INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT EUROFAST (EUROFAST)

Composition:

Active substance: ibuprofen;

1 capsule contains 200 mg or 400 mg of ibuprofen;

Excipients (200 mg): polyethylene glycol, sorbitol-sorbitan solution, sorbitan oleate (sorbitan 80), potassium hydroxide, purified water;

capsule shell: gelatin, polyethylene glycol 400, sorbitol-sorbitan solution, FD&C Green No. 3, purified water, medium-chain triglycerides (Miglyol 812);

Excipients (400 mg): polyethylene glycol 400, povidone PVP K-30, sorbitan oleate, potassium hydroxide, purified water;

capsule shell: gelatin, polyethylene glycol 400, sorbitol-sorbitan solution, purified water, medium-chain triglycerides.

Pharmaceutical form. Soft gelatin capsules.

Main physicochemical properties:

200 mg capsules: oval soft gelatin capsules of light blue-green to light green color, containing a clear viscous liquid ranging from colorless to pale yellow, with black marking "133" on the capsule shell. (A change in the shade of the capsule contents to light green may occur during the shelf life);

400 mg capsules: oval soft gelatin capsules containing a clear viscous liquid ranging from colorless to pale yellow, with black marking "125" on the capsule shell.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. ATC code M01A E01.

Pharmacological properties.

Pharmacodynamics.

Exerts analgesic, antipyretic, and anti-inflammatory effects.

The mechanism of action involves inhibition of prostaglandin synthesis – mediators of pain, inflammation, and temperature response.

Pharmacokinetics.

After oral administration, ibuprofen is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration of the active substance is reached within 1–2 hours after administration, and in synovial fluid – within 3 hours after administration. Ibuprofen is metabolized in the liver and excreted by the kidneys in unchanged form and as metabolites.

The elimination half-life is approximately 2 hours.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, dental pain, menstrual pain, fever, neuralgia, back pain, joint pain, muscle pain, and pain associated with rheumatic conditions.

Contraindications.

Hypersensitivity to ibuprofen or to any of the excipients.
Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid (aspirin), or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more distinct episodes of peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Severe hepatic impairment, severe renal impairment, or severe heart failure (NYHA Class IV).
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).

Interaction with other medicinal products and other forms of interaction.

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

Acetylsalicylic acid: because this may increase the risk of adverse reactions, except when acetylsalicylic acid (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 on platelet aggregation. However, limitations in extrapolating these data to the clinical setting do not allow definitive conclusions regarding whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant effects are considered unlikely with occasional, non-systematic use of ibuprofen.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors:

Concomitant use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. 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: Ibuprofen may enhance the effects of anticoagulants such as warfarin.

Antihypertensive agents (ACE 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 renal 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 used with caution, particularly in elderly patients. In cases of prolonged treatment, adequate hydration should be ensured, and monitoring of renal function should be considered at the start of combination therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of ibuprofen.

Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium levels should be checked).

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

Lithium: Evidence suggests a potential increase in plasma lithium levels.

Methotrexate: Administration of ibuprofen within 24 hours before or after methotrexate may lead to increased methotrexate concentrations and enhanced toxicity.

Cyclosporine: Increased risk of nephrotoxicity.

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

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are used concomitantly with tacrolimus.

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

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

Sulfonylureas: As a precaution, blood glucose levels should be monitored during concomitant use.

Probenecid and sulfinpyrazone: May delay the elimination of ibuprofen.

Special precautions for use.

Adverse reactions associated with ibuprofen and the entire class of NSAIDs in general can be minimized by using the lowest effective dose required to control symptoms, for the shortest possible duration.

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

Respiratory effects

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

Other NSAIDs

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

Systemic lupus erythematosus and mixed connective tissue disorders

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

Porphyrin metabolism

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

Cardiovascular and cerebrovascular effects

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

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, especially 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 be treated with ibuprofen only after careful clinical assessment. High doses of the drug (2400 mg per day) should be avoided.

Careful clinical evaluation should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking), particularly if high doses of ibuprofen (2400 mg per day) are required.

Cases of Kounis syndrome have been reported in patients receiving treatment with Eurofast. 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.

Renal effects

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

Hepatic effects

Impairment of liver function is possible.

Surgical procedures

Caution should be exercised immediately after major surgical procedures.

Effects on female fertility

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

Gastrointestinal effects

The medicinal product should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as these conditions may worsen. Cases of gastrointestinal bleeding, perforation, and ulcers (possibly fatal) have been reported, occurring 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 doses, in patients with a history of peptic ulcer (especially complicated by bleeding or perforation), and in elderly patients. Such patients should start 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, the need for combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered.

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 should be exercised when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents (e.g., acetylsalicylic acid).

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

Serious skin adverse reactions (SSARs)

Serious skin adverse reactions (SSARs), 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 of these reactions occurred within the first month. 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. A potential influence of the drug on worsening these infections cannot be excluded; therefore, the use of ibuprofen is not recommended in cases of varicella.

Allergy

Caution should be exercised when administering the drug to patients with allergic reactions to other substances, as such patients have an increased risk of hypersensitivity reactions with ibuprofen.

