Ibufen® junior

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUFEN® Junior (IBUFEN Junior)

Composition:

Active substance: ibuprofenum;

One soft capsule contains 200 mg of ibuprofen;

Excipients: macrogol 600 (E 1521), potassium hydroxide (E 525), purified water;

gelatin capsule: maltitol liquid (E 965), non-crystallizing sorbitol solution (E 420), gelatin (E 441), purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: oval-shaped soft gelatin capsules with a semi-transparent shell of light yellow color, containing a viscous liquid.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives. ATC code M01A E 01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a propionic acid derivative. It exerts analgesic, antipyretic, and anti-inflammatory effects.

The mechanism of action of ibuprofen is primarily due to inhibition of prostaglandin biosynthesis by reducing the activity of cyclooxygenase (COX), the enzyme responsible for converting arachidonic acid into prostaglandins, prostacyclin, and thromboxane. As a result of irreversible inhibition of the cyclooxygenase pathway of arachidonic acid metabolism, the production of prostaglandins is decreased. Reduced prostaglandin concentrations at the site of inflammation lead to decreased formation of bradykinin, endogenous pyrogens, other biologically active substances, oxygen radicals, and nitric oxide (NO). This results in reduced inflammatory activity (anti-inflammatory effect of ibuprofen) and is accompanied by diminished pain perception (analgesic effect). Decreased prostaglandin concentrations in cerebrospinal fluid lead to normalization of body temperature (antipyretic effect).

Pharmacokinetics

Ibufen® Junior soft gelatin capsules contain ibuprofen in liquid form. The gelatin capsule ensures high dosing accuracy of the contained substance. The capsule shell protects the active ingredient from light, air, and moisture, and also masks the unpleasant taste and odor of the drug during administration. The capsule dissolves faster in the gastrointestinal tract (GI tract) than dragees and tablets, and its liquid content is absorbed more rapidly and easily in the human body, providing high bioavailability of ibuprofen.

After oral administration, more than 80% of ibuprofen is absorbed from the gastrointestinal tract. Approximately 90% of the drug binds to plasma proteins (mainly albumins).

The time to reach maximum plasma concentration is 45 minutes when taken on an empty stomach and 1.5–2.5 hours when taken after food; in synovial fluid, it is 2–3 hours, where concentrations higher than in plasma are achieved.

The drug does not accumulate in the body.

Ibuprofen is metabolized primarily in the liver. It undergoes presystemic and postsystemic metabolism. After absorption, about 60% of the pharmacologically inactive R-form of ibuprofen slowly converts into the active S-form.

60–90% of the drug is excreted via the kidneys as metabolites and conjugation products with glucuronic acid, to a lesser extent with bile, and less than 1% is excreted unchanged. After a single dose, the drug is completely eliminated within 24 hours.

Clinical characteristics.

Indications.

Symptomatic treatment of headache (including migraine), toothache, dysmenorrhea, neuralgia, back pain, joint pain, muscle pain, rheumatic pain, as well as symptoms of cold and flu.

Contraindications.

• Hypersensitivity to ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs), or to any component of the medicinal product.
• Hypersensitivity reactions (e.g., asthma, rhinitis, angioedema, or urticaria) previously observed after taking ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more confirmed episodes of peptic ulcer or bleeding).
• Gastrointestinal bleeding or perforation related to previous use of NSAIDs.
• Severe heart failure (NYHA Class IV), severe renal impairment, or severe hepatic impairment.
• Third trimester of pregnancy.
• Active inflammatory bowel disease.
• Cerebrovascular or other hemorrhages.
• Hematopoietic or coagulation disorders of unknown etiology (hemorrhagic diathesis, thrombocytopenia).
• Dehydration caused by vomiting, diarrhea, or insufficient fluid intake.

Interaction with other medicinal products and other forms of interaction.

In general, caution should be exercised when using NSAIDs in combination with other medicinal products that may increase the risk of gastrointestinal ulcers, gastrointestinal bleeding, or worsening of renal function.

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

• aspirin (acetylsalicylic acid): concomitant use of ibuprofen with acetylsalicylic acid is generally not recommended due to the potential for increased adverse reactions, except when low-dose aspirin (not exceeding 75 mg per day) has been prescribed by a physician.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation. Although uncertainty exists 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. Such a clinically significant effect is considered unlikely with occasional, non-regular use of ibuprofen.

• other NSAIDs, including selective cyclooxygenase-2 inhibitors: simultaneous use of two or more NSAIDs should be avoided, as this may increase the risk of adverse reactions.

