Eurofast forte

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

Composition:

Active substance: ibuprofen;

1 soft capsule contains 600 mg of ibuprofen;

Excipients: macrogol 600; potassium hydroxide; purified water;

capsule shell: gelatin 160 Bloom; sorbitol solution, partially dehydrated (Polysorb® 85/70/00); purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: light-yellow, oval-shaped soft gelatin capsules containing a clear, colorless liquid.

Pharmacotherapeutic group.

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

ATC code M01A E01.

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 reduce 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 effect of acetylsalicylic acid (aspirin) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding extrapolation of these data to the clinical setting, it cannot be excluded that regular long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely.

Pharmacokinetics.

Ibuprofen is rapidly absorbed from the gastrointestinal tract (GI tract). Peak plasma concentration is reached within 1–2 hours after administration. The elimination half-life is approximately 2 hours.

Ibuprofen is metabolized in the liver into two inactive metabolites, which are excreted by the kidneys along with unchanged ibuprofen, either in free form or as conjugates. Renal excretion is rapid and complete. Ibuprofen is highly bound to plasma proteins.

Clinical characteristics.

Indications.

Rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis, and other non-rheumatoid (seronegative) arthropathies.

Non-articular rheumatic and periarticular conditions such as periarthritis of the shoulder (capsulitis), bursitis, tendinitis, tenosynovitis, and low back pain; soft tissue injuries, such as sprains and ligament strains.

For relief of mild to moderate pain, such as dysmenorrhea, dental pain, and postoperative pain, as well as for symptomatic relief of headache, including migraine.

Contraindications.

• Hypersensitivity to ibuprofen or to any component of the medicinal product.
• Hypersensitivity reactions (e.g. bronchial asthma, rhinitis, angioedema, or urticaria) previously observed following administration of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active or history of recurrent peptic ulcer/gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding).
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Severe hepatic impairment, severe renal impairment, severe heart failure (NYHA class IV).
• Third trimester of pregnancy.
• The medicinal product should not be used in patients with conditions associated with increased tendency to bleeding.

Interaction with other medicinal products and other forms of interaction.

Caution should be exercised when co-administering the following medicinal products due to possible drug interactions reported in some patients.

Antihypertensive agents, β-blockers, and diuretics. NSAIDs may reduce the effect of antihypertensive agents such as ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and diuretics. Diuretics may also increase the risk of NSAID-induced nephrotoxicity.

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

Cholestyramine. Concomitant administration of ibuprofen and cholestyramine may reduce gastrointestinal absorption of ibuprofen. However, the clinical significance of this interaction is unknown.

Lithium. NSAIDs may reduce lithium clearance.

Metotrexate. NSAIDs may inhibit tubular secretion of methotrexate and reduce methotrexate clearance.

Cyclosporine. Increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Mifepristone. A reduction in efficacy 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 prostaglandin on cervical ripening or uterine contractility, nor does it reduce the clinical efficacy of medical termination of pregnancy.

Other NSAIDs, including selective COX-2 inhibitors. Concomitant administration of two or more NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to the risk of additive effects (see section "Special precautions for use").

Acetylsalicylic acid. As with other NSAID-containing products, concomitant use of ibuprofen and acetylsalicylic acid is generally not recommended due to the increased risk of adverse reactions.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly.

However, despite uncertainties regarding the 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. No clinically significant interactions have been observed with occasional use of ibuprofen (see section "Pharmacodynamics").

Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding when co-administered with NSAIDs (see section "Special precautions for use").

Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use").

Quinolone antibiotics. Data from animal studies indicate that NSAIDs may increase the risk of convulsions associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones concomitantly have an increased risk of developing convulsions.

Sulfonylureas. NSAIDs may potentiate the effects of sulfonylurea agents. Rare cases of hypoglycemia have been reported in patients receiving sulfonylureas during ibuprofen therapy.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding when used concomitantly with NSAIDs (see section "Special precautions for use").

Tacrolimus. Possible increased risk of nephrotoxicity when NSAIDs are administered to patients receiving tacrolimus.

Zidovudine. NSAIDs increase the risk of hematological toxicity when administered concomitantly with zidovudine. Evidence suggests an increased risk of hemarthrosis and hematomas in HIV-positive patients with hemophilia who are receiving zidovudine and ibuprofen.

Aminoglycosides. NSAIDs may reduce the elimination of aminoglycosides.

Herbal extracts. Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.

CYP2C9 inhibitors. Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (ibuprofen is a CYP2C9 substrate). One study demonstrated that voriconazole and fluconazole (CYP2C9 inhibitors) increased exposure to S(+)-ibuprofen 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 receiving voriconazole or fluconazole.

Special precautions for use

General warnings

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

As with other NSAIDs, ibuprofen may mask signs of infection.