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

This medicinal product contains sorbitol. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or deficiencies of sucrase or isomaltase enzymes should not take ibuprofen.

Masking symptoms of underlying infections: Eurofast may mask symptoms of infectious diseases, potentially delaying the initiation of appropriate treatment and thereby complicating the disease course. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When Eurofast 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.

Other

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. At the first signs of a hypersensitivity reaction after taking Eurofast, treatment must be discontinued. In such cases, both symptomatic and specialized treatment should be initiated.

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

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

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

Regular 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.

Concomitant use of alcohol with the drug may increase the risk of adverse effects related to the active substance, particularly on the gastrointestinal tract or CNS.

Use during pregnancy or breastfeeding

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

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

Starting from the 20th week of pregnancy, the use of Eurofast may cause oligohydramnios due to fetal renal 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, Eurofast should not be prescribed during the first and second trimesters unless necessary. If this medicinal product is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to Eurofast for several days starting from the 20th gestational week. Eurofast 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:

For the fetus: cardiopulmonary toxicity (characterized by premature closure of the arterial duct and pulmonary hypertension); impaired renal function, which may progress to renal failure accompanied by oligohydramnios;
For the mother and newborn (at the end of pregnancy): 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 the breastfed infant. However, the drug is not recommended during breastfeeding.

Fertility

Ibuprofen may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, ibuprofen is not recommended for women with fertility problems.

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. No special precautions are required with single or short-term use of the drug. This primarily applies when the drug is used concomitantly with alcohol.

When used according to recommended doses and treatment duration, the drug does not affect reaction speed when driving or operating machinery.

Method of Administration and Dosage.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

The medication is recommended for adults and children aged 12 years and older: the initial dose is 1–2 capsules, followed, if necessary, by 1–2 capsules every 4–6 hours. Do not exceed 1200 mg (6 or 3 capsules, respectively) within 24 hours.

Capsules are usually taken with food, without chewing, and with water.

Elderly patients do not require special dose adjustment.

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

Children.

Contraindicated in children under 12 years of age.

Overdose.

Administration of the drug to children in doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the effect of overdose is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients who have taken clinically significant amounts of the drug, only nausea, vomiting, epigastric pain, and very rarely diarrhea develop. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic CNS effects may occur, manifesting as vertigo, drowsiness, occasionally agitation, disorientation, or coma. Seizures may occasionally be observed in patients. 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 damage, arterial hypotension, respiratory failure, and cyanosis may develop. In patients with bronchial asthma, disease exacerbation is possible.

Treatment. Treatment should be symptomatic and supportive, including ensuring airway patency and monitoring cardiac function and vital signs until condition stabilizes. 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, alkalizing agents may be administered to enhance urinary excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be used. Bronchodilators should be used to treat bronchial asthma exacerbation.

Adverse Reactions

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

Adverse reactions associated with ibuprofen use are listed by organ systems and frequency of occurrence. Frequency 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, reactions are listed in order of decreasing severity.

The most commonly observed adverse reactions are gastrointestinal in nature and largely dose-dependent, particularly the risk of gastrointestinal bleeding, which depends on both dose and duration of treatment. Adverse reactions occur less frequently when the maximum daily dose does not exceed 1200 mg.

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, such as myocardial infarction or stroke.

Blood and lymphatic system disorders

Very rare: blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms may include fever, sore throat, oral mucosal ulceration, flu-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Immune system disorders

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 not known: respiratory tract reactivity, including bronchial asthma, asthma exacerbation, bronchospasm.

Nervous system disorders

Uncommon: headache; very rare: aseptic meningitis, individual symptoms of which (nuchal rigidity, headache, nausea, vomiting, fever, or confusion) may occur in patients with pre-existing autoimmune disorders such as systemic lupus erythematosus or mixed connective tissue disease; frequency not known: dizziness, paraesthesia, somnolence.

Cardiac disorders

Frequency not known: heart failure, edema, Couine’s syndrome.

Vascular disorders

Frequency not known: arterial hypertension.

Gastrointestinal disorders

Uncommon: abdominal pain, nausea, and dyspepsia; rare: diarrhea, flatulence, constipation, and vomiting;
very rare: peptic ulcer, gastrointestinal perforation or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (particularly in elderly patients), ulcerative stomatitis, gastritis; frequency not known: exacerbation of colitis and Crohn’s disease.

Hepatic disorders

Very rare: liver function abnormalities.

Skin and subcutaneous tissue disorders

Rare: various skin rashes; very rare: severe skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis); frequency not known: photosensitivity reactions, drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

Renal and urinary disorders

Very rare: acute renal dysfunction, papillary necrosis, particularly with prolonged use, associated with increased serum urea levels and edema.

Investigations

Very rare: decreased hemoglobin levels.

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

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach of children.

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

Availability. Over-the-counter.

Manufacturer. Marcsans Pharma Ltd.

Manufacturer's address and location of business operations.

Plot No. L-82, L-83, Verna Industrial Estate, Verna Goa, IN-403 722, India.