Ibuprom for children forte: detailed information

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

Composition:

Active substance: ibuprofen;

5 ml of suspension contains 200 mg of ibuprofen;

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

Pharmaceutical form. Oral suspension.

Main physicochemical properties: a thick, homogeneous suspension, free from foreign inclusions, white or almost white, with a characteristic strawberry taste.

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

ATC code M01AE01.

Pharmacological Properties.

Pharmacodynamics.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated its efficacy by inhibiting the synthesis of prostaglandins—mediators of pain and inflammation. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. In addition, ibuprofen reversibly inhibits platelet aggregation.

The clinical efficacy of ibuprofen has been demonstrated in the symptomatic treatment of mild to moderate pain, such as dental pain, headache, and in the symptomatic management of fever.

The analgesic dose for children is 7 to 10 mg/kg body weight, with a maximum dose of 30 mg/kg/day. The medicinal product Ibuprom for Children Forte contains ibuprofen, which in an open study demonstrated the onset of antipyretic effect within 15 minutes after administration and reduction of body temperature in children over a period of up to 8 hours.

Experimental data indicate that ibuprofen may interfere with the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation when both agents are administered concomitantly. In one study, a single 400 mg dose of ibuprofen administered within 8 hours before or 30 minutes after immediate-release acetylsalicylic acid (81 mg) resulted in reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty exists regarding extrapolation of these data to the clinical setting, it cannot be excluded that chronic, long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interaction is considered unlikely with occasional, non-chronic use of ibuprofen.

Pharmacokinetics.

No specific pharmacokinetic studies in children have been conducted. Published data confirm that absorption, metabolism, and elimination of ibuprofen in children occur in the same manner as in adults.

After oral administration, ibuprofen is partially absorbed in the stomach and then completely absorbed in the small intestine. Following hepatic metabolism (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are excreted predominantly via the kidneys (90%) and also through bile. The elimination half-life in healthy adult volunteers, as well as in patients with renal or hepatic impairment, ranges from 1.8 to 3.5 hours. Plasma protein binding is approximately 99%.

Renal Insufficiency.

Since ibuprofen and its metabolites are primarily excreted by the kidneys, the pharmacokinetics of the drug may be altered in patients with various degrees of renal impairment. In patients with impaired renal function, lower plasma protein binding, increased plasma levels of total ibuprofen and unbound (S)-ibuprofen, higher values of the area under the plasma concentration-time curve (AUC) for (S)-ibuprofen, and elevated enantiomeric AUC (S/R) ratio have been observed compared to healthy control volunteers. In patients with end-stage renal disease undergoing dialysis, the mean fractional excretion of ibuprofen was approximately 3%, compared to 1% in healthy volunteers. Severe renal impairment may lead to accumulation of ibuprofen metabolites. The clinical significance of this effect is unknown. Metabolites may be removed by hemodialysis.

Hepatic Impairment.

Alcoholic liver disease with mild to moderate hepatic dysfunction did not result in significant changes in pharmacokinetic parameters. Liver disease may alter the distribution kinetics of ibuprofen. In patients with cirrhosis and moderate hepatic impairment (Child–Pugh class 6–10) a mean two-fold increase in elimination half-life and significantly lower enantiomeric AUC (S/R) ratio were observed compared to healthy control volunteers, indicating impaired metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer.

Clinical characteristics.

Indications.

Symptomatic treatment of fever and pain of various origin in children aged 6 months to 12 years with body weight of at least 7 kg (including fever after vaccination, acute respiratory viral infections, influenza, teething pain, pain after tooth extraction, toothache, headache, sore throat, pain due to ligament sprains, 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 (such as bronchospasm, rhinitis, angioedema or urticaria) following administration of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
Active inflammatory bowel disease.
Severe heart failure (NYHA class IV), severe hepatic impairment, or severe renal impairment.
Cerebrovascular or other hemorrhages.
Hemorrhagic diathesis or other coagulation disorders.
- Hereditary fructose intolerance.
- Third trimester of pregnancy.
- Disorders of hematopoiesis or blood coagulation.
- Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).

