Ibuslin

INSTRUCTIONS for medical use of the medicinal product IBUCLIN® (IBUCLIN®)

Composition:

Active substance: ibuprofen;

5 ml of suspension contains ibuprofen 100 mg;

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

Pharmaceutical form. Oral suspension.

Main physicochemical properties: viscous suspension, free from foreign 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), a propionic acid derivative, which has demonstrated efficacy due to inhibition of prostaglandin synthesis. In humans, ibuprofen reduces pain associated with inflammation, swelling, and fever. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. The onset of analgesic and antipyretic action of ibuprofen occurs within 30 minutes. In addition, ibuprofen reversibly inhibits platelet aggregation. Experimental data indicate that ibuprofen may interfere with the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when both agents are administered concomitantly. In a study where a single 400 mg dose of ibuprofen was taken within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg), a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions regarding the systematic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen.

Pharmacokinetics. Ibuprofen is rapidly absorbed after administration and quickly distributed throughout the body. Elimination is rapid and complete, occurring via the kidneys.

Maximum plasma concentrations are reached within 45 minutes after oral administration on an empty stomach. When administered with food, peak levels are observed within 1–2 hours. This time may vary depending on different pharmaceutical forms. The elimination half-life is approximately 2 hours.

In some studies, ibuprofen has been detected in breast milk at very low concentrations.

Clinical characteristics

Indications. For symptomatic treatment of fever and pain of various origins in children aged from 3 months to 12 years with body weight of at least 5 kg (including fever after vaccination, acute respiratory viral infections, influenza, teething pain, post-extraction dental pain, toothache, headache, sore throat, pain due to ligament sprains, and other types of pain, including those of inflammatory origin).

Contraindications

• Hypersensitivity to ibuprofen or to any of the excipients of the medicinal product.
  • History of hypersensitivity reactions (e.g., bronchospasm, bronchial asthma, rhinitis, angioedema, or urticaria) following administration of acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Active gastric ulcer / gastrointestinal bleeding or history of recurrent episodes (two or more confirmed episodes of peptic ulcer or bleeding).
  • History of gastrointestinal bleeding or perforation associated with the use of NSAIDs.
  • Severe hepatic insufficiency, severe renal insufficiency, or severe heart failure.
  • Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
  • Third trimester of pregnancy.
  • Cerebrovascular or other hemorrhages.
  • Hematopoietic disorders of unknown etiology or coagulation disorders.
  • Hereditary fructose intolerance.

Interaction with other medicinal products and other forms of interactions

Ibuprofen, like other NSAIDs, should not be used in combination with:

• acetylsalicylic acid: concomitant use of ibuprofen with acetylsalicylic acid is generally not recommended, as it increases the risk of adverse effects. According to experimental data, ibuprofen may competitively inhibit the antiplatelet effect of low-dose acetylsalicylic acid when administered concomitantly. Although there is uncertainty regarding extrapolation of 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. Occasional use of ibuprofen is considered unlikely to have clinically significant effects (see section "Pharmacological properties");
• other NSAIDs, including selective cyclooxygenase-2 inhibitors: concomitant use of two or more NSAIDs should be avoided, as this increases the risk of adverse effects (see section "Special precautions for use").

Ibuprofen should be used with caution in combination with the following drugs:

• phenytoin: concomitant use of ibuprofen with phenytoin may increase serum phenytoin levels. With appropriate use (for no more than 4 days), monitoring of serum phenytoin levels is not mandatory;
• antihypertensive agents (ACE inhibitors, beta-blockers, and angiotensin II antagonists) and diuretics: NSAIDs may reduce the efficacy of these drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors, beta-blockers, angiotensin II antagonists, and cyclooxygenase inhibitors may lead to further deterioration of renal function, including development of acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should maintain adequate fluid intake; renal function should also be monitored after initiation of concomitant therapy and periodically thereafter. Diuretics increase the risk of nephrotoxic effects of NSAIDs;
• cardiac glycosides, such as digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate (GFR), and increase plasma levels of glycosides. Concomitant use of ibuprofen with digoxin may increase serum digoxin levels. With appropriate use (for no more than 4 days), monitoring of serum digoxin levels is not mandatory;
• lithium: there is evidence of potential increase in plasma lithium levels. With appropriate use (for no more than 4 days), monitoring of serum lithium levels is not mandatory;
• probenecid and sulfinpyrazone: medicinal products containing probenecid or sulfinpyrazone may delay excretion of ibuprofen;
• potassium-sparing diuretics: concomitant use of ibuprofen with potassium-sparing diuretics may lead to hyperkalemia (monitoring of serum potassium levels is recommended);
• methotrexate: there is evidence of potential increase in methotrexate plasma levels. Administration of ibuprofen within 24 hours before or after methotrexate may lead to increased methotrexate concentrations and enhanced toxic effects;
• sulfonylurea derivatives: clinical studies indicate an interaction between NSAIDs and antidiabetic agents (sulfonylurea derivatives). Although there are no published data on interaction between ibuprofen and sulfonylureas, measurement of blood glucose levels is recommended when these drugs are used concomitantly;
• quinolone antibiotics: animal studies suggest 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 exposure to ibuprofen (a CYP2C9 substrate). Studies using voriconazole and fluconazole (CYP2C9 inhibitors) demonstrated an approximately 80–100% increase in exposure to S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, a reduction in ibuprofen dose is recommended, especially when high doses of ibuprofen are used together with voriconazole or fluconazole;
• corticosteroids: increased risk of gastrointestinal ulcers or bleeding (see section "Special precautions for use");
• anticoagulants: NSAIDs may potentiate the effects of anticoagulants such as heparin and its derivatives, vitamin K antagonists such as acenocoumarol or warfarin, and non-vitamin K oral anticoagulants such as rivaroxaban, apixaban, or dabigatran (see section "Special precautions for use");
• antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section "Special precautions for use");
• tacrolimus: concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity;
• cyclosporine: increased risk of nephrotoxicity;
• mifepristone: NSAIDs should not be used earlier than 8–12 days after administration of mifepristone, as NSAIDs may reduce its efficacy;
• zidovudine: increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. Some evidence indicates an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

Alcohol

Concomitant use with alcohol may enhance adverse effects caused by NSAIDs, particularly those affecting the gastrointestinal tract or central nervous system.

Special precautions for use

Adverse effects associated with ibuprofen can be minimized by using the lowest effective dose required to treat symptoms, for the shortest possible duration.

Elderly individuals have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal. Elderly patients are at increased risk of serious adverse reactions. Long-term use of NSAIDs is not recommended in elderly patients. If prolonged therapy is necessary, patients should be monitored continuously.

Caution is required when administering to patients with the following conditions:

• Systemic lupus erythematosus or mixed connective tissue disease — due to an increased risk of aseptic meningitis;
• Inherited disorders of porphyrin metabolism, such as acute intermittent porphyria;
• Gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• History of hypertension and/or heart failure, as fluid retention and edema associated with NSAID therapy have been reported;
• Renal impairment — due to the possibility of worsening kidney function;
• Hepatic dysfunction;
• Immediately after major surgical procedures;
• Hay fever, nasal polyps, or chronic obstructive respiratory diseases — due to an increased risk of allergic reactions, including asthma attacks (so-called analgesic-induced asthma), Quincke's edema (angioedema), or urticaria;
• History of allergic reactions to other substances — due to an increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects

Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with a history of such conditions.

Other NSAIDs

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided, as this increases the risk of adverse reactions.

Systemic lupus erythematosus and mixed connective tissue disease

Ibuprofen should be used with caution in patients with systemic lupus erythematosus or mixed connective tissue disease due to an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects

Patients with a history of hypertension and/or heart failure should begin treatment cautiously (medical consultation is required), as fluid retention, hypertension, and edema have been reported during treatment with ibuprofen and other NSAIDs.

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 lead to myocardial infarction.

Clinical trial data and epidemiological evidence indicate that the use of ibuprofen, particularly at high doses (2400 mg per day) and during long-term treatment, slightly increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not show that low doses of ibuprofen (e.g., ≤ 1200 mg per day) are associated with an increased risk of myocardial infarction.

Renal effects

Prolonged regular use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy).