Ibuprofen should be used with caution in combination with:

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

antihypertensive agents (ACE inhibitors, angiotensin II antagonists, beta-blockers) and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised kidney function), concomitant use of ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including potentially reversible acute renal failure. Therefore, such combinations should be prescribed with caution, especially in elderly patients. In cases requiring prolonged treatment, adequate hydration of the patient should be ensured, and monitoring of renal function should be considered at the start of combined therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Concomitant use of potassium-sparing diuretics with ibuprofen may lead to hyperkalemia.

Glucocorticoids may increase the risk of gastrointestinal ulcers and bleeding.

Lithium: evidence exists for potential elevation of plasma lithium levels.

Methotrexate: evidence exists for potential elevation of plasma methotrexate levels.

NSAIDs inhibit tubular excretion of methotrexate, which may lead to reduced methotrexate clearance. Concomitant use of ibuprofen (NSAIDs) should be avoided during high-dose methotrexate therapy. The risk of interaction between NSAIDs and methotrexate should also be considered during low-dose methotrexate therapy, particularly in patients with impaired renal function. Renal function should be monitored when methotrexate and NSAIDs are used concomitantly. NSAIDs and methotrexate should be administered with a 24-hour interval due to the potential for increased plasma methotrexate concentration and consequent increased toxicity.

Zidovudine: increased risk of hematological toxicity is known when zidovudine is used concomitantly with NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia who are concurrently treated with zidovudine and ibuprofen.

Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): risk of gastrointestinal bleeding may be increased.

Cyclosporine, tacrolimus: potential risk of nephrotoxicity may be increased.

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

Quinolone antibiotics: concomitant use with ibuprofen may increase the risk of seizures.

Sulfonylurea derivatives and phenytoin: possible potentiation of effect.

Phenytoin: ibuprofen may increase the pharmacologically active free fraction of phenytoin.

Aminoglycosides: NSAIDs may reduce aminoglycoside excretion.

Oral hypoglycemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged elimination half-life, and increased risk of hypoglycemia.

Probenecid and sulfinpyrazone: medicinal products containing probenecid or sulfinpyrazone may delay excretion of ibuprofen.

Baclofen: toxic effects of baclofen may occur after initiation of ibuprofen therapy.

Cholestyramine: concomitant use of cholestyramine and ibuprofen delays and reduces ibuprofen absorption by approximately 25%. Ibuprofen should be administered with a several-hour interval.

Voriconazole and fluconazole: studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in S(+)-ibuprofen exposure. Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors, particularly when high doses of ibuprofen are used with voriconazole or fluconazole.

Antacids and cholestyramine: possible reduction in absorption.

Caffeine: possible enhancement of analgesic effect.

Special precautions for use.

Adverse effects associated with the use of ibuprofen and nonsteroidal anti-inflammatory drugs (NSAIDs) in general can usually be minimized by using the lowest effective dose required to control symptoms over the shortest possible treatment period.

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

Cardiovascular and cerebrovascular effects

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure should be treated with caution when initiating long-term therapy (medical consultation is required), as fluid retention, arterial hypertension, and edema have been reported during treatment with ibuprofen and other NSAIDs.

Clinical trial data indicate that the use of ibuprofen, especially at high doses (2400 mg daily), may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤1200 mg daily) 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 their clinical condition. High doses (2400 mg daily) should be avoided.

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

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is characterized by cardiovascular symptoms associated with coronary artery spasm due to allergy or hypersensitivity reactions, which may lead to myocardial infarction.

Respiratory effects

Bronchospasm may occur in patients with 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, increases the risk of adverse reactions and should be avoided.

Ibuprofen should not be prescribed to adults who are already receiving other NSAIDs, analgesics, or acetylsalicylic acid at daily doses exceeding 75 mg.

Systemic lupus erythematosus and mixed connective tissue diseases

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

Cases of aseptic meningitis have been reported during ibuprofen use. Although this effect is more likely in patients with systemic lupus erythematosus and other connective tissue diseases, cases have also been reported in some patients without chronic conditions; therefore, this should be considered when using this medicinal product.

Renal/hepatic effects

Patients with renal impairment should be treated with caution 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. Such patients should receive the lowest possible dose of ibuprofen, and renal function should be monitored regularly. In cases of dehydration, adequate fluid intake should be ensured. There is a risk of renal impairment in children (aged 6 years and older) and adolescents who are dehydrated.

In general, chronic use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy). The highest risk of this reaction occurs in elderly patients, patients with renal, cardiac, or hepatic impairment, and those receiving diuretics or angiotensin-converting enzyme (ACE) inhibitors. After discontinuation of NSAID therapy, renal function usually returns to the pre-treatment state.

Like other NSAIDs, ibuprofen may cause a slight, temporary increase in certain liver function parameters, as well as significant elevations in AST and ALT levels. Treatment should be discontinued if substantial increases in these parameters occur.

