Affida syrup
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AFFIDA SYRUP (AFFIDASYRUP)
Composition:
Active substance: ibuprofen;
5 ml of suspension contains 100 mg of ibuprofen;
Excipients: glycerol; sorbitol solution 70%, non-crystallizing (E 420); xanthan gum; microcrystalline cellulose and sodium carmellose; polysorbate 80; disodium edetate; sodium saccharin; citric acid monohydrate; sodium citrate dihydrate; sodium benzoate (E 211); apricot flavor (propylene glycol; flavoring components: gamma-decalactone, linalool, ethyl butyrate, benzaldehyde, hexyl acetate, diethyl carbonate, vanillin; natural flavoring components: natural citral; flavoring components: orange oil, lemon oil); taste-masking agent (potato maltodextrin; flavoring components: glycyrrhizic acid, ammonium glycyrrhizinate, sugar, aspartame (E 951), acesulfame K (E 950)); simethicone emulsion 30%; sodium chloride; purified water.
Pharmaceutical form. Oral suspension with apricot flavor.
Main physicochemical properties: a homogeneous suspension of yellowish-white to brownish color with an apricot odor.
Pharmacotherapeutic group.
Non-steroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen.
ATC code M01A E01.
Pharmacological properties.
Pharmacodynamics.
Ibuprofen is a derivative of propionic acid, a non-steroidal anti-inflammatory drug (NSAID) that exerts analgesic, anti-inflammatory, and antipyretic effects. In addition, ibuprofen reversibly inhibits platelet aggregation. The therapeutic effect of the drug is believed to result from inhibition of the enzyme cyclooxygenase, leading to a marked reduction in prostaglandin synthesis. These properties provide relief from inflammation, pain, and fever.
Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both agents are administered concomitantly. Some pharmacodynamic studies have shown that a single 400 mg dose of ibuprofen taken 8 hours before or 30 minutes after an immediate-release formulation of acetylsallylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane production or platelet aggregation.
Although there is uncertainty regarding extrapolation of these findings to the clinical setting, the possibility cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant effects are unlikely with occasional, non-regular use of ibuprofen.
Pharmacokinetics.
Ibuprofen is rapidly absorbed following oral administration. After administration on an empty stomach, maximum plasma concentration is reached in approximately 45 minutes.
When the same dose is taken after food, absorption occurs more slowly, with peak plasma concentration achieved within 1.5–3 hours. The elimination half-life from plasma is 2 hours. Ibuprofen is metabolized in the liver to form two inactive metabolites, which, together with unchanged ibuprofen, are excreted by the kidneys either unchanged or as conjugates.
Elimination is rapid, and plasma concentrations show no signs of accumulation. 44% of the dose of ibuprofen is excreted in urine as two pharmacologically inactive metabolites and 20% in unchanged form.
Clinical characteristics.
Indications.
Short-term treatment of fever and pain in children.
Contraindications.
Known hypersensitivity to the active substance or to any other component of the medicinal product.
History of hypersensitivity reactions (such as bronchial asthma, rhinitis, angioedema, or urticaria) in response to administration of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
Increased tendency to bleeding or active bleeding.
Active or recurrent peptic ulceration or gastrointestinal hemorrhage (two or more episodes of confirmed ulcer formation or bleeding).
History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
Severe heart failure (NYHA functional class IV).
Severe hepatic impairment.
Severe renal impairment (glomerular filtration rate <30 mL/min).
Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
Third trimester of pregnancy.
Cerebrovascular or other hemorrhages.
Hematopoietic or blood coagulation disorders.
Hereditary fructose intolerance.
Interaction with other medicinal products and other forms of interaction.
The following medicinal products should be used with caution when administered concomitantly with ibuprofen, as interactions have been reported in some patients.
Diuretics, ACE inhibitors, beta-blockers, and angiotensin II receptor antagonists. NSAIDs may reduce the effect of diuretics and other antihypertensive agents. Diuretics may increase the risk of nephrotoxicity associated with NSAID use. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant administration of ACE inhibitors, beta-blockers, or angiotensin II receptor antagonists with cyclooxygenase inhibitors may lead to further deterioration of renal function, including the possibility of acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, particularly in elderly patients.
Patients should consume adequate amounts of water; renal function should also be monitored at the start of concomitant therapy and periodically thereafter.
Cardiac glycosides. NSAIDs may worsen cardiac decompensation, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides (e.g., digoxin). Monitoring of serum glycoside levels is recommended.
