Darfen® kids

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DARFEN® KIDS

Composition:

Active substance: ibuprofen;

5 ml of suspension contain ibuprofen 100 mg;

Excipients: sodium benzoate, anhydrous citric acid, sodium citrate, sodium saccharin, sodium chloride, hypromellose 15 cP, xanthan gum, maltitol liquid, glycerin (E 422), strawberry flavor, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: a viscous suspension free from extraneous particles, white or almost white in color, with a characteristic strawberry odor.

Pharmacotherapeutic group

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ibuprofen. ATC code M01AE01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated efficacy in inhibiting the synthesis of prostaglandins. In humans, ibuprofen reduces pain associated with inflammation, swelling, and fever. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. The onset of analgesic and antipyretic action of ibuprofen has been shown to occur within 30 minutes. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when these medicinal products are administered concomitantly. In one study, when a single 400 mg dose of ibuprofen was taken within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg), a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. However, the limited nature of these data and uncertainty regarding the extrapolation of ex vivo findings to the clinical setting preclude definitive conclusions about the systematic use of ibuprofen. Clinically significant effects are considered unlikely with occasional use of ibuprofen.

Pharmacokinetics

Ibuprofen is rapidly absorbed after administration and quickly distributed throughout the body. Elimination is rapid and complete, occurring via the kidneys.

Maximum plasma concentration is reached within 45 minutes after oral administration on an empty stomach. When administered with food, peak levels are observed within 1–2 hours. This time may vary depending on the pharmaceutical form.

The elimination half-life is approximately 2 hours.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations.

Clinical characteristics.

Indications. Symptomatic treatment of fever and pain of various origins in children aged from 3 months to 12 years with body weight of at least 5 kg (including fever after vaccination, acute respiratory viral infections, influenza, teething pain, post-extraction dental pain, toothache, headache, sore throat, ligament sprain pain, and other types of pain, including those of inflammatory origin).

Contraindications.

• Hypersensitivity to ibuprofen or to any of the excipients of the medicinal product.
• History of hypersensitivity reactions (e.g., bronchospasm, bronchial asthma, rhinitis, angioedema, or urticaria) following administration of acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer disease / gastrointestinal bleeding or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
• Severe hepatic insufficiency, severe renal insufficiency, or severe heart failure.
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
• Third trimester of pregnancy.
• Cerebrovascular or other hemorrhages.
• Unexplained hematological disorders or coagulation abnormalities.
• Hereditary fructose intolerance.

Interaction with other medicinal products and other forms of interaction.

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

− acetylsalicylic acid, as this increases the risk of adverse reactions, except when acetylsalicylic acid (at a dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose acetylsalicylic acid. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to the clinical setting do not allow definitive conclusions regarding the systematic use of ibuprofen. With occasional (non-systematic) use of ibuprofen, such clinically significant effects are considered unlikely;

− other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use of two or more NSAIDs should be avoided, as this increases the risk of adverse effects.

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

− anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin;

− antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, beta-blockers, angiotensin II antagonists) and diuretics: NSAIDs may reduce the efficacy of these drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised kidney function), concomitant use of ACE inhibitors, beta-blockers, or angiotensin II antagonists with cyclooxygenase inhibitors may lead to further deterioration of renal function, including potentially reversible acute renal failure. Therefore, such combinations should be used cautiously, especially in elderly patients. Patients should maintain adequate fluid intake, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter. Diuretics 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, e.g., digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides. Concomitant administration of ibuprofen with digoxin may increase serum levels of digoxin. With appropriate use (maximum duration of 4 days), routine monitoring of serum digoxin levels is generally not required;

− lithium: possible increase in plasma lithium levels. With appropriate use (maximum duration of 4 days), routine monitoring of serum lithium levels is generally not required;

− methotrexate: potential for increased plasma methotrexate levels. Administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate concentration and enhance its toxic effects;

− cyclosporine: increased risk of nephrotoxicity;

− mifepristone: NSAIDs should not be used earlier than 8–12 days after administration of mifepristone, as they may reduce its efficacy;

− tacrolimus: increased risk of nephrotoxicity when NSAIDs are used concomitantly with tacrolimus;

− zidovudine: increased risk of hematological toxicity when zidovudine is used concomitantly with NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen;

− quinolone antibiotics: animal studies indicate that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients taking both NSAIDs and quinolones may have an increased risk of developing seizures;

− sulfonylurea derivatives: possible potentiation of effect. Clinical studies have demonstrated interactions between NSAIDs and antidiabetic agents (sulfonylureas). Although interactions between ibuprofen and sulfonylureas have not been specifically reported to date, blood glucose levels should be monitored when these medicinal products are used concomitantly;