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 (dose not exceeding 75 mg per day) is 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 the clinical setting do not allow a definitive conclusion regarding systematic use of ibuprofen. Therefore, occasional use of ibuprofen is considered unlikely to result in clinically significant effects;
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 reactions.

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

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

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of these drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors, beta-blockers, angiotensin II antagonists, and cyclooxygenase inhibitors may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. 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.

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. NSAIDs may increase plasma digoxin levels and thus increase the risk of digoxin toxicity; with appropriate use (maximum for 3 days), monitoring of serum digoxin levels is usually not required;
Pentoxifylline: patients receiving ibuprofen in combination with pentoxifylline may have an increased risk of hemorrhage; therefore, bleeding time should be monitored;
Lithium: evidence suggests a potential increase in plasma lithium levels, possibly due to reduced renal clearance. Concomitant use of these medicinal products should be avoided unless lithium levels are monitored. Consideration should be given to reducing the lithium dose. With appropriate use (maximum for 3 days), monitoring of serum lithium levels is usually not required;
Methotrexate at doses of 15 mg/week or higher: administration of NSAIDs within 24 hours before or after methotrexate may increase methotrexate plasma concentrations (likely due to reduced renal clearance of methotrexate caused by NSAIDs) and further increase its toxic effects. Therefore, ibuprofen should be avoided in patients receiving high-dose methotrexate;
Methotrexate at doses below 15 mg/week: ibuprofen increases methotrexate levels. When ibuprofen is used in combination with low-dose methotrexate, careful monitoring of the patient's blood count is required, especially during the first weeks of concomitant therapy. Monitoring should be intensified in case of worsening renal function, even minimally, and in elderly patients, and renal function should be monitored to prevent possible reduction in methotrexate clearance;
Cyclosporine and tacrolimus: increased risk of nephrotoxicity may occur when used concomitantly with NSAIDs due to reduced renal prostaglandin synthesis. Renal function should be closely monitored when these medicinal products are used together with NSAIDs;
Mifepristone: NSAIDs should not be used earlier than 8–12 days after administration of mifepristone, as they may reduce its efficacy;
Sulfonylurea derivatives: interactions between NSAIDs and hypoglycemic agents (sulfonylureas) have been observed. NSAIDs may enhance the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding sites; monitoring of blood glucose levels is recommended when sulfonylureas are used concomitantly with ibuprofen;
Probenecid and sulfinpyrazone: possible increase in plasma ibuprofen concentration and delayed elimination of ibuprofen from the body, possibly due to an inhibitory mechanism at the site of renal tubular secretion and glucuronidation; therefore, dose adjustment of ibuprofen may be necessary;
Baclofen: baclofen toxicity may develop after initiation of ibuprofen;
Ritonavir: may increase plasma concentrations of NSAIDs;
Aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides;
Captopril: experimental studies have shown that ibuprofen inhibits the natriuretic effect of captopril;
Voriconazole and fluconazole (CYP2C9 inhibitors): concomitant use of ibuprofen with CYP2C9 inhibitors may enhance the effect of ibuprofen (a CYP2C9 substrate). Studies using voriconazole and fluconazole (CYP2C9 inhibitors) have demonstrated an approximately 80–100% increase in the effect of S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, reduction of ibuprofen dosage is recommended, especially when high doses of ibuprofen are used together with voriconazole or fluconazole;
Cholestyramine: ibuprofen and cholestyramine should be taken several hours apart due to delayed and reduced (by 25%) absorption of ibuprofen when administered concomitantly;
Zidovudine: increased risk of hematological toxicity when zidovudine and NSAIDs are used concomitantly. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen;
Herbal extracts: Ginkgo biloba, when used concomitantly with NSAIDs, may potentiate the risk of bleeding;
Quinolone antibiotics: 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;
Hydantoins and sulfonamides: possible increase in the toxic effects of these medicinal products. Plasma phenytoin levels may increase with concomitant use of ibuprofen; with appropriate use (maximum for 3 days), monitoring of serum phenytoin levels is usually not required;
Thiazides, thiazide-like agents, loop diuretics, and potassium-sparing diuretics: NSAIDs may counteract the diuretic effect of these medicinal products. Concomitant use of NSAIDs and diuretics may increase the risk of NSAID-induced nephrotoxicity (e.g., in dehydrated patients or elderly patients with impaired renal function) due to deterioration of renal blood flow. 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. As with other NSAIDs, concomitant therapy with potassium-sparing diuretics may be associated with elevated potassium levels; therefore, plasma potassium levels should be monitored.