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

Effect on female fertility

Limited data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect the process of ovulation. This effect is reversible upon discontinuation of treatment. Long-term use of ibuprofen (referring to a dose of 2400 mg daily and treatment duration exceeding 10 days) may impair female fertility and is not recommended for women attempting to conceive. This medication should be discontinued in women experiencing difficulty conceiving or undergoing infertility investigations.

Gastrointestinal effects

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. Cases of gastrointestinal bleeding, ulcer perforation, which may be fatal, have been reported at any stage of NSAID therapy, 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.

Such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, should be prescribed concomitant protective therapy (e.g., misoprostol or proton pump inhibitors).

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

Prolonged use of any analgesic for headache treatment may worsen the condition. In such cases, medical advice should be sought and treatment discontinued. Medication-overuse headache should be considered in patients with frequent or daily headaches despite (or due to) regular use of headache medications.

Caution is required when treating patients receiving concomitant medications that may increase the risk of ulcers or bleeding, such as oral corticosteroids or anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., aspirin).

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

Serious skin adverse reactions (SSARs)

Serious skin adverse reactions (SSARs) associated with ibuprofen use have been reported, 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 (see section "Adverse reactions"). Most of these reactions occurred within the first month of treatment.

If signs or symptoms suggestive of 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, a negative influence of NSAIDs on the course of these infections cannot be excluded; therefore, the use of this medicinal product is not recommended in cases of varicella.

Serious acute hypersensitivity reactions, such as anaphylactic shock, have occurred very rarely. Ibuprofen treatment should be discontinued immediately upon the first signs of hypersensitivity. Medical personnel should be informed about appropriate treatment measures for managing such symptoms.

Ibuprofen may temporarily inhibit platelet activity (platelet aggregation) and prolong bleeding time in healthy individuals. Therefore, careful monitoring is required in patients with coagulation disorders.

Experimental data indicate reduced platelet aggregation and interference with the antiplatelet effect of acetylsalicylic acid when administered concomitantly with ibuprofen. This interaction may limit the desired cardioprotective effect of acetylsalicylic acid. Therefore, ibuprofen should be used with particular caution in patients receiving acetylsalicylic acid for platelet aggregation inhibition.

There is a risk of renal impairment in dehydrated children. Ibuprofen should be prescribed with caution in children with significant dehydration.

Masking symptoms of underlying infections: ibuprofen may mask symptoms of infectious diseases, potentially delaying the initiation of appropriate treatment and thereby worsening the course of the disease. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief during infection, monitoring of the infectious condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Use during pregnancy or breastfeeding

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

In animal studies, prostaglandin synthesis inhibitors have led to increased pre- and post-implantation losses and embryonic/fetal mortality. In addition, increased frequencies of various developmental abnormalities, including cardiovascular malformations, have been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, the use of the medicinal product Ibufen® Junior may cause oligohydramnios due to fetal renal dysfunction. Renal impairment may occur almost immediately after starting treatment and is usually reversible upon discontinuation of ibuprofen. Additionally, arterial duct constriction has been reported after second-trimester treatment, which resolved after treatment cessation. Therefore, the medicinal product should not be used during the first two trimesters of pregnancy, except when absolutely necessary. If the drug is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose should be used for the shortest possible duration. Antenatal monitoring for oligohydramnios and arterial duct constriction may be advisable after several days of ibuprofen use starting from the 20th week of pregnancy. Ibuprofen should be discontinued if signs of oligohydramnios or arterial duct constriction are detected.

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

• For the fetus: cardiopulmonary toxicity (characterized by premature constriction/closure of the arterial duct and pulmonary hypertension); renal dysfunction, which may progress to renal failure associated with oligohydramnios (see above);

• For the mother at the end of pregnancy and the newborn: prolonged bleeding time, antiplatelet effect (which may occur even at very low doses), and inhibition of uterine contractions leading to delayed or prolonged labor.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations, making it unlikely to adversely affect a breastfed infant.

Ability to affect reaction speed when driving or operating machinery

When used according to recommended doses and treatment duration, the drug does not affect reaction speed in driving or operating machinery. However, patients who experience dizziness, drowsiness, disorientation, or visual disturbances while taking NSAIDs should refrain from driving or operating machinery.

Dosage and Administration

For oral use.

Children with body weight 20–29 kg: the recommended initial dose is 1 capsule (equivalent to 200 mg of ibuprofen). The maximum daily dose is 3 capsules (600 mg of ibuprofen).

Children with body weight 30–39 kg: the recommended initial dose is 1 capsule (equivalent to 200 mg of ibuprofen). The maximum daily dose is 4 capsules (800 mg of ibuprofen).

Adults and children with body weight ≥ 40 kg: the recommended initial dose is 1–2 capsules, then, if necessary, 1–2 capsules (200–400 mg of ibuprofen) every 4–6 hours. The maximum daily dose is 6 capsules (1200 mg of ibuprofen).

