INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN 200 IBUPROFEN 400 (IBUPROFEN 200 IBUPROFEN 400)

Composition:

Active ingredient: ibuprofen;

1 tablet contains 200 mg or 400 mg of ibuprofen;

Excipients: microcrystalline cellulose, sodium croscarmellose, monohydrate lactose, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, magnesium stearate, hypromellose, titanium dioxide (E 171), talc, macrogol 4000.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

200 mg tablets: film-coated tablets, straight-sided cylinders, white or almost white, with convex ends;

400 mg tablets: film-coated tablets, elongated shape, white or almost white, with convex upper and lower surfaces.

Pharmacotherapeutic group.

Drugs affecting the musculoskeletal system. Anti-inflammatory and antirheumatic agents. Nonsteroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ibuprofen.

ATC code M01AE01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which exerts analgesic, antipyretic, and anti-inflammatory effects by inhibiting the synthesis of prostaglandins—mediators of pain and inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid / aspirin on platelet aggregation when both agents are used concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid / aspirin (81 mg) reduces the effect of acetylsalicylic acid / aspirin on thromboxane production or platelet aggregation. Although there are uncertainties regarding extrapolation of these data to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid / aspirin. Such a clinically significant effect is considered unlikely with occasional, intermittent use of ibuprofen (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Pharmacokinetics

Absorption

Ibuprofen is rapidly absorbed primarily in the small intestine and binds to plasma proteins. After oral administration of 200–600 mg of ibuprofen, maximum plasma concentration (Cmax) of 15–55 µg/mL is reached on average within 1–2 hours (tmax).

When the drug is taken after food intake, absorption of ibuprofen is significantly slower and peak plasma concentrations are lower.

After oral administration of a single 400 mg dose of ibuprofen, peak plasma concentrations of 8–13 µg/mL are reached within 6 hours.

Distribution

Approximately 99% of ibuprofen is bound to plasma proteins. Binding is reversible.

Metabolism

More than 50–60% of an oral dose of ibuprofen is metabolized in the liver into two inactive metabolites. The metabolism of ibuprofen is similar in children and adults.

Excretion

The elimination half-life in plasma is 1½–2 hours. The short half-life indicates that even with repeated dosing, accumulation of ibuprofen does not occur. Ibuprofen and its metabolites are almost completely excreted via the kidneys within 24 hours after drug administration.

No significant differences in pharmacokinetic profile have been observed in elderly patients.

Clinical characteristics

Indications

Symptomatic treatment of mild to moderate pain of various origins (headache, toothache, dysmenorrhea), including pain associated with colds and fever.

Contraindications

Hypersensitivity to ibuprofen or to any component of the medicinal product.
Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid / aspirin, or other NSAIDs.
Active peptic ulcer or duodenal ulcer, gastrointestinal bleeding, or history of recurrent episodes (two or more distinct episodes of peptic ulcer or bleeding in the past).
Acute or previous inflammatory bowel diseases (such as Crohn’s disease, ulcerative colitis).
History of gastrointestinal bleeding or perforation related to previous use of NSAIDs.
Increased tendency to bleeding.
Severe renal impairment (creatinine clearance < 30 mL/min).
Severe hepatic insufficiency (liver cirrhosis, ascites).
Severe heart failure (NYHA Class III–IV).
Postoperative pain treatment following coronary artery bypass grafting (or use of cardiopulmonary bypass).
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction

Other NSAIDs, including selective cyclooxygenase-2 inhibitors: concomitant use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions").
Corticosteroids: increase the risk of gastrointestinal ulcers and bleeding (see section "Special precautions").
Alcohol: enhances gastrointestinal adverse effects and increases the risk of gastrointestinal bleeding.
Antihypertensive agents, β-blockers, and diuretics: NSAIDs may reduce the efficacy of diuretics and other antihypertensive drugs such as ACE inhibitors, angiotensin II antagonists, and β-blockers. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with reduced kidney function), concomitant use of an ACE inhibitor or angiotensin II antagonist with cyclooxygenase-inhibiting agents 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. In cases of long-term treatment, adequate hydration of the patient should be ensured, and monitoring of renal function should be considered at the beginning of combined therapy and periodically thereafter. Diuretics increase the risk of nephrotoxic effects of NSAIDs.
Probenecid and sulfinpyrazone: may delay excretion of ibuprofen; the uricosuric effect of probenecid and sulfinpyrazone is reduced.
Anticoagulants: NSAIDs may enhance the therapeutic effect of anticoagulants such as warfarin (see section "Special precautions").
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding when used with NSAIDs (see section "Special precautions").
Aminoglycosides: NSAIDs may reduce the elimination of aminoglycosides.
Acetylsalicylic acid / aspirin: should not be used in combination with ibuprofen, as this increases the risk of adverse reactions. Experimental data indicate that when used concomitantly, ibuprofen may inhibit the effect of low-dose acetylsalicylic acid / aspirin on platelet aggregation. However, uncertainty regarding the extrapolation of these data to clinical settings prevents definitive conclusions about whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid / aspirin. With occasional use of ibuprofen, such clinically significant effects are considered unlikely (see section "Special precautions").
Sulfonylurea derivatives: the effect of oral antidiabetic drugs (sulfonylureas) may be enhanced by ibuprofen and other NSAIDs. Hypoglycemia has been rarely reported in patients receiving sulfonylureas and ibuprofen. Blood glucose levels should be monitored regularly, and antidiabetic drug dosage adjusted if necessary.
H2-histamine antagonists: no clinically significant interaction between ibuprofen and cimetidine or ranitidine has been established.
Digoxin: NSAIDs may increase digoxin plasma concentrations.
Phenytoin: NSAIDs may increase phenytoin plasma concentrations.
Lithium: NSAIDs may reduce lithium excretion.
Methotrexate: NSAIDs may inhibit tubular secretion of methotrexate and reduce methotrexate clearance.
Baclofen: NSAID use increases baclofen toxicity.
Cholestyramine: concomitant use with cholestyramine may reduce ibuprofen absorption in the gastrointestinal tract, but the clinical significance of this is unknown.
Cyclosporine: increased risk of nephrotoxicity.
Tacrolimus: increased risk of nephrotoxicity.
Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.
Mifepristone: reduced efficacy of the drug is theoretically possible due to the anti-prostaglandin properties of NSAIDs. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not alter the effect of mifepristone or prostaglandins on cervical ripening or uterine contractility, nor does it reduce the clinical efficacy of medical termination of pregnancy.
Quinolone antibiotics: animal studies have shown that seizures associated with quinolones may occur more frequently when combined with NSAIDs. Concomitant use with ibuprofen increases the risk of seizures.
Zidovudine: an increased risk of hematological toxicity is known with concomitant use of zidovudine and NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.
CYP2C9 inhibitors: concomitant administration of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (ibuprofen is a CYP2C9 substrate). One study showed that voriconazole and fluconazole (CYP2C9 inhibitors) increased S(+)-ibuprofen exposure by approximately 80–100%. Dose reduction of ibuprofen should be considered when co-administered with CYP2C9 inhibitors, especially when high doses of ibuprofen are prescribed to patients taking voriconazole or fluconazole.
Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium monitoring is recommended).
Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Special precautions for use

General warnings

Adverse effects of ibuprofen can generally be minimized by using the lowest effective dose needed to treat symptoms for the shortest possible duration (see section "Dosage and administration" and gastrointestinal, cardiovascular risks below).

Prolonged use of any analgesics for headache treatment may worsen the condition. If this situation is suspected or confirmed, medical advice should be sought and treatment discontinued. Medication-overuse headache should be considered in patients suffering from frequent or daily headaches, despite (or because of) regular use of headache medications.

