Eurofast Combi capsules 200 mg + 500 mg blister No. 10

Instructions for Eurofast Combi capsules 200 mg + 500 mg blister No. 10

Composition

active ingredients: ibuprofen; paracetamol;

1 soft capsule contains ibuprofen 200 mg and paracetamol 500 mg;

excipients: polyethylene glycol 400 (macrogol 400), propylene glycol, potassium hydroxide, purified water;

capsule shell: gelatin 180 Bloom, glycerin, sorbitol solution, partially dehydrated (Polysorb® 85/70/00), titanium dioxide, red iron oxide, yellow iron oxide, purified water.

Dosage form

Soft capsules.

Main physicochemical properties: soft gelatin capsules of oval shape, opaque white on one side and opaque light brown on the other, containing an almost white to white suspension.

Pharmacotherapeutic group

Preparations for the treatment of the musculoskeletal system, anti-inflammatory and antirheumatic drugs, non-steroidal drugs, propionic acid derivatives. Ibuprofen, combinations.

ATX code M01A E51.

Pharmacological properties

Pharmacodynamics.

The pharmacological action of ibuprofen and paracetamol differs in site and mode of action, but is synergistic, leading to increased analgesic and antipyretic properties compared to those when each substance is used separately.

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

Experimental data suggest 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 ibuprofen 400 mg were administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), a reduction in the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although there is uncertainty about the extrapolation of these data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely.

The mechanism of action of paracetamol is still not fully understood, but there is convincing evidence of an analgesic effect on the central nervous system. Biochemical studies indicate inhibition of cyclooxygenase-2 (COX-2) activity in the central nervous system. Paracetamol can also stimulate descending pathways of activation
5-hydroxytryptamine (serotonin), which inhibits the transmission of pain signals in the spinal cord.

The drug is particularly suitable for the treatment of pain requiring a stronger analgesic effect than ibuprofen 400 mg or paracetamol 1000 mg alone. Studies using this combination in models of acute pain (postoperative dental pain) and chronic knee pain have shown high efficacy of this combination in reducing the severity of acute pain (93.2%) and long-term treatment of chronic pain (60.2%). This drug has a rapid onset of action with a confirmed significant reduction in pain, which is noted on average after 18.3 minutes. Significant pain relief is noted on average after 44.6 minutes. The analgesic effect of this drug is significantly longer (9.1 hours) than that of paracetamol 500 mg (4 hours).

Pharmacokinetics.

Ibuprofen is rapidly absorbed from the gastrointestinal tract and is extensively bound to plasma proteins. Ibuprofen is detected in plasma within 5 minutes, reaching peak concentrations 1-2 hours after administration on an empty stomach. Ibuprofen is metabolized in the liver and excreted by the kidneys. The half-life is approximately 2 hours.

Paracetamol is rapidly absorbed from the gastrointestinal tract. At therapeutic concentrations, the level of binding to plasma proteins is low, although it depends on the dose. Paracetamol in the blood plasma is determined after 5 minutes, reaching a maximum concentration after 0.5-0.67 hours after administration on an empty stomach.

Paracetamol is metabolized in the liver and excreted in the urine mainly as conjugates. Less than 5% of paracetamol is excreted unchanged. The hydroxylated metabolite, which is formed in very small quantities in the liver under the influence of mixed oxidases and is detoxified by binding to hepatic glutathione, can accumulate in case of paracetamol overdose and cause liver tissue damage. The half-life is approximately 3 hours. No significant difference in the pharmacokinetic profile of paracetamol and ibuprofen in elderly patients has been found. The bioavailability and pharmacokinetic profile of ibuprofen and paracetamol in this preparation do not change when taking a single or repeated dose of such a combination.

The composition of this drug is developed using technology that ensures the simultaneous release of ibuprofen and paracetamol in such a way as to potentiate the effects of each of the active ingredients.

Indication

Symptomatic treatment of mild to moderate pain in migraine, headache, backache, menstrual pain, toothache, rheumatic and muscular pain, pain in mild forms of arthritis, symptoms of colds and flu, sore throat and fever. This medicine is particularly suitable for the treatment of pain that requires a stronger analgesic effect than that of ibuprofen or paracetamol used alone.

