Ibuprofen-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN-DARNITSA (IBUPROFEN-DARNITSA)

Composition:

Active substance: ibuprofen;

1 tablet contains ibuprofen 200 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silicon dioxide, maize starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, round-shaped tablets with a biconvex surface.

Pharmacotherapeutic group.

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

ATC code M01AE01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid, which demonstrates its efficacy by 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 inhibit the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation when these medicinal products 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 aspirin (acetylsalicylic acid) (81 mg) resulted in reduced effects of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although uncertainty exists regarding the extrapolation of these data to clinical settings, the possibility cannot be excluded 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 unlikely.

Ibuprofen relieves pain, reduces inflammation, and lowers body temperature.

Pharmacokinetics

Ibuprofen is rapidly absorbed from the gastrointestinal tract and binds to plasma proteins.

Maximum serum concentration is reached within 45 minutes after administration on an empty stomach. When the drug is taken with food, peak levels are observed 1–2 hours after administration. Ibuprofen is metabolized in the liver and excreted by the kidneys either unchanged or as metabolites. The elimination half-life is approximately 2 hours. No significant differences in pharmacokinetic profile have been observed in elderly patients.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, toothache, dysmenorrhea, neuralgia, back pain, joint pain, muscle pain, rheumatic pain, as well as treatment of symptoms associated with cold and influenza.

Contraindications.

• Hypersensitivity to ibuprofen or to any component of the medicinal product.
• History of hypersensitivity reactions (such as asthma, rhinitis, angioedema, or urticaria) following administration of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active peptic ulceration or gastrointestinal bleeding, or history of recurrent episodes (two or more confirmed episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
• Severe heart failure (NYHA class IV), severe renal impairment, or severe hepatic impairment.
• Active inflammatory bowel disease.
• Hemorrhagic diathesis or other coagulation disorders.
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

In general, caution should be exercised when using NSAIDs in combination with other medicinal products that may increase the risk of gastrointestinal ulcers, gastrointestinal bleeding, or worsening of renal function.

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

• acetylsalicylic acid (aspirin), as this may increase the risk of adverse reactions, except when aspirin (at a dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, due to the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical settings, definitive conclusions regarding the systemic use of ibuprofen cannot be drawn. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen;
• other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use of two or more NSAIDs should be avoided, as this may increase the risk of adverse effects.

Ibuprofen should be used with caution in combination with the following medicinal products:

Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin.

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of these medicinal products. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised kidney function), concomitant use of an ACE inhibitor or angiotensin II antagonist with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients receiving coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, such combinations should be used cautiously, especially in elderly patients. If treatment is necessary, adequate hydration of the patient should be ensured, and monitoring of renal function should be considered at the start of combination therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulceration and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased 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 plasma lithium levels.

Methotrexate: possible increase in methotrexate plasma levels.

Cyclosporine: increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be administered earlier than 8–12 days after mifepristone use, as they may reduce its efficacy.

Tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Zidovudine: increased risk of hematologic toxicity when zidovudine is used concomitantly with NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia who are concurrently treated with zidovudine and ibuprofen.

Quinolone antibiotics: in patients receiving both ibuprofen and quinolone antibiotics, there may be an increased risk of seizures.

Special precautions for use.

Adverse effects associated with ibuprofen can be minimized by using the lowest effective dose required to treat symptoms for the shortest possible duration.

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

Respiratory system 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 COX-2 inhibitors, should be avoided, as this increases the risk of adverse reactions.

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. Cases of aseptic meningitis have been reported during ibuprofen therapy. Although this effect is more likely in patients with systemic lupus erythematosus and other connective tissue disorders, such cases have also been reported in some patients without chronic diseases; therefore, this should be considered when using this medicinal product.

Cardiovascular and cerebrovascular effects.

Patients with a history of hypertension and/or heart failure should begin treatment with caution (medical consultation is 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 per day) and with prolonged treatment, may lead to a small increase in the 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) increases the risk of myocardial infarction.

Patients with uncontrolled hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful assessment of the clinical condition. High doses (2400 mg per day) should be avoided.