Caution is required in patients with renal impairment due to the possibility of worsening kidney function.

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

Hepatic effects

The medicinal product may cause disturbances in liver function.

Gastrointestinal effects

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as their condition may worsen. Such patients should consult a physician.

Cases of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, have been reported at any stage of NSAID treatment, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest dose. Combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) is recommended for these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal disorders.

Patients with a history of gastrointestinal toxicity, especially elderly individuals, should be informed about any unusual gastrointestinal symptoms (particularly gastrointestinal bleeding), especially at the beginning of treatment.

Caution is required when treating patients who are concurrently using medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid).

If gastrointestinal bleeding or ulcers occur in patients receiving ibuprofen, treatment should be discontinued immediately.

Impairment of fertility in women

Available data suggest that cyclooxygenase/prostaglandin synthesis inhibitors may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Severe cutaneous adverse reactions (SCARs)

Severe skin adverse reactions have been reported with ibuprofen, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

If signs or symptoms indicating these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment (if necessary) should be considered.

In rare cases, varicella may lead to severe skin and soft tissue infections. At present, a potential negative influence of NSAIDs on these infections cannot be excluded; therefore, the use of ibuprofen is not recommended in cases of varicella.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If the first signs of a hypersensitivity reaction occur after taking ibuprofen, treatment should be discontinued immediately and medical help should be sought.

Masking symptoms of underlying infections

This medicinal product may mask symptoms of infectious diseases and thus delay the initiation of appropriate treatment and complicate the course of the disease. Such symptom masking has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When the medicinal product is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Ibuprofen may temporarily inhibit platelet aggregation. Therefore, careful monitoring is recommended in patients with coagulation disorders.

During prolonged use of ibuprofen, liver function, kidney function, and hematological parameters/blood counts should be monitored regularly.

Prolonged use of any analgesic for headache treatment may worsen this condition. In such cases, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered if a patient suffers from frequent or daily headaches, despite (or because of) regular use of headache medications.

Concomitant alcohol consumption and NSAID use may intensify adverse reactions related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

This medicinal product contains liquid maltitol. It should not be administered to patients with rare hereditary fructose intolerance. Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect.

This medicinal product contains 27.75 mg of sodium per 15 mL of suspension (equivalent to 1.85 mg of sodium per 1 mL of suspension). This should be taken into account for patients on a low-sodium diet.

Consultation with a physician or pharmacist is recommended before taking this medicinal product for: pregnant women, women attempting to conceive, elderly individuals, and smokers.

Use during pregnancy or breastfeeding

The medicinal product is intended for use in children under 12 years of age.

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 use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with higher doses and longer duration of treatment. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%.

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus constriction after second-trimester treatment, which in most cases resolved after treatment cessation. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by women attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction may be advisable after ibuprofen exposure for several days starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

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

For the fetus:

• Cardio-pulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• Renal dysfunction (see above);

Risks for the mother at the end of pregnancy and for the newborn:

• Prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

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

Breastfeeding. Ibuprofen and its metabolites are excreted in breast milk in low concentrations. Currently, there is no evidence of adverse effects on the infant; therefore, breastfeeding usually does not need to be interrupted during short-term treatment of pain and fever at recommended doses.

Fertility. Some evidence suggests that drugs inhibiting cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Therefore, the use of ibuprofen is not recommended in women experiencing difficulty conceiving.

Ability to influence reaction speed when driving or operating machinery

The medicinal product is intended for children under 12 years of age.

When used at recommended doses and for the recommended duration, the product is not expected to affect the ability to drive or operate machinery.

Dosage and Administration

The medicinal product should be administered orally.

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

The recommended daily dose of the medicinal product is 20–30 mg per kilogram of body weight, divided into several doses administered at 6–8 hour intervals, depending on age and body weight.

The dosing syringe provided in the package allows accurate measurement of the medicinal product dose.

The recommended dose should not be exceeded.

The medicinal product is intended for short-term use only.

