Ibuprom for children: detailed information

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

Composition:

Active ingredient: ibuprofen;

5 ml of suspension contains 100 mg of ibuprofen;

Excipients: liquid maltitol, glycerol, sodium citrate, citric acid, sodium chloride, hypromellose 15 cP, xanthan gum, sodium benzoate (E 211), strawberry flavor 501094 APO551 (contains maltodextrin), sodium saccharin, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: a thick, free-flowing suspension, free from foreign particles, white or almost white, with a characteristic strawberry taste.

Pharmacotherapeutic group. Nonsteroidal 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 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 both agents 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 clinical outcomes preclude definitive conclusions about the systematic use of ibuprofen. Therefore, with occasional use of ibuprofen, such clinically significant interactions 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 occur within 1–2 hours. This time may vary depending on the pharmaceutical formulation. 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, pain following tooth extraction, 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 episodes of confirmed 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.
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 (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 concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical settings do not allow definitive conclusions regarding the 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 effect of anticoagulants such as warfarin.

Antihypertensive agents (ACE inhibitors, beta-blockers, and 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 with caution, 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 may increase serum levels of digoxin. When used appropriately (maximum for up to 4 days), monitoring of serum digoxin levels is usually not required.

Lithium: Evidence suggests a potential increase in plasma lithium levels. When used appropriately (maximum for up to 4 days), monitoring of serum lithium levels is usually 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 administered 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: Data from animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.

Sulfonylurea agents: 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 described, 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 medicinal products. When used appropriately (maximum for up to 4 days), monitoring of serum phenytoin levels is usually 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 effects 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 possible duration.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal. In elderly patients, there is an increased risk of complications from 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 and mixed connective tissue disease – due to an 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 have been 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 an 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 an increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects.

Bronchospasm may occur in patients with bronchial asthma or allergic diseases, or those with a history of these 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 an 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 treatment with ibuprofen and other NSAIDs.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, especially at high doses (2400 mg per day) 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 doses of ibuprofen (e.g., ≤1200 mg per day) are associated with an increased risk of myocardial infarction.

Cases of Kounis syndrome have been reported in patients treated with Ibuprom for children. 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.

Generally, regular use of analgesics, especially combinations of different 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.

Effects on the liver.

Hepatic dysfunction.

Effects on the gastrointestinal tract.

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.

Cases of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, have been reported during NSAID therapy at any stage, 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 disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest dose. For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, concomitant protective therapy (e.g., misoprostol or proton pump inhibitors) is recommended.

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

Caution is advised 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 fertility in women.

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

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), and erythema multiforme, 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 is not recommended in cases of varicella.

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

Masking symptoms of underlying infections: Ibuprom for children may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby complicating the course of the illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If Ibuprom for children 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.

During prolonged use of ibuprofen, liver function, 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 enhance adverse effects related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

Medical advice should be sought before taking this medicine in the following cases: if the patient is pregnant or trying to become pregnant, if the patient is elderly, or if the patient is a smoker.

Use during pregnancy or breastfeeding.

The medicine is intended for 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 the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed 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, the use of Ibuprom for children may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after stopping treatment. Therefore, Ibuprom for children should not be used during the first and second trimesters unless clearly necessary. If Ibuprom for children is used by a woman 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 oligohydramnios and ductus arteriosus constriction should be considered after exposure to Ibuprom for children for several days starting from the 20th gestational week. Treatment with Ibuprom for children 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:

Cardiopulmonary toxicity (premature constriction/closure 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, Ibuprom for children is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Ibuprofen and its metabolites pass into 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 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 medicine is intended for 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.

Warnings regarding the composition of the medicinal product.

This medicinal product contains liquid maltitol and maltodextrin (as a source of glucose). If you have been diagnosed with an intolerance to certain sugars, consult your doctor before using this medicine.

This medicinal product contains 0.78 mmol of sodium per 5 mL of suspension (or 17.96 mg of sodium per 5 mL of suspension). This should be taken into account by patients on a sodium-controlled diet.

Dosage and Administration

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use"). 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 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.

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 directed 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 more than 24 hours after starting 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 after starting 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, another 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.

