Ibufen® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUFEN FORTE

Composition:

Active ingredient: ibuprofen;

5 ml of suspension contains 200 mg of ibuprofen;

Excipients: hypromellose, xanthan gum, glycerin, sodium benzoate (E 211), citric acid monohydrate, sodium citrate, sodium saccharin, maltitol liquid, sodium chloride, strawberry or raspberry flavor, purified water.

Pharmaceutical form. Oral suspension with raspberry or strawberry flavor.

Main physicochemical properties: white or almost white suspension with uniform opalescence and with a strawberry or raspberry odor.

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 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 treatment of fever.

The analgesic dose for children ranges from 7 to 10 mg/kg body weight, with a maximum daily dose of 30 mg/kg. The medicinal product contains ibuprofen. In an open study, the onset of antipyretic effect was observed within 15 minutes after administration, with temperature reduction in children lasting up to 8 hours.

Experimental data indicate that ibuprofen may interfere with the effect of low-dose acetylsalicylic acid on platelet aggregation when both drugs are administered concomitantly. In one study, when a single 400 mg dose of ibuprofen was taken within 8 hours before or 30 minutes after immediate-release aspirin (81 mg), a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although uncertainty exists regarding the extrapolation of these data to the clinical setting, it cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-regular 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 similarly to those 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 entirely, 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 Insufficiency.

Since ibuprofen and its metabolites are primarily excreted 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, a lower degree of plasma protein binding has been observed, along with increased plasma levels of total and unbound (S)-ibuprofen, higher AUC values for (S)-ibuprofen, and elevated enantiomeric AUC (S/R) ratios 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. 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 was observed, and the enantiomeric AUC (S/R) ratio was significantly lower 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 origins in children aged 6 months to 12 years with body weight of at least 8 kg (including fever following immunization, acute respiratory viral infections, influenza, teething pain, pain after tooth extraction, dental pain, 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 component of the medicinal product.
• History of hypersensitivity reactions (e.g., bronchospasm, asthma, rhinitis, angioedema, or urticaria) following administration of ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Active peptic ulcer disease or gastrointestinal bleeding, or history of recurrent episodes (two or more episodes of confirmed peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Active inflammatory bowel disease.
• Cerebrovascular or other hemorrhages.
• Hemorrhagic diathesis or other disorders of blood coagulation.
• Severe heart failure (NYHA class IV), severe hepatic insufficiency, or severe renal insufficiency.
• 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, as this may increase the risk of adverse reactions, except when acetylsalicylic acid (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 acetylsalicylic acid. However, limited data and uncertainty regarding extrapolation of ex vivo data to clinical settings do not allow definitive conclusions about systematic ibuprofen use. 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 therapeutic effect of anticoagulants such as warfarin.

antihypertensive agents (ACE inhibitors and angiotensin II antagonists): NSAIDs may reduce the efficacy of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of an ACE inhibitor or angiotensin II antagonist and cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, especially in elderly patients. If long-term treatment is necessary, adequate hydration should be ensured, and monitoring of renal function should be initiated at the start of combination therapy and continued periodically.

Glucocorticoids may increase the risk of gastrointestinal ulcers and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): risk of gastrointestinal bleeding may be increased.

Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Pentoxifylline: in patients receiving ibuprofen in combination with pentoxifylline, the risk of hemorrhage may be increased; therefore, bleeding time should be monitored.

Lithium: NSAIDs may increase plasma lithium levels, possibly due to reduced renal clearance. Concomitant use of these medicinal products should be avoided unless lithium levels are closely monitored. Dose reduction of lithium should be considered.

Methotrexate at doses of 15 mg/week or higher: concomitant use of NSAIDs within 24 hours before or after methotrexate administration may lead to increased plasma concentrations of methotrexate (likely due to reduced renal clearance caused by NSAIDs) and subsequent increased toxicity. Therefore, ibuprofen should be avoided in patients receiving high-dose methotrexate.

Methotrexate at doses below 15 mg/week: ibuprofen may increase methotrexate levels. When ibuprofen is used concomitantly with low-dose methotrexate, blood parameters should be closely monitored, especially during the first weeks of combination therapy. Monitoring should be intensified in case of worsening renal function, even minimally, and in elderly patients. Renal function should also be monitored to prevent possible reduction in methotrexate clearance.

Cyclosporine and tacrolimus: increased risk of nephrotoxicity may occur with concomitant use of NSAIDs due to reduced renal prostaglandin synthesis. Renal function should be carefully 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 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 sites; therefore, blood glucose levels should be monitored when sulfonylureas are used concomitantly with ibuprofen.

