Ibuprofen alkaloid
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN ALKALOID (IBUPROFEN ALKALOID)
Composition:
Active ingredient: ibuprofen;
5 ml of suspension contains ibuprofen 100.00 mg;
Excipients: glycerin; sorbitol, 70 % solution, non-crystallizing; xanthan gum; microcrystalline cellulose and sodium carmellose; polysorbate 80; disodium edetate; sodium saccharin; citric acid monohydrate; sodium citrate dihydrate; sodium benzoate; apricot flavor (components: propylene glycol 96 %; flavoring substance: gamma-decalactone, linalool, ethyl butyrate, benzaldehyde, hexyl acetate, diethyl malonate, vanillin; natural flavoring substance: citral; flavoring preparations: orange oil, lemon oil);
flavoring agent for taste masking (components: potato maltodextrin, flavoring components: glycyrrhizic acid (glycyrrhizin), ammoniated glycyrrhizic acid, sugar, aspartame E 951, acesulfame-K E 950);
simethicone emulsion, sodium chloride, purified water.
Pharmaceutical form. Oral suspension.
Main physicochemical characteristics: homogeneous suspension of almost white to brownish color with an apricot odor.
Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.
Pharmacological Properties.
Pharmacodynamics.
Ibuprofen is a propionic acid derivative and 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 significant 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 (aspirin) on platelet aggregation when administered concomitantly. Some pharmacodynamic studies have shown that a single 400 mg dose of ibuprofen taken 8 hours before or 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane production or platelet aggregation.
Although there are uncertainties regarding extrapolation of these findings to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically relevant effects are unlikely with occasional ibuprofen use.
Pharmacokinetics.
Ibuprofen is rapidly absorbed following oral administration. After administration on an empty stomach, peak plasma concentrations are reached within approximately 45 minutes.
When the same dose is taken after food, absorption is slower, with peak plasma concentrations occurring 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 ibuprofen dose 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 (bronchial asthma, rhinitis, angioneurotic edema, or urticaria) in response to administration of acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Increased tendency to bleeding or active bleeding.
Active or recurrent peptic ulcer disease or gastrointestinal hemorrhage in history (2 or more episodes of confirmed ulcer formation or bleeding).
History of gastrointestinal bleeding or perforation associated with use of NSAIDs.
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 types of interactions.
Any of the following medicinal products should be used with caution concomitantly with ibuprofen, as interactions have been observed 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 use of ACE inhibitors, beta-blockers, or angiotensin II receptor antagonists with cyclooxygenase inhibitors may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, especially in elderly patients.
Patients should consume adequate amounts of water. Renal function should be monitored at the beginning 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.
Methotrexate. NSAIDs may inhibit tubular secretion of methotrexate, reduce methotrexate clearance, and increase the risk of toxicity.
Moclobemide increases the effect of ibuprofen.
Cyclosporine increases the risk of NSAID-induced renal damage. This adverse effect cannot be excluded when combining cyclosporine with ibuprofen.
Mifepristone. A reduction in drug efficacy may theoretically occur due to the anti-prostaglandin properties of NSAIDs, including acetylsalicylic acid. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not alter the effect 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 used 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 and other medicinal products containing NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, is not recommended due to 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 are observed with occasional, non-regular use of ibuprofen (see section "Pharmacodynamics").
Sulfonylureas. NSAIDs may potentiate the effects of sulfonylurea drugs. Rare cases of hypoglycemia have been reported in patients receiving sulfonylureas when ibuprofen was prescribed. Glucose monitoring is recommended when used concomitantly.
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 used during zidovudine therapy. Hematological evaluation 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 gastrointestinal absorption of ibuprofen. 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 increase 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 use of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (CYP2C9 substrate). One study demonstrated that 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 effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and the effects on the gastrointestinal tract and cardiovascular system described below).
