Nurofen® for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUROFEN® FOR CHILDREN (NUROFEN® FOR CHILDREN)

Composition:

Active ingredient: ibuprofen;

5 ml of suspension contain ibuprofen 100 mg;

Excipients: maltitol liquid; citric acid monohydrate; sodium citrate; sodium chloride; sodium saccharin; domiphen bromide; polysorbate 80; xanthan gum; strawberry flavoring 5002442; glycerin; purified water.

Pharmaceutical form. Oral strawberry-flavored suspension.

Main physicochemical properties: white or almost white suspension with a strawberry odor.

Pharmacotherapeutic group.

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

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated efficacy by inhibiting prostaglandin synthesis. 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 impair the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when these drugs are used concomitantly. In a study, when a single 400 mg dose of ibuprofen was administered 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 extrapolation of ex vivo data to clinical outcomes preclude definitive conclusions about 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 quickly distributed throughout the body. Elimination is rapid and complete, occurring via the kidneys.

Maximum plasma concentrations are 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 for 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 origins in children aged from 3 months to 12 years weighing at least 5 kg (including fever after vaccination, acute respiratory viral infections, influenza, teething pain, post-dental extraction 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 the intake of acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer/gastrointestinal bleeding or history of recurrence (two or more documented episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation related to 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 of unknown etiology or blood coagulation disorders.
• 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 (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 when administered concomitantly. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions about the systematic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional ibuprofen use;
• 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, angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of these agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal 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 ulcers 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 these drugs. When used appropriately (maximum duration of 4 days), monitoring of digoxin serum levels is generally not required.

Lithium: Evidence suggests a potential increase in plasma lithium levels. When used appropriately (maximum duration of 4 days), monitoring of lithium serum levels is generally not required.

Methotrexate: There is a possibility of increased plasma methotrexate levels. Administration of ibuprofen within 24 hours before or after methotrexate may lead to elevated methotrexate concentrations and increased toxicity.

Cyclosporine: Increased risk of nephrotoxicity.

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

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

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: Animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotic use. Patients receiving both NSAIDs and quinolones may have an increased risk of developing seizures.

Sulfonylurea derivatives: Potentiation of effect is possible. Clinical studies have demonstrated interactions between NSAIDs and antidiabetic agents (sulfonylurea derivatives). Although interactions between ibuprofen and sulfonylureas have not been reported 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 levels of these drugs. When used appropriately (maximum duration of 4 days), monitoring of phenytoin serum 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).

CYP2C9 inhibitors: Concomitant use of ibuprofen with CYP2C9 inhibitors may enhance the effect of ibuprofen (a CYP2C9 substrate). A study using voriconazole and fluconazole (CYP2C9 inhibitors) demonstrated an approximately 80–100% increase in the effect of S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, a reduction in ibuprofen dosage is recommended, especially when high doses of ibuprofen are used 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. Elderly patients are at increased risk of experiencing serious consequences of adverse reactions. Long-term use of NSAIDs is not recommended in elderly individuals. If long-term 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;
• Inherited disorders of porphyrin metabolism, such as acute intermittent porphyria;
• Gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease);
• History of hypertension and/or heart failure, as there are reports of fluid retention and edema associated with NSAID therapy;
• Renal impairment – due to the possibility of worsening kidney function;
• Hepatic dysfunction;
• 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 (angioedema), 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 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 increased risk of aseptic meningitis.

Effects on the cardiovascular and cerebrovascular systems.

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 ibuprofen therapy, as with 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 be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not show that low-dose ibuprofen (e.g., ≤1200 mg daily) is associated with an increased 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.

Effects on the kidneys.

Prolonged regular use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy).

Caution should be exercised in patients with renal impairment due to the possibility of worsening kidney function.

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

Effects on the liver.

Hepatic function disorders.

Effects on the gastrointestinal tract.

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 prior warning symptoms or history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, 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 informed 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 ulcers 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 female fertility.

Limited data suggest that cyclooxygenase/prostaglandin synthesis inhibitors may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Serious skin adverse reactions.

Serious 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 syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

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

In rare cases, varicella (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 ruled out; therefore, the use of ibuprofen in cases of varicella is not recommended.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If signs of hypersensitivity occur after taking ibuprofen, treatment should be stopped immediately and medical advice sought without delay.

Masking symptoms of underlying infections.

This medicinal product may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby worsening the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When the drug is used for fever or pain relief during infection, monitoring of the infectious condition 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 ibuprofen use, 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 use of alcohol and NSAIDs may intensify undesirable effects related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

This medicinal product contains liquid maltitol. It should not be administered to patients with rare hereditary fructose intolerance. Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect.

This medicinal product contains 27.75 mg of sodium per 15 mL of suspension (equivalent to 1.85 mg of sodium per 1 mL of suspension). This should be taken into account for patients on a low-sodium diet.

If you are an adult, consult your doctor or pharmacist before taking this medicinal product in the following cases: if you are pregnant, trying to become pregnant, elderly, or a smoker.

Use during pregnancy or breastfeeding.

