Darfen® kids forte: detailed information

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DARFEN® KIDS FORTE

Composition:

Active substance: ibuprofen;

5 ml of suspension contains ibuprofen 200 mg;

Excipients: sodium benzoate, anhydrous citric acid, sodium citrate, sodium saccharin, sodium chloride, hypromellose 15 cP, xanthan gum, maltitol liquid, glycerol (E 422), thaumatin, strawberry flavor, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: viscous suspension free from foreign particles, white or almost white in color, with a characteristic strawberry odor.

Pharmacotherapeutic group

Non-steroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated efficacy in inhibiting prostaglandin synthesis. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. The onset of analgesic and antipyretic action of ibuprofen occurs within 30 minutes. 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. In an open study, ibuprofen demonstrated 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 acetylsalicylic acid (aspirin) on platelet aggregation when both drugs are administered concomitantly. In one study, when a single 400 mg dose of ibuprofen was taken within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg), a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions about the systematic use of ibuprofen. Clinically significant interactions are considered unlikely with occasional (non-systematic) use of ibuprofen.

Pharmacokinetics

Ibuprofen is rapidly absorbed after administration and quickly distributed throughout the body. Elimination is rapid and complete, occurring via the kidneys.

Maximum plasma concentrations are reached within 45 minutes after oral administration on an empty stomach. When administered with food, peak levels are observed within 1–2 hours.

This time may vary depending on the pharmaceutical formulation.

The elimination half-life is approximately 2 hours.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations.

Clinical characteristics

Indications. Symptomatic treatment of fever and pain of various origins in children aged 6 months to 12 years weighing at least 8 kg (including post-vaccination fever, acute respiratory viral infections, influenza, teething pain, post-extraction dental pain, toothache, headache, sore throat, ligament sprain pain, 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, or other NSAIDs.
Active peptic ulceration or gastrointestinal bleeding, or history of recurrent episodes (two or more episodes of confirmed peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Active inflammatory bowel disease.
Cerebrovascular or other hemorrhages.
Hemorrhagic diathesis or other coagulation disorders.
Severe heart failure (NYHA Class IV [New York Heart Association]), severe hepatic insufficiency, or severe renal insufficiency.
Third trimester of pregnancy.
Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
Hereditary fructose intolerance.

Interaction with other medicinal products and other forms of interaction

Ibuprofen, like other NSAIDs, should not be used in combination with:

− acetylsalicylic acid, as this increases the risk of adverse reactions, except when acetylsalicylic acid (dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose acetylsalicylic acid. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical outcomes preclude definitive conclusions regarding the systematic use of ibuprofen. With occasional use of ibuprofen, such clinically significant effects are considered unlikely;

− other NSAIDs, including selective cyclooxygenase-2 inhibitors, as this increases the risk of adverse effects.

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

− anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin;

− antihypertensive agents (angiotensin-converting enzyme inhibitors [ACE inhibitors], beta-blockers, and angiotensin II antagonists): NSAIDs may reduce the efficacy of these drugs. 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 possible acute renal failure, which is usually reversible. 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 levels of glycosides. NSAIDs may elevate digoxin plasma concentrations, thereby increasing the risk of digoxin toxicity;

− pentoxifylline: in patients receiving ibuprofen in combination with pentoxifylline, the risk of hemorrhage is increased;

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

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

− methotrexate at doses below 15 mg/week: ibuprofen may increase methotrexate levels. Careful monitoring of the patient's blood count is required when ibuprofen is used concomitantly with low-dose methotrexate. Enhanced monitoring is necessary in cases of worsening renal function, even minimally, and in elderly patients. Renal function should be monitored to prevent potential reduction in methotrexate clearance;

− cyclosporine and tacrolimus: increased risk of nephrotoxicity with concomitant use of NSAIDs due to reduced renal prostaglandin synthesis. Renal function should be closely monitored when these medicinal products are used together with NSAIDs;

