Ibuslin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUCLIN® (IBUCLIN®)

Composition:

Active substance: ibuprofen;

5 ml of suspension contain 200 mg of ibuprofen;

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

Pharmaceutical form. Oral suspension.

Main physicochemical properties: viscous suspension, free from foreign particles, white or almost white, 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 derivative of propionic acid, which has analgesic, antipyretic, and anti-inflammatory effects. Ibuprofen inhibits the synthesis of prostaglandins. In addition, ibuprofen reversibly inhibits platelet aggregation.

According to experimental data, ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly. However, with occasional use of ibuprofen, such clinically significant effects are considered unlikely (see section "Interaction with other medicinal products and other types of interactions").

Clinical efficacy and safety

The clinical efficacy of ibuprofen has been demonstrated in the symptomatic treatment of mild to moderate pain, such as dental pain, headache, and in the symptomatic treatment of fever.

Pharmacokinetics

Specific pharmacokinetic studies in children have not been conducted. Published data confirm that absorption, metabolism, and elimination of ibuprofen in children occur in the same manner as in adults.

Absorption

After oral administration, ibuprofen is partially absorbed in the stomach and then completely absorbed in the small intestine; peak serum concentrations are reached within 1–2 hours after oral administration of the immediate-release formulation.

Distribution

Ibuprofen is rapidly distributed throughout the body. The drug is approximately 99% bound to plasma proteins.

Biotransformation

Ibuprofen is extensively metabolized in the liver (via hydroxylation, carboxylation, and conjugation), forming pharmacologically inactive metabolites.

Elimination

Following hepatic metabolism, pharmacologically inactive metabolites are excreted completely, primarily via the kidneys (90%), and also through bile. The elimination half-life of ibuprofen in healthy volunteers, as well as in patients with hepatic or renal disease, ranges from 1.8 to 3.5 hours.

Renal impairment

Since ibuprofen and its metabolites are primarily eliminated by the kidneys, the pharmacokinetics of the drug may be altered in patients with various degrees of renal impairment. In patients with impaired renal function, lower plasma protein binding, increased plasma levels of total ibuprofen and unbound (S)-ibuprofen, higher AUC values of (S)-ibuprofen, and increased enantiomeric AUC (S/R) ratios have been observed compared to healthy control volunteers. In patients with end-stage renal disease undergoing dialysis, the mean fractional excretion 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 effect is unknown. Metabolites may be removed by hemodialysis.

Hepatic impairment

Alcoholic liver disease with mild to moderate hepatic dysfunction did not result in significant changes in pharmacokinetic parameters. However, liver disease may alter the distribution kinetics of ibuprofen. In patients with cirrhosis and moderate hepatic dysfunction (Child–Pugh class 6–10), an approximately two-fold increase in elimination half-life was observed, and the enantiomeric AUC (S/R) ratio was significantly lower compared to healthy control volunteers, indicating impaired metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer.

Clinical characteristics

Indications. Symptomatic treatment of fever and pain of various origins in children aged 6 months to 12 years with body weight of at least 7 kg (including post-vaccination fever, acute respiratory viral infections, influenza, teething pain, pain after tooth extraction, 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, asthma, rhinitis, angioedema, or urticaria) following the administration of acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more episodes of confirmed peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
• Active inflammatory bowel disease.
• Cerebrovascular or other hemorrhages.
• Hemorrhagic diathesis or coagulation disorders of unknown etiology.
• Severe hepatic insufficiency, severe renal insufficiency, or severe heart failure (NYHA Class IV [New York Heart Association]).
• Third trimester of pregnancy.
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).

Interaction with other medicinal products and other forms of interaction

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

• acetylsalicylic acid (aspirin), as this increases the risk of adverse reactions, except when aspirin (dose not exceeding 75 mg per day) is prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo data to the clinical setting do not allow definitive conclusions regarding the systematic use of ibuprofen. Therefore, with occasional use of ibuprofen, such clinically significant effects are considered unlikely;
• other NSAIDs, including selective cyclooxygenase-2 inhibitors, as this increases the risk of adverse effects.