For patients with sensitive stomach, the medication should be taken during meals.

Shake well before use.

Special patient groups.

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 is administered to children aged 3 months to 12 years with body weight of at least 5 kg.

Overdose.

In pediatric patients, overdose symptoms 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 who have ingested clinically significant amounts of NSAIDs, symptoms may include only nausea, vomiting, epigastric pain, or very rarely diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may manifest as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally develop in patients. Severe poisoning may lead to hyperkalemia and metabolic acidosis, as well as prolongation of prothrombin time/INR due to effects on blood coagulation factors. Acute renal failure and liver damage, hypotension, respiratory depression, and cyanosis may occur. In patients with bronchial asthma, disease exacerbation may be observed. Nystagmus, visual disturbances, and loss of consciousness are also possible.

Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia.

Treatment.

There is no specific antidote. Treatment may be symptomatic and supportive, including airway management, monitoring of cardiac parameters and vital signs until stable condition is achieved. Oral administration of activated charcoal or gastric lavage is recommended if less than 1 hour has passed since ingestion of a potentially toxic amount. If ibuprofen has already been absorbed, alkalizing agents may be used to enhance urinary excretion of acidic ibuprofen. For frequent or prolonged seizures, treatment should be carried out by intravenous administration of diazepam or lorazepam. In case of bronchial asthma, bronchodilators should be used. 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 rheumatic diseases.

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 adverse reactions listed are predominantly dose-dependent and may vary individually for each patient.

Adverse reactions reported with 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 based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

The most commonly observed adverse reactions are gastrointestinal. Adverse reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on both dose and duration of treatment. Gastric and intestinal ulcers, perforation, or gastrointestinal bleeding, 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 have been reported in association with NSAID therapy.

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 events (e.g., myocardial infarction or stroke).

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

If signs or symptoms of infection develop or worsen during ibuprofen use, 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 seek immediate medical attention and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose. Immediate medical intervention is required in such cases.

In case of severe epigastric pain, melena, or hematemesis, the drug should be discontinued and immediate medical advice sought.

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 dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms may include sore throat, oral ulceration, influenza-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 edema, 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 blood loss, which in rare cases may lead to anemia.

Uncommon: gastric and duodenal ulceration, 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: serious skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis)¹, alopecia.

Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP); 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 impairment, particularly with prolonged NSAID use, associated with increased serum urea levels. Also includes papillary necrosis.

Very rare: fluid retention, particularly in patients with arterial hypertension or renal impairment, nephrotic syndrome, interstitial nephritis, which may lead to 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 prolonged treatment.

Ear and labyrinth disorders

Frequency not known: dizziness may occur with prolonged treatment.

Rare: tinnitus.

General disorders and administration site conditions

Frequency not known: malaise and fatigue.

Description of selected adverse reactions

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

Shelf life. 3 years.

After first opening – 6 months.

Storage conditions.

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

Packaging.

100 ml, 150 ml or 200 ml in a bottle. One bottle with a 5 ml dosing syringe in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

Farmasierra Manufacturing, S.L. /
Farmasierra Manufacturing, S.L.

Delpharm Bladel B.V. /
Delpharm Bladel B.V.

Farmalider, S.A. /
Farmalider, S.A.

US Pharmacia Sp. z o.o. /
US Pharmacia Sp. z o.o.

Manufacturer's address and place of business.

Ctra. Irun, Km. 26,200, San Sebastian de los Reyes, 28709 Madrid, Spain /
Ctra. Irun, Km. 26,200, San Sebastian de los Reyes, 28709 Madrid, Spain.

Industrieweg 1, Bladel, 5531AD, Netherlands /
Industrieweg 1, Bladel, 5531AD, Netherlands.

C/Aragoneses, 2, Alcobendas, Madrid, 28108, Spain /
C/Aragoneses, 2, Alcobendas, Madrid, 28108, Spain.

ul. Ziebicka 40, 50-507 Wroclaw, Poland /
ul. Ziebicka 40, 50-507 Wroclaw, Poland.

Marketing Authorization Holder.

Unilab, LP, USA /
Unilab, LP, USA.

Address of Marketing Authorization Holder.

966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA /
966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA.