INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EUROFAST SOFTCAPS (EUROFASTSOFTCAPS)

Composition:

Active substance: ibuprofen;

1 soft capsule contains 200 mg or 400 mg of ibuprofen;

Excipients (200 mg): macrogol 600; potassium hydroxide; purified water;

capsule shell: gelatin 160 Bloom; sorbitol solution, partially dehydrated; Ponzo 4R; purified water;

Excipients (400 mg): macrogol 600; potassium hydroxide; purified water;

capsule shell: gelatin 160 Bloom; sorbitol solution, partially dehydrated; purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical properties:

200 mg soft capsules: red, transparent, oval-shaped soft gelatin capsules containing a colorless or slightly red transparent liquid;

400 mg soft capsules: transparent, colorless or slightly yellow, oval-shaped soft gelatin capsules containing a transparent colorless liquid.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01AE01.

Pharmacological Properties.

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

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when these drugs 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 (81 mg) was associated with reduced effects of acetylsalicylic acid (aspirin) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding the extrapolation of these data to the clinical setting, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional (intermittent) use of ibuprofen, such a clinically significant interaction is considered unlikely.

The capsule contains ibuprofen dissolved in a hydrophilic solvent. After oral administration, the gelatin capsule disintegrates under the action of gastric juice, thereby releasing the pre-dissolved ibuprofen.

Pharmacokinetics. After oral administration, ibuprofen is rapidly absorbed partially already in the stomach and completely in the small intestine.

Following hepatic metabolism (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are excreted predominantly in urine (90%) and also in bile. The elimination half-life in healthy volunteers, as well as in patients with hepatic or renal disease, ranges from 1.8 to 3.5 hours. Plasma protein binding is approximately 99%. After oral administration of the conventional release dosage form, maximum plasma concentration is reached within 1–2 hours. In a pharmacokinetic study, the time to peak plasma concentration (Tmax) on an empty stomach was 90 minutes for the tablet formulation and 40 minutes for soft gelatin capsules. Ibuprofen remains detectable in plasma for more than 8 hours after administration of the soft gelatin capsule formulation.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain of various origin (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 or history of recurrent peptic ulcer/gastrointestinal bleeding (two or more distinct episodes of peptic ulcer or bleeding in the past).

History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.

Severe impairment of liver function, severe impairment of kidney function, severe heart failure (NYHA Class IV (New York Heart Association)).

Third trimester of pregnancy.

Active cerebrovascular or other bleeding.

Hemorrhagic diathesis or coagulation disorders.

Unexplained disturbances of blood formation.

Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).

Patient weight less than 40 kg or patient age under 12 years.

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 (at a dose not exceeding 75 mg per day) has been prescribed by a physician.

Experimental data indicate that concomitant use of ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation. However, the limited data available for extrapolation to clinical settings do not allow definitive conclusions regarding whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional use of ibuprofen, such clinically significant effects are considered unlikely;

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.

Ibuprofen should be used with caution in combination with the following medicinal products:

anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin;

antihypertensive agents (ACE inhibitors (angiotensin-converting enzyme inhibitors) and angiotensin II antagonists) and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised kidney function), concomitant use of an ACE inhibitor or angiotensin II antagonist with drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, particularly 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 start of combined therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium monitoring is recommended);

corticosteroids: increased risk of gastrointestinal ulcers and bleeding;

antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): may increase the risk of gastrointestinal bleeding;

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

lithium: evidence suggests a potential increase in plasma lithium levels;

phenytoin: concomitant use with phenytoin preparations may increase its serum levels;

methotrexate: administration of ibuprofen within 24 hours before or after methotrexate may lead to elevated methotrexate concentrations and increased toxicity;

cyclosporine: increased risk of nephrotoxicity;

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

tacrolimus: possible increased risk of nephrotoxicity when NSAIDs are used concomitantly with tacrolimus;

zidovudine: increased risk of hematologic 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;

quinolone antibiotics: concomitant use with ibuprofen may increase the risk of seizures;

sulfonylureas: blood glucose levels should be monitored during concomitant use;

probenecid and sulfinpyrazone: may delay elimination of ibuprofen;

CYP2C9 inhibitors: concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). A study with voriconazole and fluconazole (CYP2C9 inhibitors) showed an approximately 80–100% increase in the effect of S(+)-ibuprofen. Dose reduction of ibuprofen should be considered when potent CYP2C9 inhibitors are used concomitantly, especially when high doses of ibuprofen are administered with voriconazole or fluconazole.

