Instructions for Darfen film-coated tablets 400 mg blister No. 7
Composition
active ingredient: ibuprofen in the form of ibuprofen sodium dihydrate;
1 tablet contains 200 mg or 400 mg of ibuprofen in the form of ibuprofen sodium dihydrate;
Excipients: microcrystalline cellulose, croscarmellose sodium, xylitol, colloidal anhydrous silica, magnesium stearate, sucrose, talc, titanium dioxide (E 171), acacia dried dispersion, carmellose sodium, macrogol 6000.
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a white or almost white coating.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated efficacy in inhibiting the synthesis of prostaglandins, mediators of pain and inflammation. Ibuprofen relieves pain, reduces inflammation, and lowers fever. In addition, ibuprofen reversibly inhibits platelet aggregation.
Clinical efficacy and safety
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid (ASA) on platelet aggregation when these drugs are used concomitantly. Some pharmacodynamic studies have shown that single doses of ibuprofen 400 mg administered within 8 hours before or within 30 minutes after immediate-release ASA (81 mg) have been shown to reduce the effect of ASA on thromboxane formation or platelet aggregation. Although the extrapolation of these data to the clinical situation is questionable, it cannot be ruled out that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose ASA. Such a clinically significant effect is unlikely with non-systematic use of ibuprofen.
Ibuprofen has been clinically proven to be effective for headaches, toothaches, dysmenorrhea, fever due to colds and flu, as well as sore throats, muscles, and back pain.
According to clinical studies, the analgesic effect of ibuprofen can be observed for 8 hours.
In a study of toothache treatment, ibuprofen compared to placebo provided significant pain relief within 15 minutes. In this study, significantly more patients reported significant pain relief after taking ibuprofen compared to taking paracetamol. These patients also had a significant reduction in pain intensity and greater pain relief over 6 hours compared to taking paracetamol.
Pharmacokinetics.
Absorption.
Ibuprofen is rapidly absorbed from the gastrointestinal tract (GI), binds to plasma proteins and is distributed throughout the body. It should be noted that the bioavailability of ibuprofen sodium salt is significantly higher and the effect occurs twice as quickly as when using regular ibuprofen tablets.
Distribution: Ibuprofen enters the synovial fluid. Peak serum concentrations of ibuprofen sodium dihydrate are reached 35 minutes after administration. Peak serum concentrations of ibuprofen acid are reached 1–2 hours after administration. Absorption may be delayed by food.
Biotransformation. After metabolism in the liver (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are completely excreted mainly in the urine (90%), as well as in bile. The half-life in healthy volunteers, as well as in patients with liver and kidney diseases, is 1.8–3.5 hours. Binding to plasma proteins is approximately 99%.
Elimination: Ibuprofen is metabolized in the liver to two inactive metabolites, which are rapidly and completely excreted by the kidneys. The elimination half-life of ibuprofen is approximately 2 hours.
No significant differences in the pharmacokinetic profile are observed in elderly patients.
Indication
Symptomatic treatment of mild to moderate pain of various origins, including headache, toothache, migraine, dysmenorrhea, neuralgia, back pain, muscle pain, rheumatic pain (except severe cases of arthritis), as well as sore throat, cold and flu symptoms, and fever.
Contraindication
Hypersensitivity to the active substance or to any of the components of the medicinal product.
Patients with hypersensitivity reactions (e.g. bronchospasm, asthma, rhinitis, angioedema or urticaria) that occurred previously after taking ibuprofen or other NSAIDs (e.g. ASA).
History of gastrointestinal bleeding or perforation associated with NSAID use.
History of active or recurrent gastric or duodenal ulcer/bleeding (two or more severe episodes of confirmed ulceration or bleeding).
Concomitant use with other NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors, due to an increased risk of adverse reactions.
Cerebrovascular or other bleeding in the active phase.
Disorders of hematopoiesis and/or blood clotting.
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
Ibuprofen should not be used in combination with:
Other NSAIDs, particularly selective COX-2 inhibitors, as the simultaneous use of multiple NSAIDs may increase the risk of adverse reactions.
ASA, as this increases the risk of adverse reactions.