In placebo-controlled studies, selective COX-2 inhibitors have been associated with an increased risk of thrombotic cardiovascular and cerebrovascular complications. It is currently unknown whether this risk is directly correlated with COX-1/COX-2 selectivity of individual NSAIDs. Since comparable clinical trial data on ibuprofen at maximum doses and long-term therapy are currently lacking, a similar increased risk cannot be excluded. Until appropriate data become available, ibuprofen should be used in patients with clinically confirmed ischemic heart disease, cerebrovascular disease, peripheral arterial disease, or patients with significant risk factors (e.g., high blood pressure, hyperlipidemia, diabetes, smoking) only after careful assessment of risks and benefits. Due to this risk, the lowest effective dose should be used for the shortest possible treatment duration.

Renal effects of NSAIDs include fluid retention with edema and/or arterial hypertension. Therefore, ibuprofen should be used with caution in patients with cardiac impairment and other conditions predisposed to fluid retention. Caution is also advised in patients taking diuretics or ACE inhibitors concomitantly, as well as in those at increased risk of hypovolemia.

Concomitant use of NSAIDs with alcohol may increase adverse effects related to the active substance, particularly those affecting the gastrointestinal tract or the central nervous system (CNS).

Masking symptoms of underlying infections. Ibuprofen may mask symptoms of infectious disease, potentially delaying initiation of appropriate treatment and thereby complicating the disease course. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. If ibuprofen is used for fever or to relieve pain associated with infection, monitoring for infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Respiratory disorders. Ibuprofen should be prescribed with caution in patients with bronchial asthma, chronic rhinitis, allergic diseases, or a history thereof, as cases of bronchospasm, urticaria, or angioedema have been reported in such patients.

Impairment of heart, kidney, and liver function. NSAIDs should be used with caution in patients with impaired kidney, liver, or heart function, as this may lead to worsening of renal function.

Regular concomitant use of similar analgesic drugs further increases this risk.

Patients with impaired kidney, liver, or heart function should use the lowest effective dose for the shortest possible duration, and renal function should be monitored, especially during long-term treatment (see section "Contraindications").

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

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

Gastrointestinal bleeding, ulcers, perforations. NSAIDs should be used with caution in patients with chronic inflammatory bowel diseases (e.g., ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Contraindications").

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

The risk of gastrointestinal bleeding, perforation, and ulcers increases with higher NSAID doses, in patients with a history of peptic ulcer (especially if complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest doses. Caution is advised when treating patients receiving concomitant medications that increase the risk of gastotoxicity or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents such as acetylsalicylic acid / aspirin (see section "Interaction with other medicinal products and other forms of interaction"). For long-term treatment of these patients, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid / aspirin or other drugs increasing gastrointestinal risk, combined therapy with misoprostol or proton pump inhibitors may be necessary, as prescribed by a physician.

Patients with a history of gastrointestinal disorders, particularly elderly patients, should report any unusual gastrointestinal symptoms (especially bleeding), particularly gastrointestinal bleeding at the beginning of treatment.

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

Ibuprofen should be prescribed only under strict indications and under medical supervision for gastrointestinal complaints and liver dysfunction, as these conditions may worsen (see "Adverse reactions").

Cardiovascular and cerebrovascular effects. Long-term treatment should be initiated with caution in patients with uncontrolled arterial hypertension or a history of congestive heart failure (NYHA class II), requiring medical consultation, as fluid retention, arterial hypertension, and edema have been reported with ibuprofen and other NSAIDs.

Clinical trial data indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with an increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤ 1200 mg per day) is associated with an increased risk of arterial thrombotic complications.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful assessment of the clinical condition. High doses (2400 mg per day) should be avoided. Clinical evaluation should also be carefully performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg per day) are 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, potentially leading 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 indicating these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

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

Effects on kidneys. Treatment with ibuprofen should be initiated with caution in patients with significant dehydration. There is a risk of impaired renal function, particularly in children, adolescents, and elderly patients with dehydration. As with other NSAIDs, prolonged use of ibuprofen may lead to renal papillary necrosis and other renal pathological changes. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. Administration of NSAIDs to such patients may cause dose-dependent reduction in prostaglandin synthesis and, secondarily, reduced renal blood flow, potentially leading to renal failure.

