EUROFAST EXPRESS

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ЄВРОФАСТ ЕКСПРЕС (EUROFAST EXPRESS)

Composition:

Active substance: ibuprofen;

1 soft capsule contains ibuprofen 400 mg;

Excipients: polyethylene glycol 600, potassium hydroxide, purified water;

Capsule shell: gelatin, sorbitol solution, purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical characteristics: slightly yellow, transparent, oval-shaped soft gelatin capsules containing a clear, slightly yellow 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 derivative of propionic acid, which has demonstrated its effectiveness 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.

Clinical data show that after administration of 400 mg of ibuprofen, the analgesic effect may last up to 8 hours.

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 when single doses of 400 mg ibuprofen are administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), a reduced effect of acetylsalicylic acid (aspirin) on thromboxane formation or platelet aggregation was observed. Although uncertainty remains regarding the extrapolation of these data to clinical situations, it cannot be ruled out that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional (non-regular) use of ibuprofen, such a clinically significant effect is considered unlikely.

Pharmacokinetics

After oral administration, ibuprofen is rapidly absorbed when taken on an empty stomach. Cmax is reached within 0.6 hours compared to conventional tablets (¾–1½ hours). When taken with food, peak levels are observed within 1–2 hours. Protein binding in plasma is approximately 99%. After oral administration, 75–85% of ibuprofen is excreted in urine within the first 24 hours (mainly as two metabolites), the remainder being excreted in feces following biliary excretion. Elimination is completed within 24 hours. The plasma half-life of ibuprofen is approximately 2 hours.

In limited studies, it has been found that ibuprofen penetrates into breast milk at very low concentrations.

Clinical Characteristics

Indications

Symptomatic treatment of mild to moderate pain of various origins (rheumatic pain, muscle pain, back pain, headache, toothache, painful menstruation), including pain associated with colds and fever.

Contraindications

• Hypersensitivity to ibuprofen or to any of the excipients.
• Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after intake of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active peptic ulcer / 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 use of NSAIDs.
• Severe impairment of liver function, severe impairment of kidney function, severe heart failure (NYHA class IV).
• Third trimester of pregnancy.
• Active cerebrovascular or other bleeding.
• Hemorrhagic diathesis or coagulation disorders.
• Blood dyscrasias of unknown etiology.

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 may increase the risk of adverse reactions.

Experimental data indicate that concomitant administration of ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation. However, limitations in extrapolating these data 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. For occasional use of ibuprofen, such clinically significant effects are considered unlikely.

• Other NSAIDs: 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 effect of anticoagulants such as warfarin; when anticoagulants are used, it should be considered that prolonged use of ibuprofen may increase the risk of bleeding.

Antihypertensives and diuretics: NSAIDs may attenuate the effect of thiazide diuretics and other antihypertensive agents. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

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 lithium plasma levels.

MTX (methotrexate): Concomitant use of ibuprofen with moderate or high doses of methotrexate may lead to severe and potentially fatal methotrexate toxicity. Patients with impaired renal function may be at additional risk of toxicity from this combination, even when low-dose methotrexate (20 mg/week) is used.

Cyclosporine: Increased risk of nephrotoxicity.

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 NSAIDs. 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. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.

Phenytoin: Concomitant use with phenytoin may increase its serum levels. Patients receiving long-term ibuprofen therapy should be monitored.

Antacids: Some antacids may increase the gastrointestinal absorption of ibuprofen. This is considered clinically relevant, particularly during prolonged ibuprofen use.

Special precautions for use

The adverse effects associated with the use of ibuprofen and nonsteroidal anti-inflammatory drugs (NSAIDs) in general can be minimized by using the lowest effective dose required to control symptoms, for the shortest possible duration.

In elderly patients, there is an increased incidence 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 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 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.

Renal, cardiac, and hepatic impairment

The drug should be used with caution in patients with renal, cardiac, or hepatic impairment, as renal function may deteriorate (see sections "Contraindications" and "Adverse reactions"). The dose should be kept as low as possible, and renal function should be monitored. There is a risk of developing renal failure in children and adolescents aged 12 to 18 years with dehydration.

Effects on the cardiovascular and cerebrovascular systems

Treatment should be initiated with caution in patients with a history of hypertension and/or heart failure (medical consultation required), as fluid retention, hypertension, and edema have been reported during therapy with ibuprofen and other NSAIDs.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly 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 studies do not suggest that low-dose ibuprofen (e.g., ≤1200 mg daily) increases the risk of arterial thrombotic complications.

Patients with uncontrolled hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful assessment of the clinical condition. High doses (2400 mg daily) 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., hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg daily) are required.

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

Effect on female fertility

Limited data suggest that medicinal products which inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Gastrointestinal effects

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. Cases of gastrointestinal bleeding, perforation, and ulcers, possibly fatal, have been reported during NSAID therapy at any stage, regardless of the presence of prior 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. Such patients should start treatment with the lowest possible dose.

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), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents (e.g., aspirin).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Serious skin adverse reactions

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 during ibuprofen use (see section "Adverse reactions").

Most of these reactions occurred within the first month of treatment.

If signs or symptoms suggesting these reactions occur, ibuprofen should be discontinued immediately and alternative therapy should be considered (if necessary).

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

Masking symptoms of underlying infections

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

The pharmacological activity of ibuprofen may reduce fever and inflammation, thereby diminishing their usefulness as diagnostic signs for identifying underlying diseases.

