Nurofen® for children forte: detailed information

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

Composition:

Active ingredient: ibuprofen;

5 ml of suspension contains 200 mg of ibuprofen;

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

Pharmaceutical form. Orange-flavored oral suspension.

Main physicochemical characteristics: nearly white, syrup-like suspension with a characteristic orange odor.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. 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—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 symptomatic treatment of mild to moderate pain, such as dental pain, headache, and in symptomatic management of fever.

The analgesic dose for children ranges from 7 to 10 mg/kg body weight, with a maximum dose of 30 mg/kg/day. Nurofen® for Children Forte contains ibuprofen, which in an open study demonstrated onset of antipyretic action 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 drugs are administered concomitantly. In one study, a single 400 mg dose of ibuprofen taken within 8 hours before or 30 minutes after immediate-release aspirin (81 mg) resulted in reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty remains regarding extrapolation of these data to the clinical setting, it cannot be excluded that chronic, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional (non-chronic) use of ibuprofen, a clinically significant interaction is considered unlikely.

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 eliminated completely, primarily via the kidneys (90%) and also through bile. The elimination half-life in healthy volunteers as well as in patients with kidney or liver disease ranges from 1.8 to 3.5 hours. Plasma protein binding is approximately 99%.

Renal impairment.

Since ibuprofen and its metabolites are primarily eliminated by the kidneys, the pharmacokinetics of the drug may be altered in patients with varying 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 AUC values for (S)-ibuprofen, and increased enantiomeric AUC (S/R) ratios 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 dysfunction 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. However, liver disease may alter the distribution kinetics of ibuprofen. In patients with cirrhosis and moderate hepatic impairment (Child–Pugh class 6–10), an approximately two-fold increase in elimination half-life has been observed, along with significantly lower enantiomeric AUC (S/R) ratios compared to healthy control subjects, 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 inflammatory origin).

Contraindications.

Hypersensitivity to ibuprofen or to any component of the medicinal product.
History of hypersensitivity reactions (such as bronchospasm, asthma, 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 confirmed episodes of peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
Active inflammatory bowel disease.
Cerebrovascular or other hemorrhages.
Hemorrhagic diathesis or other coagulation disorders.
Severe heart failure (NYHA class IV), severe hepatic insufficiency, or severe renal insufficiency.
Hereditary fructose intolerance.
Third trimester of pregnancy.
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) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, limited data and uncertainty regarding extrapolation of ex vivo data to the clinical setting do not allow definitive conclusions regarding systematic use of ibuprofen. Therefore, with occasional use of ibuprofen, such clinically significant effects are considered unlikely;
other NSAIDs, including selective cyclooxygenase-2 inhibitors, as this may increase the risk of adverse effects.

Ibuprofen (like other NSAIDs) 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): NSAIDs may reduce the effectiveness of these agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of ACE inhibitors, beta-blockers, or angiotensin II antagonists with 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 digoxin plasma 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: in patients receiving ibuprofen in combination with pentoxifylline, there may be an increased risk of hemorrhage; therefore, bleeding time should be monitored;

lithium: NSAIDs may increase lithium plasma 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 lead to increased methotrexate plasma concentrations (likely due to reduced renal clearance of methotrexate caused by NSAIDs) and subsequent increase in 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 concomitantly 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 cases 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 concomitantly with NSAIDs.

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

sulfonylurea agents: 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; monitoring of blood glucose levels is recommended when sulfonylureas are used concomitantly with ibuprofen;

probenecid and sulfinpyrazone: possible increase in ibuprofen plasma concentration and delayed elimination; this may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronidation; therefore, dose adjustment of ibuprofen may be necessary;

baclofen: may increase the risk of baclofen toxicity after initiation of ibuprofen therapy.

ritonavir: possible increase in plasma concentrations of NSAIDs;

aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides;

captopril: experimental studies have shown that ibuprofen inhibits the sodium-excreting effect of captopril;

voriconazole and fluconazole (CYP2C9 inhibitors): concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). Studies 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 dose is recommended, especially when high doses of ibuprofen are used with voriconazole or fluconazole;

cholestyramine: ibuprofen and cholestyramine should be taken with an interval of several hours due to delayed and reduced (by 25%) absorption of ibuprofen when administered concomitantly;

zidovudine: increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with 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 taking NSAIDs and quinolones may have an increased risk of developing seizures;

hydantoins and sulfonamides: possible increase in the toxic effect of these medicinal products. Plasma levels of phenytoin may increase during concomitant treatment with 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 reduced 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 increased potassium levels; therefore, plasma potassium levels should be monitored.