Lithium. Concomitant use of ibuprofen and lithium-containing preparations leads to increased plasma levels of lithium.
Metotrexate. NSAIDs may inhibit tubular secretion of methotrexate, reduce methotrexate clearance, and increase the risk of toxicity.
Moclobemide enhances the effect of ibuprofen.
Cyclosporine increases the risk of renal damage associated with NSAIDs. This effect cannot be excluded for the combination of cyclosporine and ibuprofen.
Mifepristone. A reduction in efficacy may theoretically occur due to the anti-prostaglandin properties of NSAIDs, particularly acetylsalicylic acid. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not alter the effects of mifepristone or prostaglandin on cervical ripening or uterine contractility, nor does it reduce the clinical efficacy of medical termination of pregnancy.
Corticosteroids. Ibuprofen should be prescribed with caution in combination with corticosteroids due to the possible increased risk of adverse reactions, particularly gastrointestinal (gastrointestinal ulcers or bleeding; see sections "Contraindications" and "Special precautions").
Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions").
Acetylsalicylic acid. Concomitant use of ibuprofen with acetylsalicylic acid or other medicinal products containing NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, is not recommended due to an increased risk of adverse reactions. Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly. However, despite uncertainties regarding the extrapolation of these data to clinical settings, it cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. No clinically significant effects have been observed with occasional, irregular use of ibuprofen (see section "Pharmacodynamics").
Sulfonylureas. NSAIDs may potentiate the effects of sulfonylurea preparations. Rare cases of hypoglycemia have been reported in patients receiving sulfonylureas when ibuprofen was administered. Monitoring of blood glucose levels is recommended during concomitant use.
Zidovudine. NSAIDs increase the risk of hematological toxicity when used concomitantly with zidovudine. Evidence suggests an increased risk of hemarthrosis and hematomas in HIV-positive patients with hemophilia when ibuprofen is administered during zidovudine therapy. Hematological monitoring is recommended 1–2 weeks after initiation of treatment.
Other NSAIDs, including salicylates and selective COX-2 inhibitors. Concomitant use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions").
Aminoglycosides. NSAIDs may reduce the elimination of aminoglycosides.
Cholestyramine. Concomitant use of ibuprofen and cholestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance of this interaction is unknown.
Tacrolimus. Increased risk of nephrotoxicity when both drugs are used concomitantly.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) increase the risk of gastrointestinal bleeding (see section "Special precautions").
Herbal extracts. Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.
Quinolone antibiotics. Data from animal experiments indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones concomitantly have an increased risk of developing seizures.
CYP2C9 inhibitors. Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (ibuprofen is a CYP2C9 substrate). In one study, voriconazole and fluconazole (CYP2C9 inhibitors) increased S(+)-ibuprofen exposure by approximately 80–100%. A reduction in ibuprofen dose should be anticipated when co-administered with CYP2C9 inhibitors, especially when high doses of ibuprofen are prescribed to patients taking voriconazole or fluconazole.
Special precautions for use.
General warnings
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and effects on the gastrointestinal tract and cardiovascular system described below).
Concomitant use of ibuprofen with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to the potential for additive effects (see section "Interaction with other medicinal products and other forms of interaction").
Ibuprofen may temporarily inhibit platelet function (platelet aggregation).
Prolonged use of any analgesic may lead to medication-overuse headache, which should not be treated with increased doses of this medicinal product.
The concomitant intake of alcohol during NSAID therapy may increase the risk of adverse reactions caused by the active substance, particularly affecting the gastrointestinal tract or central nervous system.
Elderly patients
Elderly patients have an increased frequency of adverse reactions when taking NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
Cardiovascular and cerebrovascular disorders
Caution (consultation with a physician or pharmacist) is advised before initiating treatment in patients with a history of hypertension and/or heart failure, as fluid retention and edema have been reported with NSAID use.
NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents (see section "Interaction with other medicinal products and other forms of interaction").
Clinical trial data indicate that the use of ibuprofen, especially at high doses (2400 mg per day), may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological data suggest that low-dose ibuprofen (e.g., ≤1200 mg per day) does not increase the risk of arterial thrombotic events. Ibuprofen should be prescribed with particular caution to patients with uncontrolled hypertension, congestive heart failure (NYHA functional class II–III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, avoiding the use of high doses of ibuprofen (2400 mg per day). Great caution is required when treating long-term patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes, smoking), especially if high-dose ibuprofen (2400 mg per day) is necessary.
Cases of Kounis syndrome have been reported in patients taking ibuprofen. Kounis syndrome is defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction associated with coronary artery spasm, potentially leading to myocardial infarction.
Gastrointestinal bleeding, ulceration, and perforation
During treatment with all NSAIDs at any stage, cases of gastrointestinal bleeding, perforation, or ulceration have been reported, which may be fatal. These events may occur without preceding symptoms or a history of serious gastrointestinal disorders.
In patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients, increasing NSAID doses increases the risk of gastrointestinal bleeding, ulceration, or perforation. Treatment in these patients should begin with the lowest available dose.
For such patients, as well as for patients requiring concomitant therapy with low-dose acetylsalicylic acid or other medicinal products that may increase the risk of gastrointestinal complications, consideration should be given to the use of combination therapy with protective agents, such as misoprostol or proton pump inhibitors (see section "Interaction with other medicinal products and other forms of interaction").
Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed of the need to report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Ibuprofen should be prescribed with caution to patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").
Treatment with ibuprofen should be discontinued in patients who develop gastrointestinal bleeding or ulcers.
Ibuprofen should be prescribed with caution in patients with a history of peptic ulcers or other gastrointestinal disorders, such as ulcerative colitis or Crohn’s disease, due to the possibility of exacerbation of these conditions (see section "Adverse reactions").
Use with caution in patients with coagulation disorders.
Renal effects
Caution should be exercised when prescribing the medicinal product to dehydrated patients, especially children, adolescents, and elderly patients, due to the risk of developing renal impairment.
Chronic use of analgesics, particularly when combined with multiple pain-relieving substances, may lead to irreversible kidney damage with a risk of renal failure (analgesic nephropathy). This risk may be increased under conditions of physical exertion associated with salt loss and dehydration. Therefore, such use should be avoided.
Caution is required when prescribing the medicinal product to patients with hypertension and/or cardiac disorders due to possible impairment of renal function (see sections "Contraindications" and "Adverse reactions").
Renal tubular acidosis and hypokalemia may occur after acute overdose and in patients taking high doses of ibuprofen over a prolonged period (usually longer than 4 weeks), including doses exceeding the recommended daily dose.
Long-term use of ibuprofen, as with other NSAIDs, has been associated with renal papillary necrosis and other pathological renal function disorders. Toxic renal injury has been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. NSAID use in these patients may lead to dose-dependent reduction in prostaglandin synthesis and, as a secondary effect, reduced renal blood flow, which may rapidly result in renal decompensation. The highest risk of such reactions exists in patients with impaired renal function, cardiac decompensation, hepatic dysfunction, elderly patients, and those taking diuretics and ACE inhibitors. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.
Respiratory effects
Ibuprofen should be prescribed with caution to patients with bronchial asthma, chronic rhinitis, or allergic disorders, including a history thereof, as cases of bronchospasm, urticaria, or Quincke’s edema associated with NSAID use have been reported in such patients.
Serious skin adverse reactions (SSARs)
Serious skin adverse reactions (SSARs), including exfoliative dermatitis, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.
If signs or symptoms indicating these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment options should be considered (if necessary).
In rare cases, serious skin and soft tissue infections may be associated with varicella. At present, the influence of NSAIDs on the exacerbation of such infections cannot be excluded. Therefore, the use of ibuprofen is not recommended in patients with varicella.
Systemic lupus erythematosus (SLE) and mixed connective tissue disorders
Caution should be exercised when prescribing the medicinal product to patients with SLE or mixed connective tissue disorders. There is an increased risk of aseptic meningitis (see section "Adverse reactions").
Cardiac, renal, and hepatic impairment
Particular caution should be exercised when treating patients with cardiac, hepatic, or renal impairment, as NSAID use may lead to renal dysfunction.
Regular concomitant use of analgesics may increase this risk. Patients with cardiac, hepatic, or renal impairment should receive treatment with the lowest effective dose for the shortest possible duration, and their clinical and laboratory parameters should be monitored periodically, especially during long-term therapy (see section "Contraindications").
Hematological effects
Like other NSAIDs, ibuprofen may inhibit platelet aggregation and has been shown to prolong bleeding time in healthy volunteers. Therefore, patients with coagulation disorders or those receiving anticoagulant therapy should be closely monitored.
Aseptic meningitis
In rare cases, symptoms of aseptic meningitis have been observed in patients taking ibuprofen. Although this is more likely in patients with SLE and related connective tissue disorders, it has also been observed in patients without chronic disease manifestations (see section "Adverse reactions").
Ibuprofen may mask symptoms of infection (fever, pain, and swelling).