− phenytoin: possible increase in serum phenytoin levels. With appropriate use (maximum duration of 4 days), routine monitoring of serum phenytoin levels is generally not required;

− probenecid and sulfinpyrazone: medicinal products containing probenecid or sulfinpyrazone may delay the elimination of ibuprofen;

− potassium-sparing diuretics: concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (monitoring of serum potassium levels is recommended);

− voriconazole and fluconazole (CYP2C9 inhibitors): concomitant use of ibuprofen with CYP2C9 inhibitors may enhance the effect of ibuprofen (a CYP2C9 substrate). In a study using voriconazole and fluconazole, the effect of S(+)-ibuprofen was increased by approximately 80–100%. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, a reduction in ibuprofen dosage is recommended, especially when high doses of ibuprofen are required together with voriconazole or fluconazole.

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 individuals have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal. Patients of advanced age are at increased risk of developing adverse reactions. Prolonged use of NSAIDs is not recommended in elderly individuals. If long-term therapy is necessary, patients should be monitored regularly.

Caution is advised in patients with the following conditions:

− Systemic lupus erythematosus, as well as mixed connective tissue disease — due to an increased risk of aseptic meningitis;

− Inherited disorders of porphyrin metabolism, for example acute intermittent porphyria;

− Gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);

− History of arterial hypertension and/or heart failure — due to reports of fluid retention and edema associated with NSAID therapy;

− Renal impairment — due to the possibility of worsening kidney function;

− Hepatic impairment;

− Immediately after major surgical procedures;

− Hay fever, nasal polyps, or chronic obstructive respiratory diseases — due to an increased risk of allergic reactions, including asthma attacks (so-called analgesic-induced asthma), Quincke’s edema, or urticaria;

− History of allergic reactions to other substances — due to an increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects.

Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with such conditions in their medical history.

Other NSAIDs.

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided, as this increases the risk of adverse reactions.

Systemic lupus erythematosus and mixed connective tissue disease.

Ibuprofen should be used with caution in patients with systemic lupus erythematosus and mixed connective tissue disease due to an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects.

Patients with a history of arterial hypertension and/or heart failure should initiate treatment cautiously (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 indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and during prolonged treatment, may cause a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Epidemiological studies do not show that low-dose ibuprofen (e.g., ≤ 1200 mg per day) increases the risk of myocardial infarction.

Cases of Kounis syndrome have been reported in patients receiving Darfen® Kids. Kounis syndrome manifests as cardiovascular symptoms associated with coronary artery spasm due to an allergic or hypersensitivity reaction, potentially leading to myocardial infarction.

Renal effects.

Long-term use of analgesics, particularly in combination with other painkillers, may lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy).

Caution is advised in patients with renal impairment due to the possibility of worsening kidney function.

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

Hepatic effects.

The medicinal product may cause hepatic function impairment.

Gastrointestinal 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. Such patients should consult a physician.

There have been reports of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, occurring at any stage of NSAID therapy, regardless of prior warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. Adverse effects may occur even with short-term therapy.

Such patients should start treatment with the lowest available dose. Patients with such conditions, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal bleeding, are recommended to receive concomitant protective therapy (e.g., misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal toxicity, particularly elderly individuals, should inform their physician of any unusual gastrointestinal symptoms.

Caution is required when treating patients who are concurrently taking medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid).

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

Impairment of fertility in women.

According to some data, cyclooxygenase/prostaglandin synthesis inhibitors may impair fertility in women by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Severe skin adverse reactions.

Severe skin adverse reactions have been reported with ibuprofen use, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions"). Most such reactions occurred within the first month.

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

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

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. At the first signs of a hypersensitivity reaction after ibuprofen administration, therapy should be discontinued and immediate medical attention sought.

Masking symptoms of underlying infections.

NSAIDs may mask symptoms of infection and fever.

Darfen® Kids may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby complicating the course of illness. This phenomenon has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Ibuprofen may temporarily inhibit platelet aggregation. Therefore, careful monitoring is recommended in patients with coagulation disorders.

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

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

Concomitant alcohol consumption and NSAID use may enhance undesirable effects related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system (CNS).

Before taking this medicinal product, consultation with a physician is recommended for: pregnant women, women attempting to conceive, elderly individuals, and smokers.

Important information about excipients

Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect. The energy value of 1 g of maltitol is 2.3 kcal. It should not be administered to patients with rare hereditary fructose intolerance.

The medicinal product contains sodium compounds. Caution is advised in patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

The medicinal product is intended for use in children under 12 years of age.

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 use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with higher doses and longer duration of therapy. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%.