The product is indicated for children under 12 years of age.

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

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there are reports of ductus arteriosus constriction after second-trimester treatment, most of which resolved after stopping therapy. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by women trying to conceive 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. Fetal monitoring for oligohydramn游戏副本 and ductus arteriosus constriction should be considered after several days of ibuprofen exposure, starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

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

Risks to the fetus:

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

Risks to the mother at the end of pregnancy and to the newborn:

• Possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Ibuprofen and its metabolites are excreted in breast milk in low concentrations. No adverse effects on the infant are currently known; therefore, interruption of breastfeeding is usually not required during short-term treatment of pain and fever at 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 rate when driving or operating machinery.

The product is indicated for children under 12 years of age. When used according to recommended doses and treatment duration, the product is not expected to affect the ability to drive or operate machinery.

Dosage and method of administration

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

For oral administration. The recommended daily dose of the medicinal product is 20 – 30 mg per kg of body weight, divided into equal doses depending on age and body weight, with intervals between doses 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.

Age	Body weight (kg)	Recommended dose
3-6 months	5-7.6	2.5 ml of suspension (50 mg) up to 3 times a day.
6-12 months	7.7-9	2.5 ml of suspension (50 mg) up to 3-4 times a day.
1-3 years	10-16	5 ml of suspension (100 mg) up to 3 times a day.
4-6 years	17-20	7.5 ml of suspension (150 mg) up to 3 times a day.
7-9 years	21-30	10 ml of suspension (200 mg) up to 3 times a day.
10-12 years	31-40	15 ml of suspension (300 mg) up to 3 times a day.

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

Do not use this medicinal product in children with body weight less than 5 kg.

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

Patients with sensitive stomach should take the medication during meals.

Shake well before use.

Special patient categories.

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

Hepatic impairment: dose adjustment 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 is indicated for children aged 3 months to 12 years with body weight not less than 5 kg.

Overdose.

In pediatric patients, symptoms of overdose may occur following ibuprofen doses exceeding 400 mg/kg. Adults are generally less sensitive to overdose effects. 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 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. Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, prolonged prothrombin time/INR may occur (likely due to interaction with circulating blood coagulation factors). Acute renal failure, liver damage, hypotension, respiratory depression, and cyanosis may develop. 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 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 acidic ibuprofen. In cases of frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. In case of bronchial asthma exacerbation, bronchodilators should be prescribed. Seek immediate medical assistance.

Side effects.

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

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

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

The adverse reactions observed during ibuprofen use are listed below by system organ class 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 from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

The most commonly observed adverse reactions were gastrointestinal in nature. Adverse reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, especially in elderly patients. 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 have been reported in association with NSAID treatment.

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).

There are case reports of worsening infections, including the development of necrotizing fasciitis, temporally associated with NSAID use. This may be related to the mechanism of action of NSAIDs.

If signs of infection occur or worsen during ibuprofen use, patients should be 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 seek immediate medical advice and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even upon first use of the drug. Immediate medical intervention is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the drug should be discontinued immediately and medical advice sought urgently.

Infections and infestations.

Very rare: worsening of infection-related inflammation (e.g., development of necrotizing fasciitis). In exceptional cases, varicella 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 malaise, sore throat, oral ulceration, flu-like symptoms, severe fatigue, epistaxis, skin bleeding, and bruising.

Immune system disorders.

Hypersensitivity reactions¹; uncommon: 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.

Nervous system disorders.

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

Cardiac disorders.

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

Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: arterial hypertension, vasculitis.

Gastrointestinal disorders.

Common: abdominal pain, nausea, dyspepsia, diarrhea, flatulence, 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, hepatic injury, particularly during long-term therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders.

Uncommon: various skin rashes¹.

Very rare: severe skin reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis¹, alopecia.

Frequency not known: drug-induced eosinophilia with 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 dyspnea¹.

Renal and urinary disorders.

Rare: acute renal dysfunction, particularly with prolonged use of NSAIDs, associated with increased serum urea levels. Also includes papillary necrosis.

Very rare: fluid retention, particularly in patients with hypertension or renal impairment, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Investigations.

Rare: decreased hemoglobin levels.

Psychiatric disorders.

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

Eye disorders.

Frequency not known: visual disturbances, optic neuritis may occur with long-term treatment.

Ear and labyrinth disorders.

Frequency not known: dizziness may occur with long-term treatment.

Rare: tinnitus.

General disorders and administration site conditions.

Frequency not known: malaise and fatigue.

Description of selected adverse reactions

¹ Reports exist of hypersensitivity reactions 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, angioedema, 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 resolution of symptoms after drug discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during ibuprofen treatment.

Shelf life.

3 years.

Storage conditions.

Store in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging.

100 ml or 200 ml of suspension in a bottle. The bottle is packaged in a cardboard box with a dosing syringe.

Availability.

Over-the-counter.

Manufacturer.

Reckitt Benckiser Healthcare (UK) Limited.

Manufacturer’s address and place of business.

Dansom Lane, Hull, HU8 7DS, United Kingdom.