Experimental data suggest that ibuprofen may inhibit the effect of low-dose ASA on platelet aggregation when used concomitantly. However, the limitations of extrapolation of these data to the clinical situation preclude definitive conclusions that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose ASA. Such clinically significant effects are considered unlikely with non-systematic use of ibuprofen;
Ibuprofen should be used with caution in combination with the following drugs:
Corticosteroids.
Increased risk of gastrointestinal ulceration or bleeding when used concomitantly with NSAIDs (see section "Special warnings and precautions for use").
Antihypertensive drugs (angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists) and diuretics.
NSAIDs may reduce the effect of antihypertensive drugs such as ACE inhibitors, angiotensin II receptor antagonists and diuretics. 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 COX may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, 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 also increase the risk of nephrotoxicity of NSAIDs.
Anticoagulants.
NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special warnings and precautions for use").
Antiplatelet agents and selective serotonin reuptake inhibitors: Increased risk of gastrointestinal bleeding when taken with NSAIDs (see section "Special warnings and precautions for use").
Cardiac glycosides.
NSAIDs can worsen heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.
Lithium.
NSAIDs may reduce the excretion of lithium, which is accompanied by an increase in lithium plasma concentrations.
Methotrexate.
The use of NSAIDs may lead to increased plasma concentrations of methotrexate.
Cyclosporine.
Increased risk of nephrotoxicity when used with NSAIDs.
Mifepristone.
NSAIDs are not recommended for use earlier than 8–12 days after mifepristone administration, as this will reduce its effectiveness.
Tacrolimus.
There may be an increased risk of nephrotoxicity when NSAIDs are administered concomitantly with tacrolimus.
Zidovudine.
There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia when treated concomitantly with zidovudine and ibuprofen.
Quinolone antibiotics.
Animal studies suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Concomitant use with ibuprofen may increase the risk of seizures.
Sulfonylurea drugs.
The effect of sulfonylureas may be enhanced.
Voriconazole and fluconazole.
Potentiation of the effect of ibuprofen is possible when used simultaneously with voriconazole and fluconazole.
Application features
Adverse reactions can be minimized by using the lowest effective dose of ibuprofen for the shortest period of time sufficient to control symptoms (see section "Dosage and Administration" and information on gastrointestinal and cardiovascular risks).
Elderly patients.
Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Systemic lupus erythematosus and mixed connective tissue diseases.
Patients with systemic lupus erythematosus and mixed connective tissue diseases may be at increased risk of aseptic meningitis (see below and section “Adverse reactions”).
Severe skin reactions.
The risk of these reactions is high at the beginning 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 after the use of ibuprofen-containing medicines.
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.
Kidney dysfunction.
Chronic use of analgesics, especially in combination with several analgesics, may lead to persistent renal impairment with a risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration. Ibuprofen should be used with caution in patients with impaired renal function, as renal function may deteriorate.
Effect on the liver.
Liver dysfunction is possible.
Children.
Children and adolescents with dehydration are at risk of kidney dysfunction.
Gastrointestinal bleeding, ulcers and perforations.
Gastrointestinal bleeding, ulceration or perforation has been reported with all NSAIDs at any time during treatment. These adverse reactions may be fatal and may occur with or without life-threatening symptoms or a history of serious gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, especially if complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment with minimal doses. The possibility of concomitant administration of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered in such patients, as well as in patients taking concomitant low doses of ASA or other drugs that increase the risk of gastrointestinal damage (see below and section "Interaction with other medicinal products and other forms of interaction").
Patients, especially the elderly, with a history of gastrointestinal disease should report any unusual abdominal symptoms (including gastrointestinal bleeding), especially in the initial stages of treatment.
Ibuprofen should be prescribed with caution to patients receiving concomitant treatment with drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as ASA (see section "Interaction with other medicinal products and other types of interactions").
If gastrointestinal bleeding or ulceration is diagnosed in patients receiving Darfen, treatment should be discontinued immediately.
NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated.
Effects on the respiratory system.
Bronchospasm may occur in patients who suffer from bronchial asthma or allergic diseases or have a history of these diseases.