Concomitant use of this product with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to increased risk of ulceration or bleeding.

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Elderly patients

The incidence of adverse reactions to NSAIDs is higher in elderly patients, particularly gastrointestinal bleeding and perforation, which may be fatal.

Paediatric population

There is a risk of impaired renal function in dehydrated children and adolescents.

Gastrointestinal bleeding, ulceration and perforation

NSAIDs should be used with caution in patients with a history of peptic ulcer or other gastrointestinal disorders, as their condition may worsen (see section "Contraindications").

Gastrointestinal bleeding, ulceration or perforation may occur at any time during therapy with all NSAIDs. These adverse reactions may be fatal and may occur with or without warning symptoms or serious gastrointestinal disorders in history.

The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of ibuprofen, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment with the lowest effective dose.

Concomitant use of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered in these patients, as well as in patients who are concurrently taking low-dose acetylsalicylic acid or other drugs increasing the risk of gastrointestinal damage (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use of ibuprofen with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to increased risk of ulceration or bleeding (see section "Interaction with other medicinal products and other forms of interaction").

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

Ibuprofen should be prescribed with caution to patients receiving concomitant therapy with drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors (SSRIs) or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in a patient receiving ibuprofen, the drug should be discontinued.

NSAIDs should be used with caution in patients with a history of ulcerative colitis or Crohn’s disease, as these conditions may be exacerbated.

Respiratory disorders and hypersensitivity reactions

Ibuprofen should be used with caution in patients suffering from bronchial asthma, chronic rhinitis, allergic conditions or with a history of such disorders, as ibuprofen has been reported to cause bronchospasm, urticaria or angioneurotic edema in such patients.

Impairment of heart, kidney and liver function

NSAIDs should be used with caution in patients with impaired renal, hepatic or cardiac function, as this may lead to worsening of renal function. NSAID use may cause dose-dependent reduction in prostaglandin formation and may lead to worsening of renal insufficiency.

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

Patients with impaired renal, hepatic or cardiac function, patients taking diuretics and elderly patients are at greatest risk of this reaction. The lowest effective dose should be used for the shortest possible duration, and renal function should be monitored, especially during long-term treatment (see section "Contraindications").

Ibuprofen should be prescribed with caution to patients with a history of heart failure or arterial hypertension, as edema has been reported with ibuprofen use.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and medical advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported in association with NSAID therapy. Clinical studies indicate that ibuprofen, particularly at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest a significant association between low-dose ibuprofen (i.e. ≤ 1200 mg daily) and increased risk of arterial thrombotic events.

Ibuprofen should be prescribed to patients with uncontrolled hypertension, congestive heart failure (NYHA functional class II–III), diagnosed ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease only after careful consideration, and high-dose ibuprofen (2400 mg daily) should be avoided.

Careful consideration is also required before initiating long-term ibuprofen therapy in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high-dose ibuprofen (2400 mg daily) is required.

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

Treatment with ibuprofen should be initiated with caution in patients with significant dehydration. There is a risk of impaired renal function, especially in dehydrated children, adolescents and elderly patients. As with other NSAIDs, prolonged use of ibuprofen may lead to renal papillary necrosis and other renal pathological changes. Toxic effects on the kidneys may also occur 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 a reaction include those with impaired renal, cardiac or hepatic function, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and elderly patients. Discontinuation of NSAIDs is usually followed by recovery to the pre-treatment state.

SLE and mixed connective tissue diseases

Caution should be exercised when prescribing the drug to patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases. There is an increased risk of aseptic meningitis (see section "Adverse reactions").

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 such reactions occurred within the first month. If signs or symptoms suggesting these reactions occur, ibuprofen should be discontinued immediately and alternative therapy considered (if necessary).

Haematological effects

Ibuprofen, like other NSAIDs, may inhibit platelet aggregation and prolong bleeding time in healthy volunteers.

Aseptic meningitis

Aseptic meningitis has been rarely observed in patients treated with ibuprofen. Although aseptic meningitis is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, cases have been reported in patients without these chronic conditions.

Use during pregnancy or breastfeeding

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 risk is considered to increase with increasing dose and duration of therapy. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and embryonic/fetal mortality. In addition, increased incidence of various developmental abnormalities, including cardiovascular malformations, was observed in animals treated with a prostaglandin synthesis inhibitor during organogenesis.

From the 20th week of pregnancy, use of Eurofast Forte may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus constriction after second-trimester treatment, most of which resolved after discontinuation. Therefore, Eurofast Forte should not be prescribed during the first and second trimesters unless clearly necessary. If Eurofast Forte 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. Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after several days of exposure to Eurofast Forte starting from the 20th gestational week. Treatment with Eurofast Forte should be discontinued if oligohydramnios or ductus arteriosus 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 ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above);

Risks to the mother at the end of pregnancy and to 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, Eurofast Forte is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Use during breastfeeding

In a limited number of studies, ibuprofen was detected in breast milk at very low concentrations. Ibuprofen is not recommended for use in breastfeeding women.