Like other NSAIDs, ibuprofen may mask signs of infection, potentially leading to delayed initiation of appropriate treatment and thus worsening the patient's condition. Such events have been observed in community-acquired bacterial pneumonia and bacterial complications during varicella. If ibuprofen is used to relieve pain and fever during an infectious disease, the course of infection should be monitored. Medical advice should be sought if symptoms do not resolve or worsen.
Concomitant use of ibuprofen with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to the possibility of 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 by increasing the dose of this medicinal product.
Concomitant alcohol consumption during NSAID use may increase the risk of adverse effects caused by the active substance, particularly those affecting the gastrointestinal tract or central nervous system (CNS).
Elderly patients
Elderly patients have an increased frequency of adverse reactions when taking NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
Cardiovascular 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 oedema 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, particularly at high doses (2400 mg daily), may increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological data show that low-dose ibuprofen (≤1200 mg daily) does not increase the risk of arterial thrombotic events. Ibuprofen should be prescribed with great caution in patients with uncontrolled hypertension, congestive heart failure (NYHA functional class II–III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, avoiding high-dose ibuprofen (2400 mg daily). Particular caution is required for long-term treatment in patients with risk factors for cardiovascular disorders (hypertension, hyperlipidaemia, diabetes, smoking), especially if high doses (2400 mg daily) of ibuprofen are needed.
Cases of Kounis syndrome have been reported in patients receiving ibuprofen. 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.
Gastrointestinal bleeding, ulceration, and perforation
Gastrointestinal bleeding, perforation, or ulceration, which may be fatal, have been reported with all NSAIDs at any stage of treatment. These events may occur without warning 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 such patients should be initiated at the lowest available dose.
For these patients, as well as for patients requiring concomitant therapy with low-dose acetylsalicylic acid or other agents that may increase the risk of gastrointestinal complications, the use of combination therapy with protective agents such as misoprostol or proton pump inhibitors should be considered (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 in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, 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 ulceration.
NSAIDs should be used with caution in patients with a history of peptic ulcers and other gastrointestinal disorders such as ulcerative colitis and Crohn’s disease, due to the potential for 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 failure.
Chronic use of analgesics, particularly when multiple pain-relieving substances are used concomitantly, may lead to irreversible kidney damage with a risk of renal failure (analgesic nephropathy). This risk may be increased during physical exertion associated with salt loss and dehydration. Therefore, such use should be avoided.
Caution should be exercised when prescribing the medicinal product to patients with hypertension and/or cardiac disorders due to the potential worsening of renal function (see sections "Contraindications" and "Adverse reactions").
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. Administration of NSAIDs to these patients may lead to dose-dependent reduction in prostaglandin synthesis and, as a secondary effect, to decreased 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 treatment is usually followed by recovery to the pre-treatment state.
Respiratory effects
Ibuprofen should be prescribed with caution in patients with bronchial asthma, chronic rhinitis, or allergic diseases, including those in their medical history, as cases of bronchospasm, urticaria, or Quincke's oedema induced by NSAIDs have been reported in such patients.
Serious skin adverse reactions (SSARs)
Serious skin adverse reactions (SSARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occur within the first month of treatment. If signs or symptoms suggestive of these reactions occur, ibuprofen should be discontinued immediately and alternative therapy considered (if necessary).
In rare cases, serious skin and soft tissue infections may be associated with varicella.
Currently, the influence of NSAIDs on the exacerbation of these infections cannot be excluded. Therefore, the use of ibuprofen is not recommended in patients with varicella.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Caution should be exercised when prescribing the medicinal product to patients with SLE and mixed connective tissue diseases. There is an increased risk of aseptic meningitis (see section "Adverse reactions").
Cardiac, renal, and hepatic function disorders
Particular caution should be exercised when treating patients with cardiac, hepatic, or renal dysfunction, as NSAID use may lead to worsening renal function.
Regular concomitant use of analgesics may increase this risk. Patients with cardiac, hepatic, or renal dysfunction should receive treatment at the lowest effective dose for the shortest possible duration, and clinical and laboratory parameters should be monitored periodically, especially during long-term treatment (see section "Contraindications").