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

Special precautions for use.

Adverse effects of ibuprofen therapy can be minimized by using the lowest effective dose required to treat symptoms for the shortest duration necessary.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal. Elderly patients are at increased risk of serious outcomes from adverse reactions.

Long-term use of NSAIDs is not recommended in elderly patients. With prolonged therapy, 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 an increased risk of aseptic meningitis;
Congenital porphyrin metabolism disorders, 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 an increased risk of allergic reactions, including asthma attacks (so-called analgesic-induced asthma), Quincke's edema, or urticaria;
History of allergic reactions to other substances – due to an increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects.

Bronchospasm may occur in patients with 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.

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 and mixed connective tissue disease due to an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects.

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

Clinical studies and epidemiological data indicate 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 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 evaluation should also be performed 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 ibuprofen therapy. 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 renal function. Such patients should receive the lowest possible dose of ibuprofen, and renal function should be monitored regularly. 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 a risk of renal failure (analgesic nephropathy). The highest risk of this reaction occurs in elderly patients, patients with renal, heart, or liver failure, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, kidney function usually returns to the pre-treatment state.

Liver function may be impaired. Like other NSAIDs, ibuprofen may cause temporary increases in certain liver function parameters, as well as significant elevations in AST and ALT levels. If these parameters increase significantly, 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.

There have been reports of gastrointestinal bleeding, perforation, and ulcers, potentially fatal, occurring at any stage of NSAID therapy, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, or ulcers 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 doses. For these 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, particularly elderly individuals, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

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

In case of gastrointestinal bleeding or ulcers 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 skin adverse reactions

Severe 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 during ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

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

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

Masking symptoms of underlying infections.

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

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

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

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

Prolonged use of any analgesic for headache treatment may worsen 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 undesirable 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. Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect.

This medicinal product contains sodium, which should be considered for patients on a low-sodium diet.

15 ml of suspension contains 28.09 mg of sodium (=1.87 mg of sodium per 1 ml of suspension). Caution is advised when administering to patients on a sodium-controlled diet.

When used by adults, consult a physician before taking this medicinal product in the following cases: if you are pregnant, trying to become pregnant, elderly, or a smoker.

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 concentration and serum creatinine and potassium concentrations may increase;

liver function tests: increased transaminase levels.

Use during pregnancy or breastfeeding.

The drug is administered to 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 the 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 increases from less than 1% to approximately 1.5%. The risk increases with higher doses and longer treatment duration.

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal kidney dysfunction. This may occur shortly after starting 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 stopping treatment. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless necessary. If ibuprofen 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 ibuprofen for several days 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 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, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding.

Ibuprofen and its metabolites are excreted into 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 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.

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

Ability to influence reaction speed when driving or operating machinery.

Patients who experience dizziness, vertigo, visual disturbances, or other central nervous system disorders during ibuprofen use should avoid driving or operating machinery during therapy with this medicinal product.

When a single dose of ibuprofen is used or the drug is taken for a short period, special precautions are not required.

Dosage and 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 medication may be taken diluted with water or undiluted. The recommended daily dose is 20–30 mg per 1 kg of body weight, divided into equal doses administered at 6–8 hour intervals.

To ensure accurate dosing, use the dosing syringe provided in the package.

Body weight and child's age	Dose and dosing method	Maximum daily dose within 24 hours
7-9 kg (6-11 months)	1 x 50 mg (1.25 ml, single use of dosing syringe)	3–4 times
10-15 kg (1-3 years)	1 x 100 mg (2.5 ml, single use of dosing syringe)	3 times
16-19 kg (4-5 years)	1 x 150 mg (3.75 ml, single use of dosing syringe)	3 times
20-29 kg (6-9 years)	1 x 200 mg (5 ml, single use of dosing syringe)	3 times
30-40 kg (10-12 years)	1 x 300 mg (7.5 ml, double use of dosing syringe (1 x 2.5 ml, and 1 x 5 ml)	3 times

Do not exceed the recommended dose. For short-term use only. Shake well before use.