Contraindication

This drug is contraindicated:

patients with known individual hypersensitivity to ibuprofen, paracetamol or other components of the drug;

patients with a history of hypersensitivity reactions (e.g. bronchospasm, angioedema, bronchial asthma, rhinitis or urticaria) after taking ibuprofen, acetylsalicylic acid or other NSAIDs;

with gastric and duodenal ulcer/bleeding in active form or history of relapses (two or more severe episodes of ulcer or bleeding);

patients with a history of gastrointestinal bleeding or perforation associated with the use of NSAIDs;

patients with blood clotting disorders;

patients with severe hepatic, renal or cardiac insufficiency (NYHA class IV);

when used simultaneously with other drugs containing paracetamol, due to an increased risk of serious adverse reactions;

with simultaneous use of other drugs containing NSAIDs, including COX-2 inhibitors and acetylsalicylic acid in a daily dose of more than 75 mg, due to an increased risk of adverse reactions;

during the last trimester of pregnancy due to the risk of premature closure of the fetal ductus arteriosus with possible pulmonary hypertension.

Interaction with other medicinal products and other types of interactions

This drug, like other paracetamol-containing drugs, is contraindicated when used with other drugs containing paracetamol due to an increased risk of serious adverse reactions.

This drug (like other ibuprofen-containing drugs and NSAIDs) should not be used in combination with the following drugs:

Acetylsalicylic acid, as this may increase the risk of adverse reactions, unless acetylsalicylic acid (dose not exceeding 75 mg per day) has been prescribed by a doctor.

Experimental data suggest that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. However, the extrapolation of these data to the clinical situation is limited, and therefore there is no definitive conclusion that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Such clinically significant effects are considered unlikely with non-systematic use of ibuprofen.

Other NSAIDs (including selective COX-2 inhibitors), as this may lead to an increased incidence of side effects.

This drug (like other paracetamol-containing drugs) should be used with caution in combination with the following drugs:

Cholestyramine: The rate of absorption of paracetamol is reduced by cholestyramine, therefore paracetamol should be administered 1 hour before cholestyramine if maximum analgesia is required.

Metoclopramide and domperidone: Absorption of paracetamol is increased when used with metoclopramide and domperidone, however, concomitant administration should not be avoided.

Warfarin: The anticoagulant effect of warfarin and other coumarins may be enhanced by long-term regular use of paracetamol with an increased risk of bleeding; intermittent use has no significant effect.

This drug (as well as other ibuprofen-containing drugs and NSAIDs) should be used with caution in combination with the following drugs:

Anticoagulants: NSAIDs may increase the therapeutic effect of anticoagulants such as warfarin. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol, and there may be an increased risk of bleeding.

Antihypertensives (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the concomitant use of an ACE inhibitor or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, in particular possible acute renal failure, which is usually reversible. Therefore, such combinations should be administered with caution, especially in elderly patients. If long-term treatment is necessary, the patient should be adequately hydrated and consideration should be given to monitoring renal function at the beginning of the combination treatment and periodically thereafter. Diuretics may increase the risk of nephrotoxicity of NSAIDs.

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

Cardiac glycosides: NSAIDs increase the level of glycosides in the blood plasma, can aggravate heart function disorders, and reduce the glomerular filtration function of the kidneys.

Cyclosporine: increased risk of nephrotoxicity.

Corticosteroids: may increase the risk of adverse reactions in the digestive tract (gastrointestinal ulcers or bleeding).

Lithium: decreased lithium excretion.

Methotrexate: decreased excretion of methotrexate.

Mifepristone: NSAIDs should not be used earlier than 8-12 days after mifepristone administration, as they reduce its effectiveness.

Quinolone antibiotics: Animal studies suggest that NSAIDs may increase the risk of seizures associated with the use of quinoline antibiotics; the risk of seizures is increased with concomitant use of NSAIDs and quinolones.