Probenecid and sulfinpyrazone: increased plasma concentrations of ibuprofen and delayed elimination may occur, possibly due to inhibition at the site of renal tubular secretion and glucuronidation; therefore, dose adjustment of ibuprofen may be required.

Baclofen: baclofen toxicity may develop after initiation of ibuprofen therapy.

Ritonavir: ritonavir may increase plasma concentrations of NSAIDs.

Aminoglycosides: NSAIDs may reduce excretion of aminoglycosides.

Captopril: experimental studies have shown that ibuprofen inhibits the natriuretic effect of captopril.

Voriconazole and fluconazole (CYP2C9 inhibitors): consideration should be given to reducing the dose of ibuprofen when used concomitantly with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are administered. Studies with voriconazole and fluconazole (CYP2C9 inhibitors) showed approximately 80–100% increase in the excretion of S(+)-ibuprofen.

Cholestyramine: when cholestyramine and ibuprofen are used concomitantly, absorption of ibuprofen is delayed and reduced by 25%. Ibuprofen should be administered with a several-hour interval.

Zidovudine: increased risk of hematological toxicity is known with concomitant use of zidovudine and NSAIDs. Evidence suggests increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen therapy.

Quinolone antibiotics: concomitant use with ibuprofen may increase the risk of seizures.

Phenytoin: ibuprofen may increase the pharmacologically active free fraction of phenytoin.

Herbal extracts: Ginkgo biloba, when used concomitantly with NSAIDs, may potentiate the risk of bleeding.

Hydantoins and sulfonamides: increased toxicity of these medicinal products may occur. Plasma phenytoin levels may increase during concomitant therapy with ibuprofen.

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

Special precautions for use.

Adverse effects associated with the use of ibuprofen and other non-selective NSAIDs in general can be minimized by using the lowest effective dose needed to control symptoms for the shortest possible duration.

Respiratory effects.

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

Other NSAIDs.

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should therefore be avoided. 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 diseases.

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

Cardiovascular and cerebrovascular effects.

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

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg daily) and during prolonged treatment, may lead to a small increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤1200 mg daily) increases the risk of myocardial infarction.

Long-term treatment with ibuprofen in patients with uncontrolled arterial hypertension, congestive heart failure (NYHA II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be initiated after careful risk assessment. Long-term treatment with NSAIDs should be prescribed to patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful consideration, and high-dose ibuprofen (2400 mg daily) should be avoided.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome manifests as cardiovascular symptoms associated with coronary artery spasm due to allergy or hypersensitivity reaction, which may lead to myocardial infarction.

Effects on kidneys and liver.

Caution should be exercised in patients with renal impairment due to the potential for worsening renal function. Ibuprofen should be used with caution in patients with kidney or liver disease, especially when used concomitantly 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. Adequate fluid intake should be ensured in cases of dehydration. There is a risk of renal impairment in dehydrated children and adolescents.

Generally, chronic use of analgesics, particularly combinations of different painkillers, may lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy). The highest risk is in elderly patients, those with pre-existing renal, cardiac, or hepatic impairment, and those receiving diuretics or angiotensin-converting enzyme (ACE) inhibitors. Renal function typically returns to pre-treatment levels after discontinuation of NSAIDs.

Liver 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 chronic inflammatory bowel diseases (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. Such patients should consult a physician.

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

The risk of gastrointestinal bleeding, perforation, and ulcers increases with higher NSAID doses, particularly in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment with the lowest possible doses. Caution is advised when treating patients receiving concomitant medications that may increase the risk of gastropathy or bleeding, such as oral corticosteroids or anticoagulants (e.g., warfarin) or antiplatelet agents (e.g., acetylsalicylic acid). For long-term treatment in these patients, as well as in those requiring concomitant low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risk, consideration should be given to combination therapy with misoprostol or proton pump inhibitors.

Patients with a history of gastrointestinal disorders, particularly elderly patients, should be advised to report any unusual gastrointestinal symptoms (especially bleeding), particularly at the beginning of treatment. If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Effects on female fertility.

Limited data suggest that drugs inhibiting cyclooxygenase/prostaglandin synthesis may affect ovulation. This effect is reversible upon discontinuation of treatment.

Severe cutaneous adverse reactions (SCARs).

Severe cutaneous adverse reactions (SCARs) associated with ibuprofen use have been reported, 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 (see section "Adverse reactions"). Most of these reactions occur within the first month of treatment.

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

In rare cases, varicella may lead to severe skin and soft tissue infections. A potential negative influence of NSAIDs on the course of such infections cannot be excluded; therefore, the use of ibuprofen is not recommended in cases of varicella.

Very rare cases of severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been reported. If signs of hypersensitivity occur after ibuprofen administration, treatment should be stopped immediately and medical advice sought.