Hematological effects
Like other NSAIDs, ibuprofen may inhibit platelet aggregation and has demonstrated evidence of prolonged 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 diseases, it has also been observed in patients without chronic disease manifestations (see section "Adverse reactions").
Infections
Ibuprofen may mask symptoms of infection (fever, pain, swelling).
Female fertility disorders
The use of ibuprofen, like any inhibitor of prostaglandin and cyclooxygenase synthesis, is contraindicated in women attempting to conceive (see section "Use during pregnancy or breastfeeding"). Treatment should be discontinued in women experiencing fertility problems or undergoing fertility testing.
hypersensitivity 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 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 with ibuprofen.
Caution is advised when prescribing ibuprofen to patients with bronchial hyperreactivity (asthma), hay fever, nasal polyps, or chronic obstructive respiratory diseases or previous episodes of angioedema, due to an increased risk of allergic reactions. These may manifest as asthma attacks (so-called analgesic-induced asthma), Quincke's oedema, or urticaria.
Information on excipients
The medicinal product contains aspartame (E 951), a phenylalanine derivative, which may be hazardous for patients with phenylketonuria.
The medicinal product contains sorbitol. If you have been diagnosed with intolerance to certain sugars, consult your physician before taking this medicinal product.
Contains 0.442 mmol (or 10.17 mg) of sodium in 5 ml; therefore, patients on a sodium-restricted diet should use this product with caution.
Use during pregnancy or breastfeeding.
Effect on fertility
Data indicate that drugs which 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 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. Additionally, the frequency of various malformations, including cardiovascular defects, increased 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 may occur shortly after starting treatment and is usually reversible upon discontinuation. 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 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. Monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to ibuprofen for several days starting from the 20th gestational week. Treatment with ibuprofen should be discontinued if oligohydramnios or arterial duct constriction is detected.
During the third trimester, all prostaglandin synthesis inhibitors cause:
Risks to the fetus:
- cardiopulmonary toxicity (with premature closure of the arterial duct 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 labour.
Thus, the use of ibuprofen during the third trimester of pregnancy is contraindicated (see section "Contraindications").
Labour and delivery
The use of ibuprofen during labour is not recommended. Labour may be delayed or prolonged, and bleeding time may be increased in both mother and child.
Use during breastfeeding
In a limited number of studies, ibuprofen has been detected in breast milk at very low concentrations. Ibuprofen is not recommended for use in breastfeeding women.
Ability to influence reaction speed when driving or operating machinery
The use of 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 increased attention, such as driving or operating machinery. This is particularly relevant when ibuprofen is taken concomitantly with alcohol.
Method of Administration and Dosage
Dosage
For oral use only and short-term treatment.
Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").
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 (aged 12 years and older)
200–400 mg (10–20 mL) as a single dose, repeated 3–4 times daily.
For children, the daily dose is 20 mg/kg, divided into 3–4 doses, as described in the table below (data in the table are provided as examples for children with body weight from 7 to 30 kg, but are not limited to these values).
To correctly calculate the daily dose, consider that 1 mL of suspension corresponds to 1 kg of body weight, which is equivalent to 20 mg of ibuprofen (for example, for a child weighing 9 kg, the daily dose is 9 mL of suspension, equivalent to 180 mg of ibuprofen). To determine the single dose, divide the total daily dose by 3–4 administrations.
Ibuprofen Alkaloid, 20 mg/mL suspension, is not recommended for use in children with body weight less than 7 kg.
The suspension can be administered using the dosing device provided in the package.
| Body weight, kg |
Amount of ibuprofen (milligrams per dose) |
Dosing frequency per day |
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 rapid onset of action. For patients suffering from gastrointestinal disorders, the drug should be taken with food.
There are no specific recommendations regarding whether the drug should be taken with water.