Tacrolimus: There may be an increased risk of nephrotoxicity with concomitant use of NSAIDs and tacrolimus.

Zidovudine: Increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

Flucloxacillin.

Caution should be exercised when using paracetamol with flucloxacillin, as concomitant administration has been associated with metabolic acidosis with an increased anion gap, especially in patients with risk factors (see section "Special warnings and precautions for use").

Application features

Do not exceed recommended doses.

If symptoms progress, you should consult a doctor.

Paracetamol should be administered with caution to patients with severe renal and hepatic impairment. The risk of paracetamol overdose is higher in patients with non-cirrhotic alcoholic liver disease. In case of overdose, seek medical attention immediately, even if the patient feels well, because of the risk of delayed serious liver damage.

Do not use other medicines containing paracetamol. If this happens, you should immediately consult a doctor, even if the patient feels well, as this may lead to an overdose.

Caution is advised when using paracetamol concomitantly with flucloxacillin due to the increased risk of high anion gap metabolic acidosis (HAGMA). Patients at high risk of developing HAGMA include those with severe renal impairment, sepsis or malnutrition, especially when using the maximum daily dose of paracetamol.

Undesirable effects can be minimized by using the lowest effective dose necessary to relieve symptoms, for the shortest period of time necessary to eliminate symptoms, and with food.

Respiratory effects: Patients with bronchial asthma or allergic diseases after taking NSAIDs or with a history of these diseases may experience bronchospasm.

Cardiovascular, hepatic and renal insufficiency. NSAIDs may cause a dose-dependent decrease in prostaglandin formation and the development of renal insufficiency. Patients with impaired renal function, cardiac dysfunction, hepatic dysfunction, patients taking diuretics and elderly patients are at increased risk. In such patients, renal function should be monitored.

Effects on the cardiovascular and cerebrovascular system: Patients with a history of hypertension and/or heart failure should be treated with caution (consultation with a doctor is necessary), since, as with other NSAIDs, fluid retention, hypertension and edema have been reported with ibuprofen therapy.

Clinical trial data suggest that ibuprofen use, particularly at high doses (2400 mg/day), may be associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g.
≤1200 mg per day) is associated with an increased risk of arterial thrombotic complications.

Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should only use ibuprofen after careful clinical assessment. High doses (2400 mg/day) should be avoided.

The clinical picture should also be carefully assessed before starting long-term treatment in patients with risk factors for cardiovascular complications (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Effect on the gastrointestinal system.

The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, with a history of ulcer, especially ulcer complicated by bleeding or perforation, and in the elderly. In these patients, treatment should be initiated at the lowest effective dose.

Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, as well as for patients who require concomitant low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events. Patients with a history of gastrointestinal disorders, especially elderly patients, should be informed of any adverse gastrointestinal symptoms (especially bleeding), especially at the beginning of treatment.

The drug should be prescribed with caution to patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, SSRIs, or antiplatelet drugs such as acetylsalicylic acid.

The occurrence of gastrointestinal bleeding or ulceration in patients receiving a drug containing ibuprofen requires immediate discontinuation of treatment with this drug.

NSAIDs should be prescribed with caution to patients with a history of gastrointestinal disorders (ulcerative colitis and Crohn's disease), as these conditions may be exacerbated.

Systemic lupus erythematosus and mixed connective tissue disease: Patients with systemic lupus erythematosus and mixed connective tissue disease may be at increased risk of developing aseptic meningitis.

Severe skin reactions. Rare serious skin reactions, which can be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs (see section 4.8). The risk of these reactions is highest at the start of therapy. The onset of the reaction occurs in most cases within the first month of treatment. A case of acute generalized exanthematous pustulosis has also been reported following the use of ibuprofen-containing medicinal products.

Ibuprofen should be discontinued at the first signs and symptoms of skin lesions, such as skin rashes, mucosal lesions, or any other signs of hypersensitivity.

Masking of symptoms of underlying infections. The drug may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment and thereby complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When the drug is used for fever or to relieve pain in an infection, monitoring of the infectious disease is recommended. In the setting of treatment outside a medical institution, the patient should consult a doctor if symptoms persist or worsen.