The use of AFFIDA SYRUP, like any inhibitor of prostaglandin synthesis and cyclooxygenase, is contraindicated in women intending to become pregnant (see section "Use during pregnancy or breastfeeding"). AFFIDA SYRUP should be discontinued in women experiencing fertility problems or undergoing fertility testing.
Allergic reactions
Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. If the first signs of hypersensitivity occur after taking ibuprofen, therapy should be discontinued immediately, and qualified medical personnel should be involved to provide appropriate medical interventions based on symptoms.
Caution should be exercised when prescribing ibuprofen to patients who have experienced hypersensitivity or allergic reactions to other substances, such as other analgesics, antipyretics, or NSAIDs, as they are at increased risk of hypersensitivity reactions when taking ibuprofen.
Caution is also required when prescribing ibuprofen to patients with bronchial hyperreactivity (asthma), hay fever, nasal polyps, chronic obstructive pulmonary diseases, or previous episodes of angioedema, due to the increased risk of allergic reactions in such patients. These may manifest as asthma attacks (so-called analgesic-induced asthma), Quincke’s edema, or urticaria.
Masking symptoms of underlying infections
Like other NSAIDs, ibuprofen may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief in infectious disease, monitoring of the condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.
Information on excipients
The medicinal product contains sucrose and sorbitol. Therefore, it should not be administered to patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency. These factors should also be considered when treating patients with diabetes mellitus. The medicinal product may be harmful to teeth.
The medicinal product contains methylparahydroxybenzoate and propylparahydroxybenzoate, which may cause allergic reactions (possibly delayed).
The medicinal product contains the colorant sunset yellow (E 110), which may cause allergic reactions.
The medicinal product contains aspartame (E 951), a phenylalanine derivative, which poses a risk to patients with phenylketonuria.
Use during pregnancy or breastfeeding.
Effects on fertility
Data indicate that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects, and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with higher doses and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation losses and embryonic/fetal mortality. In addition, an increased frequency of various developmental abnormalities, including cardiovascular malformations, was observed in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, which in most cases resolved after stopping treatment. Therefore, ibuprofen should not be prescribed during the first and second trimesters of pregnancy unless absolutely necessary. If ibuprofen is prescribed to women planning pregnancy or during the first or second trimester, the lowest possible dose should be used for the shortest possible duration.
Prenatal monitoring for oligohydramnios and arterial duct constriction may be advisable after exposure to ibuprofen for several days starting from the 20th gestational week. The use of the medicinal product containing ibuprofen should be discontinued if oligohydramnios or arterial duct constriction is detected.
The use of any prostaglandin synthesis inhibitors during the third trimester of pregnancy may affect the fetus, causing:
- cardiovascular and pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
- renal dysfunction (see above).
Towards the end of pregnancy, prostaglandin synthesis inhibitors may affect both the mother and the fetus:
- possible prolongation of bleeding time, antiplatelet effect, which may occur even with very low doses;
- inhibition of uterine contractions, potentially leading to delayed and prolonged labor.
Thus, the use of ibuprofen during the third trimester of pregnancy is contraindicated (see section "Contraindications").
Labor
The use of ibuprofen during labor is not recommended. Possible effects include delayed and prolonged labor, as well as prolonged bleeding time in both mother and child.
Use during breastfeeding
In a limited number of studies, ibuprofen was detected in breast milk at very low concentrations. Ibuprofen is not recommended for administration to breastfeeding women.
Ability to influence reaction speed when driving or operating machinery.
Ibuprofen may affect patients' reaction speed, as headache, drowsiness, dizziness, fatigue, and visual disturbances may occur. This should be taken into account during activities requiring high concentration, such as driving or operating machinery. This is of particular concern when ibuprofen is taken concomitantly with alcohol.
Method of Administration and Dosage.
Doses
For oral use only and short-term treatment.
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Precautions").
The dose of ibuprofen depends on the patient's age and body weight. The maximum single dose for adolescents should not exceed 400 mg of ibuprofen.
A single dose exceeding 400 mg does not provide better analgesic effect. The interval between doses should be at least 4 hours.
The total daily dose for adolescents should not exceed 1200 mg of ibuprofen within 24 hours.
Adolescents (from 12 years of age)
200–400 mg (10–20 mL) as a single dose or 3–4 times daily.
For children, the daily dose is 20 mg/kg/day, divided into 3–4 doses, as described in the table below (data in the table are given as an example for children with body weight from 7 to 30 kg, but are not limited to these values).