Patients at high risk of such reactions include those with impaired renal function, heart failure, hepatic dysfunction, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and elderly patients. Discontinuation of NSAIDs is usually followed by recovery to the pre-treatment condition.

Regular use of analgesic medicinal products, especially combinations of multiple analgesics, may lead to persistent impairment of renal function with a risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration.

Hematological effects. Ibuprofen may temporarily inhibit platelet function (affect platelet aggregation) and prolong bleeding time. Therefore, careful monitoring is recommended in patients with coagulation disorders.

Aseptic meningitis, systemic lupus erythematosus, and mixed connective tissue diseases. Ibuprofen should be used with caution in patients with manifestations of systemic lupus erythematosus and mixed connective tissue diseases due to an increased risk of aseptic meningitis. However, symptoms of aseptic meningitis have also occurred in patients without any of these chronic conditions during ibuprofen use.

Effect on female fertility. Some data suggest that medicinal products inhibiting cyclooxygenase/prostaglandin synthesis may affect ovulation. This effect is reversible upon discontinuation of treatment. Long-term use (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days) of ibuprofen may impair female fertility and is not recommended for women attempting to conceive. This medicinal product should not be used in women experiencing difficulty conceiving or undergoing infertility evaluation.

Porphyrin metabolism. Caution should be exercised in patients with inherited disorders of porphyrin metabolism (e.g., acute intermittent porphyria).

Surgical procedures. Caution should be exercised immediately after major surgical procedures.

Other. Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rarely observed. If signs of hypersensitivity occur after drug administration, treatment must be discontinued. In such cases, both symptomatic and specialized treatment are required.

During long-term use of the drug, liver and kidney function tests and blood counts should be monitored regularly.

This medicinal product contains lactose monohydrate (one tablet of Ibuprofen 400 – 26.37 mg, one tablet of Ibuprofen 200 – 13.34 mg). This medicinal product should not be taken by patients with rare hereditary forms of fructose intolerance, glucose-galactose malabsorption syndrome, or deficiencies of sucrase or isomaltase enzymes.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Fertility

Ibuprofen may impair female fertility and is not recommended for women planning pregnancy. If a woman has problems with fertility or is undergoing infertility evaluation, discontinuation of ibuprofen should be considered.

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 after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and embryonic/fetal mortality. Furthermore, increased incidence of various developmental abnormalities, including cardiovascular defects, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

First and second trimesters. From the 20th week of pregnancy, use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. Additionally, cases of ductus arteriosus constriction after treatment in the second trimester have been reported, most of which resolved after treatment discontinuation. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary.

If ibuprofen is used by a woman 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.

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

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

Risks for the fetus:

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

Risks for the mother near term and for the newborn:

Possible prolongation of bleeding time, antiplatelet 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").

Labour and delivery. Ibuprofen is not recommended during labour. Onset of labour may be delayed, its duration prolonged, and susceptibility to bleeding in both mother and child increased.

Breastfeeding

NSAIDs pass into breast milk. Ibuprofen should not be taken by women who are breastfeeding. If treatment is necessary, the infant should be switched to artificial feeding.

Ability to influence reaction speed when driving or operating machinery

No specific studies have been conducted. Ibuprofen may affect patients' reaction speed, which should be considered when engaging in activities requiring heightened attention, such as driving or operating machinery. The effect on reaction speed is significantly enhanced when combined with alcohol.

Undesirable effects such as dizziness, drowsiness, fatigue, and visual disturbances may occur after NSAID use. If such effects occur during NSAID treatment, patients should not drive or operate machinery.

Dosage and Administration

Administer orally. For short-term use only. Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Tablets should be taken preferably with or after food, without chewing, and swallowed with water.

Adults and children aged 12 years and older with body weight of 40 kg or more: administer 1 tablet of 400 mg or 2 tablets of 200 mg every 6 hours as needed. The maximum daily dose is 1200 mg of ibuprofen. Use the lowest effective dose required to treat symptoms for the shortest possible duration.

If symptoms worsen or persist for more than 3 days in adolescents, consult a physician for diagnosis clarification and treatment adjustment.