Excipients

This medicinal product contains sorbitol. If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

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 following the 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.

NSAIDs should not be used during the first two trimesters of pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus, as judged by the physician.

Furthermore, increased incidence of various developmental abnormalities, including cardiovascular defects, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of gestation, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of 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, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible duration.

If ibuprofen is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to ibuprofen for several days starting from the 20th gestational week. Ibuprofen use 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); renal dysfunction, which may progress to renal failure associated with oligohydramnios;
• For the mother and neonate, near term: prolonged bleeding time, antiplatelet effects that may occur even at very low doses; inhibition of uterine contractions, leading to delayed or prolonged labor.

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

Breastfeeding

In limited 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 who have difficulty conceiving.

Ability to influence reaction speed when driving or operating machinery

Studies on the effect on the ability to drive or operate machinery have not been conducted.

Method of Administration and Dosage

For oral use only and short-term use only.

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

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

Adults, elderly patients, and children and adolescents aged 12 to 18 years

The single dose for children aged 12 years and older with body weight > 40 kg and for adults is 400 mg of ibuprofen (1 capsule). The interval between doses should be at least 6 hours. The maximum daily dose is 1200 mg (3 capsules per day).

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment.

If symptoms worsen or persist for more than 3 days, medical advice should be sought to confirm diagnosis and adjust treatment. Treatment duration is determined individually by a physician depending on disease progression and patient condition.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Children

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

Overdose

Administration of doses exceeding 400 mg/kg of the drug in children 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 ingested clinically significant amounts of NSAIDs, only nausea, vomiting, epigastric pain, or very rarely diarrhea, have been observed. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system (CNS) may develop, manifesting as drowsiness, sometimes agitation, hypertension, disorientation, or coma. Seizures may occasionally occur in patients. Prolonged use at doses higher than recommended or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, metabolic acidosis may develop. Prolongation of prothrombin time / increase in prothrombin index may be observed, possibly due to effects on circulating blood coagulation factors. Acute renal failure and liver damage may occur. In patients with bronchial asthma, disease exacerbation is possible.

Treatment. Treatment should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac and vital functions until recovery. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators should be used to treat bronchial asthma exacerbation.

Side effects

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

Adverse reactions occur less frequently when the maximum daily dose does not exceed 1200 mg.

The adverse reactions associated with ibuprofen use are listed by organ systems and frequency of occurrence. Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and not known (cannot be estimated from available data). Within each frequency category, reactions are listed in order of decreasing severity.

Laboratory investigations

Very rare: Decreased hemoglobin and hematocrit levels.

Cardiac disorders

Frequency not known: Heart failure, edema, hypertension, angina pectoris. Clinical studies indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke), Kounis syndrome.

Blood and lymphatic system disorders

Very rare: Blood dyscrasias (anemia, hemolytic anemia, aplastic anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include malaise, sore throat, oral ulcers, influenza-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Nervous system disorders

Uncommon: Headache, dizziness, cerebrovascular disorders.

Very rare: Aseptic meningitis – isolated cases have been reported very rarely.

Eye disorders

Very rare: Visual disturbances.

Ear and labyrinth disorders

Very rare: Tinnitus and vertigo.

Respiratory, thoracic and mediastinal disorders

Very rare: Asthma, bronchospasm, dyspnea, wheezing.

Gastrointestinal disorders

Adverse reactions are most commonly associated with the gastrointestinal tract.

Uncommon: Abdominal pain, bloating, nausea, dyspepsia;

Rare: Diarrhea, flatulence, constipation, vomiting;

Very rare: Peptic ulcer, gastrointestinal perforation or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, oral ulcers;

Frequency not known: Exacerbation of colitis and Crohn’s disease.

Renal and urinary disorders

Very rare: Acute renal failure, papillary necrosis (particularly with prolonged use), associated with increased serum urea levels and edema, interstitial nephritis, nephrotic syndrome, hematuria, proteinuria.

Skin and subcutaneous tissue disorders

Uncommon: Various skin rashes;

Very rare: Serious skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis).

Not known: Acute generalized exanthematous pustulosis (AGEP); drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); photosensitivity reactions.

Infections and infestations

Frequency not known: Meningitis, aseptic meningitis.

Vascular disorders

Very rare: Arterial hypertension.

General disorders and administration site conditions

Very rare: Swelling, edema, and peripheral edema.

Immune system disorders

Uncommon: Hypersensitivity reactions including urticaria and pruritus.

Very rare: Severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, hypotension, anaphylactic reactions, angioedema, or severe shock.

Frequency not known: Non-specific allergic reactions. Respiratory tract reactivity, including bronchial asthma, asthma exacerbation, bronchospasm. Various skin reactions, including exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

In patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease), isolated cases of aseptic meningitis symptoms such as neck stiffness, headache, nausea, vomiting, fever, or disorientation have been observed during ibuprofen treatment.

Hepatobiliary disorders

Very rare: Liver function abnormalities, hepatitis, jaundice.

Psychiatric disorders

Very rare: Restlessness.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

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

Packaging

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

Release category

Over-the-counter (without prescription).

Manufacturer

Softgel Healthcare Pvt. Ltd.

Manufacturer's address and place of business

Survey No. 20/1, Vandalur, Kelambakkam Road, Puduppakkam Village, Kanchipuram District, Tamil Nadu, 603103, India.