Age	Body weight (kg)	Recommended dose
3–6 months	5–7.6	2.5 ml of suspension (50 mg) up to 3 times a day
6–12 months	7.7–9	2.5 ml of suspension (50 mg) up to 3–4 times a day
1–3 years	10–16	5 ml of suspension (100 mg) up to 3 times a day
4–6 years	17–20	7.5 ml of suspension (150 mg) up to 3 times a day
7–9 years	21–30	10 ml of suspension (200 mg) up to 3 times a day
10–12 years	31–40	15 ml of suspension (300 mg) up to 3 times a day

Do not use in children under 3 months of age unless directed by a physician.

Do not use this medicinal product in children weighing less than 5 kg.

If symptoms persist for more than 24 hours from the start of treatment or worsen (after administration of 3 doses) in children aged 3 to 6 months, immediate medical advice must be sought.

If symptoms persist for more than 3 days from the start of treatment or worsen in children aged 6 months to 12 years, medical advice should be sought.

For fever following vaccination (children aged 3–6 months), the recommended daily dose is 2.5 mL of suspension (50 mg), and if necessary, another 2.5 mL of suspension (50 mg) after 6 hours, but not more than 5 mL of suspension (100 mg) within 24 hours. If symptoms persist, medical advice must be sought.

For patients with a sensitive stomach, the medicinal product should be taken during meals.

Shake well before use.

Special patient categories

Renal impairment: dose reduction is not required in patients with mild to moderate renal function impairment (for patients with severe renal impairment, see section "Contraindications").

Hepatic impairment: dose reduction is not required in patients with mild to moderate hepatic function impairment (for patients with severe hepatic impairment, see section "Contraindications").

In case of overdose, seek immediate medical advice.

Children. The medicinal product should be used in children aged 3 months to 12 years weighing at least 5 kg.

Overdose

In children, symptoms of overdose may occur with ibuprofen doses exceeding 400 mg/kg. In adults, the dose-response relationship is less clearly defined. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients who have ingested clinically significant amounts of NSAIDs, only nausea, vomiting, epigastric pain, and less frequently diarrhea occur. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, such as dizziness, drowsiness, occasionally excitement, disorientation, or coma. In individual cases, seizures may occur. In severe poisoning, metabolic acidosis and prolonged prothrombin time/international normalized ratio (INR) may develop, possibly due to interaction with circulating coagulation factors. Acute renal failure and hepatic injury may occur. In patients with bronchial asthma, exacerbation of the disease may be observed. Additionally, arterial hypotension, respiratory depression, and cyanosis may occur.

Treatment. There is no specific antidote.

Treatment may be symptomatic and supportive, including airway clearance, monitoring of cardiac parameters and vital signs until a stable condition is achieved. Gastric lavage or oral administration of activated charcoal is recommended if less than 1 hour has passed since ingestion of a potentially toxic amount of the drug. If ibuprofen has already been absorbed, alkalizing agents promoting urinary excretion of ibuprofen may be used. In cases of frequent or prolonged seizures, intravenous administration of diazepam or lorazepam is required. Bronchodilators should be used in bronchial asthma. Medical consultation with toxicology centers may be sought.

Adverse Reactions

The adverse reactions listed below have been reported during treatment with ibuprofen, including those observed with high doses and long-term therapy in patients with rheumatism.

Adverse reactions occurring more frequently than very rare reports were observed during short-term use of oral forms of ibuprofen at doses of up to 1200 mg per day.

The listed adverse reactions are predominantly dose-dependent and may vary individually in each patient.

The adverse reactions of ibuprofen are listed below by organ systems and frequency of occurrence. Frequency categories are defined as follows: 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), and frequency not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

The most commonly observed adverse reactions are gastrointestinal. These reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal hemorrhage, sometimes fatal, especially in elderly patients, may occur. Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported after ibuprofen use. Gastritis has been observed less frequently.

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

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses of 2400 mg per day and during long-term treatment, is associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Cases of worsening infection-related inflammation, such as the development of necrotizing fasciitis, temporally associated with NSAID use, have been described. This may be explained by the mechanism of action of NSAIDs.

If signs of infection occur or worsen during ibuprofen treatment, patients are advised to seek immediate medical attention. The need for antimicrobial/antibiotic therapy should be evaluated.

Blood tests should be performed regularly during long-term therapy.