Children with body weight ≥ 39 kg: the drug may be administered to children with body weight of at least 20 kg. The maximum daily dose of ibuprofen is 20–30 mg per kilogram of body weight, divided into 3–4 doses, with dosing intervals of 6–8 hours. Do not exceed the maximum recommended daily dose.

The capsule should be swallowed whole with a small amount of water. Capsules must not be chewed, crushed, or sucked. When administering the drug to children, body weight should be taken into account for accurate dosing.

If symptoms persist for more than 3 days, or if used for pain relief for more than 4 days, consult a physician for diagnosis clarification and treatment adjustment.

Hepatic impairment

Ibuprofen should be used with caution in patients with mild to moderate hepatic impairment. The lowest possible dose should be used. Ibuprofen is contraindicated in patients with severe hepatic dysfunction (see section "Contraindications").

Children

The use of this drug is contraindicated in children with body weight less than 20 kg.

Overdose

Administration of the drug to children at 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 participating in clinical trials, ingestion of large amounts of NSAIDs caused only nausea, vomiting, epigastric pain, or very rarely diarrhea. Tinnitus, headache, dizziness, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, manifesting as drowsiness, nystagmus, visual disturbances, and occasionally excitement, disorientation, or coma. Seizures may sometimes occur. Severe poisoning may lead to hyperkalemia and metabolic acidosis, acute renal failure, liver damage, arterial hypotension, respiratory failure, and cyanosis. In patients with bronchial asthma, asthma exacerbation may occur.

Treatment. Treatment should be symptomatic and supportive, including ensuring airway patency and monitoring vital functions until the condition normalizes. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkaline agents may be administered to accelerate urinary excretion of the acidic ibuprofen.

Adverse Reactions.

The most common adverse reactions are gastrointestinal and are mostly dose-dependent. Adverse reactions occur least frequently when the maximum daily dose is 1200 mg.

Cardiovascular system.

Frequency unknown – heart failure, edema, Couinaud's syndrome.

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, may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Vascular system.

Frequency unknown – arterial hypertension.

Gastrointestinal tract.

Uncommon – dyspepsia, abdominal pain, nausea, bloating;

Rare – diarrhea, flatulence, constipation, vomiting;

Very rare – peptic ulceration, perforations or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis;

Frequency unknown – exacerbation of colitis and Crohn's disease.

Nervous system.

Uncommon – headache;

Very rare – aseptic meningitis*.

Renal and urinary system.

Very rare – acute impairment of kidney function, papillary necrosis, particularly with prolonged use, associated with increased plasma urea levels and edema;

Frequency unknown – renal failure, hematuria, interstitial nephritis, nephrotic syndrome, proteinuria.

Hepatic system.

Very rare – liver function abnormalities, especially with prolonged use;

Frequency unknown – liver failure, hepatitis, jaundice.

Skin and subcutaneous tissue.

Rare – various skin rashes;

Very rare – severe skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis);

Frequency unknown – photosensitivity reactions, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

In exceptional cases, serious infections of the skin and subcutaneous tissue may develop as complications of varicella.

Blood and lymphatic system.

Very rare – anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur during prolonged treatment, with initial signs including malaise, sore throat, superficial oral ulcers, flu-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Psychiatric disorders.

Frequency unknown – only with prolonged use: depression, hallucinations, confusion, psychotic reactions.

Eye disorders.

Frequency unknown – with prolonged treatment, visual disturbances and optic neuritis may occur.

Ear and labyrinth disorders.

Frequency unknown – with prolonged treatment, tinnitus and vertigo may occur.

Immune system.

Rare – hypersensitivity reactions, including urticaria and pruritus;

Very rare – severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, hypotension, anaphylactic reactions, angioneurotic edema, or severe shock;

Frequency unknown – respiratory tract reactivity, including bronchial asthma, asthma exacerbation, bronchospasm.

General disorders.

Malaise and fatigue.

Laboratory investigations.

Very rare – decreased hemoglobin levels.

Very rare cases of exacerbation of inflammatory conditions associated with infectious diseases (e.g., development of necrotizing fasciitis) have been reported following the use of nonsteroidal anti-inflammatory drugs. This is likely related to the mechanism of action of NSAIDs. Patients should be advised to seek medical attention promptly if symptoms of infection or worsening of infection occur during ibuprofen treatment.

*The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal relationship to drug intake and resolution of symptoms after discontinuation of the drug). In particular, isolated cases of aseptic meningitis symptoms (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) during treatment with ibuprofen.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years. Do not use after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

10 capsules per blister. 1 or 2 blisters per cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Pharmaceutical Works POLPHARMA S.A.

Manufacturer's address and location of manufacturing site.

Medana Branch in Sieradz, 10 Wladyslawa Lokietka Str., 98-200 Sieradz, Poland