Without consulting a physician, the drug can be used for no more than 3 days.
Children under 6 months of age: if symptoms worsen or persist for more than 24 hours from the start of treatment, medical advice should be sought immediately.
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 to moderate renal impairment, the lowest possible dose should be used for the shortest duration necessary to control symptoms. Renal function should also be monitored (for patients with severe renal impairment, see section "Contraindications").
Patients with hepatic impairment (see section "Pharmacological properties")
For patients with mild to moderate hepatic impairment, the lowest possible dose should be used for the shortest duration necessary to control symptoms, and liver function should be monitored. Ibuprofen Alkaloid is contraindicated in patients with severe hepatic insufficiency (for patients with severe hepatic impairment, see section "Contraindications").
Children.
For use in children with body weight of at least 7 kg.
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. In children, signs of toxicity have been observed after doses of 400 mg/kg or higher. In adults, the dose-dependent effect is 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 are nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) manifestations include headache, tinnitus, dizziness, seizures, and loss of consciousness.
Rarely reported are nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, coma, apnea, CNS depression, and respiratory depression.
Cardiovascular toxicity has been reported, including the development of arterial hypotension, bradycardia, and tachycardia. In cases of significant overdose, kidney and liver damage may occur. Significant overdose is usually well tolerated if no other drugs are co-ingested. Severe poisoning may result in metabolic acidosis.
Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia.
Treatment
There is no specific antidote for ibuprofen overdose. If the ingested amount exceeds 400 mg/kg, gastric lavage or gastric emptying is recommended within 1 hour of ingestion, followed by symptomatic treatment. Management should include ensuring airway patency and monitoring cardiac function and vital signs until the patient's condition stabilizes. For the most up-to-date information, contact the local toxicology 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"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn's disease have been reported after taking the drug (see section "Special precautions").
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 NSAID therapy, including non-specific allergic reactions and anaphylactic reactions, respiratory tract reactivity (including bronchial asthma, worsening of bronchial asthma, bronchospasm, or dyspnea), or mixed skin manifestations such as various types of rashes, pruritus, urticaria, purpura, angioedema. In very rare cases, multi-form erythema and bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported.
- Infections and infestations
Exacerbations of skin inflammation due to infection (e.g., development of necrotizing fasciitis) have been reported during NSAID use. If signs of infection appear or worsen during ibuprofen treatment, the patient should seek immediate medical advice.
- Skin and subcutaneous tissue disorders
Severe skin infections and soft tissue complications may exceptionally occur during varicella (chickenpox) (see also sections "Side effects" ("Infections and infestations") and "Special precautions").
- Cardiovascular 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").
The following adverse reactions, potentially associated with ibuprofen, are classified by frequency and by organ system according to MedDRA. Frequency categories are defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <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 mucosal ulcers, influenza-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, anxiety.
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: liver injury.
Very rare: liver failure.
Skin and subcutaneous tissue disorders
Uncommon: rash, urticaria, pruritus, purpura.
Very rare: bullous dermatosis, severe skin adverse reactions (SSARs) (including multi-form erythema, 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 (AGEP), photosensitivity reactions.
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.
General disorders and administration site conditions
Common: fatigue.
Rare: edema.
Cardiovascular disorders
Very rare: heart failure, myocardial infarction (see section "Special precautions"), hypertension.
Frequency not known: Kounis syndrome.
Reporting suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: http://aisf.dec.gov.ua/.
Shelf life. 3 years.
Shelf life after opening the packaging – 3 months.
Storage conditions. Store out of reach of children. Store in the original packaging at a temperature not exceeding 25°C.
Packaging. 100 ml in a bottle. Each bottle, together with a dosing device and instructions for medical use, is placed in a carton.
Availability. Over-the-counter (without prescription).
Manufacturer. ALKALOID AD Skopje.
Manufacturer's address and location of operations.
Republic of North Macedonia, 1000 Skopje, Alexander the Great Boulevard, 12.