If a child's symptoms persist for more than 3 days from the start of treatment or worsen, medical advice should be sought.

Patients with sensitive stomach should take the medication during meals.

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 impairment.

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

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

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

In case of overdose, seek immediate medical advice.

Children.

The product is indicated for children aged 6 months and older with body weight of at least 7 kg, up to 12 years of age.

Overdose.

In pediatric patients, overdose symptoms may occur following ingestion of 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 clinically significant amounts of NSAIDs causes only nausea, vomiting, epigastric pain, or less frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, including nystagmus, blurred vision, vertigo, dizziness, somnolence, occasionally excitement and disorientation, loss of consciousness, or coma. Seizures may occasionally occur. Severe intoxication may lead to hyperkalemia, metabolic acidosis, hypothermia, and prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors). Acute renal failure, liver damage, hypotension, respiratory depression, and cyanosis may also occur. In patients with bronchial asthma, an exacerbation of asthma symptoms may occur. Nystagmus, visual disturbances, and loss of consciousness are possible.

Treatment.

There is no specific antidote.

Treatment is symptomatic and supportive, including maintaining airway patency and monitoring cardiac function and vital signs until the patient stabilizes. Consider administering activated charcoal orally or performing gastric lavage if less than 1 hour has passed since ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be used to enhance renal excretion of acidic ibuprofen. For frequent or prolonged seizures, treatment with intravenous diazepam or lorazepam should be initiated. Bronchodilators should be used in cases of bronchial asthma. Seek immediate medical assistance.

Side effects

The list of adverse reactions below includes all undesirable effects reported during treatment with ibuprofen, including those observed with high doses and long-term therapy in patients with rheumatism. The frequencies exceeding "very rare" 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. Frequency categories are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

The most frequently observed adverse reactions are gastrointestinal. Most adverse reactions are dose-dependent; in particular, the risk of gastrointestinal bleeding depends on dose and duration of treatment. Gastric or intestinal 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 or 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 indicate that the use of ibuprofen, particularly at high doses of 2400 mg daily and during prolonged 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 development of 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 treatment, patients should seek immediate medical advice. The need for antimicrobial/antibiotic therapy should be assessed.

Regular blood monitoring is 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 upon first use of the drug. Immediate medical intervention is required in such cases.

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

Infections and infestations

Very rare: Exacerbation 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 fever, sore throat, oral ulceration, influenza-like symptoms, severe exhaustion, epistaxis, skin bleeding, and bruising. In such cases, patients should discontinue the medication, avoid use of 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 not known: Respiratory tract reactivity, including asthma, bronchospasm, or dyspnea.

Psychiatric disorders

Very rare: Psychotic reactions, depression.

Nervous system disorders

Uncommon: Headache, dizziness, insomnia, restlessness, irritability, or fatigue;

Very rare: Aseptic meningitis².

Eye disorders

Uncommon: Visual disturbances, optic neuritis during prolonged treatment.

Ear and labyrinth disorders

Rare: Tinnitus.

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 ulceration, perforation, or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (particularly in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis or Crohn’s disease;

Very rare: Esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders

Very rare: Liver function abnormalities, hepatic injury (especially with long-term therapy), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: Various skin rashes;

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

Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis; photosensitivity reactions.

Renal and urinary disorders

Rare: Acute renal dysfunction (papillary necrosis), especially with long-term NSAID use, increased blood urea concentration, elevated serum uric acid levels;

Very rare: Edema formation, particularly in patients with hypertension or renal impairment, nephrotic syndrome, interstitial nephritis, which may lead to acute renal failure.

Investigations

Rare: Decreased hemoglobin levels.

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 association with drug intake and resolution of symptoms after drug discontinuation). In particular, isolated symptoms of aseptic meningitis (such as nuchal rigidity, headache, nausea, vomiting, fever, or confusion) 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

2 years.

After first opening of the bottle, do not store for more than 6 months.

Storage conditions

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging

100 ml or 150 ml of suspension in a bottle. One bottle with a dosing syringe in a cardboard box.

Classification

Over-the-counter (without prescription).

Manufacturer

Reckitt Benckiser Healthcare (UK) Limited.

Manufacturer's address

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