Patients should immediately consult a physician and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose of the drug. Immediate medical assistance is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the drug should be discontinued immediately and medical advice should be sought urgently.

Infections and infestations

Very rare: Exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis). In exceptional cases, varicella may lead to severe skin and soft tissue infections.

Blood and lymphatic system disorders

Very rare: Blood disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms may include fever, sore throat, oral ulcers, flu-like symptoms, severe fatigue, epistaxis, skin hemorrhages, and bruising.

Immune system disorders

Hypersensitivity reactions¹; uncommon: urticaria and pruritus.

Very rare: Severe hypersensitivity reactions, symptoms of which may include facial, lingual, or laryngeal edema, dyspnea, tachycardia, and hypotension (anaphylactic reaction, angioedema, or severe shock). Asthma exacerbation.

Nervous system disorders

Uncommon: Headache, dizziness, insomnia, restlessness, irritability, or fatigue.

Very rare: Aseptic meningitis².

Cardiac disorders

Very rare: Heart failure, tachycardia, edema, myocardial infarction.

Frequency not known: Kounis syndrome.

Vascular disorders

Very rare: Arterial hypertension, vasculitis.

Gastrointestinal disorders

Common: Abdominal pain, nausea, dyspepsia, diarrhea, flatulence, constipation, heartburn, vomiting, and minor gastrointestinal bleeding, which in exceptional cases may lead to anemia.

Uncommon: Peptic ulcer, perforation, or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis and Crohn’s disease.

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

Hepatobiliary disorders

Very rare: Liver function abnormalities, liver injury (especially during long-term therapy), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: Various skin rashes¹.

Very rare: Severe skin reactions, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis¹, alopecia.

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

Respiratory, thoracic and mediastinal disorders

Frequency not known: Respiratory tract reactivity, including asthma, bronchospasm, or dyspnea¹.

Renal and urinary disorders

Rare: Acute renal function impairment, especially with prolonged NSAID use, associated with increased serum urea levels. Also includes papillary necrosis.

Very rare: Edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may lead to acute renal failure.

Laboratory investigations

Rare: Decreased hemoglobin levels.

Psychiatric disorders

Very rare: Psychotic reactions, depression; with prolonged use: hallucinations, confusion.

Eye disorders

Frequency not known: Visual disturbances, optic neuritis may occur with prolonged treatment.

Ear and labyrinth disorders

Frequency not known: Dizziness may occur with prolonged treatment.

Rare: Tinnitus.

General disorders

Frequency not known: Malaise and fatigue.

Description of selected adverse reactions

¹ Hypersensitivity reactions have been reported following ibuprofen therapy. These include non-specific allergic reactions and anaphylaxis; respiratory tract reactions, such as bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea; and various skin disorders, including rashes of different types, pruritus, urticaria, purpura, angioedema, and less frequently, exfoliative and bullous dermatoses (including epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme).

² The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug intake). In particular, isolated cases of aseptic meningitis symptoms (such as neck stiffness, headache, nausea, vomiting, fever, or disorientation) have been observed during ibuprofen treatment in patients with autoimmune disorders (e.g., systemic lupus erythematosus, mixed connective tissue disease).

Reporting suspected adverse reactions

Reporting of adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to 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 first opening of the bottle — 6 months.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 100 mL of suspension in a bottle; 1 bottle with a dosing syringe in a cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer

1. EDEFARM, S.L.
2. Farmalider, S.A.

Manufacturer's address

1. Polígono Industrial Enchilar del Rullo, 117. CP. 46191 Villamarchante, Valencia, Spain
2. Calle de los Aragoneses 2, Polígono Industrial Calabozos, Alcobendas, 28108, Spain

Marketing Authorization Holder. LLC "Dr. Reddy’s Laboratories", Ukraine.

Address of Marketing Authorization Holder. 121-A Kyivske Shose St., village of Velyka Oleksandrivka, Boryspil district, Kyiv region, 08320, Ukraine.

You can report an adverse reaction or lack of efficacy of the medicinal product by calling the following phone numbers (24/7): +380 44 207 51 97 or +380 50 414 39 39; or by email: [email protected]