Administration of ibuprofen with food delays absorption, although this does not affect the extent of absorption (see section "Pharmacokinetics").

Special precautions for use.

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

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

Prolonged use of NSAIDs is not recommended in elderly patients. In cases of long-term therapy, regular monitoring of the patient's condition is required.

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 disorders of porphyrin metabolism, e.g., acute intermittent porphyria;
gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease);
history of arterial 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 after 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;
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.

Like other NSAIDs, ibuprofen may cause allergic reactions such as anaphylactic/anaphylactoid reactions, even when the drug is used for the first time.

Systemic lupus erythematosus and mixed connective tissue disease

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

Cardiovascular and cerebrovascular effects

Patients with a history of arterial hypertension and/or heart failure should begin long-term treatment with caution (medical consultation required), as fluid retention, development of arterial hypertension, and edema have been reported during therapy with ibuprofen and other NSAIDs.

Clinical studies and epidemiological data indicate that the use of ibuprofen, particularly at high doses (2400 mg per day) and during prolonged treatment, may be associated with a small increase in the risk of arterial thrombotic complications (such as 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.

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

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

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

Effects on kidneys and liver

Caution should be exercised in patients with renal impairment due to the possibility of worsening kidney function. Ibuprofen should be used with caution in patients with kidney or liver disease, particularly when concomitantly treated with diuretics, as prostaglandin inhibition may lead to fluid retention and further deterioration of kidney function. Such patients should receive the lowest possible dose of ibuprofen and require regular monitoring of kidney function. In cases of dehydration, adequate fluid intake should be ensured. There is a risk of renal failure in dehydrated children and adolescents.

Generally, chronic use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy). The highest risk of this reaction occurs in elderly patients, patients with renal, cardiac, or hepatic impairment, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, kidney function usually returns to the pre-treatment state.

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

Gastrointestinal effects

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

Cases of gastrointestinal bleeding, perforation, and ulcers, potentially fatal, have been reported during NSAID therapy at any stage, regardless of prior warning symptoms or history of severe gastrointestinal disorders.

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

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

Caution is advised when treating patients who are simultaneously using medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., aspirin).

In case of gastrointestinal bleeding or ulceration in patients taking 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.

Serious skin adverse reactions (SSARs)

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 indicating these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

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

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) occur. At the first signs of hypersensitivity after taking ibuprofen, therapy should be discontinued and immediate medical attention sought.

Masking symptoms of underlying infections: Ibuprom for Children Forte may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby worsening the course of the 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 use of ibuprofen, liver function tests, kidney function, and hematological parameters/blood count should be monitored regularly.

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

Concomitant use of alcohol and NSAIDs may enhance adverse reactions 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.

Effect on laboratory test results:

bleeding time may be prolonged up to one day after discontinuation of treatment;
blood glucose concentration may decrease;
creatinine clearance may decrease;
hematocrit or hemoglobin may decrease;
blood urea nitrogen, serum creatinine, and potassium concentrations may increase;
liver function tests: increased transaminase levels.

Warnings regarding composition of the medicinal product.

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

This medicinal product contains 1.26 mmol of sodium per 5 mL of suspension (or 28.99 mg of sodium per 5 mL of suspension). This should be taken into account by patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

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

Ibuprofen is contraindicated during the third trimester of pregnancy. Use of ibuprofen should be avoided during the first 6 months of pregnancy.

Pregnancy.

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed to increase with higher doses and longer duration of therapy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%.