Special precautions for use.

Adverse effects associated with the use of ibuprofen, as with all NSAIDs, can be minimized by using the lowest effective dose required to relieve symptoms, for the shortest possible duration.

Caution is necessary when treating patients:

with systemic lupus erythematosus or mixed connective tissue disease – increased risk of aseptic meningitis (see section "Adverse reactions");
with congenital porphyrin metabolism disorders (e.g. acute intermittent porphyria) (see section "Adverse reactions");
with gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) (see section "Adverse reactions");
with arterial hypertension and/or heart failure (see sections "Contraindications" and "Adverse reactions");
with impaired renal function, as kidney function may deteriorate (see sections "Contraindications" and "Adverse reactions");
with impaired hepatic function (see sections "Contraindications" and "Adverse reactions");
following major surgical procedures;
with allergic reactions to other substances, as they also have an increased risk of hypersensitivity reactions when using the medicinal product;
suffering from hay fever, nasal polyps, chronic obstructive respiratory diseases, or with a history of allergic diseases, as they have an increased risk of allergic reactions. In such patients, asthma attacks (so-called analgesic-induced asthma), Quincke's edema (angioedema), or urticaria may occur.

Elderly patients experience a higher frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal.

Respiratory effects

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

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.

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.

Porphyrin metabolism

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

Effects on the cardiovascular and cerebrovascular systems

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

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g., ≤ 1200 mg per day) increases the 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 only be treated with ibuprofen after careful assessment of their clinical condition. High doses (2400 mg per day) should be avoided.

A careful evaluation of the clinical condition should also be performed 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 per day) are required.

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

Effects on the kidneys

Ibuprofen should be used with caution in patients with impaired renal function, as kidney function may deteriorate.

Effects on the liver

Impairment of liver function is possible.

Surgical procedures

Caution should be exercised immediately after major surgical procedures.

Effects on female fertility

Available data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, when used long-term (referring to doses of 2400 mg per day and treatment duration exceeding 10 days), may impair fertility in women by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Effects on the gastrointestinal system

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated. Cases of gastrointestinal bleeding, perforation, and ulcers, including fatal outcomes, have been reported during NSAID therapy at any stage, regardless of prior 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 complicated by bleeding or perforation), and in elderly patients. Such patients should initiate treatment with the lowest possible doses. For these patients, as well as for individuals requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase gastrointestinal risk, consideration should be given to combining therapy with gastroprotective agents (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 gastrointestinal bleeding), particularly at the beginning of treatment.

Caution is required when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, 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.

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 occur within the first month of treatment. If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment options should be considered (if necessary). In rare cases, varicella (chickenpox) may lead to severe skin and soft tissue infections. At present, a potential negative influence of NSAIDs on such infections cannot be excluded; therefore, the use of ibuprofen in cases of varicella is not recommended.

Masking symptoms of underlying infections

Eurofast Softcaps 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 Eurofast Softcaps are used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Allergy

Caution should be exercised when treating patients with allergic reactions to other substances, as such patients also have an increased risk of hypersensitivity reactions when using ibuprofen.

Patients with hay fever, nasal polyps, chronic obstructive respiratory diseases, or a history of allergic diseases have an increased risk of allergic reactions, which may manifest as asthma attacks (so-called analgesic-induced asthma), Quincke's edema (angioedema), or urticaria.

This medicinal product contains sorbitol. Patients with known sugar intolerance should consult a physician before taking this medicinal product.

This medicinal product contains Ponceau 4R, which may cause allergic reactions.

NSAIDs may mask symptoms of infection and fever.

Other

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) may occur. At the first signs of a hypersensitivity reaction after taking Eurofast Softcaps, treatment must be discontinued. In such cases, both symptomatic and specialized treatment are required.

