Imet® for children 4 %

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IMET® FOR CHILDREN 4% (IMET® FOR CHILDREN 4%)

Composition:

Active substance: ibuprofen;

5 ml of oral suspension contains 200 mg of ibuprofen;

Excipients: sodium benzoate, anhydrous citric acid, sodium citrate, sodium saccharin, sodium chloride, hypromellose, xanthan gum, maltitol liquid, glycerin, thaumatin, purified water, strawberry flavor.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: viscous suspension free from extraneous particles, white or almost white in color, with a characteristic strawberry odor.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. ATC code M01AE01.

Pharmacological Properties.

Pharmacodynamics.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) whose mechanism of action involves inhibition of prostaglandin synthesis in typical inflammatory responses in animals. In humans, ibuprofen reduces pain, swelling, and inflammatory fever. Additionally, ibuprofen inhibits platelet aggregation by suppressing the synthesis of ADP and collagen.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when these drugs are used concomitantly. In one study, when a single 400 mg dose of ibuprofen was administered within 8 hours before or 30 minutes after immediate-release acetylsalicylic acid (81 mg), a reduction in the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although there is uncertainty regarding extrapolation of these data to the clinical setting, it cannot be excluded that systematic long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With non-systematic use of ibuprofen, a clinically significant effect is considered unlikely (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics.

After oral administration, ibuprofen is partially absorbed in the stomach and further completely absorbed in the small intestine. Following hepatic metabolism (hydroxylation, carboxylation), pharmacologically inactive metabolites are excreted predominantly in urine (90%) and also in bile. The elimination half-life in healthy volunteers and patients with liver or kidney disease ranges from 1.8 to 3.5 hours. The drug is approximately 99% bound to plasma proteins. After oral administration of the immediate-release dosage form, maximum plasma concentration (Cmax) is reached within 1–2 hours. Ibuprofen has been shown to exhibit linear kinetics over the dose range of 200 mg to 400 mg. At higher doses, the drug exhibits non-linear kinetics.

Renal impairment. In patients with mild renal impairment, increased levels of unbound (S)-ibuprofen, higher values of the area under the plasma concentration-time curve (AUC) for (S)-ibuprofen, and an increased enantiomeric AUC (S/R) ratio were observed compared to healthy volunteers.

In patients with end-stage renal disease undergoing hemodialysis, the mean free fraction of ibuprofen was approximately 3%, compared to 1% in healthy volunteers. Severe renal impairment may lead to accumulation of ibuprofen metabolites. The clinical significance of this phenomenon is unknown. Metabolites may be removed by hemodialysis.

Hepatic impairment. In patients with liver cirrhosis and moderate hepatic impairment (Child–Pugh score 6–10), who received racemic ibuprofen, the elimination half-life was on average twice as long, and the enantiomeric AUC (S/R) ratio was significantly lower compared to healthy volunteers, indicating impaired metabolic conversion of (R)-ibuprofen to the active (S)-enantiomer.

Preclinical safety data.

Subchronic and chronic toxicity of ibuprofen in animal experiments was primarily manifested as gastrointestinal lesions and ulcers.

In vitro and in vivo studies provided no clinically relevant evidence of mutagenic potential of ibuprofen. No evidence of carcinogenic effects of ibuprofen was found in studies in rats and mice. Ibuprofen inhibited ovulation in rabbits and disrupted implantation in various animal species (rabbits, rats, mice). Experimental studies in rats and rabbits showed that ibuprofen crosses the placenta. Following administration of doses toxic to the mother, increased incidence of developmental abnormalities (ventricular septal defects) was observed in rat offspring.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of fever and mild to moderate pain.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Known history of bronchospasm, asthma, rhinitis, angioedema (Quincke's edema), or urticaria after taking acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Hematopoietic disorders of unknown origin.
• Presence of, or history of recurrent peptic ulcers or gastrointestinal bleeding (two or more separate episodes of confirmed ulceration or bleeding).
• History of gastrointestinal bleeding or perforation related to previous use of NSAIDs.
• Cerebrovascular or other active bleeding.
• Severe impairment of liver, kidney, or heart function (NYHA class IV).
• Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Ibuprofen should be used with caution when co-administered with the following agents.

Other NSAIDs and acetylsalicylic acid. Concomitant use of two or more NSAIDs increases the risk of gastrointestinal ulceration and bleeding due to synergistic effects. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided.

