Blockmax forte for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BlokMAX Forte for kids (BlokMAX Forte for kids)

Composition:

Active substance: ibuprofen;

5 ml of oral suspension contains 200 mg of ibuprofen;

Excipients: glycerol; xanthan gum; microcrystalline cellulose and sodium carmellose; sodium carmellose; polysorbate 80; disodium edetate; sucralose; citric acid, monohydrate; sodium citrate, dihydrate; sodium benzoate (E 211); grape flavor (propylene glycol (E 1520), flavoring substances); flavoring substances (water, propylene glycol (E 1520), flavor components); simethicone emulsion 30%; sodium chloride; purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical characteristics: homogeneous suspension, from almost white to creamy white in color, with a grape aroma.

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 derivative of propionic acid, 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 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. BlockMAX Forte for children 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 suggest 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, when a single 400 mg dose of ibuprofen was taken within 8 hours before or 30 minutes after immediate-release aspirin (81 mg), a reduction in the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although uncertainty remains regarding the 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. 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 eliminated entirely, primarily via the kidneys (90%) and also through bile. The elimination half-life in healthy 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 impairment.

Since ibuprofen and its metabolites are primarily eliminated 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 AUC values for (S)-ibuprofen, and increased enantiomeric AUC ratio (S/R) have been observed compared to control healthy 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. 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 ratio (S/R) 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 post-vaccination fever, 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 of the excipients 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 episodes of confirmed peptic ulcer or bleeding).

History of gastrointestinal bleeding or perforation related to previous NSAID therapy.

Active inflammatory bowel disease.

Cerebral or other hemorrhages.

Haemorrhagic 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, diarrhoea, 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 (at a dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo data to the clinical setting do not allow definitive conclusions regarding regular use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen;
• other NSAIDs, including selective cyclooxygenase-2 inhibitors, as this may increase the risk of adverse effects.

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

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

Antihypertensive agents (ACE inhibitors, beta-blockers, 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 potentially reversible acute renal failure. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should maintain adequate fluid intake, and renal function should be monitored after initiation of concomitant therapy and periodically thereafter.

Corticosteroids: increased risk of gastrointestinal ulceration and bleeding.

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

Cardiac glycosides, e.g., digoxin: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides. NSAIDs may increase plasma digoxin levels, thereby increasing the risk of digoxin toxicity.

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 plasma lithium levels, possibly due to reduced renal clearance. Concomitant use of these medicinal products should be avoided if lithium levels are not monitored. Consideration should be given to reducing the lithium dose.

Methotrexate at doses of 15 mg/week or higher: use of NSAIDs within 24 hours before or after methotrexate administration may lead to increased methotrexate plasma concentrations (likely due to reduced renal clearance of methotrexate caused by NSAIDs) and subsequent enhancement of 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 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 closely monitored when these medicinal products are used concomitantly with NSAIDs.

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

Sulfonylurea derivatives: interactions between NSAIDs and hypoglycemic agents (sulfonylurea derivatives) have been observed. NSAIDs may enhance the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding sites; blood glucose levels should be monitored when sulfonylureas are used concomitantly with ibuprofen.

Probenecid and sulfinpyrazone: possible increase in plasma ibuprofen concentration and delayed elimination, possibly due to inhibitory mechanisms at the site of renal tubular secretion and glucuronidation; therefore, dose adjustment of ibuprofen may be required.

Baclofen: risk of baclofen toxicity may arise after initiation of ibuprofen therapy.

Ritonavir: possible increase in plasma concentrations of NSAIDs.

Aminoglycosides: NSAIDs may reduce aminoglycoside excretion.

Captopril: experimental studies have shown that ibuprofen inhibits captopril's sodium-excreting effect.

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) 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 ibuprofen doses 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: evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen therapy.

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 antibiotic use. Patients taking 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 during concomitant therapy with ibuprofen.

Thiazides, thiazide-like agents, loop diuretics, and potassium-sparing diuretics: NSAIDs may counteract the diuretic effect of these agents. 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.

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 adverse reaction outcomes. Long-term use of NSAIDs is not recommended in elderly patients. In cases of prolonged 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;
• Inherited disorders of porphyrin metabolism, e.g., acute intermittent porphyria;
• Gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease);
• History of hypertension and/or heart failure, as there are reports of fluid retention and edema associated with NSAID therapy;
• Renal impairment – due to the potential for 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 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 administered 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 increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects.