Ibuprofen may temporarily inhibit platelet function (affect platelet aggregation). Therefore, careful monitoring of patients with coagulation disorders is recommended.

During prolonged treatment with Eurofast Softcaps, regular monitoring of liver and kidney function tests, as well as blood counts, is necessary.

Long-term use of any analgesic for headache treatment may worsen the condition. If this cause is suspected or confirmed, treatment should be discontinued and medical advice sought. Medication-overuse headache should be suspected in patients suffering from frequent or daily headaches despite regular use of headache medications.

Systematic use of analgesics, especially combinations of multiple analgesics, may lead to persistent kidney dysfunction with risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration.

The risk of adverse effects related to the active substance, particularly on the gastrointestinal tract or CNS (central nervous system), may increase when NSAIDs are used concomitantly with alcohol.

There is a risk of impaired kidney function in dehydrated adolescents.

Use during pregnancy or breastfeeding.

Suppression of prostaglandin synthesis may negatively 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 in early pregnancy. The absolute risk of cardiovascular malformations increases from 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

NSAIDs should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible duration.

From the 20th week of pregnancy, the use of Eurofast Softcaps may cause oligohydramnios due to fetal kidney dysfunction. This may occur shortly after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction following treatment in the second trimester, most of which resolved after stopping treatment. Therefore, during the first and second trimesters of pregnancy, Eurofast Softcaps should not be prescribed unless necessary. If Eurofast Softcaps 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 arterial duct constriction should be considered after exposure to Eurofast Softcaps for several days starting from the 20th gestational week. Treatment with Eurofast Softcaps should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

Risks to the fetus:

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

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

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

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

In some studies, ibuprofen has been detected in breast milk at very low concentrations, making it unlikely to adversely affect the breastfed infant. However, NSAIDs are not recommended during breastfeeding.

Fertility

The use of ibuprofen may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, the use of ibuprofen is not recommended in women experiencing difficulty conceiving.

Ability to influence reaction speed when driving or operating machinery.

Patients experiencing dizziness, drowsiness, or visual disturbances while taking ibuprofen should avoid driving or operating machinery. Single-dose administration or short-term use of ibuprofen generally does not require special precautions. This primarily applies to concomitant use of the product with alcohol.

When following dosage and treatment duration recommendations, the product does not affect reaction speed when driving or operating machinery.

Dosage and Administration

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

Administer orally to adults and children aged 12 years and older with body weight > 40 kg. For short-term use only. Adverse effects can be minimized by using the lowest effective dose for the shortest duration required to control symptoms.

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

The single dose for children aged 12 years and older with body weight > 40 kg and adults is 1 capsule (400 mg of ibuprofen). If necessary, 1 capsule may be administered every 6 hours. The maximum daily dose is 1200 mg (3 capsules per day). Use the minimum 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 in adults fever persists for more than 3 days, pain does not resolve within 4 days, or symptoms worsen, consult a physician for diagnosis clarification and treatment adjustment.

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

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 "Special Precautions".

Dose reduction is not necessary in patients with mild or moderate hepatic impairment; for patients with severe hepatic impairment, see section "Special Precautions".

Children

Do not administer to children under 12 years of age or to children with body weight < 40 kg.

Overdose

Administration of doses exceeding 400 mg/kg in children 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 who have ingested clinically significant quantities of NSAIDs, only nausea, vomiting, epigastric pain, or very rarely diarrhea occur. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, manifesting as vertigo, drowsiness, occasionally agitation, disorientation, or coma. Seizures may occasionally occur. Severe poisoning may lead to hyperkalemia and metabolic acidosis. Prolongation of prothrombin time/increased prothrombin index may be observed, possibly due to effects on circulating blood coagulation factors. Acute renal failure, liver injury, arterial hypotension, respiratory depression, and cyanosis may develop. In patients with bronchial asthma, disease exacerbation may occur.

Treatment. Management should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac and vital functions until stabilization. Oral activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalinizing agents may be administered to enhance urinary excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators should be used to treat bronchial asthma exacerbation.

There is no specific antidote.

Side effects.