A careful evaluation of the clinical condition is also required before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Cases of Kounis syndrome have been reported in patients receiving treatment with Ibuprofen-Darnitsia. 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.

Effects on kidneys/liver.

Caution should be exercised in patients with renal impairment due to the potential for worsening kidney function. Ibuprofen should be used with caution in patients with kidney or liver disease, especially when used concomitantly with diuretics, as prostaglandin inhibition may lead to fluid retention and further deterioration of renal function. These patients should receive the lowest possible dose of ibuprofen, and renal function should be monitored regularly. In cases of dehydration, adequate fluid intake should be ensured. There is a risk of renal failure in children (from 6 years of age) and adolescents who are dehydrated.

In general, chronic use of analgesics, particularly combinations of different painkillers, may lead to persistent kidney damage with a risk of renal failure (analgesic nephropathy). The highest risk of this reaction exists in elderly patients, patients with renal, cardiac, or hepatic insufficiency, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, the pre-treatment condition is usually restored.

Like other NSAIDs, ibuprofen may cause slight transient increases in certain liver function parameters, as well as significant increases in AST and ALT levels. If significant elevations in these parameters occur, treatment should be discontinued.

During prolonged ibuprofen use, liver function tests, kidney function, and hematological parameters/blood counts should be monitored regularly.

Effects on female fertility.

Limited data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect the process of ovulation. This effect is reversible after discontinuation of treatment.

Gastrointestinal tract effects.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as their condition may worsen.

Cases of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, have been reported during NSAID therapy at any stage of treatment, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, or ulcers increases with higher NSAID doses, particularly in patients with a history of peptic ulcer disease, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest doses.

These patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase gastrointestinal risk, should be prescribed combination therapy with protective agents (such as misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

Long-term use of any analgesic for headache treatment may worsen this condition. In such cases, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients suffering from frequent or daily headaches despite (or because of) regular use of headache medications.

Caution should be exercised when treating patients who are concurrently taking medicinal products that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., aspirin).

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

Severe skin adverse reactions (SSARs).

Severe 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), 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 ibuprofen treatment.

If signs or symptoms indicating these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment options should be considered (if necessary).

Important information about excipients.

This medicinal product contains 6.8 mg of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

During the first and second trimesters of pregnancy, the use of this medicinal product should be avoided. The drug is contraindicated during the third trimester of pregnancy.

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with higher doses and longer duration of therapy.

From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after the start of treatment and is usually reversible upon discontinuation of therapy. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, which in most cases resolved after treatment cessation. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman attempting to become pregnant 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 may be advisable after ibuprofen exposure for several days starting from the 20th gestational week. Treatment with Ibuprofen-Darnitsia 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:

• to 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;
• to the mother and newborn at the end of pregnancy: possible prolonged bleeding time, antiplatelet effect (which may develop even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations; therefore, it is unlikely to have a negative effect on a breastfed infant.

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

For short-term oral use only. Tablets should be swallowed whole with water; do not chew.

The lowest effective dose required to treat symptoms should be used for the shortest possible duration. If symptoms persist for more than 5 days from the start of treatment or worsen, medical advice should be sought.

The medicinal product is intended for adults and children with body weight above 20 kg (approximately from 6 years of age). The recommended daily dose is 20–30 mg/kg body weight. Do not exceed 30 mg/kg body weight per day.

Children with body weight from 20 to 30 kg (aged 6 to 11 years): 200 mg (1 tablet) per dose. Repeat dose may be administered as needed every 6 hours. Do not exceed 600 mg (3 tablets) per day.

Adults and children with body weight above 30 kg: 200–400 mg (1–2 tablets) per dose. Repeat dose may be administered as needed every 4–6 hours. Do not exceed 1200 mg (6 tablets) per day.

Elderly patients do not require special dosage adjustments.

Children

Do not use in children with body weight below 20 kg or under 6 years of age.

Overdose

Symptoms of overdose typically occur within 4 hours after administration.