Acetylsalicylic acid. In general, concomitant use of ibuprofen and acetylsalicylic acid is not recommended due to the potential for increased adverse reactions. Experimental data indicate that ibuprofen may interfere with the antiplatelet effect of low-dose acetylsalicylic acid when both are administered together. However, due to limitations and uncertainty in extrapolating these data to clinical practice, it cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interactions are considered unlikely with occasional, short-term use of ibuprofen (see section "Pharmacodynamics").

Digoxin, phenytoin, lithium. Concomitant use of Imet® for children 4% with digoxin, phenytoin, or lithium preparations may increase serum concentrations of these drugs. Routine monitoring of serum digoxin, phenytoin, or lithium concentrations is generally not required (for periods not exceeding 4 days).

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and angiotensin II antagonists. NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors, beta-blockers, or angiotensin II antagonists with agents that inhibit the cyclooxygenase system may lead to further deterioration in renal function, including acute renal failure, which is usually reversible. Therefore, concomitant therapy requires caution, especially in elderly patients. Adequate hydration should be ensured, and renal function should be closely monitored after initiation of concomitant treatment.

Concomitant use of Imet® for children 4% with potassium-sparing diuretics may lead to hyperkalemia.

Glucocorticoids. Increased risk of gastrointestinal ulceration and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding.

Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin.

Methotrexate. If Imet® for children 4% is administered within 24 hours before or after methotrexate, increased methotrexate blood levels and enhanced toxicity may occur.

Sulfonylurea agents. Clinical studies have shown interactions between antidiabetic sulfonylurea agents and NSAIDs. Therefore, as a precaution, blood glucose levels should be monitored when these agents are used concomitantly with ibuprofen.

Zidovudine. Concomitant use with Imet® for children 4%, oral suspension, may increase the risk of hemarthrosis and hematomas in HIV-infected patients with hemophilia.

Cyclosporine. Concomitant use of cyclosporine with certain NSAIDs may increase nephrotoxic effects; this cannot be excluded when cyclosporine is combined with ibuprofen.

Tacrolimus. Increased risk of nephrotoxicity when this medicinal product is used concomitantly with Imet® for children 4%, oral suspension.

Probenecid and sulfinpyrazone. Medicinal products containing probenecid or sulfinpyrazone may delay the elimination of ibuprofen from the body.

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

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

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms.

Gastrointestinal safety

The use of the medicine Imet® for Children 4% is not recommended in children under 4 years of age in combination with NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors.

Gastrointestinal bleeding, ulcers, and perforations, including fatal outcomes, have been reported during treatment with all NSAIDs at any time during therapy; these may occur with or without prior warning symptoms and may occur in patients without a history of severe gastrointestinal complications.

The risk of gastrointestinal bleeding, ulcers, and perforations increases with higher NSAID doses, particularly in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (including elderly patients). Treatment in such patients should be initiated with the lowest dose. For these patients, as well as for patients requiring concomitant therapy with low-dose acetylsalicylic acid or other drugs increasing the risk of gastrointestinal complications, consideration should be given to concomitant use of gastroprotective agents such as misoprostol or proton pump inhibitors.

Patients with a history of gastrointestinal disorders should inform their physician about any unusual symptoms in the abdominal area (particularly signs of gastrointestinal bleeding), especially during the initial stages of treatment.

Particular caution is required when using concomitantly medications that increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants like warfarin, selective serotonin reuptake inhibitors, and antiplatelet agents such as acetylsalicylic acid.

If gastrointestinal bleeding or ulceration occurs, treatment with Imet® for Children 4% must be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated.

Effects on the cardiovascular and cerebrovascular systems

Patients with a history of arterial hypertension and/or heart failure require careful monitoring (consultation with a physician or pharmacist) prior to initiating treatment, as NSAIDs may cause fluid retention, edema, and elevated blood pressure.

Clinical evidence indicates that the use of ibuprofen, especially at high doses (2400 mg daily) and during prolonged therapy, may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Available epidemiological data suggest that low doses of ibuprofen (e.g., less than 2400 mg daily) do not increase the risk of arterial thrombotic complications.

Ibuprofen should be prescribed only after careful consideration in patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. High doses (2400 mg per day) should be avoided in such patients.

Particular attention should also be paid prior to initiating long-term treatment in patients with cardiovascular risk factors (such as hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high-dose ibuprofen (2400 mg daily) is required.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may potentially lead to myocardial infarction.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse Reactions"). Most such reactions occurred 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).