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

With prolonged use of ibuprofen, regular monitoring of liver function, renal function, and hematological parameters/blood counts is necessary.

Prolonged use of any analgesic for headache treatment may worsen the condition. In such cases, medical advice should be sought and treatment discontinued. Medication-overuse headache should be considered in patients with frequent or daily headaches despite regular use of headache medications.

Concomitant alcohol consumption and NSAID use 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.

Masking of underlying infection symptoms: ibuprofen may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby worsening the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief during infection, monitoring of the infectious condition is recommended. In outpatient settings, patients should seek medical advice if symptoms persist or worsen.

The medicinal product contains liquid maltitol and should therefore 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.

The product contains sodium benzoate and may therefore cause allergic reactions (possibly delayed).

The product is contraindicated in patients with rare hereditary fructose intolerance.

Adults should consult a physician before taking this medicinal product in the following cases: if pregnant, trying to become pregnant, elderly, or a smoker.

Effects 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.

Use during pregnancy or breastfeeding.

The product is not intended for use in 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 and congenital malformations 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 increased from less than 1% to approximately 1.5%. The risk increases with increasing dose and duration of treatment.

From the 20th week of pregnancy, the use of Ibufen® Forte may cause oligohydramnios due to fetal renal dysfunction. Renal impairment may occur almost immediately after starting treatment and is usually reversible upon discontinuation of ibuprofen. Additionally, arterial duct constriction has been reported after second-trimester treatment, which resolved after treatment cessation. Therefore, ibuprofen should not be used during the first two trimesters of pregnancy unless the physician considers the potential benefit to the mother to outweigh the potential risk to the fetus. If ibuprofen is used by women trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose for the shortest possible duration should be used. Antenatal monitoring for oligohydramnios and arterial duct constriction may be appropriate after several days of ibuprofen use starting from the 20th week of pregnancy. Ibuprofen should be discontinued if signs of oligohydramnios or arterial duct constriction are detected.

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

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

to the mother at the end of pregnancy and to the newborn: prolonged bleeding time, antiplatelet effect (which may occur even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

Increased risk of edema in the mother is possible.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding period. Ibuprofen and its metabolites are excreted in breast milk in low concentrations. No adverse effects on the infant have been reported to date; therefore, breastfeeding usually does not need to be discontinued during short-term treatment of pain and fever at recommended doses.

Fertility.

Data indicate 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 rate when driving or operating machinery.

Patients experiencing dizziness, vertigo, visual disturbances, or other central nervous system disorders during ibuprofen use should avoid driving or operating machinery while on this medication.

No special precautions are required when a single dose of ibuprofen is used or when the product is used for a short duration.

Dosage and Administration.

Adverse effects can be minimized by using the lowest effective dose necessary to control symptoms for the shortest duration of time.

For oral use. A single dose of ibuprofen is usually 5 to 10 mg/kg body weight. The recommended daily dose is 20–30 mg per 1 kg body weight, divided into equal doses, with intervals of 6–8 hours between doses. To ensure accurate dosing, use the oral syringe provided in the package. Do not exceed the recommended dose. For short-term use only. Shake well before use.

Age Body weight (kg)	Dosage	Frequency of administration per day
Children 6–12 months (8–10 kg)	1.25 ml (50 mg)	3–4 times
Children 1–3 years (10–15 kg)	2.5 ml (100 mg)	3 times
Children 3–6 years (15–20 kg)	3.75 ml (150 mg)	3 times
Children 6–9 years (20–30 kg)	5 ml (200 mg)	3 times
Children 9–12 years (30–40 kg)	7.5 ml (300 mg)	3 times

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

The medication should be taken with food by patients with sensitive stomachs.

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 in patients with mild to moderate hepatic insufficiency should be initiated with low doses and careful monitoring. Ibuprofen should not be used in patients with severe hepatic insufficiency (see section "Contraindications").

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

In case of overdose, medical advice should be sought immediately.

Children. The medication is intended for children aged 6 months and older, weighing at least 8 kg, up to 12 years of age.

Instructions for using the dosing syringe.

1. Unscrew the cap on the bottle (press down and turn counterclockwise).
2. Firmly insert the dosing syringe into the bottle neck opening.
3. Shake the bottle contents vigorously.
4. To fill the syringe, turn the bottle upside down, then slowly pull the syringe plunger down to draw the liquid up to the desired mark on the scale.
5. Return the bottle to its upright position and carefully remove the dosing syringe by gently twisting it out.
6. Place the syringe tip into the child’s mouth, then slowly press the plunger to administer the dose.
7. After use, close the bottle by screwing the cap back on, and rinse the syringe with water and dry it.

Overdose.