If fever persists for more than 3 days in adults, or pain persists for more than 4 days, or if symptoms worsen, consult a physician for diagnosis clarification and treatment adjustment.

The duration of treatment is determined individually by a physician, depending on the course of the disease and the patient's condition.

Children aged 6 to 11 years with body weight from 20 to 40 kg: the usual dose is 20 to 30 mg/kg body weight per day, divided into several doses. The recommended initial dose is 1 tablet of 200 mg, with a repeat dose after 6 hours if needed. The maximum daily dose is 600 mg ibuprofen (3 tablets of 200 mg) for children weighing 20 to 30 kg, and 800 mg ibuprofen (4 tablets of 200 mg) for children weighing 30 to 39 kg.

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment. Due to the risk of adverse effects, elderly patients require careful monitoring.

Patients with mild to moderate renal impairment do not require dose reduction (for patients with severe renal impairment, see section "Contraindications").

Patients with mild to moderate hepatic impairment do not require dose reduction (for patients with severe hepatic impairment, see section "Contraindications").

Children

200 mg tablets – not to be used in children under 6 years of age or with body weight below 20 kg.

400 mg tablets – not to be used in children under 12 years of age or with body weight below 40 kg.

Overdose

Toxicity

Toxic symptoms are generally not observed with doses below 100 mg/kg in children and adults. However, supportive measures may be required in some cases. Administration of ibuprofen to children in doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the dose effect is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients, overdose symptoms develop within 4–6 hours after ingestion of a significant amount of ibuprofen.

The most common symptoms of overdose include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) manifestations: headache, tinnitus, dizziness, seizures, and loss of consciousness. Rarely reported: nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, coma, apnea, and CNS and respiratory depression. Cardiovascular toxicity has been reported, including arterial hypotension, bradycardia, and tachycardia.

Significant overdose may lead to renal failure and liver injury. Significant overdose is generally well tolerated if no other drugs are ingested. Severe poisoning may result in metabolic acidosis.

Prolonged use at doses higher than recommended or overdose may lead to renal tubular acidosis and hypokalemia. Symptoms may include confusion and generalized weakness.

Treatment. There is no specific antidote for ibuprofen overdose. Patients should be treated symptomatically as needed. If the ingested dose exceeds 400 mg/kg, gastric lavage or emptying of the stomach is recommended within 1 hour of ingestion, followed by symptomatic treatment. Activated charcoal should be administered within 1 hour after ingestion of a potentially toxic amount, and the patient should be observed for at least 4 hours.

If the drug has already been absorbed, alkalizing agents should be used to enhance urinary excretion of ibuprofen.

Treatment should include maintaining airway patency and monitoring cardiac function and vital signs until the patient's condition normalizes.

Frequent or prolonged seizures should be treated with intravenous diazepam. Other interventions may be indicated based on the patient's clinical condition.

Side effects

The adverse reactions listed below were observed during short-term use of ibuprofen doses not exceeding 1200 mg per day. Additional adverse effects may occur during treatment of chronic conditions with prolonged use.

Adverse reactions associated with ibuprofen use are listed by organ systems and frequency of occurrence.

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 not known (cannot be estimated from available data).

The most commonly observed adverse reactions with NSAIDs are gastrointestinal in nature and mostly dose-dependent, including a dose- and duration-dependent risk of gastrointestinal bleeding.

Peptic ulcers, perforations, or gastrointestinal bleeding, sometimes fatal, may occur, especially in elderly patients (see section "Special precautions"). Other gastrointestinal reactions include nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, and hematemesis.

Ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported after use (see "Precautions"). Gastritis occurs rarely. Gastrointestinal tract perforation has been rarely reported with ibuprofen use.

Exacerbation of skin infections caused by infection (e.g., development of necrotizing fasciitis) has been described during concomitant use of NSAIDs. In rare cases, severe skin infections and soft tissue complications may occur during varicella infection. If signs of infection appear or worsen during ibuprofen use, the patient should seek immediate medical attention.