In rare cases, severe skin infections and soft tissue complications may develop in patients with chickenpox. A negative influence of NSAIDs on the course of this infectious disease cannot be excluded; therefore, the use of Imet® for Children 4% is not recommended in chickenpox.

Masking symptoms of underlying infections

NSAIDs may mask signs of infection and fever.

Imet® for Children 4% may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby worsening the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of chickenpox. When Imet® for Children 4% is used for fever or pain relief in infection, monitoring for infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen (see also section "Adverse Reactions. Infections and infestations").

Elderly patients

Elderly individuals have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

Other

Imet® for Children 4% should be prescribed only after careful benefit-risk assessment in the following cases:

• congenital porphyrin metabolism disorders (e.g., acute intermittent porphyria);
• systemic lupus erythematosus and mixed connective tissue disease, due to an increased risk of aseptic meningitis.

Close monitoring is required in patients with:

• renal function impairment (as acute renal failure may occur in patients with pre-existing kidney disease);
• dehydration (risk of renal impairment in dehydrated children);
• hepatic function impairment;
• recent major surgical procedures;
• hay fever, nasal polyps, and chronic obstructive respiratory diseases due to increased risk of allergic reactions, which may manifest as asthma attacks, including analgesic-induced asthma, angioedema (Quincke's edema), and urticaria;
• allergic reactions to other substances, as these patients also have an increased risk of hypersensitivity reactions to Imet® for Children 4%.

Severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been very rarely observed. If the first signs of hypersensitivity occur, Imet® for Children 4% should be discontinued immediately. Medical interventions appropriate to the symptoms should be performed by qualified specialists.

Respiratory system disorders

Imet® for Children 4% should be used with caution in patients with current or past history of bronchial asthma, as cases of NSAID-induced bronchospasm have been reported in such patients.

Ibuprofen, the active ingredient in Imet® for Children 4%, may temporarily inhibit platelet function (platelet aggregation). Therefore, careful monitoring is required in patients with coagulation disorders.

During prolonged use of Imet® for Children 4%, liver function tests, renal function, and blood counts should be monitored regularly.

Caution is required when prescribing the medicine to patients already taking other analgesics, antipyretics, or antibiotics.

Prolonged use of any analgesic for headache may lead to worsening of headache. If this situation occurs or is suspected, the patient should consult a physician and treatment should be discontinued. Medication-overuse headache should be suspected in patients who experience frequent or daily headaches despite regular analgesic use or as a result of it.

Generally, habitual use of analgesics, especially when using a combination of several analgesics, may lead to persistent renal dysfunction and development of renal failure (analgesic nephropathy).

Concomitant use of NSAIDs and alcohol may enhance the adverse effects of active ingredients on the gastrointestinal tract and the central nervous system.

This medicinal product contains 500 mg of liquid maltitol per 1 ml. Patients with rare hereditary fructose intolerance should not take this medicine.

This medicinal product contains 6.0 mg of sodium per 1 ml, equivalent to 0.3% of the WHO recommended maximum daily intake of 2 g sodium for adults. This should be taken into account for patients on a sodium-controlled diet.

Imet® for Children 4% contains 1 mg of sodium benzoate per milliliter.

This medicinal product contains 0.0002 mg of benzyl alcohol per milliliter.

Benzyl alcohol may cause allergic reactions. Increased risk due to accumulation in young children.

Large volumes should be used with caution and only when necessary, especially in pregnant or breastfeeding women, and in individuals with hepatic or renal impairment due to the risk of accumulation and toxicity (metabolic acidosis).

Use during pregnancy or breastfeeding

Pregnancy

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

In animal studies, administration of a prostaglandin synthesis inhibitor was associated with increased pre- and post-implantation losses and embryofetal mortality. Furthermore, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various developmental abnormalities, including cardiovascular malformations, was observed.

From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, ibuprofen should be prescribed during the first and second trimesters only if clearly necessary. When prescribing ibuprofen to women planning pregnancy or during the first and second trimesters, the lowest effective dose for the shortest duration necessary to relieve symptoms should be used.

Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after several days of ibuprofen exposure starting from the 20th gestational week. Ibuprofen treatment should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

During the third trimester of pregnancy, prostaglandin synthesis inhibitors may cause:

• In the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);

• renal dysfunction, which may progress to renal failure with oligohydramnios (see above);

• At the end of pregnancy, in the mother and newborn:

• prolonged bleeding time due to inhibition of platelet aggregation, even with very low doses;

• inhibition of uterine activity, leading to delayed or prolonged labor.

