Kiddiphen

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KIDDIFEN (KIDDIFEN)

Composition:

Active substance: ibuprofen;

5 ml of suspension contains ibuprofen 100 mg;

Excipients: sodium benzoate (E 211), anhydrous citric acid, sodium citrate, sodium saccharin, sodium chloride, hypromellose 15 cP, xanthan gum, maltitol liquid, glycerin, strawberry flavoring, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: viscous suspension, free from foreign 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 its efficacy by 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 interfere with the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when these drugs are used concomitantly. In a study, when a single dose of ibuprofen 400 mg 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 clinical outcomes do not allow definitive conclusions to be drawn regarding the systematic use of ibuprofen. Therefore, with occasional use of ibuprofen, such clinically significant effects are considered unlikely.

Pharmacokinetics.

Ibuprofen is rapidly absorbed after administration and rapidly 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 taken with food, peak levels are observed within 1–2 hours. This time may vary depending on different pharmaceutical forms.

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 origin in children aged from 3 months to 12 years with body weight of at least 5 kg (including post-vaccination fever, acute viral respiratory infections, influenza, teething pain, pain after tooth extraction, dental pain, 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/gastrointestinal bleeding or history of recurrences (two or more documented episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
• 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.
• Hematopoietic disorders or blood coagulation disorders of unknown etiology.
• 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 may increase the risk of adverse reactions, except when acetylsalicylic acid (dose not exceeding 75 mg per day) is prescribed by a physician. Experimental data indicate that 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 data to clinical settings do not allow definitive conclusions about systematic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen;

− other NSAIDs, including selective cyclooxygenase-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 effects of anticoagulants such as warfarin;

− antihypertensive agents (ACE inhibitors, beta-blockers, and 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 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, e.g., digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides. Concomitant use of ibuprofen with digoxin preparations may increase serum levels of these drugs. With appropriate use (maximum for 4 days), monitoring of digoxin levels in serum is usually not required;

− lithium: evidence suggests a potential increase in plasma lithium levels. With appropriate use (maximum for 4 days), monitoring of lithium levels in serum is usually not required;

− methotrexate: possible increase in plasma methotrexate levels. Administration of ibuprofen within 24 hours before or after methotrexate may result in elevated methotrexate concentrations and increased toxicity;

− 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: possible 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 indicates an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen;

− quinolone antibiotics: data from animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving 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 sulfonylurea derivatives have not been described to date, monitoring of blood glucose levels is recommended as a precautionary measure when these medicinal products are used concomitantly;

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

− probenecid and sulfinpyrazone: medicinal products containing probenecid or sulfinpyrazone may delay 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). A study using voriconazole and fluconazole demonstrated an approximately 80–100% increase in the effect of S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, dose reduction of ibuprofen 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 duration necessary.

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

Caution should be exercised in patients with the following conditions:

− systemic lupus erythematosus and mixed connective tissue disease − due to increased risk of aseptic meningitis;

− congenital porphyrin metabolism disorders, such as acute intermittent porphyria;

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

− history of hypertension and/or heart failure, as there have been reports of fluid retention and edema associated with NSAID therapy;

− renal impairment − due to the potential for worsening kidney function;

− hepatic dysfunction;

− use immediately following major surgical procedures;

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

− patients with a history of allergic reactions to other substances − due to increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects.

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

Other NSAIDs.

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, 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 increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects.

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

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

Renal effects.

Prolonged use of analgesics, particularly in combination with other pain-relieving agents, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy).

Caution is advised in patients with renal impairment due to the potential for worsening renal function.

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

Hepatic effects.

Hepatic function disorders.

Gastrointestinal effects.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., 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 the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment at the lowest dose. Combined therapy with protective agents (e.g., misoprostol or proton pump inhibitors) is recommended for such patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk.

Patients with a history of gastrointestinal toxicity, particularly elderly individuals, should be advised to report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

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

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

Severe skin reactions.

Severe skin reactions, 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, have been reported during ibuprofen use (see section "Adverse reactions"). Most such reactions occur within the first month of treatment.