From the 20th week of pregnancy, use of Ibuprom for Children Forte may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus constriction after treatment in the second trimester, most of which resolved after treatment cessation. Therefore, Ibuprom for Children Forte should not be prescribed during the first and second trimesters unless clearly necessary. If Ibuprom for Children Forte is used by a woman attempting 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 several days of exposure to Ibuprom for Children Forte, starting from the 20th gestational week. Treatment with Ibuprom for Children Forte 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 Forte is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding.

Ibuprofen and its metabolites are excreted in breast milk in low concentrations. There is currently no evidence of adverse effects on the infant; therefore, breastfeeding usually does not need to be discontinued during short-term treatment of pain and fever at recommended doses.

Fertility.

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

The use of ibuprofen is not recommended in women attempting to conceive. For women experiencing difficulties with conception or undergoing infertility investigations, discontinuation of this medicinal product should be considered.

Ability to affect reaction speed when driving or operating machinery. The product is intended for use in children under 12 years of age. Patients experiencing dizziness, vertigo, visual disturbances, or other central nervous system disorders during ibuprofen use should avoid driving or operating machinery during treatment with this medicinal product. It is known that when ibuprofen is used according to recommended doses and treatment duration, no effect on psychomotor reaction speed is expected.

Dosage and Administration

For oral use.

The recommended daily dose of the medicinal product is 20–30 mg per 1 kg of body weight, divided into equal doses administered at 6–8 hour intervals.

The recommended dose should not be exceeded.

For short-term use only.

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

Shake before use.

For accurate dosing, use the oral dosing syringe provided in the package.

Age Body weight (kg)	Dosage Single dose	Frequency of administration (maximum daily dose)
Children 6–11 months (7–9 kg)	1.25 ml (50 mg)	3–4 times daily
Children 1–3 years (10–15 kg)	2.5 ml (100 mg)	3 times daily
Children 4–5 years (16–19 kg)	3.75 ml (150 mg)	3 times daily
Children 6–9 years (20–29 kg)	5 ml (200 mg)	3 times daily
Children 10–12 years (30–40 kg)	7.5 ml (300 mg)	3 times daily

If symptoms persist for more than 3 days from the start of treatment or worsen in children, medical advice should be sought.

The product should be taken with food in patients with sensitive stomach.

Special patient categories:

NSAIDs should be used with caution in patients with impaired kidney function, as ibuprofen is primarily excreted by the kidneys. Lower doses should be used in patients with mild to moderate renal insufficiency.

Ibuprofen should not be used in patients with severe renal insufficiency (see section "Contraindications").

Although no differences in the pharmacokinetic profile of ibuprofen have been observed in patients with hepatic insufficiency, NSAIDs should be used with caution in such patients. Treatment should be initiated with low doses and careful monitoring in patients with mild to moderate hepatic insufficiency. Ibuprofen should not be used in patients with severe hepatic insufficiency (see section "Contraindications").

Patients should consult a physician if symptoms persist or worsen during treatment.

Children.

The product is indicated for use in children aged 6 months to 12 years with body weight of at least 7 kg.

Overdose.

In pediatric patients, overdose symptoms may occur at doses of ibuprofen exceeding 400 mg/kg. In adults, reactions to overdose are less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms.

In most patients who have ingested clinically significant doses 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, as well as disorientation or coma. Seizures may occasionally develop in patients. In severe poisoning, hyperkalemia, metabolic acidosis, hypothermia, and prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors) may occur. Acute renal failure and liver damage, hypotension, respiratory depression, and cyanosis are possible. In patients with bronchial asthma, exacerbation of asthma may occur. Nystagmus, visual disturbances, and loss of consciousness are also possible.

Prolonged use at doses higher than recommended or overdose may lead to renal tubular acidosis and hypokalemia.

Treatment.

There is no specific antidote. Treatment should be symptomatic and supportive, including airway management, monitoring of cardiac function and vital signs until a stable condition is achieved. Oral administration of activated charcoal is recommended if less than 1 hour has passed since ingestion of a potentially toxic amount of the drug. If ibuprofen has already been absorbed, alkalizing agents may be used to promote urinary excretion of acidic ibuprofen. In cases of frequent or prolonged muscle spasms, treatment should be carried out by intravenous administration of diazepam or lorazepam. Bronchodilators should be used in case of bronchial asthma. Medical help should be sought immediately.

