed 3 days.

Adequate hydration of the patient should be maintained to minimize the risk of possible renal adverse reactions.

The recommended dose of ibuprofen for children and adolescents depends on body weight or age.

Generally, the recommended daily dose is 20–30 mg/kg body weight given in 3–4 divided doses (single doses of 5–10 mg/kg).

Children weighing 20–29 kg (6–9 years of age): 200 mg ibuprofen up to 3 times daily; do not exceed the maximum daily dose of 600 mg.

Children weighing 30–39 kg (10–11 years of age): 200 mg ibuprofen up to 4 times daily; do not exceed the maximum daily dose of 800 mg.

Children weighing 40 kg and above (12–17 years of age): 200 mg to 400 mg ibuprofen up to 3 times daily; do not exceed the maximum daily dose of 1200 mg.

Not recommended for children weighing less than 20 kg or under 6 years of age.

The dosing interval should be selected according to symptom severity and the maximum daily dose. The interval between doses should not be less than 6 hours. The recommended maximum daily dose should not be exceeded.

Renal Impairment

When using NSAIDs, patients with renal impairment require careful monitoring, including monitoring of kidney function. In patients with mild to moderate renal impairment, the dose should be reduced and maintained as low as possible for the shortest duration necessary to control symptoms. This medicinal product is contraindicated in patients with severe renal impairment (see section "Contraindications").

Hepatic Impairment

Precautions should be taken when using NSAIDs in this population, although no differences in pharmacokinetic profile have been observed. In patients with mild to moderate hepatic impairment, treatment should be initiated with reduced doses, maintained as low as possible for the shortest duration, and patients should be under close monitoring. "Ibuprofen B. Braun" is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

Method of Administration

For intravenous use only.

"Ibuprofen B. Braun" is prescribed by a physician and should be administered only by qualified healthcare professionals in settings where appropriate equipment is available.

The medicinal product should be administered as an intravenous infusion over 30 minutes.

Children

"Ibuprofen B. Braun" is indicated for use in children with a body weight of at least 20 kg and aged 6 years and above.

Not recommended for children weighing less than 20 kg or under 6 years of age.

Overdose

Symptoms

Central nervous system disturbances: headache, tinnitus, confusion, ataxia, nystagmus, as well as abdominal pain, nausea, vomiting, which may occur as symptoms of overdose. In severe poisoning, drowsiness, loss of consciousness, seizures (predominantly in children), dizziness, hematuria, and hypothermia may occur. Additionally, gastrointestinal bleeding, hepatic and renal functional impairments may occur. Arterial hypotension, respiratory depression, and cyanosis may also be observed.

Metabolic acidosis may occur in cases of severe poisoning.

Prolonged use of ibuprofen at doses higher than recommended, or overdose, may lead to renal tubular acidosis and hypokalemia.

Treatment

Treatment is symptomatic; there is no specific antidote.

Therapeutic management of intoxication should be based on the severity, plasma levels, and clinical symptoms, in accordance with standard intensive care practices.

Adverse reactions

The most common adverse reactions are gastrointestinal. Peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal, especially in elderly patients, may occur (see section "Special precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported (see section "Special precautions"). Gastritis has been observed less frequently. The risk of gastrointestinal bleeding depends on the dose range and duration of treatment.

Very rarely, severe hypersensitivity reactions (including infusion site reactions, anaphylactic shock) and serious skin reactions such as bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), as well as erythema multiforme and alopecia have been reported.

Exacerbation of inflammation associated with infection (e.g. development of necrotizing fasciitis) has been described in connection with the use of nonsteroidal anti-inflammatory drugs. This may be related to the mechanism of action of NSAIDs.

During chickenpox, photosensitivity, allergic vasculitis, and, in exceptional cases, severe skin infections and soft tissue complications may occur (see section "Special precautions").

Edema, arterial hypertension and heart failure have been reported in association with NSAID therapy.

Clinical studies indicate that the use of ibuprofen, particularly at high doses (2400 mg/day), is associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section "Special precautions").

The frequency categories of adverse reactions to ibuprofen listed below are defined as follows:

Reporting of suspected adverse reactions

Reporting of adverse reactions after marketing authorization is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

From a microbiological standpoint, the medicinal product should be used immediately after opening. Otherwise, the user is responsible for the duration and conditions of storage prior to use.

Incompatibilities.

Compatibility studies have not been conducted; this medicinal product must not be mixed with other medicinal products.

Storage conditions. No special storage conditions required.

Prescription status. Prescription-only.

Packaging

200 mg / 50 ml:

50 ml in polyethylene bottles without secondary packaging;

50 ml in polyethylene bottles, packs of 10 or 20 bottles in a cardboard box.

Manufacturer. B. Braun Medical SA.

Manufacturer's location and address of the site of operation. Carretera de Terrassa 121, 08191 Rubi (Barcelona), Spain / Carretera de Terrassa 121, 08191 Rubi (Barcelona), Spain.