Affida forte for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AFFFIDA FORTE FOR CHILDREN (AFFIDAFORTE FOR CHILDREN)

Composition:

Active ingredient: ibuprofen;

5 ml of suspension contains 200 mg of ibuprofen;

Excipients: glycerol (E 422), xanthan gum (E 415), microcrystalline cellulose and sodium carmellose, sodium carmellose (E 466), polysorbates 80, disodium edetate, sucralose (E 955), citric acid monohydrate (E 330), sodium citrate anhydrous; sodium benzoate (E 211), grape flavor (propylene glycol 84 % (E 1520), flavoring substances), taste-masking flavor (water, propylene glycol (E 1520), flavoring compounds), simethicone emulsion 30 %, sodium chloride, purified water.

Pharmaceutical form. Oral grape-flavored suspension.

Main physicochemical properties: 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 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 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 is 7 to 10 mg/kg body weight, with a maximum daily dose of 30 mg/kg. AFFFIDA 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 indicate that ibuprofen may interfere with the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation when both agents are administered concomitantly. In one study, when a single dose of ibuprofen 400 mg 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 exists regarding the extrapolation of these data to clinical outcomes, it cannot be excluded that chronic, regular use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interaction is considered unlikely with occasional, non-regular 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, predominantly 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 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 the control group of 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 impairment of renal function 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 impairment of liver function (Child–Pugh class 6–10), an approximately twofold 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 weighing at least 7 kg (including post-vaccination fever, fever associated with acute respiratory viral infections and influenza, teething pain, post-dental extraction pain, toothache, headache, sore throat, pain due to ligament sprains, and other types of pain, including those of inflammatory origin).

Contraindications.

• Hypersensitivity to ibuprofen or to any 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 (at a dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions regarding systematic 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 (like other NSAIDs) 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 in renal function, including potentially reversible acute renal failure. Therefore, such combinations should be used cautiously, 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 glycoside levels. NSAIDs may increase digoxin plasma concentrations, thereby increasing the risk of digoxin toxicity; serum digoxin monitoring is generally not required with appropriate use (maximum duration of 3 days);

pentoxifylline: patients receiving ibuprofen in combination with pentoxifylline may have 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; serum lithium monitoring is generally not required with appropriate use (maximum duration of 3 days);

methotrexate at doses of 15 mg/week: administration of NSAIDs within 24 hours before or after methotrexate may increase methotrexate plasma concentrations (likely due to reduced renal clearance of methotrexate caused by NSAIDs) and further increase its toxic effects. Therefore, ibuprofen use 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, and renal function should be monitored to prevent possible reduction in methotrexate clearance;

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

probenecid and sulfinpyrazone: possible increase in ibuprofen plasma concentration and delayed elimination, possibly due to inhibitory effects on renal tubular secretion and glucuronidation; dose adjustment of ibuprofen may therefore be necessary;

baclofen: risk of baclofen toxicity may increase after initiation of ibuprofen;

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;

voriconazole and fluconazole (CYP2C9 inhibitors): concomitant use of ibuprofen with CYP2C9 inhibitors may enhance the effect of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have demonstrated an approximately 80–100% increase in the effect of S(+)-ibuprofen. When ibuprofen is used concomitantly with strong CYP2C9 inhibitors, dose reduction of ibuprofen is recommended, especially when high doses of ibuprofen are used with voriconazole or fluconazole;

cholestyramine: ibuprofen and cholestyramine should be taken at intervals 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 zidovudine and ibuprofen therapy;

herbal extracts: concomitant use of Ginkgo biloba 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 effects of these medicinal products. Plasma phenytoin levels may increase during concomitant treatment with ibuprofen; serum phenytoin monitoring is generally not required with appropriate use (maximum duration of 3 days);

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 cautiously, 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 of ibuprofen therapy can be minimized by using the lowest effective dose needed 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 experiencing adverse reaction outcomes.