Effects on female fertility. There is limited evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. This is reversible after discontinuation of treatment. Women who have difficulty conceiving or are undergoing investigation for infertility should refrain from using the drug.

Elderly patients: Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding or perforation, which can be fatal. If NSAIDs are necessary, they should be used at the lowest effective dose for the shortest duration possible.

Patients should be regularly monitored for the possibility of gastrointestinal bleeding during NSAID therapy.

Use during pregnancy or breastfeeding

Pregnancy.

There is no experience with the use of the drug in pregnant women.

A large amount of pregnancy data indicates neither malformative nor

Congenital anomalies have been reported after the use of NSAIDs in humans, but they are of low frequency and usually do not show a discernible pattern. From the 20th week of pregnancy onwards, the use of Eurofast Combi may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus following treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment. Therefore, Eurofast Combi should not be given during the first and second trimesters of pregnancy unless clearly necessary. If Eurofast Combi is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose should be kept as low and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be considered after exposure to Eurofast Combi for several days, starting from the 20th week of gestation. The use of Eurofast Combi should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected. Given the known effect of NSAIDs on the cardiovascular system of the fetus (threat of premature closure of the ductus arteriosus), the use of the drug in the third trimester is contraindicated. Delayed labor or prolonged labor may occur with an increased tendency to bleeding in the mother and child. The drug should be avoided during the first and second trimesters of pregnancy, as well as during labor; the drug is contraindicated during the third trimester of pregnancy.

Breastfeeding period.

Ibuprofen and its metabolites may pass into breast milk in very low concentrations (0.0008% of the maternal dose). Harmful effects on infants are unknown. Paracetamol is excreted in breast milk, but in clinically insignificant quantities. Available published data do not rule out the possibility of taking the drug during breastfeeding. Therefore, there is no need to stop breastfeeding during short-term therapy with this drug at recommended doses.

Fertility.

The use of the drug may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, the use of the drug is not recommended for women who have difficulty conceiving.

Ability to influence reaction speed when driving vehicles or other mechanisms

Adverse effects such as dizziness, drowsiness, fatigue, and visual disturbances may occur after taking NSAIDs. Patients experiencing these adverse reactions should not drive or operate machinery.

Method of administration and doses

For oral short-term use only.

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

Adults should take 1 capsule up to 3 times a day with an interval of at least 6 hours between doses. Wash down the capsules with water.

If 1 capsule does not relieve the symptoms of the disease, 2 capsules should be used per dose, but not more than 3 times a day. The interval between doses should be at least 6 hours. Do not take more than 6 capsules (3000 mg of paracetamol, 1200 mg of ibuprofen) per day.

If the symptoms of the disease persist for more than 3 days, it is necessary to consult a doctor to clarify the diagnosis and adjust the treatment regimen. The duration of treatment is determined by the doctor individually, depending on the course of the disease and the patient's condition.

To reduce the likelihood of side effects, it is recommended to take the drug with food.

Elderly patients.

No dosage adjustment is required. Due to the possibility of developing undesirable effects, the condition of elderly patients should be monitored especially carefully. If it is necessary to take NSAIDs, the lowest effective dose should be used for the shortest possible period of time. The patient should be regularly monitored for signs of possible gastrointestinal bleeding during NSAID therapy.

Children.

Not for use in children under 18 years of age.

Overdose

Paracetamol: Liver damage is possible in adults who have taken 10 g (equivalent to 20 capsules) or more of paracetamol. Taking 5 g (equivalent to 10 capsules) or more of paracetamol may cause liver damage if:

- the patient is receiving long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's wort or drugs that induce liver enzymes;

- the patient regularly consumes alcohol;

Symptoms. Symptoms of paracetamol overdose during the first 24 hours are pallor, nausea, vomiting, aversion to food and abdominal pain. Liver damage may occur 12-48 hours after overdose, manifested by abnormal liver function tests. Glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and be fatal. Acute renal failure with acute tubular necrosis may present with severe back pain, hematuria, proteinuria and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Treatment. Paracetamol overdose requires immediate medical attention. The patient should be taken to hospital for medical examination immediately, even if there are no early symptoms of overdose. Symptoms may be limited to nausea and vomiting and may not reflect the severity of the overdose or the risk of organ damage. Treatment should be carried out in accordance with established treatment guidelines.