Clinical studies indicate that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a slightly increased risk of arterial thrombotic events (such as myocardial infarction or stroke) (see section "Special precautions").

Infections and infestations: uncommon – rhinitis; rare – aseptic meningitis (particularly in patients with pre-existing autoimmune disorders such as systemic lupus erythematosus and mixed connective tissue diseases), with symptoms such as nuchal rigidity, headache, nausea, vomiting, fever, or confusion (see section "Special precautions").

Exacerbations of skin inflammation due to infection (e.g., development of necrotizing fasciitis) have been reported during NSAID use. If signs of infection appear or worsen during ibuprofen use, the patient should seek immediate medical attention.

Blood and lymphatic system disorders: rare – aplastic anemia, leukopenia, thrombocytopenia, neutropenia, agranulocytosis, hemolytic anemia, which may occur during prolonged treatment. Initial symptoms may include malaise, sore throat, oral ulcers, flu-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Immune system disorders: uncommon – hypersensitivity. There have been reports of hypersensitivity reactions following ibuprofen treatment. 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 commonly, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Rare – anaphylactic reaction, lupus-like syndrome, autoimmune hemolytic anemia.

Psychiatric disorders: uncommon – insomnia, anxiety disorders; rare – depression, confusion, restlessness, hallucinations; very rare – psychiatric disorders.

Nervous system disorders: common – headache, dizziness, hypoesthesia (especially when combined with alcohol); uncommon – paresthesia, somnolence.

Eye disorders: uncommon – visual disturbances, usually reversible upon discontinuation of treatment; rare – toxic amblyopia, toxic optic neuropathy, optic neuritis.

Ear and labyrinth disorders: uncommon – hearing impairment, vertigo; tinnitus and dizziness may occur with prolonged treatment.

Cardiac disorders: very rare – heart failure, edema, infarction; frequency not known – Kounis syndrome.

Vascular disorders: very rare – arterial hypertension.

Clinical data indicate that ibuprofen use, especially at high doses (2400 mg per day), may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions").

Respiratory, thoracic and mediastinal disorders: uncommon – bronchial asthma, bronchospasm, dyspnea, risk of acute pulmonary edema in patients with heart failure.

Gastrointestinal disorders: common – abdominal pain, dyspepsia, diarrhea, vomiting, nausea, flatulence, constipation, melena, hematemesis, gastrointestinal perforation or bleeding; uncommon – gastritis, duodenal ulcer, gastric ulcer, ulcerative stomatitis, gastrointestinal bleeding, which in some cases may be fatal, especially in elderly patients; very rare – pancreatitis; frequency not known – heartburn, oral ulceration, esophagitis, intestinal stricture formation, exacerbation of ulcerative colitis and Crohn’s disease (see section "Contraindications").

Hepatobiliary disorders: uncommon – hepatitis, jaundice, liver function abnormalities; very rare – liver failure.

Skin and subcutaneous tissue disorders: common – rash; rare – urticaria, pruritus, purpura, angioedema, photosensitivity reactions; very rare – serious skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis); frequency not known – drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

In rare cases, severe skin infections and soft tissue complications may occur during varicella infection (see also "Infections and infestations").

Renal and urinary disorders: rare – toxic nephropathy in various forms, including tubulointerstitial nephritis, nephrotic syndrome, and renal failure; very rare – acute renal impairment, papillary necrosis, especially with prolonged use, associated with increased plasma urea levels, edema, hypernatremia (sodium retention), oliguria.

General disorders and administration site conditions: common – malaise/fatigue, irritability; rare – edema.

Investigations: very rare – decreased hemoglobin levels.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life: 3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging

Tablets 200 mg: 10 tablets per blister; 2 or 5 blisters per cardboard pack.

Tablets 400 mg: 10 tablets per blister; 1, 2, or 5 blisters per cardboard pack.

Prescription status

Over-the-counter (without prescription).

Manufacturer

PJSC "Tekhnolohiya".

Manufacturer's address and location of business activity

8 Stara Prorynna Street, Uman, Cherkasy region, 20300, Ukraine.