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

Clinical studies and epidemiological data suggest that the use of ibuprofen, especially at high doses (2400 mg per day) and during long-term treatment, may be associated with a small increase in the risk of arterial thrombotic 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 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 assessment of the clinical picture. High doses (2400 mg per day) should be avoided.

Careful evaluation of the clinical picture is also required before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes, 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 is advised in patients with renal impairment due to the potential for worsening kidney function. Ibuprofen should be used with caution in patients with kidney or liver disease, particularly 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 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 is in elderly patients, patients with renal, heart, 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.

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 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 (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, 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 drugs that may increase the risk of ulceration or bleeding, including oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents (e.g., acetylsalicylic acid).

In cases of gastrointestinal bleeding or ulceration in patients receiving ibuprofen, treatment should be discontinued immediately.

Impairment of fertility in women.

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

Skin and subcutaneous tissue.

Severe cutaneous adverse reactions (SCARs), 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 lead to fatal outcomes, have been reported during ibuprofen use (see section "Adverse reactions").

Most such reactions occurred within the first month. If signs or symptoms indicating these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment considered (if necessary).

In rare cases, chickenpox may lead to severe skin and soft tissue infections. At present, the influence of NSAIDs on worsening these infections cannot be excluded; therefore, it is recommended to avoid using ibuprofen in cases of chickenpox.

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

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

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

Long-term use of any analgesic for headache treatment may worsen this condition. In such cases, patients should consult a physician and discontinue treatment. The possibility of 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 intensify adverse reactions related to the active substance, especially those affecting the gastrointestinal tract or central nervous system (CNS).

NSAIDs may mask symptoms of infection and fever.

This medicinal product contains 2 mg of sodium benzoate per ml.

This product contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially sodium-free.

Adults should consult a physician before taking this medicinal product in the following cases: if the patient is 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 concentration and serum creatinine and potassium concentrations may increase;
• Liver function tests: increased transaminase levels.

Use during pregnancy or breastfeeding.

This medicinal product is not intended for use in children under 12 years of age.

Pregnancy.

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is 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, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after starting treatment and is usually reversible upon discontinuation of therapy. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after stopping treatment. Therefore, ibuprofen should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose should be used for the shortest possible duration. Prenatal monitoring for oligohydramnios and arterial duct 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 arterial duct constriction is detected.

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

For the fetus: cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension); renal dysfunction (see above).

For the mother and newborn at the end of pregnancy: possible prolongation of bleeding time, antiplatelet effect that may develop 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.

Breastfeeding.

Ibuprofen and its metabolites are excreted in breast milk in low concentrations. There is currently no evidence of negative 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 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 affect reaction speed when driving or operating machinery.

This medicinal product is not intended for use in children under 12 years of age.

Patients who experience dizziness, vertigo, visual disturbances, or other CNS disorders while taking ibuprofen 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, no special precautions are required.

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. 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 measuring syringe provided in the package. The recommended dose should not be exceeded. For short-term use only. Shake well before use.

Age Body weight (kg)	Dosage	Dosing frequency 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 administered with food to patients with a 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 must 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 must 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 exceeding the recommended dose, immediate medical advice should be sought.

Children.

The medication is indicated for children aged from 6 months, with body weight of at least 8 kg, up to 12 years of age.

Overdose.

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

Symptoms. In most patients, ingestion of clinically significant amounts of NSAIDs results only in nausea, vomiting, epigastric pain, or less frequently, diarrhea. Other possible symptoms include tinnitus, headache, and gastrointestinal bleeding. In more severe poisoning, toxic effects on the CNS may occur, such as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally develop in patients. Severe poisoning may lead to hyperkalemia, metabolic acidosis, 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, asthma exacerbation may occur. Nystagmus, visual disturbances, and loss of consciousness are also possible.

Treatment. There is no specific antidote. Treatment is symptomatic and supportive, including ensuring airway patency and monitoring cardiac function and vital signs until the patient's condition normalizes. Consider administering activated charcoal orally or gastric lavage if less than 1 hour has passed since ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be used to promote urinary excretion of acidic ibuprofen. For frequent or prolonged seizures, treatment should include intravenous administration of diazepam or lorazepam. In case of bronchial asthma, bronchodilators should be administered. Immediate medical attention should be sought.