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

In rare cases, chickenpox may lead to severe skin and soft tissue infections. At present, a negative influence of NSAIDs on the course of these infections cannot be excluded; therefore, the use of ibuprofen in cases of chickenpox is not recommended.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If early signs of hypersensitivity occur after taking ibuprofen, treatment should be discontinued immediately and medical advice should be sought.

Masking symptoms of underlying infections.

NSAIDs may mask symptoms of infection and fever.

Kiddifen may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. If ibuprofen is used to reduce fever or relieve pain associated with 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.

During prolonged use of ibuprofen, liver function, kidney function, and hematological parameters/blood count 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 suffering from frequent or daily headaches, despite (or because of) regular use of headache medications.

Concomitant use of alcohol and NSAIDs may intensify adverse reactions related to the active substance, particularly those affecting the gastrointestinal tract or the central nervous system (CNS).

If the patient is an adult, medical advice from a physician or pharmacist should be sought before taking this medication in the following cases: if the patient is pregnant, if the patient is trying to become pregnant, if the patient is elderly, or if the patient smokes.

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.

This medicinal product contains 56.85 mg of sodium per 15 mL of suspension (equivalent to 3.79 mg of sodium per 1 mL of suspension). This should be taken into account by patients on a low-sodium diet.

Use during pregnancy or breastfeeding.

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following the use of prostaglandin synthesis inhibitors during early pregnancy. The risk is believed 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, the use of Kiddifen may cause oligohydramnios due to fetal renal dysfunction. Impaired renal function may occur almost immediately after starting treatment and is usually reversible upon discontinuation of ibuprofen. Additionally, constriction of the ductus arteriosus has been reported after second-trimester treatment, which resolved after stopping therapy. Therefore, ibuprofen should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the expected 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 possible time should be used. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction may be advisable after several days of ibuprofen use starting from the 20th week of pregnancy. Ibuprofen should be discontinued if signs of oligohydramnios or ductus arteriosus constriction are detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose the following risks:

to the fetus: cardiopulmonary toxicity (characterized by premature constriction/closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure associated with oligohydramnios (see above);

to the mother and newborn, near term: prolonged bleeding time, antiplatelet effect (which may occur even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor. Increased risk of edema in the mother may also occur. 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 evidence of adverse effects on the infant; therefore, interruption of breastfeeding is usually not necessary during short-term treatment of pain and fever with recommended doses.

Fertility. There is some evidence that medicinal products which inhibit 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.

This 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

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Instructions"). Adverse effects can be minimized by using the lowest effective dose required to control symptoms for the shortest possible time.

For oral administration. The recommended daily dose of the drug is 20–30 mg per kg of body weight, divided into equal doses according to age and body weight, administered at intervals of 6–8 hours. To ensure accurate dosing, the package contains a dosing syringe. The recommended dose should not be exceeded. For short-term use only.

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

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

For children aged 3 to 6 months: if symptoms persist for more than 24 hours from the start of treatment or worsen (after 3 doses), consult a doctor immediately.

For children aged 6 months to 12 years: if symptoms persist for more than 3 days from the start of treatment or worsen, consult a physician.

For fever after vaccination (children aged 3–6 months), the recommended daily dose is

2.5 ml of suspension (50 mg), and if necessary, an additional 2.5 ml of suspension (50 mg) after 6 hours, but not more than 5 ml of suspension (100 mg) within 24 hours. If symptoms persist, consult a doctor.

Patients with sensitive stomach should take the medication during meals.

Shake well before use.

Special patient categories.

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

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

In case of overdose, seek immediate medical advice.

Children.

The medication should be used in children aged 3 months to 12 years weighing at least 5 kg.

Overdose.

In children, overdose symptoms may occur after ingestion of 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 clinically significant amounts of NSAIDs causes only nausea, vomiting, epigastric pain, or less frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, such as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally occur. Severe poisoning may lead to hyperkalemia and metabolic acidosis, as well as prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors). Acute renal failure, liver damage, hypotension, respiratory depression, and cyanosis may occur. In patients with bronchial asthma, asthma exacerbation 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 ensuring airway patency and monitoring cardiac function and vital signs until the patient's condition stabilizes. Consider administering activated charcoal orally or performing 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 acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. In case of bronchial asthma exacerbation, bronchodilators should be administered. Seek immediate medical assistance.