Fertility

Ibuprofen use may impair female fertility and is not recommended for women attempting to conceive. Women experiencing infertility or undergoing fertility investigations should consider discontinuing ibuprofen.

Ability to influence the speed of reactions while driving or operating machinery

Patients who experience drowsiness, dizziness, fatigue or visual disturbances while taking ibuprofen should avoid driving or operating machinery.

Dosage and Administration

Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").

Adults and children aged 12 years and older

The recommended dose is 1200–1800 mg daily, administered in divided doses. Some patients may respond adequately to 600–1200 mg daily. In severe or acute conditions, dosage may be increased until the acute phase is under control, provided the total daily dose does not exceed 2400 mg, given in several divided doses.

For juvenile rheumatoid arthritis, up to 40 mg/kg body weight daily in divided doses may be used.

Elderly patients

There is an increased risk of serious adverse reactions when using the drug in elderly patients. If NSAID therapy is necessary, the lowest effective dose should be prescribed for the shortest possible duration. Regular monitoring for gastrointestinal bleeding during NSAID therapy is required. Dose adjustment should be individualized in cases of hepatic or renal impairment.

For oral use

Patients with gastrointestinal disorders should take the medication with food.

Taking the drug immediately after a meal may delay the onset of action of Eurofast Forte. It is preferable to take it during or after a meal with a large amount of liquid. Capsules should be swallowed whole, without opening, to avoid oral discomfort and throat irritation.

Children

Do not use in children under 12 years of age.

Overdose

Toxicity

Toxic symptoms are generally not observed at doses below 100 mg/kg in adults and children. However, supportive measures may be required in some cases. In children, toxic symptoms have been reported after ingestion of 400 mg/kg or more.

Symptoms

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

The most common symptoms include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) manifestations: headache, tinnitus, dizziness, seizures, and loss of consciousness. Rarely reported are nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, coma, apnea, and CNS and respiratory depression.

In severe poisoning, metabolic acidosis may occur. Disorientation, agitation, unconsciousness, and cardiovascular toxicity including hypotension, bradycardia, and tachycardia have been reported. With substantial overdose, renal failure and hepatic injury may develop. Significant overdose is generally well tolerated if no other drugs are co-ingested.

Treatment
Treatment should be symptomatic. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose.

Ensure adequate diuresis.

Renal and hepatic function should be closely monitored.

Patients should be observed for at least 4 hours after ingestion of a potentially toxic amount of the drug.

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

Adverse reactions

Gastrointestinal tract: Adverse reactions of the gastrointestinal tract (GI) are the most commonly observed. Peptic ulcers, gastrointestinal perforation, or gastrointestinal hemorrhage, sometimes resulting in fatal outcomes, may occur, particularly in elderly patients (see section "Special precautions").

Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, gastrointestinal bleeding, and exacerbation of colitis and Crohn's disease have been reported during ibuprofen use (see section "Special precautions"). Gastritis, duodenal ulcer, gastric ulcer, and gastrointestinal perforation have been observed less frequently.

Immune system: Hypersensitivity reactions have been reported with ibuprofen use. These include non-specific allergic reactions and anaphylaxis; respiratory tract reactivity, including asthma, exacerbation of asthma, bronchospasm, or dyspnea; and various skin manifestations, including rash of different types, pruritus, urticaria, purpura, angioneurotic edema, and very rarely – erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

Cardiovascular system

Edema, hypertension, and heart failure have been reported in connection with NSAID therapy.

Clinical trial data indicate that the use of ibuprofen, 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").

Infections and infestations

Rhinitis and aseptic meningitis (particularly in patients with pre-existing autoimmune disorders such as systemic lupus erythematosus and mixed connective tissue diseases) with symptoms such as neck stiffness, headache, nausea, vomiting, fever, or disorientation have been reported (see section "Special precautions").

Cases of worsening skin inflammation due to infection during NSAID use have been described. If signs or symptoms of infection develop or worsen during ibuprofen treatment, patients should seek immediate medical advice.

Skin and subcutaneous tissue disorders

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

The adverse reactions listed below are possibly related to ibuprofen and are classified by frequency and organ system according to MedDRA.

Adverse reactions are categorized by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and frequency not known (cannot be estimated from the available data).

Reporting of adverse reactions after drug registration is of great importance. It enables monitoring of the benefit-risk balance of this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug effectiveness to 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 25 °C.

Keep out of reach of children.

Packaging. 10 capsules or 12 capsules per blister; 1 or 2 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. Olive Healthcare.

Manufacturer's address and location of business activity.

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