Ibuprofen (like other NSAIDs) should be used with caution in combination with the following drugs:

anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin.

antihypertensive agents (angiotensin-converting enzyme inhibitors [ACE inhibitors], beta-blockers, and angiotensin II antagonists): NSAIDs may reduce the effectiveness 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, or angiotensin II antagonists with cyclooxygenase inhibitors may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Adequate fluid intake is recommended, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter.

corticosteroids: increased risk of gastrointestinal ulceration and bleeding.

antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding. NSAIDs should not be combined with ticlopidine due to the risk of additive effects on platelet function inhibition.

cardiac glycosides, e.g., digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides. NSAIDs may increase digoxin plasma levels, thereby increasing the risk of digoxin toxicity; with appropriate use (maximum for 3 days), serum digoxin level monitoring is usually not required.

pentoxifylline: patients receiving ibuprofen in combination with pentoxifylline may have an increased risk of hemorrhage; therefore, bleeding time should be monitored.

lithium: NSAIDs may increase lithium plasma levels, possibly due to reduced renal clearance. Concomitant use of these medicinal products should be avoided unless lithium levels are monitored. Consideration should be given to reducing the lithium dose; with appropriate use (maximum for 3 days), serum lithium level monitoring is usually not required.

methotrexate at doses of 15 mg/week or higher: NSAID use within 24 hours before or after methotrexate administration may increase methotrexate plasma concentrations (likely due to reduced renal clearance of methotrexate caused by NSAIDs) and further increase its toxic effects. Therefore, ibuprofen should be avoided in patients receiving high-dose methotrexate.

methotrexate at doses below 15 mg/week: ibuprofen increases methotrexate levels. When ibuprofen is used concomitantly with low-dose methotrexate, careful monitoring of the patient's blood count is required, especially during the first weeks of concomitant therapy. Monitoring should be intensified in case of worsening renal function, even minimally, and in elderly patients, and renal function should be monitored to prevent possible reduction in methotrexate clearance.

cyclosporine and tacrolimus: increased risk of nephrotoxicity when used concomitantly with NSAIDs due to reduced renal prostaglandin synthesis. Renal function should be closely monitored when these medicinal products are used concomitantly with NSAIDs.

mifepristone: NSAIDs should not be used earlier than 8–12 days after mifepristone administration, as they may reduce its efficacy.

sulfonylurea derivatives: interactions between NSAIDs and hypoglycemic agents (sulfonylurea derivatives) have been observed. NSAIDs may enhance the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding—monitoring of blood glucose levels is recommended when sulfonylureas are used concomitantly with ibuprofen.

probenecid and sulfinpyrazone: possible increase in ibuprofen plasma concentration and delayed elimination, possibly due to an inhibitory mechanism at the site of renal tubular secretion and glucuronidation; therefore, dose adjustment of ibuprofen may be required.

baclofen: risk of baclofen toxicity after initiation of ibuprofen therapy.

ritonavir: possible increase in NSAID plasma concentrations.

aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides.

captopril: experimental studies have shown that ibuprofen inhibits captopril's effect on sodium excretion.

voriconazole and fluconazole (CYP2C9 inhibitors): concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). In a study using voriconazole and fluconazole (CYP2C9 inhibitors), an approximately 80–100% increase in the effect of S(+)-ibuprofen was demonstrated. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, dose reduction of ibuprofen is recommended, especially when high doses of ibuprofen are used with voriconazole or fluconazole.

cholestyramine: ibuprofen and cholestyramine should be taken with an interval of several hours due to delayed and reduced (by 25%) absorption of ibuprofen when administered concomitantly.

zidovudine: increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen therapy.

herbal extracts: concomitant use of Ginkgo biloba with NSAIDs increases the risk of bleeding.

quinolone antibiotics: animal studies indicate that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.

hydantoins and sulfonamides: possible increase in the toxic effects of these medicinal products. Plasma phenytoin levels may increase with concomitant ibuprofen therapy; with appropriate use (maximum for 3 days), serum phenytoin level monitoring is usually not required.

thiazides, thiazide-like agents, loop diuretics, and potassium-sparing diuretics: NSAIDs may counteract the diuretic effect of these medicinal products. Concomitant use of NSAIDs and diuretics increases the risk of NSAID-induced nephrotoxicity (e.g., in dehydrated patients or elderly patients with impaired renal function) due to deterioration of renal blood flow. Therefore, such combinations should be used with caution, especially in elderly patients. Adequate fluid intake is recommended, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter. As with other NSAIDs, concomitant therapy with potassium-sparing diuretics may be associated with elevated potassium levels; therefore, plasma potassium levels should be monitored.