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

Side effects.

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

Adverse reactions associated with ibuprofen use are listed below by system organ class and frequency of occurrence. The frequency of adverse reactions is defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Gastrointestinal adverse reactions were most frequently observed. Adverse reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on dose and duration of treatment. Gastric or intestinal ulcers, perforation, or gastrointestinal hemorrhage, sometimes fatal, especially in elderly patients, may occur. Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported after ibuprofen use. Gastritis was observed less frequently.

Edema, hypertension, and heart failure have been reported in association with NSAID therapy.

Clinical trial data suggest that the use of ibuprofen, particularly at high doses of 2400 mg per day and during long-term treatment, may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Cases of exacerbation of infection-related inflammation, such as the development of necrotizing fasciitis, temporally associated with NSAID use, have been described. This may be related to the mechanism of action of NSAIDs.

If signs or symptoms of infection occur or worsen during ibuprofen use, patients should seek immediate medical advice. The need for antimicrobial/antibiotic therapy should be evaluated.

Regular blood tests are recommended during long-term therapy.

Patients should seek immediate medical attention and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose of the drug. Immediate medical intervention is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the drug should be discontinued and the patient should seek immediate medical attention.

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 disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include malaise, sore throat, oral mucosal ulceration, influenza-like symptoms, severe exhaustion, epistaxis, skin bleeding, and bruising.

Immune system disorders.

Hypersensitivity reactions¹; uncommon: urticaria and pruritus; very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, hypotension (anaphylactic reaction, angioedema, or severe shock)¹. Asthma exacerbation.

Nervous system disorders.

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

Cardiac disorders.

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

Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: arterial hypertension, vasculitis.

Gastrointestinal disorders.

Common: abdominal pain, nausea, dyspepsia, diarrhea, flatulence, constipation, heartburn, vomiting, and minor gastrointestinal blood loss, which in exceptional cases may lead to anemia; uncommon: gastric and duodenal ulcers, perforation, or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis and Crohn’s disease; very rare: esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders.

Very rare: liver function abnormalities, hepatic injury, particularly during long-term therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders.

Uncommon: various skin rashes¹;

Very rare: severe cutaneous adverse reactions (SCARs), such as bullous reactions, including Stevens-Johnson syndrome, exfoliative dermatitis, erythema multiforme, and toxic epidermal necrolysis¹, alopecia.

Frequency not known: drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

Respiratory, thoracic and mediastinal disorders.

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea¹.

Renal and urinary disorders.

Rare: acute renal function impairment, particularly with prolonged NSAID use, associated with increased serum urea levels and edema; papillary necrosis; 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.

Psychiatric disorders.

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

Eye disorders.

Frequency not known: visual disturbances, optic neuritis, photosensitivity reactions may occur during prolonged treatment.

Ear and labyrinth disorders.

Frequency not known: dizziness may occur during prolonged treatment; rare: tinnitus.

General disorders.

Frequency not known: malaise and fatigue.

______________________

¹ Reports of hypersensitivity reactions following ibuprofen therapy exist. These include non-specific allergic reactions and anaphylaxis, respiratory tract reactions such as bronchial asthma, asthma exacerbation, bronchospasm or dyspnea, or various skin disorders including rashes of different types, pruritus, urticaria, purpura, angioedema, and less frequently exfoliative and bullous dermatoses (including epidermal necrolysis, exfoliative dermatitis, 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 symptom resolution after drug discontinuation). In particular, isolated symptoms of aseptic meningitis (such as nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during ibuprofen therapy.

Reporting of adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of drug efficacy via the Automated Information System for Pharmacovigilance at: http://aisf.dec.gov.ua.

Shelf life.

2 years. Do not use after the expiry date stated on the packaging.

After first opening of the bottle, the product should be stored for no longer than 6 months.

Storage conditions.

This product does not require special storage temperature conditions.

Keep out of reach of children.

Packaging.

100 ml of suspension in a bottle, 1 bottle with a 5 ml measuring syringe in a cardboard box. The 5 ml measuring syringe has graduations at 1.25 ml, 2.5 ml, 3.75 ml, and 5 ml for dose measurement.

Dispensing category.

Over-the-counter.

Manufacturer.

ALKALOID AD Skopje /
ALKALOID AD Skopje.

Manufacturer’s address and place of business.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.