Administration of the medication to children at doses exceeding 400 mg/kg may cause symptoms of intoxication. The effect of overdose is less pronounced in adults. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients participating in clinical trials, ingestion of large amounts of NSAIDs caused only nausea, vomiting, epigastric pain, and less frequently, diarrhea. Tinnitus, headache, dizziness, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, manifesting as drowsiness, nystagmus, visual disturbances, and occasionally agitation, disorientation, or coma. Seizures may occasionally occur. Severe poisoning may lead to hyperkalemia and metabolic acidosis, prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors), acute renal failure, liver damage, arterial hypotension, respiratory failure, and cyanosis. In patients with bronchial asthma, asthma exacerbation may occur.

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 ensuring airway patency and monitoring vital signs until stabilization. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalinizing agents may be administered to enhance urinary excretion of the acidic ibuprofen. For frequent or prolonged muscle spasms, treatment should include intravenous administration of diazepam or lorazepam. In cases of bronchial asthma, bronchodilators should be used. Immediate medical attention should be sought.

Side effects.

The most common adverse reactions are gastrointestinal and are mostly dose-dependent. Adverse reactions are rarely observed when the maximum daily dose is 1200 mg.

The adverse reactions reported during the use of ibuprofen are listed below by organ systems and frequency of occurrence. The frequency of adverse reactions is defined as follows: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations.

Very rare – exacerbation of inflammation associated with infection (e.g., development of necrotizing fasciitis; in exceptional cases, varicella may lead to severe skin and soft tissue infections).

Cardiac disorders.

Very rare – heart failure, edema; very rare – tachycardia, myocardial infarction.

Clinical studies indicate that use of the medicinal product, particularly at high doses (2400 mg per day), may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions for use").

Frequency not known – Kounis syndrome.

Gastrointestinal disorders.

Common – abdominal pain, dyspepsia, nausea; rare – 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 and Crohn's disease; very rare – esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis, duodenitis.

Nervous system disorders.

Uncommon – headache; rare – dizziness, insomnia, fatigue, restlessness, irritability; very rare – aseptic meningitis, with individual symptoms (nuchal rigidity, headache, nausea, vomiting, fever, or confusion) occurring in patients with pre-existing autoimmune disorders such as systemic lupus erythematosus or mixed connective tissue disease; frequency not known – paresthesia, somnolence.

Renal and urinary disorders.

Rare – acute renal impairment, papillary necrosis (especially with prolonged use), associated with increased plasma urea levels; edema, decreased urea excretion, increased plasma sodium concentration (sodium retention), glomerulonephritis, oliguria, cystitis, hematuria, increased plasma urea levels; very rare – renal failure, nephrotoxicity including interstitial nephritis and nephrotic syndrome.

Hepatobiliary disorders.

Very rare – hepatic function abnormalities; frequency not known – with prolonged treatment, acute hepatitis, jaundice, hepatic failure may occur.

Vascular disorders.

Frequency not known — arterial hypertension, arterial thrombosis (myocardial infarction or stroke), vasculitis.

Skin and subcutaneous tissue disorders.

Rare – various skin rashes; very rare — severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis); frequency not known — photosensitivity, alopecia, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

Blood and lymphatic system disorders.

Very rare – anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur during prolonged treatment, with initial signs including fever, sore throat, oral mucosal ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding, and bruising.

Psychiatric disorders.

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

Visual disorders.

Frequency not known — with prolonged treatment, visual disturbances, optic neuritis, blurred vision or diplopia, scotoma, dryness and irritation of eyes, allergic-type conjunctival and eyelid edema may occur.

Auditory and labyrinth disorders.

Frequency not known — with prolonged treatment, tinnitus and dizziness may occur.

Immune system disorders.

Rare – hypersensitivity reactions including urticaria and pruritus; very rare – severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, hypotension, anaphylactic reactions, angioneurotic edema, or severe shock; frequency not known — respiratory tract reactivity, including bronchial asthma, asthma exacerbation, bronchospasm.

General disorders.

Malaise and fatigue, increased sweating.

Investigations.

Very rare – decreased hemoglobin levels.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Shelf life after opening the bottle – 6 months.

Storage conditions.

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

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

Packaging.

40 ml or 100 ml of suspension in a PET bottle with a polyethylene adapter, closed with a screw cap with a tamper-evident ring and a "child-resistant" closure mechanism ("child proof").

1 bottle with a dosing syringe in a cardboard box.

Classification of supply.

Over-the-counter (without prescription).

Manufacturer.

Pharmaceutical Works POLPHARMA S.A.

Manufacturer's address and place of business.

Medana Branch in Sieradz, 10, Wladyslawa Lokietka Str., 98-200 Sieradz, Poland