Administration of ibuprofen with food slows absorption, although this does not affect the extent of absorption (see section "Pharmacokinetics").

Special precautions for use

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see gastrointestinal and cardiovascular risks below).

Elderly patients are more likely to experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal. These patients are at increased risk of adverse outcomes. Prolonged use of NSAIDs is not recommended in elderly patients. If long-term therapy is required, regular monitoring of the patient is necessary.

Caution should be exercised when administering to patients with the following conditions:

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

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

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. NSAIDs may mask symptoms of infection and fever.

Like other NSAIDs, ibuprofen may cause allergic reactions, such as anaphylactic/anaphylactoid reactions, even when used for the first time.

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 with caution (medical consultation required), as fluid retention, development of hypertension, and edema have been reported during ibuprofen therapy, as with other NSAIDs.

Clinical trials and epidemiological data indicate that the use of ibuprofen, particularly at high doses (2400 mg daily) and over prolonged periods, slightly increases the risk of arterial thrombotic complications (such as myocardial infarction or stroke). Overall, epidemiological studies do not show that low-dose ibuprofen (e.g., ≤1200 mg daily) is associated with an increased risk of myocardial infarction.

Ibuprofen should be prescribed only after careful clinical assessment to patients with uncontrolled hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. High doses (2400 mg daily) should be avoided.

Careful clinical assessment is also required before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg daily) are needed.

Effects on kidneys and liver. Caution is required in patients with renal impairment due to the potential for worsening kidney function. Ibuprofen should be used cautiously in patients with kidney or liver disease, particularly when used concomitantly with diuretics, as prostaglandin inhibition may lead to fluid retention and further deterioration of renal function. These patients should receive the lowest possible dose of ibuprofen, and kidney function should be monitored regularly. Adequate fluid intake should be ensured in cases of dehydration. There is a risk of renal failure in dehydrated children and adolescents.

Generally, chronic use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy). The highest risk of this reaction is in elderly patients, patients with renal, heart, or liver failure, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, kidney function usually returns to the pre-treatment state.

Liver function may be impaired. Like other NSAIDs, ibuprofen may cause transient increases in certain liver function parameters, including elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). If significant increases in these parameters occur, treatment should be discontinued.

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. These patients should consult a physician.

Cases of gastrointestinal bleeding, perforation, and ulcers, including fatal cases, have been reported with NSAID use at any stage of treatment, regardless of prior warning symptoms or history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, or ulcers increases with higher NSAID doses, in patients with a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest doses. Combined 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 gastrointestinal risk.

Patients with a history of gastrointestinal toxicity, particularly elderly individuals, should inform their physician of any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly 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).

In case of gastrointestinal bleeding or ulcers in patients receiving ibuprofen, treatment should be discontinued immediately.

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

Severe skin reactions. Rare but serious skin reactions, potentially fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with nonsteroidal anti-inflammatory drugs (see section "Adverse reactions"). The risk of these reactions is highest at the beginning of therapy, usually within the first month of treatment. Cases of acute generalized exanthematous pustulosis following ibuprofen use have also been reported.

Ibuprofen use should be discontinued at the first signs or symptoms of skin involvement, such as skin rash, mucosal lesions, or any other signs of hypersensitivity.

In rare cases, chickenpox may lead to severe skin and soft tissue infections. Currently, it cannot be ruled out that NSAIDs may worsen such infections; therefore, ibuprofen use is not recommended in cases of chickenpox.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) occur. If signs of hypersensitivity appear after ibuprofen use, treatment should be discontinued immediately and medical help sought.

Masking symptoms of underlying infections. This medicinal product may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating the course of the illness. Such symptom masking has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When this medicinal product is used for fever or pain relief during infection, monitoring for 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.