Treatment with activated charcoal should be considered within 1 hour of ingestion of an overdose of paracetamol. Plasma paracetamol concentrations should be measured 4 hours or later after ingestion (earlier concentrations are unreliable).

Treatment with N-acetylcysteine can be given within 24 hours of paracetamol ingestion, but the maximum protective effect is obtained when it is administered within 8 hours of taking an overdose of the drug. The effectiveness of the antidote decreases sharply after this time.

If necessary, the patient should be given intravenous N-acetylcysteine according to the established dose schedule. In the absence of vomiting, oral methionine may be used as a suitable alternative in remote areas outside the hospital.

Treatment of patients who develop severe liver dysfunction within 24 hours of taking paracetamol should be carried out in accordance with established recommendations.

Ibuprofen. The use of ibuprofen in doses greater than 400 mg/kg in children may cause symptoms of overdose. In adults, the dose-dependent effect is less pronounced. The half-life in overdose is 1.5-3 hours.

Symptoms. In most patients who have taken clinically significant amounts of NSAIDs, only nausea, vomiting, epigastric pain, and very rarely diarrhea may occur. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic lesions of the central nervous system may occur in the form of drowsiness, sometimes - nervous excitement and disorientation or coma. Sometimes patients have convulsions. In severe poisoning, metabolic acidosis may occur; the prothrombin index/international normalized ratio (INR) may be increased, probably due to the effect on blood clotting factors. Acute renal failure and liver damage may occur in the presence of dehydration. In patients with bronchial asthma, exacerbation of the disease may occur.

Treatment. Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring cardiac symptoms and vital signs until the condition returns to normal. Oral administration of activated charcoal is recommended within 1 hour of ingestion of a potentially toxic amount. Diazepam or lorazepam should be administered intravenously for frequent or prolonged seizures. Bronchodilators should be used for the treatment of bronchial asthma.

Adverse reactions

The results of clinical studies conducted with this drug do not indicate the presence of any other adverse reactions than those observed with the use of ibuprofen or paracetamol separately.

The following are adverse reactions observed in patients who used ibuprofen or paracetamol alone during short-term and long-term use.

Adverse reactions that occurred with ibuprofen or paracetamol alone are listed by system organ class and frequency. The frequency is defined 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 not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Description of selected adverse reactions

1 Examples include agranulocytosis, anemia, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia. Early signs include fever, sore throat, mouth ulcers, flu-like symptoms, severe fatigue, unexplained bleeding, bruising, and nosebleeds.

2 Hypersensitivity reactions have been reported. These include: (a) non-specific allergic reactions; (b) respiratory tract reactions, including asthma, asthma exacerbation, bronchospasm or dyspnoea; or (c) various skin reactions, including rash of various types, pruritus, urticaria, purpura, angioedema, and less commonly, exfoliative and bullous dermatoses (including epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme).

3The mechanism of pathogenesis of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with the use of NSAIDs suggest a hypersensitivity reaction (with symptoms occurring during drug administration and resolving after drug withdrawal). In particular, isolated cases of symptoms of aseptic meningitis, such as neck stiffness, headache, nausea, vomiting, fever or disorientation, have been observed during treatment with ibuprofen in patients with pre-existing autoimmune diseases (such as systemic lupus erythematosus, mixed connective tissue disease) (see section 4.4).

4Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a small increased risk of arterial thrombotic events, such as myocardial infarction or stroke (see section 4.4).

5The most common side effects are gastrointestinal.

6 Sometimes fatal, especially in the elderly.

7See section "Application features".

8In overdose, paracetamol may cause liver failure, including acute, hepatic necrosis and liver damage (see section “Overdose”).

9Especially with long-term use associated with increased urea levels in