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

Symptoms: In most patients, ingestion of clinically significant amounts of NSAIDs causes nausea, vomiting, epigastric pain, or less commonly, diarrhea. Additional symptoms may include tinnitus, headache, and gastrointestinal bleeding. In severe poisoning, toxic effects on the central nervous system may occur, manifesting as drowsiness, vertigo, dizziness, lethargy, occasionally excitement, ataxia, disorientation, or coma. Seizures may develop in some patients. In more severe cases, hyperkalemia, metabolic acidosis, and prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors) may occur. Acute renal failure and hepatic injury, hypotension, hypothermia, cyanosis, dyspnea/acute respiratory distress syndrome, and transient episodes of apnea (in children after ingestion of large amounts of the drug) may develop. In patients with bronchial asthma, exacerbation of asthma may occur. Nystagmus, visual disturbances, and loss of consciousness are also possible.

Treatment: There is no specific antidote. Treatment should be symptomatic and supportive, including maintenance of airway patency and continuous monitoring of cardiac function and vital signs until the patient's condition stabilizes. In cases of ingestion of small amounts of the drug (less than 50 mg/kg ibuprofen), drinking water is recommended to minimize gastrointestinal disturbances. Oral administration of activated charcoal or gastric lavage within 1 hour after ingestion of a potentially toxic dose is recommended. The benefit of interventions such as forced diuresis, hemodialysis, and hemoperfusion has not been proven, as ibuprofen is highly protein-bound. In cases of frequent or prolonged muscle spasms, treatment with intravenous diazepam or lorazepam is indicated. Bronchodilators should be used in cases of bronchial asthma. Seek immediate medical attention.

Side effects.

The side effects observed during the use of ibuprofen are listed below by organ systems and frequency of occurrence. The frequency of adverse reactions is defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in descending order of severity.

The adverse reactions listed below were observed during short-term use of ibuprofen at over-the-counter doses. Additional adverse effects may occur during treatment of chronic conditions or with long-term therapy.

The most commonly observed adverse reactions were gastrointestinal in nature. Generally, adverse reactions are dose-dependent; in particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment.

Respiratory system, thoracic organs and mediastinum: frequency not known: airway reactivity, including asthma, bronchospasm, or dyspnea.

Gastrointestinal system: uncommon: abdominal pain, nausea, dyspepsia; rare: diarrhea, flatulence, constipation, vomiting; very rare: peptic ulceration of the stomach and duodenum, perforations or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis; frequency not known: exacerbation of colitis and Crohn’s disease.

Hepatobiliary system: very rare: hepatic function abnormalities.

Renal and urinary system: very rare: acute renal failure, papillary necrosis (particularly with prolonged use), associated with increased serum urea levels, and edema; frequency not known: renal failure.

Nervous system: uncommon: headache, aseptic meningitis. The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. Available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal association with drug administration and resolution of symptoms after drug discontinuation). Cases of aseptic meningitis symptoms have been reported in patients with autoimmune disorders (systemic lupus erythematosus and mixed connective tissue disease), including nuchal rigidity, headache, nausea, vomiting, fever, or confusion.

Cardiovascular system: frequency not known: arterial hypertension, heart failure, edema, Coats’ syndrome.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen (particularly at high doses of 2400 mg daily) and during long-term treatment may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Blood and lymphatic system: very rare: blood dyscrasias (including anemia, leukopenia, thrombocytopenia, pancytopenia, and agranulocytosis). Initial signs of such disorders include fever, sore throat, superficial oral ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding, and unexplained bruising.

Immune system: uncommon: hypersensitivity reactions accompanied by urticaria and pruritus; very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, and hypotension (anaphylaxis, angioneurotic edema, or severe shock). Hypersensitivity reactions may include: non-specific allergic reactions and anaphylaxis, airway reactivity including bronchial asthma, asthma exacerbation, bronchospasm and dyspnea, or various skin reactions including pruritus, urticaria, purpura, angioedema, and less commonly exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

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

Laboratory parameters: very rare: decreased hemoglobin levels.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister pack; 1, 2, or 5 blisters per carton.

Prescription status. Over-the-counter.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspylska Street, Kyiv, 02093, Ukraine.