Therefore, the use of ibuprofen is contraindicated during the third trimester of pregnancy (see sections "Contraindications" and "Preclinical safety data").

Breastfeeding period

Ibuprofen and its metabolites pass into breast milk only in very low concentrations. As no adverse effects in newborns have been reported, discontinuation of breastfeeding is generally not required during short-term use of ibuprofen at recommended doses (see section "Dosage and administration").

Fertility

There is evidence that medicinal products which inhibit cyclooxygenase/prostaglandin synthesis may negatively affect female fertility by influencing ovulation. This effect is reversible upon discontinuation of treatment.

Ability to affect reaction speed when driving or operating machinery

Ibuprofen may have a minor influence on the ability to drive or operate machinery.

During treatment with ibuprofen, adverse reactions such as fatigue and dizziness may occur. As a result, reaction time may be impaired and the ability to drive or operate machinery may be reduced in individual cases. These effects may be particularly enhanced when alcohol is consumed.

Dosage and Administration

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").

Dosage calculation is detailed in the table below. The dosage of Imet® for Children 4% is based on body weight or age. The usual dose is 7 to 10 mg/kg body weight as a single dose, with a maximum total daily dose of 30 mg/kg body weight.

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

If treatment with Imet® for Children 4% is required for more than three days or if symptoms worsen, medical advice should be sought.

The package contains an oral syringe for administering Imet® for Children 4%. The oral syringe is graduated up to 5 mL, with 0.25 mL graduations.

5 mL of oral suspension corresponds to 200 mg of ibuprofen.

The bottle should be shaken well before use.

Dosage of Imet® for Children 4% 40 mg/mL

Patient body weight (age)	Single dose of ibuprofen	Maximum daily dose of ibuprofen
10–15 kg (children aged 1–3 years)	100 mg (2.5 ml) every 8 hours, but no more than 3 times a day	300 mg
16–19 kg (children aged 4–6 years)	150 mg (3.75 ml) every 8 hours, but no more than 3 times a day	450 mg
20–29 kg (children aged 7–9 years)	200 mg (5.0 ml) every 6 hours, but no more than 3 times a day	600 mg
30–39 kg (children aged 10–11 years)	300 mg (7.5 ml) every 6 hours, but no more than 3 times a day	900 mg
≥ 40 kg (adolescents from 12 years of age)	200–400 mg (5.0–10.0 ml) every 6 hours, but no more than 3 times a day	1200 mg

Method of Administration

Oral suspension can be taken independently of food intake. For patients with a sensitive stomach, it is recommended to take the medicinal product Imet® for children 4 % during meals.

Renal impairment

Patients with mild or moderate renal impairment do not require dose adjustment. For patients with severe renal impairment, see section "Contraindications".

Hepatic impairment (see section "Pharmacokinetics").

Patients with mild or moderate hepatic impairment do not require dose adjustment. For patients with severe hepatic impairment, see section "Contraindications".

Children

The Imet® for children 4 % preparation is intended for administration to children with a body weight of 10 kg or more (from 1 year of age).

Overdose.

Symptoms

Possible central nervous system disturbances such as headache, dizziness, pre-syncope, loss of consciousness (in children – also myoclonic seizures), as well as abdominal pain, nausea and vomiting. In addition, gastrointestinal bleeding and impairment of kidney and liver function may occur. Hypotension, respiratory depression and cyanosis may also develop. In severe poisoning, metabolic acidosis may occur.

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

Treatment

There is no specific antidote for ibuprofen.

Therapeutic management options for intoxication depend on the degree, stage and clinical symptoms according to standard practices in intensive care units.

Side effects

The list of adverse reactions below includes all side effects reported during treatment with ibuprofen, including during long-term treatment with high doses of the drug in patients suffering from rheumatism. The established frequencies, except for very rare cases, refer to short-term treatment with daily doses of up to 1200 mg of ibuprofen (30 ml of Imet® for children 4% oral suspension, maximum daily dose for adolescents aged 12 years and older) for the oral dosage form, and up to 1800 mg for suppositories.

Assessment of adverse reactions is based on the following frequency classification: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

The following adverse reactions associated with the use of the drug should be considered, as they are predominantly dose-dependent and related to individual sensitivity.

The most frequently reported adverse reactions were gastrointestinal in nature. Development of ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, is possible. Cases of nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease have been reported after administration of the drug. Gastritis was observed less frequently.