For correct calculation of the daily dose, it is assumed that 1 mL of the medicinal product corresponds to 1 kg of body weight and contains 20 mg of ibuprofen (e.g., for a child weighing 9 kg, 9 mL of the medicinal product is administered daily, equivalent to 180 mg of ibuprofen). To calculate the single dose, divide the daily dose by 3–4 administrations.
AFFIDA SYRUP, 100 mg/5 mL, is not recommended for use in children with body weight less than 7 kg.
The medicinal product can be administered using the measuring syringe provided in the package.
| Body weight, kg |
Amount of ibuprofen (milligrams per dose) |
Daily frequency |
Corresponding volume in milliliters per dose |
| 7 |
46.7 |
3 times |
2.3 |
| 9 |
60 |
3–4 times |
3 |
| 12 |
80 |
3–4 times |
4 |
| 15 |
100 |
3–4 times |
5 |
| 18 |
120 |
3–4 times |
6 |
| 21 |
140 |
3–4 times |
7 |
| 24 |
160 |
3–4 times |
8 |
| 27 |
180 |
3–4 times |
9 |
| 30 |
200 |
3–4 times |
10 |
The drug can be taken on an empty stomach for faster onset of action. Patients suffering from gastrointestinal disorders should take the drug during meals.
There are no special recommendations regarding whether the drug should be taken with water.
The drug should not be used for more than 3 days without consulting a doctor.
Children under 6 months of age: if symptoms worsen or persist for more than 24 hours from the start of treatment, immediate medical advice should be sought.
If symptoms in children aged 6 months and older and adolescents persist for more than 3 days from the start of treatment or worsen, medical advice should be sought.
Patients with renal impairment
For patients with mild or moderate renal impairment, the lowest possible dose should be used for the shortest duration necessary to control symptoms, and renal function should be monitored (for patients with severe renal impairment, see section "Contraindications").
Patients with hepatic impairment (see section "Pharmacological properties")
For patients with mild or moderate hepatic impairment, the lowest possible dose should be used for the shortest duration necessary to control symptoms, and liver function should be monitored. The medicinal product AFFIDA SYRUP is contraindicated in patients with severe hepatic insufficiency (for patients with severe hepatic impairment, see section "Contraindications").
Children.
The drug is indicated for children with body weight of 7 kg and above.
Overdose.
Toxicity
Signs of toxicity in children or adults have generally not been observed at doses below 100 mg/kg. However, supportive measures may be required in some cases. Signs of toxicity in children have been observed after doses of 400 mg/kg or higher. In adults, dose-dependent effects are less pronounced. The elimination half-life in overdose is 1.5–3 hours.
Symptoms
In most patients, symptoms of ibuprofen overdose appear within 4–6 hours after ingestion.
The most common symptoms of overdose include nausea, vomiting, abdominal pain, lethargy, and drowsiness.
Central nervous system (CNS) manifestations include headache, tinnitus, dizziness, seizures, and loss of consciousness.
Rarely reported effects include nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, coma, apnea, CNS depression, and respiratory depression.
Cardiovascular toxicity has been reported, including arterial hypotension, bradycardia, and tachycardia. In cases of significant overdose, kidney and liver injury may occur. Significant overdose is usually well tolerated if no other drugs are co-ingested. In severe poisonings, metabolic acidosis and prolonged prothrombin time/international normalized ratio (INR) may occur, likely due to interaction with circulating coagulation factors. Prolonged use at doses exceeding the recommended levels may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and generalized weakness (see sections "Special precautions" and "Adverse reactions").
Treatment
There is no specific antidote for ibuprofen overdose. Symptomatic treatment is required. Within one hour after ingestion of a potentially toxic amount, administration of activated charcoal should be considered. If necessary, serum electrolyte balance should be corrected. If the ingested amount exceeds 400 mg/kg, gastric lavage or gastric emptying should be performed within one hour after ingestion, followed by symptomatic treatment. Treatment should include ensuring airway patency and monitoring cardiac function and vital signs until the patient's condition normalizes. For up-to-date information, contact the local poison control center.
Side effects.
The most commonly reported adverse reactions are gastrointestinal disorders. There is a risk of developing peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes fatal, particularly in elderly patients (see section "Special precautions for use"). After taking the medication, cases of nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn’s disease have been reported (see section "Special precautions for use").
Gastritis has been reported less frequently.
Transient burning sensation in the mouth or throat may occur during treatment.