Adverse Reactions

The list of adverse reactions mentioned below includes all adverse reactions reported during treatment with ibuprofen, including those observed with high doses and long-term therapy in patients with rheumatic diseases. The specified frequencies beyond very rare reports refer to short-term use (maximum 1200 mg ibuprofen per day) of oral dosage forms.

Adverse reactions associated with ibuprofen use are listed below by organ system 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 category, adverse reactions are listed in decreasing order of severity.

The most commonly observed adverse reactions were gastrointestinal in nature. Adverse reactions are generally 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, particularly in elderly patients. Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn's disease have been reported following ibuprofen use. Gastritis has been observed less frequently.

Cases of edema, arterial hypertension, and heart failure associated with NSAID treatment have been reported.

Clinical trial data indicate 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 worsening infections, including development of necrotizing fasciitis, temporally associated with NSAID use, have been documented. This may be related to the mechanism of action of NSAIDs.

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

During long-term therapy, regular blood monitoring is recommended.

Patients should be advised to seek immediate medical attention 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 immediately and the patient should seek urgent medical attention.

System Organ	Frequency	Adverse Reaction
Infections and infestations.	Very rare	Exacerbation of infection-related inflammation (e.g. development of necrotizing fasciitis; in exceptional cases, varicella may cause severe skin and soft tissue infections).
Blood and lymphatic system disorders.	Very rare	Blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial signs include chills, sore throat, oral ulcers, influenza-like symptoms, severe fatigue, epistaxis and skin bleeding, bruising. In such cases, patients should discontinue medication, avoid analgesics or antipyretics, and consult a physician.
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)¹. Exacerbation of asthma.
	Frequency unknown	Respiratory tract reactivity, including asthma, bronchospasm or dyspnea.
Psychiatric disorders.	Very rare	Psychotic reactions, depression.
Nervous system disorders.	Uncommon	Headache, dizziness, insomnia, excitation, irritability or fatigue.
Nervous system disorders.	Very rare	Aseptic meningitis².
Eye disorders.	Uncommon	Visual disturbances, optic neuritis may occur during prolonged treatment.
Ear and labyrinth disorders.	Rare	Tinnitus.
Cardiac disorders.	Very rare	Heart failure, tachycardia, edema, myocardial infarction.
Cardiac disorders.	Frequency unknown	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 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.
Hepatobiliary disorders.	Very rare	Liver function abnormalities, hepatic injury, particularly with long-term therapy, liver failure, acute hepatitis.
Skin and subcutaneous tissue disorders.	Uncommon	Various skin rashes.
	Very rare	Severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis)¹, alopecia.
	Frequency unknown	Drug-induced eosinophilia with systemic symptoms (DRESS syndrome). Acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.
Renal and urinary disorders.	Rare	Acute impairment of kidney function (papillary necrosis), especially with prolonged use of NSAIDs, increased blood urea concentration, elevated serum uric acid levels.
Renal and urinary disorders.	Very rare	Development of edema, particularly in patients with hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.
Investigations.	Rare	Decreased hemoglobin levels.

Description of individual adverse reactions

There have been reports of hypersensitivity reactions following treatment with ibuprofen. Such reactions include: a) non-specific allergic reactions and anaphylaxis; b) respiratory tract reactions, including bronchial asthma, exacerbation of asthma, 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).
The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal association with drug intake and resolution of symptoms after discontinuation of the drug). In particular, during treatment with ibuprofen, isolated symptoms of aseptic meningitis (such as neck stiffness, headache, nausea, vomiting, fever, or disorientation) have been observed in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Shelf life. 3 years.

After first opening of the bottle – 6 months.

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

Packaging.

30 ml, 100 ml, 150 ml, or 200 ml in a bottle. 1 bottle with a dosing syringe in a cardboard box.

Prescription status. Over-the-counter (without prescription).

Manufacturer.

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

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

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

TOV US Pharmacia Sp. z o.o.
US Pharmacia Sp. z o.o.

Manufacturer's address and location of manufacturing operations.

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 the Marketing Authorization Holder.

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