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;

100 ml of solution contains 400 mg of ibuprofen.

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

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: 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 animal models of inflammation, 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) was associated with reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty remains regarding the extrapolation of these findings to clinical settings, it is possible that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics

Absorption

"Ibuprofen B. Braun" is administered intravenously; therefore, no absorption process occurs, and the bioavailability of ibuprofen is 100%.

After intravenous administration, maximum concentrations of the S-enantiomer (active) and R-enantiomer of ibuprofen are reached approximately 40 minutes after the start of infusion, assuming 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 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 completely in the small intestine. Following hepatic metabolism (hydroxylation, carboxylation), pharmacologically inactive metabolites are completely eliminated predominantly via the kidneys (90%), as well as through bile.

Elimination

Renal elimination is rapid and complete. 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 administration and oral intake.

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 increased enantiomeric AUC (S/R) 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 impairment of renal function 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), who received racemic ibuprofen, an average two-fold prolongation of elimination half-life was observed, and the enantiomeric AUC (S/R) 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").

Clinical characteristics

Indications. "Ibuprofen B. Braun" is indicated for use in adults for the 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.
• History of bronchospasm, asthma, rhinitis, angioedema, or urticaria 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 history (two or more distinct episodes of proven ulcer or bleeding).
• History of gastrointestinal bleeding or perforation related to 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. Due to synergistic effects, concomitant use of two or more NSAIDs increases the risk of gastrointestinal ulceration and bleeding. Therefore, simultaneous use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions for use").

Acetylsalicylic acid. 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 acetylsalicylic acid on platelet aggregation when administered concomitantly. Although uncertainty exists regarding the extrapolation of these data to the clinical setting, regular long-term use of ibuprofen may potentially reduce the cardioprotective effect of low-dose acetylsalicylic acid. A clinically significant effect is considered unlikely with occasional use of ibuprofen (see section "Pharmacodynamics").

Lithium. Concomitant use of ibuprofen with lithium-containing medications 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 potentiate 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 cyclooxygenase-inhibiting drugs 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 (serum potassium levels should be checked).

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). When used concomitantly with ibuprofen, the risk of gastrointestinal bleeding is increased (see section "Special precautions for use"). NSAIDs should not be combined with ticlopidine due to the risk of additive effects on platelet function inhibition.

Methotrexate 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. The potential risk of interaction 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 required 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. When used concomitantly with ibuprofen, the risk of nephrotoxicity is increased.

Zidovudine. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia who concurrently 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 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 administration, they may reduce its effect.

Alcohol. Use of ibuprofen should be avoided in individuals who regularly consume alcohol (14–20 or more drinks per week) due to the 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 for use

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

Concomitant use of the medicinal product "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 during NSAID therapy, with or without warning symptoms, regardless of the patient's 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 start treatment with the lowest available dose. For these patients, as well as those requiring concomitant low-dose acetylsalicylic acid (ASA) or other drugs increasing gastrointestinal risk, consideration should be given to using combination 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, especially elderly individuals, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

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 used cautiously 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 do not suggest that low-dose ibuprofen (e.g., ≤1200 mg daily) increases 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 (2400 mg daily) 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, smoking), especially if high-dose ibuprofen (2400 mg daily) is required.

Serious skin adverse reactions. Serious skin adverse reactions, 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, have been reported with ibuprofen use and 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 treatment should be considered (if needed).

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

In cases of dehydration, adequate fluid intake should be ensured. Particular caution is required in treating patients with dehydration (e.g., 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 those with renal impairment, heart failure, hepatic dysfunction, or those taking diuretics or ACE inhibitors. After discontinuation of NSAID therapy, the patient's condition usually returns to baseline.

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, standard practice recommends careful monitoring of the patient, especially at the beginning of the infusion, to detect any anaphylactic reaction caused by the active or excipient substances.

Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. At the first sign of a hypersensitivity reaction after administration of "Ibuprofen B. Braun," therapy must be discontinued and symptomatic treatment should be 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 conditions, as NSAIDs have been reported to cause bronchospasm, urticaria, or angioedema in such patients.

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

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

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

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

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

The risk of adverse effects associated with the active substance, particularly gastrointestinal or central nervous system effects, increases 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, reports include visual disturbances such as blurred vision, scotoma, and color vision defects. If a patient experiences 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. Prolonged use of analgesics may cause headache, which must not be treated with increased drug doses.

The medicinal product "Ibuprofen B. Braun" should be avoided in cases of chickenpox, as, in rare instances, chickenpox 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 delaying treatment and worsening the disease course. Such symptom masking has been observed in bacterial pneumonia and bacterial complications of chickenpox. When "Ibuprofen B. Braun" is prescribed to reduce fever or relieve pain due to infection, monitoring of the infection's progression is recommended. Patients should consult a physician if symptoms persist or worsen.

Effects on laboratory test parameters:

• bleeding time (may be prolonged up to 1 day after therapy cessation);
• 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.

Warnings regarding sodium content

The medicinal product "Ibuprofen B. Braun" contains 358 mg of sodium per 100 ml vial, equivalent to 17.9% 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 suggest 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 increases 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 pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there are reports of arterial duct constriction after second-trimester treatment, which mostly resolves after stopping therapy. Therefore, ibuprofen should not be used during the first and second trimesters of pregnancy except in cases of urgent medical need. If ibuprofen is prescribed to women trying to conceive or during the first and second trimesters, the dose should be as low as possible and the treatment duration as short as possible.

Although intravenous ibuprofen is indicated for only 3 days of treatment, consideration should be given to antenatal monitoring for oligohydramnios and arterial duct constriction after ibuprofen exposure from the 20th week of pregnancy. If oligohydramnios or arterial duct constriction is detected, ibuprofen 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);
  • renal dysfunction (see above).
• may affect the mother near term and the newborn by:
  • prolonged bleeding time and antiplatelet effects, 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; therefore, for short-term treatment with lower doses, interruption of breastfeeding is generally not required. However, breastfeeding should be interrupted when doses exceeding 1200 mg daily are used, due to ibuprofen's ability to inhibit prostaglandin synthesis in newborns.

Fertility

Some data suggest that medicinal products inhibiting cyclooxygenase/prostaglandin synthesis may affect ovulation. This effect is reversible upon discontinuation of treatment.

Ability to influence reaction speed when driving or operating machinery

Single or short-term use of ibuprofen does not require precautionary measures. However, the occurrence of adverse reactions such as fatigue and dizziness may impair reaction speed, potentially reducing the ability to drive or operate machinery. This is especially relevant when the medicinal product 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.

Adults

Recommended dose: 400 mg of ibuprofen every 6–8 hours as needed.

Recommended maximum daily dose: 1200 mg — exceeding this dose is prohibited.

Elderly Patients

Caution should be exercised when using nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, in elderly patients, as such patients are generally more susceptible to adverse reactions (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"), more frequently have impaired renal, hepatic, and cardiovascular function, and often use concomitant medications. In particular, it is recommended to administer the lowest effective dose for the shortest duration necessary to control symptoms. Treatment should be regularly reviewed and discontinued if no benefit is evident or if intolerance occurs.

Renal Impairment

Patients with renal impairment require careful monitoring when NSAIDs are administered, including monitoring of renal function. Patients with mild to moderate renal impairment should receive reduced doses, 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

Caution should be exercised when using NSAIDs in this population, although no differences in pharmacokinetic profile have been observed. Patients with mild to moderate hepatic impairment should start treatment with reduced doses, maintain the dose as low as possible for the shortest duration, and remain under close supervision. "Ibuprofen B. Braun" is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

Children

This medicinal product should not be used in children and adolescents. The use of "Ibuprofen B. Braun" in children and adolescents has not been studied. Safety and efficacy have not been established.

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 a 30-minute intravenous infusion.

Overdose

Symptoms

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

In severe poisoning, metabolic acidosis may develop.

Prolonged use of ibuprofen at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia.

Treatment

Treatment is symptomatic; there is no specific antidote.

Therapeutic management options for intoxication are determined by the degree, level, and clinical symptoms according to standard intensive care practices.

Adverse Reactions

The most commonly observed adverse reactions are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes with fatal outcome, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn's disease have been reported (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently. The risk of gastrointestinal bleeding is dose- and duration-dependent.

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), erythema multiforme, and alopecia have been reported.

Exacerbations of inflammation-related infections (e.g., development of necrotizing fasciitis) have been described in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). This may be related to the mechanism of action of NSAIDs.

During varicella (chickenpox), photosensitivity, allergic vasculitis, and, in rare cases, severe skin infections and soft tissue complications may occur (see section "Special Warnings and Precautions for Use").

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 Warnings and Precautions for Use").

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

Very common:	≥ 1/10
Common:	from ≥ 1/100 to < 1/10
Uncommon:	from ≥ 1/1000 to < 1/100
Rare:	from ≥ 1/10000 to <1/1000
Very rare:	< 1/10000
Frequency not known:	cannot be estimated from available data

Body Systems	Frequency	Adverse Reactions
Infections and infestations	Very rare	Exacerbations of infection-related inflammation (e.g., development of necrotizing fasciitis) coinciding with use of nonsteroidal anti-inflammatory drugs have been reported. This may be related to the mechanism of action of NSAIDs.
Blood and lymphatic system disorders	Very rare	Disorders of blood formation (anemia, agranulocytosis, leukopenia, thrombocytopenia, and pancytopenia). Initial symptoms include fever, sore throat, oral ulcers, flu-like symptoms, severe fatigue, nosebleeds, and skin bleeding.
Immune system disorders	Uncommon	Hypersensitivity reactions with skin rash, itching, and asthma attacks (sometimes with decreased blood pressure).
	Rare	Anaphylaxis.
	Very rare	Systemic lupus erythematosus, severe hypersensitivity reactions, facial swelling, tongue swelling, laryngeal edema with airway narrowing, dyspnea, palpitations, arterial hypotension, and life-threatening shock.
	Frequency not known	Anaphylactic shock.
Psychiatric disorders	Uncommon	Anxiety, restlessness.
	Rare	Psychotic reactions, nervousness, irritability, confusion or disorientation, depression.
Nervous system disorders	Very common	Exhaustion or drowsiness, headache, dizziness.
	Uncommon	Insomnia, excitement, irritability, or fatigue.
	Rare	Paresthesia.
	Very rare	Aseptic meningitis (neck stiffness, headache, nausea, vomiting, fever, or confusion). May occur in patients with autoimmune diseases (systemic lupus erythematosus, mixed connective tissue diseases).
Eye disorders	Uncommon	Visual disturbances.
	Rare	Reversible toxic amblyopia.
	Frequency not known	Papilledema.
Ear and labyrinth disorders	Common	Dizziness.
	Uncommon	Tinnitus.
	Rare	Hearing impairment.
Cardiac disorders	Very rare	Palpitations, heart failure, myocardial infarction.
	Frequency not known	Kounis syndrome.
Vascular disorders	Very rare	Arterial hypertension.
	Frequency not known	Bleeding (see also section "Special precautions for use"), excluding gastrointestinal bleeding (see below "Gastrointestinal disorders"). Arterial thrombosis.
Respiratory, thoracic and mediastinal disorders	Very rare	Asthma, bronchospasm, dyspnea, and wheezing.
Gastrointestinal disorders	Very common	Heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, and minor gastrointestinal bleeding, which may exceptionally lead to anemia.
	Common	Gastrointestinal ulcers, potentially with bleeding and perforation. Ulcerative stomatitis, exacerbation of colitis and Crohn's disease.
	Uncommon	Gastritis.
	Rare	Esophageal stricture, exacerbation of diverticulitis, unspecified hemorrhagic colitis. If gastrointestinal bleeding occurs, it may cause anemia and hematemesis.
	Very rare	Esophagitis, pancreatitis, formation of intestinal and diaphragm-like strictures.
Hepatobiliary disorders	Rare	Jaundice, liver function abnormalities, hepatic injury, acute hepatitis.
	Frequency not known	Hepatic failure.
Skin and subcutaneous tissue disorders	Common	Skin rashes.
	Uncommon	Urticaria, pruritus, purpura (including allergic purpura), skin eruptions.
	Very rare	Severe skin adverse reactions (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis), alopecia. Photosensitivity reactions and allergic vasculitis. In exceptional cases, severe skin infections and soft tissue complications (see also "Infections and infestations" above).
	Frequency not known	Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acute generalized exanthematous pustulosis.
Musculoskeletal and connective tissue disorders	Rare	Neck rigidity.
Renal and urinary disorders	Uncommon	Reduced urine output and development of edema, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis (which may be accompanied by acute renal failure), hematuria.
	Rare	Renal tissue injury (papillary necrosis), increased serum uric acid concentration.
	Very rare	Papillary necrosis.
General disorders and administration site reactions	Common	Pain and burning sensation at the injection site.
	Very rare	Exacerbation of infection-related inflammation.
	Frequency not known	Injection site reactions such as swelling, hematoma, or bleeding.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of a medicinal product is highly important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via 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 assumes responsibility 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

400 mg / 100 ml:

100 ml in polyethylene bottles without secondary packaging;

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

Manufacturer. B. Braun Medical S.A. / B. Braun Medical SA.

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