With prolonged use of ibuprofen, regular monitoring of liver function, kidney function, and hematological parameters/blood counts is necessary.

Prolonged use of any analgesic for headache treatment may worsen the condition. In such cases, medical advice should be sought and treatment discontinued. If a patient suffers from frequent or daily headaches despite regular use of headache medications, medication-overuse headache should be considered.

Concomitant use of alcohol and NSAIDs may enhance adverse reactions related to the active substance, particularly gastrointestinal or central nervous system effects.

Before taking this medicinal product, the following individuals should consult a physician: pregnant women, women trying to conceive, elderly individuals, and smokers.

Effects on laboratory test results:

• Bleeding time may be prolonged up to one day after discontinuation of treatment;
• Blood glucose concentration may decrease;
• Creatinine clearance may decrease;
• Hematocrit or hemoglobin may decrease;
• Blood urea nitrogen concentration and serum creatinine and potassium levels may increase;
• Liver function tests: increased transaminase levels.

Important information about excipients.

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

The product contains sodium compounds. Caution is advised when administering to patients on a sodium-restricted diet.

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 negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, cardiac malformations, and gastroschisis associated with prostaglandin synthesis inhibitors during early pregnancy. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of treatment.

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. There have also been reports of arterial duct constriction after second-trimester treatment, which mostly resolves after stopping treatment. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. 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 duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction may be appropriate after exposure to ibuprofen for several days starting from the 20th gestational week. If oligohydramnios or arterial duct constriction is detected, ibuprofen use should be discontinued.

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

for the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• renal dysfunction (see above);

for the mother near term 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 are no reports of adverse effects on the infant; therefore, in cases of short-term treatment of pain and fever with recommended doses, women generally do not need to discontinue breastfeeding.

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

Ibuprofen use is not recommended for women trying to conceive. If a woman experiences difficulties with conception or is undergoing infertility evaluation, discontinuation of this medicinal product should be considered.

Ability to affect reaction speed when driving or operating machinery. The medicinal product is intended for use in children under 12 years of age.

No special precautions are required for single or short-term use.

However, adverse effects such as increased fatigue or vertigo may impair reaction speed and ability to drive or operate machinery. This effect is particularly pronounced when alcohol is consumed concurrently with the drug.

Dosage and Administration

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

The dose of ibuprofen depends on the child's body weight and age.

The maximum total daily dose of ibuprofen is 20–30 mg per kilogram of body weight, which should be divided into 3–4 doses administered at 6–8 hour intervals. The maximum recommended daily dose must not be exceeded. The total daily dose of ibuprofen of 30 mg/kg must not be exceeded within any 24-hour period.

Administration method

The contents of the bottle must be shaken well before use.

IBUKLIN® may be taken with food or independently of meals. If taken with food or immediately after eating, the onset of the drug's effect may be delayed. However, administration with food improves tolerability and reduces the risk of gastrointestinal adverse effects. IBUKLIN® can be administered directly without water or diluted with water.

To ensure accurate dosing, the package contains a dosing syringe.

The following table provides dosing recommendations according to the child's age and weight.

If a child's symptoms persist for more than 3 days from the start of treatment or worsen, a doctor should be consulted.

The medication should be administered with food to patients with a sensitive stomach.

Special patient categories

Patients with renal impairment: NSAIDs should be used with caution in patients with impaired kidney function, as ibuprofen is primarily excreted by the kidneys. Lower doses should be used in patients with mild to moderate renal insufficiency.

Ibuprofen should not be used in patients with severe renal insufficiency (see section "Contraindications").

Patients with hepatic impairment: Although no differences in the pharmacokinetic profile of ibuprofen have been observed in patients with hepatic insufficiency, NSAIDs should be used with caution in such patients. Treatment should be initiated with low doses and careful monitoring in patients with mild to moderate hepatic insufficiency.

Ibuprofen should not be used in patients with severe hepatic insufficiency (see section "Contraindications").

If symptoms persist or worsen during treatment, the patient should consult a doctor.

In case of ingestion of a dose exceeding the recommended amount, immediate medical advice should be sought.