From the 20th week of pregnancy, use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, cases of arterial duct constriction have been reported after treatment in the second trimester, most of which resolved after stopping treatment. Ibuprofen should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose for the shortest duration should be used. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to ibuprofen for several days starting from the 20th gestational week. Use of ibuprofen 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:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• Renal dysfunction (see above);

For the mother at the end of pregnancy and the newborn: prolonged bleeding time, antiplatelet effect that may occur even at very low doses; inhibition of uterine contractions leading to delayed or prolonged labor; increased risk of maternal edema.

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

Breastfeeding. Ibuprofen and its metabolites pass into breast milk in low concentrations. Currently, there is no information on negative effects on the infant; therefore, interruption of breastfeeding is usually not required during short-term treatment of pain and fever with recommended doses.

Fertility. There is some evidence that drugs inhibiting cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Therefore, the use of ibuprofen is not recommended in women experiencing difficulty conceiving.

Ability to affect reaction speed when driving or operating machinery.

The medicinal product is intended for use in children under 12 years of age. When used according to recommended doses and treatment duration, no effect on the ability to drive or operate machinery is expected.

Dosage and Administration.

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

The medicinal product is intended for oral administration. The recommended daily dose is 20–30 mg/kg body weight, divided into equal doses according to age and body weight, administered at intervals of 6–8 hours. To ensure accurate dosing, use the oral dosing syringe provided in the package. Do not exceed the recommended dose. For short-term use only.

Child's age Body weight (kg)	Recommended dose	Frequency of administration per day
3−6 months (5−7.6 kg)	2.5 ml of suspension (50 mg)	up to 3 times
6−12 months (7.7−9 kg)	2.5 ml of suspension (50 mg)	up to 3−4 times
1−3 years (10−16 kg)	5 ml of suspension (100 mg)	up to 3 times
4−6 years (17−20 kg)	7.5 ml of suspension (150 mg)	up to 3 times
7−9 years (21−30 kg)	10 ml of suspension (200 mg)	up to 3 times
10−12 years (31−40 kg)	15 ml of suspension (300 mg)	up to 3 times

Do not use in children under 3 months of age unless recommended by a physician.

Do not use this medicinal product in children weighing less than 5 kg.

If symptoms persist for longer than 24 hours after initiation of treatment or worsen (after 3 doses) in children aged 3 to 6 months, seek immediate medical advice.

If symptoms persist for more than 3 days after initiation of treatment or worsen in children aged 6 months to 12 years, seek medical advice.

For fever following vaccination (children aged 3–6 months), the recommended daily dose is 2.5 ml of suspension (50 mg); if necessary, an additional 2.5 ml of suspension (50 mg) may be given after 6 hours, but not more than 5 ml of suspension (100 mg) within 24 hours. If symptoms persist, medical advice should be sought.

Patients with sensitive stomach should take the medicinal product during or after meals.

Shake well before use.

Special patient categories.

Renal impairment: dose adjustment is not required in patients with mild to moderate renal dysfunction (for patients with severe renal impairment, see section "Contraindications").

Hepatic impairment: dose adjustment is not required in patients with mild to moderate hepatic dysfunction (for patients with severe hepatic impairment, see section "Contraindications").

In case of overdose, seek immediate medical advice.

Children. This medicinal product is intended for use in children aged 3 months to 12 years weighing at least 5 kg.

Overdose.

In pediatric patients, symptoms of overdose may occur with ibuprofen doses exceeding 400 mg/kg. Adults are generally less sensitive to overdose. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients, ingestion of a clinically significant amount of NSAIDs causes only nausea, vomiting, epigastric pain, or less commonly, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, central nervous system (CNS) toxicity may manifest as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally occur. Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, hypothermia and prolonged prothrombin time/international normalized ratio [INR] (likely due to interaction with circulating blood coagulation factors) may occur. Acute renal failure, liver damage, hypotension, respiratory depression with cyanosis, and loss of consciousness may also develop. In patients with bronchial asthma, an exacerbation of asthma symptoms may occur. Nystagmus and visual disturbances may also occur.

Treatment. There is no specific antidote. Treatment should be symptomatic and supportive, including ensuring airway patency, monitoring cardiac function and vital signs until the patient's condition stabilizes. Consider administration of oral activated charcoal or gastric lavage if less than 1 hour has passed since ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be used to enhance urinary excretion of the acidic ibuprofen. In cases of frequent or prolonged seizures, intravenous administration of anticonvulsants (e.g., diazepam or lorazepam) is required. Bronchodilators should be administered in case of bronchial asthma exacerbation. Immediate medical assistance must be sought.

Adverse reactions.

The list of adverse reactions includes all undesirable effects reported during treatment with ibuprofen, particularly those observed with high doses and long-term therapy in patients with rheumatic diseases.

The frequency indicated beyond very rare reports refers to short-term use of oral dosage forms (maximum 1200 mg ibuprofen per day).

It should be noted that the adverse reactions listed are predominantly dose-dependent and may vary individually for each patient.