Effects on the cardiovascular and cerebrovascular systems.
Patients with a history of hypertension and/or heart failure should start treatment with caution (consultation with a doctor is necessary), since cases of fluid retention, hypertension and edema have been reported with ibuprofen therapy, as with other NSAIDs.
Clinical trial data and epidemiological data suggest that the use of ibuprofen, especially at high doses (2400 mg/day), 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/day) may lead to an increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only 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.
Masking the symptoms of underlying infections.
Ibuprofen may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment, which may complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or for pain relief in an infection, monitoring for the presence of an infectious disease is recommended. In the setting of outpatient treatment, the patient should seek medical advice if symptoms persist or worsen.
The drug Darfen contains xylitol, which may have a laxative effect. The energy value of 1 g of xylitol is 2.4 kcal.
This medicinal product contains sucrose, so if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Darfen contains sodium, so caution should be exercised when administering this medicine to patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
I and II trimesters of pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular defects increased from 1% to approximately 1.5%. The risk is believed to increase with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors leads to an increase in pre- and post-implantation fetal death and embryo-foetal lethality. In addition, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal malformations, including cardiovascular anomalies, was observed.
From the 20th week of pregnancy, the use of Darfen may cause oligohydramnios due to fetal renal dysfunction. This condition is possible at the beginning of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus after treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment. Therefore, Darfen should not be taken during the first two trimesters of pregnancy unless, in the opinion of the physician, the expected benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman attempting to conceive, or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible period of time.
Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be carried out for several days after the use of Darfen, starting from the 20th week of pregnancy. If oligohydramnios or narrowing of the ductus arteriosus is detected, the use of the drug should be discontinued.
3rd trimester of pregnancy
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose the following risks:
for the fetus: cardiopulmonary toxicity (characterized by premature narrowing/closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure, accompanied by oligohydramnios;
for the mother and newborn, at the end of pregnancy: possible increase in bleeding time, antiplatelet effect, which may develop even at very low doses; suppression of uterine contractions, leading to delay or prolongation of labor. Possible increased risk of edema in the mother.
Therefore, the drug Darfen is contraindicated during the third trimester of pregnancy.
Breastfeeding period
In limited studies, ibuprofen and its metabolites have been found in breast milk at very low concentrations (0.0008% of the maternal dose), so it is unlikely that it could adversely affect the breastfed infant. Darfen is not recommended for use during breastfeeding.
Fertility
There is limited evidence that long-term use of drugs that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
When taken in accordance with the recommended doses and duration of use, the drug does not affect the reaction speed when driving or working with other mechanisms.
Method of administration and doses
For short-term use only.
Use the lowest effective dose necessary to relieve symptoms for the shortest period of time.
A single dose for adults and children over 12 years of age is 1-2 tablets (200 mg-400 mg). The interval between doses should be at least 4 hours and no more than 6 tablets of 200 mg per day or 3 tablets of 400 mg per day should be used. The maximum daily dose of 1200 mg should not be exceeded.
If symptoms of the disease worsen or persist for more than 3 days in adolescents aged 12 and over, it is necessary to consult a doctor to clarify the diagnosis and adjust the treatment regimen.
If you need to use the medicine for more than 10 days, you should consult a doctor.
Elderly patients.
No special dose adjustment is required.
Method of application.
Administer orally. Patients with stomach problems are advised to take Darfen with or after meals.
Children.
The drug Darfen should not be used in children under 12 years of age.
Overdose
In children, doses of ibuprofen exceeding 400 mg/kg body weight may cause symptoms of intoxication. In adults, the dose effect is less pronounced. The half-life in overdose is 1.5–3 hours.
Symptoms. Nausea, vomiting, epigastric pain, rarely diarrhea. Tinnitus, blurred vision, headache, dizziness, nystagmus, blurred vision, loss of consciousness and gastrointestinal bleeding may also occur. In more severe poisoning, toxic lesions of the central nervous system may occur, manifested as dizziness, vertigo, drowsiness, sometimes - an excited state and disorientation or coma. Sometimes patients have convulsions. In severe poisoning, hyperkalemia and metabolic acidosis may occur, an increase in prothrombin time/international normalized ratio (probably due to interaction with blood clotting factors circulating in the bloodstream). Acute renal failure, liver damage, arterial hypotension, respiratory depression and cyanosis may occur. In patients with bronchial asthma, asthma exacerbation is possible.