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

− sulfonylurea derivatives: interactions between NSAIDs and hypoglycemic agents (sulfonylureas) have been observed. NSAIDs may potentiate the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding sites; 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 required;

− baclofen: risk of baclofen toxicity following 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-induced sodium excretion;

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

− cholestyramine: ibuprofen and cholestyramine should be taken several hours apart due to delayed and reduced (by 25%) absorption of ibuprofen when administered concomitantly;
− zidovudine: increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. Evidence suggests increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen;
− herbal extracts: concomitant use of Ginkgo biloba with NSAIDs may potentiate the risk of bleeding;
− quinolone antibiotics: animal studies indicate that NSAIDs 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 levels of phenytoin may increase during concomitant treatment with ibuprofen. Serum phenytoin levels usually do not require monitoring with appropriate use (maximum for 4 days);
− thiazides, thiazide-like agents, loop diuretics, and potassium-sparing diuretics: NSAIDs may counteract the diuretic effect of these agents. Concomitant use of NSAIDs and diuretics increases the risk of NSAID-induced nephrotoxicity (e.g., in dehydrated patients or elderly patients with impaired renal function) due to deterioration in renal blood flow. Therefore, such combinations should be used cautiously, especially in elderly patients. Adequate fluid intake is required, 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; thus, 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 required to treat symptoms for the shortest possible duration.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal. Elderly patients are at increased risk of adverse reaction outcomes. Prolonged use of NSAIDs is not recommended in elderly patients. In cases of long-term therapy, regular monitoring of the patient's condition is required.

The following conditions require caution:

− systemic lupus erythematosus and mixed connective tissue disease — due to increased risk of aseptic meningitis;

− congenital porphyrin metabolism disorders, e.g., acute intermittent porphyria;

− gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);

− history of arterial hypertension and/or heart failure — due to reports of fluid retention and edema associated with NSAID therapy;

− renal impairment — due to possible worsening of kidney function;

− hepatic dysfunction;

− immediately after major surgical procedures;

− hay fever, nasal polyps, or chronic obstructive respiratory diseases — due to increased risk of allergic reactions, including asthma attacks (so-called analgesic-induced asthma), Quincke’s edema (angioedema), 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 suffering from bronchial asthma or allergic diseases, or with such conditions in their medical history.

Other NSAIDs

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

Like other NSAIDs, ibuprofen may cause allergic reactions, such as anaphylactic/anaphylactoid reactions, even when used for the first time.

Systemic lupus erythematosus and mixed connective tissue disease

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

Cardiovascular and cerebrovascular effects

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

Clinical studies and epidemiological data indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and during long-term treatment, may cause a small increase in the risk of arterial thrombotic complications (such as myocardial infarction or stroke). Epidemiological studies do not show that low-dose ibuprofen (e.g., ≤1200 mg per day) increases the risk of myocardial infarction.

Cases of Kounis syndrome have been reported in patients receiving Darfen® Kids Forte. Kounis syndrome manifests as cardiovascular symptoms associated with coronary artery constriction due to an allergic or hypersensitivity reaction, which may potentially lead to myocardial infarction.

Patients with uncontrolled arterial 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 clinical assessment. High doses (2400 mg per day) should be avoided.

Careful clinical assessment is also required before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Effects on kidneys and liver

Caution is required 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 during concomitant diuretic therapy, 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 kidney function should be monitored regularly. Adequate fluid intake should be ensured in cases of dehydration. There is a risk of renal failure in dehydrated children and adolescents.

Chronic 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, cardiac, or hepatic impairment, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, kidney function usually returns to the pre-treatment state.

Liver function may be impaired. Like other NSAIDs, ibuprofen may cause transient increases in certain liver function parameters, as well as significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. If these parameters increase significantly, treatment should be discontinued.

Gastrointestinal effects

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as their condition may worsen. Such patients should consult a physician.

Cases of gastrointestinal bleeding, perforation, and ulcers, potentially fatal, have been reported during NSAID therapy at any stage, 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 (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest doses. For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal damage, 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 is required when treating patients who are concurrently taking medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid).