Adverse Reactions

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

The frequency rates exceeding very rare reports refer to short-term use of doses (maximum 1200 mg ibuprofen per day) for oral dosage forms.

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

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 (≥1/10,000 to <1/1000), very rare (<1/10,000), and not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

The most frequently observed adverse reactions were gastrointestinal. Most adverse reactions are dose-dependent; in particular, the risk of gastrointestinal bleeding depends on 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, and exacerbation of colitis and Crohn’s disease have been reported after ibuprofen use. Gastritis has been observed less frequently.

Edema, arterial hypertension, and heart failure associated with NSAID therapy have been reported.

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

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

If signs or symptoms of infection occur or worsen during ibuprofen use, the patient is advised to seek immediate medical attention. The need for antimicrobial/antibiotic therapy should be evaluated.

Regular blood tests are necessary during long-term therapy.

The patient 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 advice sought.

Infections and infestations

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

Blood and lymphatic system disorders

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

Immune system disorders

Hypersensitivity reactions^1; uncommon: urticaria and pruritus.

Very rare: severe hypersensitivity reactions, symptoms of which may include facial, lingual, and laryngeal edema, dyspnea, tachycardia, hypotension (anaphylactic reaction, angioneurotic edema, or severe shock). Asthma exacerbation.

Nervous system disorders

Uncommon: headache, dizziness, insomnia, restlessness, irritability, or fatigue. Very rare: aseptic meningitis^2.

Cardiac disorders

Very rare: heart failure, tachycardia, edema, myocardial infarction.

Not known: Kounis syndrome.

Vascular disorders

Very rare: arterial hypertension, vasculitis.

Gastrointestinal disorders

Common: abdominal pain, nausea, dyspepsia, diarrhea, meteorism, constipation, heartburn, vomiting, and minor gastrointestinal blood loss, which in exceptional cases may lead to anemia.

Uncommon: gastric and duodenal ulcer, 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.

Hepatic and biliary disorders

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

Skin and subcutaneous tissue disorders

Uncommon: various skin rashes^1.

Very rare: severe skin reactions such as bullous reactions, including Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, and toxic epidermal necrolysis^1, alopecia.

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

Respiratory, thoracic and mediastinal disorders

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea^1.

Renal and urinary disorders

Rare: acute renal function impairment, particularly with prolonged NSAID use, associated with increased serum urea levels. Also includes papillary necrosis.

Very rare: development of edema, especially in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Psychiatric disorders

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

Eye disorders

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

Ear and labyrinth disorders

Frequency not known: dizziness may occur with prolonged treatment.

Rare: tinnitus.

General disorders

Frequency not known: malaise and fatigue.

Investigations

Rare: decreased hemoglobin levels.

Description of selected adverse reactions

^1 Hypersensitivity reactions have been reported following ibuprofen treatment. These include (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactions including bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea, or (c) various skin disorders including rashes of different types, pruritus, urticaria, purpura, angioneurotic edema, and less frequently exfoliative and bullous dermatoses (including epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme).

^2 The pathogenic 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 relationship to drug intake and symptom resolution after drug discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) have been observed during ibuprofen treatment in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Reporting suspected adverse reactions

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

Shelf life

3 years. After opening the bottle, use within 6 months.

Do not use after the expiry date stated on the packaging.

Storage conditions

Store at temperatures not exceeding 25°C. Keep out of reach of children.

Packaging

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

Prescription status

Over-the-counter (without prescription).

Manufacturer

1. Edefarm, S.L./Edefarm, S.L.
2. Farmalider, S.A./Farmalider, S.A.

Manufacturer's address and place of business

1. Poligono Enchilagar Del Rullo 117, Poligono Industrial Enchilagar Del Rullo, Vilamarxant, 46191, Spain.
2. Calle De Los Aragoneses, 2, Poligono Industrial Calabozos, Alcobendas, 28108, Spain.

Marketing Authorization Holder

Ukrainian-Spanish joint venture "Sperco Ukraine".

Address of Marketing Authorization Holder

21027, Vinnitsia, 600-richchia St., 25, Ukraine.

Tel.: +38(0432)52-30-36. E-mail: [email protected]

www.sperco.ua