- Hypersensitivity
Hypersensitivity reactions have been observed during treatment with NSAIDs. These include non-specific allergic reactions and anaphylactic phenomena, respiratory tract reactivity including bronchial asthma, exacerbation of bronchial asthma, bronchospasm or dyspnea, and mixed skin reactions, including various types of rashes, pruritus, urticaria, purpura, angioedema, and, rarely, erythema multiforme and bullous dermatoses (including Stevens−Johnson syndrome and toxic epidermal necrolysis).
- Infections and infestations
Cases of skin inflammation worsening due to infection (e.g., development of necrotizing fasciitis) have been described during NSAID use. If signs of infection appear or worsen during ibuprofen treatment, the patient should seek immediate medical attention.
- Skin and subcutaneous tissue disorders
In exceptional cases, severe skin infections and soft tissue complications may occur during varicella (chickenpox) (see also "Infections and infestations" and section "Special precautions for use").
- Cardiovascular system disorders
Clinical trial data indicate that the use of ibuprofen, especially at high doses (2400 mg per day), may slightly increase the risk of arterial thrombotic events such as myocardial infarction or stroke (see section "Special precautions for use").
The adverse reactions listed below may be associated with ibuprofen and are classified by frequency and organ systems according to MedRA. The following frequency categories are used: 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 (frequency cannot be estimated from available data).
The stated frequencies refer to short-term use of the drug at a daily dose not exceeding 1200 mg of ibuprofen in oral dosage forms.
Infections and infestations
Uncommon: rhinitis.
Very rare: aseptic meningitis.
Blood and lymphatic system disorders
Very rare: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Initial symptoms may include fever, sore throat, oral ulceration, flu-like symptoms, severe fatigue, bleeding, and unexplained bruising.
Immune system disorders
Uncommon: hypersensitivity.
Very rare: severe hypersensitivity reactions.
Symptoms may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema, or severe shock).
Psychiatric disorders
Uncommon: insomnia, restlessness.
Rare: depression, confusion, hallucinations.
Nervous system disorders
Common: dizziness.
Uncommon: headache, paresthesia, somnolence.
Rare: optic neuritis.
Eye disorders
Uncommon: visual disturbances.
Rare: toxic optic neuropathy.
Ear and labyrinth disorders
Uncommon: hearing disturbances.
Rare: tinnitus, vertigo.
Respiratory, thoracic and mediastinal disorders
Uncommon: bronchial asthma, bronchospasm, dyspnea.
Gastrointestinal disorders
Common: dyspepsia, diarrhea, nausea, vomiting, abdominal pain, flatulence, constipation, melena, hematemesis, gastrointestinal bleeding.
Uncommon: gastritis, duodenal ulcer, gastric ulcer, ulcerative stomatitis, gastrointestinal perforation.
Very rare: pancreatitis.
Frequency not known: colitis and Crohn’s disease.
Hepatobiliary disorders
Uncommon: hepatitis, jaundice, abnormal liver function tests.
Rare: hepatic injury.
Very rare: liver failure.
Skin and subcutaneous tissue disorders
Uncommon: rash, urticaria, pruritus, purpura.
Very rare: severe cutaneous adverse reactions (SCARs), including erythema multiforme, exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis.
Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis.
Metabolism and nutrition disorders
Frequency not known: decreased appetite, hypokalemia*.
Renal and urinary disorders
Very rare: tubulointerstitial nephritis, nephrotic syndrome, renal failure.
Acute renal failure, papillary necrosis (especially with prolonged use), associated with increased plasma urea levels.
Frequency not known: ureteric colic, dysuria, renal tubular acidosis*.
General disorders and administration site conditions
Common: fatigue.
Rare: edema.
Cardiovascular disorders
Very rare: heart failure, myocardial infarction (see section "Special precautions for use"), arterial hypertension.
Frequency not known: Coupling syndrome.
*Renal tubular acidosis and hypokalemia have been reported during the post-marketing period, usually after prolonged use of ibuprofen at doses higher than recommended.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report any suspected adverse reactions and lack of efficacy to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua.
Shelf life.
3 years.
After first opening of the bottle: 3 months.
Storage conditions.
No special storage conditions required. Keep out of reach of children.
After first opening of the bottle, store at a temperature not exceeding 25°C.
Packaging.
100 ml in a dark glass bottle; 1 bottle with a dosing syringe in a cardboard box.
Prescription status.
Over-the-counter.
Manufacturer.
ALKALOID AD Skopje.
Manufacturer's address and place of business.
Boulevard Alexander the Great, 12, Skopje, 1000, North Macedonia.