Prolonged use of NSAIDs is not recommended in elderly patients. If long-term therapy is required, 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 increased risk of aseptic meningitis;
• congenital defects in 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 possibility of worsening kidney function;
• hepatic dysfunction;
• immediately after major surgical procedures;
• hay fever, nasal polyps, or chronic obstructive respiratory diseases – due to increased risk of allergic reactions, including asthma attacks (so-called analgesic 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 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 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 hypertension and/or heart failure should begin treatment cautiously (medical consultation is required), as fluid retention, development of hypertension, and edema have been reported during ibuprofen therapy, similar to other NSAIDs.

Clinical trials and epidemiological data indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and during prolonged treatment, may be associated with a small increased risk of arterial thrombotic complications (such as myocardial infarction or stroke). Overall, epidemiological studies do not show that low-dose ibuprofen (e.g. ≤1200 mg per day) is 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.

The clinical picture should also be carefully evaluated 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. Kounis syndrome is defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction associated with coronary artery spasm and potentially leading to myocardial infarction.

Effects on kidneys and liver.

Caution should be exercised in patients with renal impairment due to the possibility of worsening kidney function. Ibuprofen should be used with caution in patients with kidney or liver disease, particularly when concomitantly treated with diuretics, as prostaglandin inhibition may lead to fluid retention and further deterioration of kidney function. Such patients should receive the lowest possible dose of ibuprofen and have kidney function 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, regular 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 is 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 cautiously 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 prior warning symptoms or history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, or ulcers increases with higher NSAID doses, history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest doses. For 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, especially elderly individuals, should be informed about any unusual gastrointestinal symptoms (particularly gastrointestinal bleeding), especially 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), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents (e.g. acetylsalicylic acid).

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

Impairment of fertility in women.

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

Severe cutaneous adverse reactions (SCARs).

Very rarely, severe forms of 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 fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month. If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In exceptional 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, the use of ibuprofen is not recommended in cases of chickenpox.

Masking symptoms of underlying infections.

Ibuprofen may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby complicating the course of the illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When using the drug for fever or to relieve pain associated with infection, monitoring for infection 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 hypersensitivity after taking ibuprofen, 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 alcohol consumption and NSAID use may intensify adverse reactions related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

This medicinal product contains 10 mg of sodium benzoate (E 211) in 5 ml of suspension.

This medicinal product contains less than 1 mmol (23 mg) of sodium per 5 ml dose, i.e. practically sodium-free. Caution should be exercised when administering to patients on a sodium-controlled diet. It is particularly important that patients or their parents be informed by physicians that the product contains a small amount of sodium, especially when the medicinal product is intended for children or patients on a sodium-controlled diet.

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.

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 product is 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, 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 increasing dose and duration of treatment.

Ibuprofen should not be taken 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.

From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal kidney dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there are reports of ductus arteriosus constriction after treatment in the second trimester, most of which resolved after stopping treatment. Therefore, during the first and second trimesters of pregnancy, the medicinal product AFFIDA FORTE FOR CHILDREN should not be prescribed unless necessary. If the product 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. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after ibuprofen exposure for several days starting from the 20th gestational week. The use of the medicinal product AFFIDA FORTE FOR CHILDREN should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

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

Risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above);

Risks to the mother at the end of pregnancy and to the newborn:

• possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

The product is contraindicated in the third trimester of pregnancy (see section "Contraindications").

Breastfeeding.

Ibuprofen and its metabolites pass into 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 trying to conceive. For women experiencing difficulties with conception or undergoing infertility evaluation, discontinuation of this medicinal product should be considered.

Ability to affect reaction speed when driving or operating machinery.

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

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

Method of Administration and Dosage

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

Adverse effects can be minimized by using the lowest effective dose required to control symptoms, for the shortest possible duration.

For oral administration. The medicine 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 oral dosing syringe provided in the package.