The most commonly observed adverse reactions were gastrointestinal. Most adverse reactions are dose-dependent; in particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal hemorrhage, sometimes fatal, especially in elderly patients, may occur. Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported after ibuprofen use. Gastritis has been observed less frequently.

Edema, arterial hypertension, heart failure, and other cardiovascular events have been reported in association with NSAID therapy.

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

Cases of exacerbation of infections, including development of necrotizing fasciitis, temporally associated with NSAID use, have been described. This may be related to the mechanism of action of NSAIDs.

If signs of infection occur or worsen during ibuprofen treatment, patients are advised to seek immediate medical attention. The need for antimicrobial/antibiotic therapy should be evaluated.

Regular blood tests are recommended during long-term therapy.

Patients should immediately consult a physician and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose of the drug. Immediate medical assistance is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the drug should be discontinued and immediate medical attention sought.

Adverse reactions reported during ibuprofen use are listed below by organ systems and frequency of occurrence. 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 (≥ 1/10000 to < 1/1000), very rare (< 1/10000), and frequency not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in decreasing order of severity.

Eye disorders:

Frequency not known: visual disturbances, optic neuritis may occur during prolonged treatment.

Ear and labyrinth disorders:

Frequency not known: dizziness may occur during prolonged treatment;
Rare: tinnitus.

Respiratory, thoracic and mediastinal disorders:

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea¹.

Gastrointestinal disorders:

Common: abdominal pain, nausea, dyspepsia, diarrhea, meteorism, constipation, heartburn, vomiting, and minor gastrointestinal bleeding, which in exceptional cases may lead to anemia;
Uncommon: gastric and duodenal ulcers, perforation, or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis and Crohn’s disease;
Very rare: esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders:

Very rare: liver function abnormalities, liver injury, particularly during long-term therapy, liver failure, acute hepatitis.

Renal and urinary disorders:

Rare: acute renal function impairment, especially with prolonged use of NSAIDs, associated with increased serum urea levels, papillary necrosis;
Very rare: edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Nervous system disorders:

Uncommon: headache, dizziness, insomnia, restlessness, irritability, or fatigue;
Very rare: aseptic meningitis².

Psychiatric disorders:

Very rare: psychotic reactions, depression; with prolonged use: hallucinations, confusion.

Cardiovascular disorders:

Very rare: heart failure, tachycardia, edema, myocardial infarction,
arterial hypertension, vasculitis;
Frequency not known: Kounis syndrome.

Blood and lymphatic system disorders:

Very rare: blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include fever, sore throat, superficial oral ulcers, influenza-like symptoms, severe exhaustion, epistaxis, skin bleeding, and bruising.

Immune system disorders:

Uncommon: hypersensitivity reactions¹, urticaria, and pruritus;
Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, hypotension (anaphylactic reaction, angioedema, or severe shock). Asthma exacerbation.

Skin and subcutaneous tissue disorders:

Uncommon: various skin rashes¹;
Very rare: severe skin reactions (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis¹), alopecia;
Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis, photosensitivity reactions.

General disorders:

Frequency not known: malaise and fatigue.

Laboratory findings:

Rare: decreased hemoglobin levels.

Infections and infestations:

Very rare: exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis). In rare cases, varicella may lead to severe skin and soft tissue infections.

¹ Reports of hypersensitivity reactions following ibuprofen treatment include:
− non-specific allergic reactions and anaphylaxis;
− respiratory tract reactions, including bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea;
− various skin disorders, including rashes of different types, pruritus, urticaria, purpura, angioedema, and less frequently exfoliative and bullous dermatoses (including epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme).

² The pathogenetic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug intake and resolution of symptoms after discontinuation). In particular, during ibuprofen treatment of patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease), isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) have been observed.

Reporting suspected adverse reactions.

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

Shelf life. 3 years. After first opening of the bottle — 6 months.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 100 ml in a bottle or 200 ml in a bottle; 1 bottle with a dosing syringe in a carton.

Authorization category. Over-the-counter (without prescription).

Manufacturer

1. Delpharm Bladel B.V. / Delpharm Bladel B.V.
2. Edefarm, S.L. / Edefarm, S.L.
3. Farmalider S.A. / Farmalider S.A.

Manufacturer’s address and place of business

1. Industrieweg 1, Bladel, 5531 AD, Netherlands
2. Polígono Industrial Enchilagar del Rullo, 117, C.P. 46191 Villamarchante, Valencia, Spain
3. Calle De Los Aragoneses 2, Poligono Industrial Calabozos, Alcobendas, 28108, Spain

Marketing Authorization Holder. JSC "Pharmaceutical Company "Darnytsia".

Address of Marketing Authorization Holder. 13, Boryspilska St., Kyiv, 02093, Ukraine