Children. The medicinal product is indicated for children aged 6 months to 12 years with a body weight of at least 7 kg.

Overdose

In children, symptoms of overdose may occur after ingestion of 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, ingestion of clinically significant amounts of NSAIDs causes only nausea, vomiting, epigastric pain, or less frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, such as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may sometimes occur in patients. In severe poisoning, hyperkalemia, metabolic acidosis, hypothermia, and prolonged prothrombin time/international normalized ratio (INR) may occur, possibly due to interaction with circulating blood coagulation factors. Acute renal failure, liver damage, hypotension, respiratory depression, and cyanosis may develop. In patients with bronchial asthma, asthma exacerbation may occur. Nystagmus, visual disturbances, and loss of consciousness may also occur.

Treatment. There is no specific antidote.

Immediate medical assistance should be sought.

Treatment is symptomatic and supportive, including ensuring airway patency and monitoring cardiac 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 may be used to enhance urinary excretion of ibuprofen. For frequent or prolonged seizures, intravenous anticonvulsants (e.g., diazepam or lorazepam) should be administered. Bronchodilators should be used in patients with bronchial asthma.

Adverse Reactions

Listed below are adverse reactions reported during treatment with ibuprofen, including those observed during long-term therapy with high doses in patients with rheumatic diseases. The frequency stated beyond very rare reports refers to short-term use of doses up to 1200 mg of ibuprofen.

Frequency of adverse reactions is 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 decreasing order of severity.

The most commonly observed adverse reactions are gastrointestinal in nature. Adverse reactions are generally dose-dependent; in particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, especially in elderly patients. 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 indicate that the use of ibuprofen, particularly at high doses of 2400 mg per day and during long-term treatment, slightly increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Cases of worsening inflammation associated with infection, such as the development of necrotizing fasciitis, have been described and coincided in time with NSAID use. This may be related to the mechanism of action of NSAIDs.

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

Regular blood tests are recommended during long-term therapy.

Patients should immediately contact 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 and medical attention sought immediately.

Infections and infestations

Very rare: worsening 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 dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial signs include malaise, sore throat, oral mucosal ulcers, flu-like symptoms, severe fatigue, epistaxis, skin bleeding, and bruising. In such cases, patients should discontinue the medication, avoid using analgesics or antipyretics, and consult a physician.

Immune system disorders. Hypersensitivity reactions¹.

Uncommon: urticaria and pruritus.

Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, and hypotension (anaphylactic reaction, angioedema, or severe shock)¹. Asthma exacerbation.

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea.

Psychiatric disorders

Very rare: psychotic reactions, depression.

Nervous system disorders

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

Very rare: aseptic meningitis².

Eye disorders

Uncommon: visual disturbances, optic neuritis during prolonged treatment.

Ear and labyrinth disorders

Rare: tinnitus.

Cardiac disorders

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

Vascular disorders

Very rare: arterial hypertension, vasculitis.

Gastrointestinal disorders

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

Uncommon: gastric and duodenal ulcers, perforations or gastrointestinal bleeding, 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 damage (especially during long-term therapy), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: various skin rashes.

Very rare: severe skin reactions such as bullous reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis, alopecia.

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

Renal and urinary disorders

Rare: acute renal impairment (papillary necrosis), especially with prolonged NSAID use, increased blood urea concentration, elevated serum uric acid levels with development of edema.

Very rare: edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Laboratory findings

Rare: decreased hemoglobin levels.

¹ Reports exist of hypersensitivity reactions following ibuprofen treatment. These include non-specific allergic reactions and anaphylaxis, respiratory tract reactions such as bronchial asthma, asthma exacerbation, bronchospasm, and dyspnea, or 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, 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 and resolution of symptoms after drug discontinuation). In particular, during ibuprofen treatment, isolated symptoms of aseptic meningitis (such as nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continued 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 category. Over-the-counter.

Manufacturer

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

Manufacturer's location and address of business activity

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 Velyka Oleksandrivka, Boryspil District, Kyiv Oblast, 08320, Ukraine.

You can report adverse reactions or lack of drug efficacy at the following phone numbers (24/7):

+380 44 207 51 97 or +380 50 414 39 39

or by email: [email protected]