The list of adverse reactions observed after treatment with ibuprofen includes all side effects reported during short-term use as well as those observed during long-term, high-dose therapy in patients with rheumatism. The specified frequencies beyond very rare reports refer to short-term use of doses (maximum 1200 mg ibuprofen per day) for oral dosage forms and up to 1800 mg per day for suppositories.

The development of adverse reactions to the medicinal product primarily depends on the dose and individual characteristics of the organism.

The most commonly observed adverse reactions are gastrointestinal in nature. Peptic ulcers, perforation, or gastrointestinal bleeding, sometimes with fatal outcomes, may occur, particularly in elderly patients. During treatment, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported. Gastritis occurs less frequently. The risk of gastrointestinal bleeding mainly depends on the dose and duration of treatment. Reports have been documented regarding edema, arterial hypertension, and heart failure associated with NSAID therapy.

Clinical studies indicate that the use of ibuprofen, especially at high doses (2400 mg per day), slightly increases the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Hypersensitivity reactions have been reported. These may manifest as:

non-specific allergic reactions and anaphylaxis;
respiratory tract reactivity, for example, asthma, worsening of asthma, bronchospasm, dyspnea;
various skin reactions, for example, pruritus, urticaria, angioneurotic edema, and less frequently – exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Patients should immediately inform their physician and discontinue the drug if any of the above-mentioned symptoms occur.

Adverse reactions observed during ibuprofen use are listed by organ systems and frequency of occurrence. The 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 based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and parasitic diseases.

Very rare: exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis), which may coincide with NSAID use.

In case of occurrence or worsening of signs of infection during treatment, patients are advised to seek immediate medical attention. It is necessary to determine whether antimicrobial/antibacterial therapy is indicated.

Aseptic meningitis symptoms, including nuchal rigidity, headache, nausea, vomiting, fever, or altered consciousness, have been observed in patients with autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease during ibuprofen use.

Blood and lymphatic system disorders.

Very rare: blood disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include malaise, sore throat, oral mucosal ulcers, flu-like symptoms, severe fatigue, unexplained bleeding, and bruising. In such cases, patients should discontinue use of this medicinal product and consult a physician.

Regular blood monitoring is necessary during prolonged therapy.

Immune system disorders.

Uncommon: hypersensitivity reactions including urticaria and pruritus, as well as asthma attacks.

Very rare: severe hypersensitivity reactions, symptoms of which may include facial, lingual, and laryngeal edema, dyspnea, tachycardia, arterial hypotension (anaphylactic reactions, angioneurotic edema, or severe shock); asthma exacerbation, bronchospasm.

Psychiatric disorders.

Very rare: psychotic reactions, depression.

Nervous system disorders.

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

Eye disorders.

Uncommon: visual disturbances.

Ear and labyrinth disorders.

Rare: tinnitus, hearing loss.

Cardiac disorders.

Very rare: palpitations, heart failure, myocardial infarction.

Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: arterial hypertension, vasculitis.

Frequency not known: edema.

Gastrointestinal disorders.

Common: dyspepsia, heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, minor gastrointestinal bleeding which may exceptionally lead to anemia.

Uncommon: peptic ulcer, perforations or gastrointestinal hemorrhages, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease, gastritis.

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

Patients must immediately discontinue the drug and consult a physician if upper abdominal pain, melena, or hematemesis occurs.

Hepatic and biliary disorders.

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

Skin and subcutaneous tissue disorders.

Uncommon: various skin rashes.

Very rare: severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis), alopecia.

In some cases, varicella may be a source of serious skin and soft tissue infections.

Frequency not known: drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

Renal and urinary disorders.

Rare: acute renal impairment (papillary necrosis), increased blood uric acid concentration, increased blood urea concentration.

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

Investigations.

Rare: decreased hemoglobin levels.

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

Shelf life. 200 mg – 30 months. 400 mg – 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 capsules in a blister; 1 or 2 blisters per cardboard box.

Prescription status. Over-the-counter.

Manufacturer. Olive Healthcare.

Manufacturer’s address and place of business.

Unit-II, Plot No. 163/2, Mahatma Gandhi Udhyog Nagar, Dabhel Village, Nani Daman, Daman – 396 210, India.

Eurofaste softcaps