Body weight and child's age	Dosage and administration 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, consult a doctor.

Patients with a 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 should be initiated with low doses and closely monitored in patients with mild to moderate hepatic impairment. Ibuprofen should not be used in patients with severe hepatic impairment (see section "Contraindications").

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

In case of exceeding the recommended dose, seek immediate medical advice.

Children.

The medication is intended for use in children aged from 6 months with body weight of at least 7 kg up to 12 years.

Overdose.

In pediatric patients, overdose symptoms may occur after 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 causes only nausea, vomiting, epigastric pain, or less commonly, 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, drowsiness, occasionally excitement and disorientation, loss of consciousness, or coma. Seizures may occasionally occur. Severe poisoning 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, 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 maintaining airway patency and monitoring cardiac function and vital signs until the patient's condition normalizes. 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 urinary excretion of acidic ibuprofen. For frequent or prolonged seizures, treatment should include intravenous administration of diazepam or lorazepam. Bronchodilators should be used in cases of bronchial asthma. Seek immediate medical assistance.

Adverse reactions.

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 reports refer to short-term use (maximum 1200 mg ibuprofen per day) of oral dosage forms.

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

The most commonly observed adverse reactions are gastrointestinal. Adverse reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on dose and duration of treatment. Gastrointestinal 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, exacerbation of colitis, and Crohn's disease have been reported after ibuprofen use. Gastritis has been observed less frequently.

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

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

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

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

Regular blood tests are recommended during long-term therapy.

Patients should seek immediate medical advice and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even upon first administration of the drug. Immediate medical assistance is required in such cases.

If severe epigastric pain, melena, or hematemesis occurs, the drug should be discontinued immediately and medical advice sought without delay.

System organ class	Frequency	Adverse reaction
Infections and infestations.	Very rare	Exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis; in exceptional cases, varicella may cause severe skin and soft tissue infectious complications).
Blood and lymphatic system disorders.	Very rare	Blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial signs include chills, sore throat, superficial oral ulcers, influenza-like symptoms, severe exhaustion, nasal and skin bleeding, and bruises. In such cases, the patient should discontinue the medication, avoid analgesics or antipyretics, and consult a physician.
Immune system disorders.	Uncommon	Hypersensitivity reactions1.
		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. 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 may occur 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 blood loss, which in exceptional cases may lead to anemia.
	Uncommon	Gastric and duodenal ulceration, perforation or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis and Crohn's disease.
	Very rare	Esophagitis, development of diaphragm-like intestinal strictures, pancreatitis.
Hepatobiliary disorders.	Very rare	Liver function abnormalities, hepatic injury, particularly with long-term therapy, liver failure, acute hepatitis.
Skin and subcutaneous tissue disorders.	Uncommon	Various skin rashes.
	Very rare	Severe skin reactions (SCARs), such as bullous 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 function impairment (papillary necrosis), particularly with prolonged use of NSAIDs, elevated blood urea nitrogen, increased serum uric acid levels.
	Very rare	Development of edema, particularly in patients with hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.
Investigations.	Rare	Decreased hemoglobin levels.

Description of individual adverse reactions

1 There have been reports of hypersensitivity reactions following ibuprofen treatment. Such reactions 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, angioneurotic edema, 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 has not been fully elucidated. However, available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal association with drug administration and resolution of symptoms upon drug discontinuation). In particular, during treatment with ibuprofen, isolated symptoms of aseptic meningitis (such as nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) have been observed in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Shelf life.

2 years.

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

Storage conditions.

No special storage conditions required. Keep out of reach of children.

Packaging.

100 ml of suspension in a bottle. 1 bottle with a dosing syringe in a cardboard box.

Category of supply.

Over-the-counter (without prescription).

Manufacturer.

ALKALOID AD Skopje.

Manufacturer's address and location of business operations.

Bul. Alexander the Great, 12, Skopje, 1000, North Macedonia.