Edema, elevated blood pressure, and heart failure have also been reported during treatment with NSAIDs.

Clinical data suggest that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Infections and infestations

Very rare: Exacerbation of infectious inflammatory processes (e.g., development of necrotizing fasciitis) following systemic use of NSAIDs. This may be related to the mechanism of action of NSAIDs. If signs of a new infection or worsening of an existing infection occur during treatment with Imet® for children 4%, immediate medical consultation is recommended. It is necessary to determine whether antibacterial/antibiotic therapy is indicated.

Blood and lymphatic system disorders

Very rare: Blood disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis).

Initial symptoms may include fever, sore throat, oral mucosal erosions, flu-like symptoms, severe fatigue, and nasal or skin bleeding. In such cases, treatment with the drug must be discontinued immediately. Self-medication with analgesics or antipyretics should be avoided, and medical advice should be sought.

Blood count monitoring is recommended during prolonged ibuprofen therapy.

Immune system disorders

Uncommon: Hypersensitivity reactions with skin rash and pruritus, as well as asthma attacks (in some cases associated with arterial hypotension). In such cases, discontinuation of Imet® for children 4% is strongly recommended, and immediate medical consultation is required.

Very rare: Aseptic meningitis symptoms, including nuchal rigidity, headache, nausea, vomiting, fever, or altered consciousness, have been observed with ibuprofen use. Patients with autoimmune diseases (systemic lupus erythematosus, connective tissue diseases) may be predisposed.

Severe systemic hypersensitivity reactions: facial, tongue, or laryngeal edema with airway narrowing, dyspnea, tachycardia, decreased blood pressure up to life-threatening shock.

If any of the above symptoms occur, even after the first dose of the drug, immediate medical assistance is required.

Psychiatric disorders

Very rare: Psychotic reactions, depression.

Nervous system disorders

Uncommon: Central nervous system disturbances such as headache, dizziness, insomnia, restlessness, irritability, or fatigue.

Eye disorders

Uncommon: Visual disturbances. In such cases, discontinuation of ibuprofen is strongly recommended, and immediate medical consultation is required.

Frequency not known: Optic neuritis.

Ear and labyrinth disorders

Rare: Tinnitus.

Cardiovascular system disorders

Very rare: Palpitations, heart failure, myocardial infarction, arterial hypertension, vasculitis.

Frequency not known: Kounis syndrome.

Respiratory, thoracic and mediastinal disorders

Very rare: Asthma, bronchospasm, dyspnea, and wheezing.

Gastrointestinal disorders

Common: Gastrointestinal disturbances such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, and minor gastrointestinal bleeding, which may rarely lead to anemia.

Uncommon: Gastric or small intestinal ulcers, sometimes with bleeding or perforation; ulcerative stomatitis; exacerbation of colitis and Crohn’s disease; gastritis.

Very rare: Esophagitis, pancreatitis, formation of intestinal diaphragm-like strictures.

Treatment with Imet® for children 4% must be discontinued if the patient develops severe upper abdominal pain, vomiting blood, presence of blood in stool, or black stools.

Hepatobiliary disorders

Very rare: Liver function abnormalities, liver damage (especially with prolonged therapy), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: Skin rashes.

Very rare: Severe skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis), alopecia.

Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis, photosensitivity reactions.

In exceptional cases, severe skin infections and soft tissue complications during varicella may occur.

Renal and urinary disorders

Rare: Renal tissue damage (papillary necrosis), especially with prolonged therapy, increased blood uric acid levels.

Very rare: Decreased urine output and development of edema, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may lead to acute kidney failure.

Treatment with Imet® for children 4% must be discontinued if these symptoms occur or worsen.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life

3 years.

After opening the bottle – 6 months, provided stored at a temperature not exceeding 30 °C.

Storage conditions

No special storage conditions required.

Keep the medicinal product out of reach of children.

Packaging

Brown glass bottle of 100 ml or 200 ml; cardboard box containing one bottle and a graduated oral dosing device (5 ml capacity) consisting of a cylinder and plunger.

Prescription status

Over-the-counter.

Manufacturer

BERLIN-CHEMIE AG

Manufacturer's location and address of business operations

Glienicker Weg 125, 12489 Berlin, Germany.

Manufacturer

Laboratorios Alcalá Farmacéutica, S.L.

Manufacturer's location and address of business operations

Avenida de Madrid, 82, Alcalá de Henares, Madrid, 28802, Spain.