Treatment. Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring cardiac and vital signs until the condition returns to normal. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour of ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkaline agents may be administered to accelerate the excretion of acidic ibuprofen in the urine. Diazepam or lorazepam should be administered intravenously for frequent or prolonged seizures. Bronchodilators should be used for the treatment of acute asthma. There is no specific antidote.
Adverse reactions
The following adverse reactions have been observed with short-term use of ibuprofen at doses not exceeding 1200 mg per day. In the treatment of chronic diseases, additional adverse reactions may occur with long-term use.
The most common adverse reactions are gastrointestinal, and are largely dose-dependent, with the risk of gastrointestinal bleeding depending on the dose and duration of treatment. Adverse reactions are least common at a maximum daily dose of 1200 mg.
Clinical trial data suggest that the use of ibuprofen, especially at high doses (2400 mg per day), increases the risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (≥ 1/10,000 - < 1/1,000), rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
On the part of the organs of vision: frequency unknown - with prolonged treatment, visual impairment and optic neuritis may occur.
On the part of the hearing organs: rarely - with prolonged treatment, tinnitus and dizziness are possible.
Gastrointestinal: infrequently - abdominal pain, nausea, dyspepsia; rarely - diarrhea, flatulence, constipation, vomiting; rare - gastric ulcer, gastrointestinal perforation or gastrointestinal bleeding, melena, hematemesis, sometimes fatal, especially in elderly patients. Ulcerative stomatitis, pancreatitis, exacerbation of colitis and Crohn's disease.
Liver and biliary tract disorders: rare - liver function disorders (especially with long-term treatment); frequency unknown - hepatitis and jaundice may occur with long-term treatment.
Renal and urinary disorders: rare - acute renal failure, papillary necrosis, especially with prolonged use, associated with increased serum urea levels and edema; frequency unknown - nephrotoxicity, including interstitial nephritis and nephrotic syndrome.
Nervous system disorders: uncommon – headache; rare – aseptic meningitis2.
On the part of the psyche: rarely - mental disorders, depression, insomnia, agitation, hallucinations, confusion.
Cardiovascular system: rare - heart failure, edema, arterial hypertension.
Blood and lymphatic system disorders: rare - hematopoietic disorders (anemia, leukopenia, thrombocytopenia, pancytopenia and agranulocytosis). The first signs of such disorders are fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, severe exhaustion, bleeding and hematomas of unknown etiology.
Immune system disorders: uncommon - hypersensitivity reactions accompanied by urticaria and pruritus1; rare - severe hypersensitivity reactions, symptoms of which may include swelling of the face, tongue and larynx, shortness of breath, tachycardia, arterial hypotension (anaphylaxis, angioedema or severe shock); frequency unknown - airway reactivity, including asthma, bronchospasm or dyspnoea.
Laboratory indicators: rare - decrease in hemoglobin level, renal clearance of urea level.
General disorders: malaise and fatigue, irritability.
Description of selected adverse reactions
1 Hypersensitivity reactions may include: non-specific allergic reactions and anaphylaxis; airway reactivity including asthma, asthma exacerbation, bronchospasm and dyspnoea; various forms of skin reactions including pruritus, urticaria, purpura, angioedema, and less commonly exfoliative and bullous dermatoses (including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme).
2 The pathogenic mechanism of drug-induced aseptic meningitis is not clear. Available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (given the temporal relationship to drug intake and the disappearance of symptoms after drug withdrawal). In patients with autoimmune diseases (systemic lupus erythematosus and mixed connective tissue disease), isolated cases of symptoms of aseptic meningitis (neck stiffness, headache, nausea, vomiting, fever or disorientation) have been observed.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
1.5 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
7 tablets in a blister; 1 or 2 blisters in a pack.
Vacation category
Without a prescription.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and address of its place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