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

Severe skin reactions

Severe skin adverse reactions have been reported with ibuprofen use, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions"). Most such reactions occurred within the first month.

If signs or symptoms indicating these reactions appear, ibuprofen should be discontinued immediately, and alternative treatment options should be considered (if necessary).

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

In exceptional cases, chickenpox may lead to severe skin and soft tissue infections. The influence of NSAIDs on worsening these infections cannot be ruled out; therefore, ibuprofen use is not recommended in cases of chickenpox.

Masking symptoms of underlying infections

NSAIDs may mask symptoms of infection and fever.

Darfen® Kids Forte may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating disease progression. This phenomenon has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When ibuprofen is used for fever or pain relief during infection, monitoring for infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

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

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

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 with frequent or daily headaches despite regular use of headache medications.

Unwanted reactions associated with the active substance, particularly those affecting the gastrointestinal tract or central nervous system, may be intensified by concomitant alcohol consumption and NSAID use.

Before taking this medication, consult a physician: pregnant women, women trying to conceive, elderly individuals, and smokers.

Effect on laboratory test results:

− bleeding time may be prolonged for up to one day after discontinuation of treatment;

− blood glucose concentration may decrease;

− creatinine clearance may decrease;

− hematocrit or hemoglobin levels may decrease;

− blood urea nitrogen concentration and serum creatinine and potassium concentrations may increase;

− liver function tests: increased transaminase levels.

Important information about excipients

Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect. The energy value of 1 g of maltitol is 2.3 kcal. It should not be administered to patients with rare hereditary fructose intolerance.

The medicinal product contains sodium compounds. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Pregnancy

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with higher doses and longer duration of therapy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%.

From the 20th week of pregnancy, the use of ibuprofen may cause oligohydramnios due to fetal kidney dysfunction. This disorder may occur soon after starting treatment and is usually reversible after discontinuation. Additionally, cases of arterial duct constriction after second-trimester treatment have been reported, most of which resolved after stopping treatment. Ibuprofen should not be used during the first two trimesters of pregnancy unless, in the physician’s opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose for the shortest duration should be used.

Prenatal 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 Darfen® Kids Forte should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

for the fetus:

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

for the mother at the end of pregnancy and the newborn:

prolonged bleeding time, antiplatelet effect (which may occur even at very low doses);
inhibition of uterine contractions, leading to delayed or prolonged labor;
increased risk of edema in the mother.

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

Breastfeeding Ibuprofen and its metabolites pass into breast milk in low concentrations. Currently, there is no information on negative effects on the infant; therefore, short-term treatment of pain and fever at recommended doses usually does not require interruption of breastfeeding.

Fertility Limited data suggest that cyclooxygenase/prostaglandin synthesis inhibitors 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 infertility or undergoing fertility investigations, 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 during ibuprofen use should avoid driving or operating machinery during treatment with this medicinal product.

When a single dose of ibuprofen is used or the drug is taken for a short period, no special precautions are required.

Dosage and Administration

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

For oral use. The medicinal product can be administered diluted with water or undiluted. The recommended daily dose of the medicinal product 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. The recommended dose should not be exceeded. For short-term use only. Shake well before use.

Child's age Body weight (kg)	Recommended dose	Daily frequency
6–12 months (8–10 kg)	1.25 ml of suspension (50 mg)	3–4 times
1–3 years (10–15 kg)	2.5 ml of suspension (100 mg)	3 times
3–6 years (15–20 kg)	3.75 ml of suspension (150 mg)	3 times
6–9 years (20–30 kg)	5 ml of suspension (200 mg)	3 times
9–12 years (30–40 kg)	7.5 ml of suspension (300 mg)	3 times

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

Patients with sensitive stomachs 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 insufficiency.

Ibuprofen should not be used in patients with severe renal insufficiency (see section "Contraindications").

Although no differences in the pharmacokinetic profile of ibuprofen have been observed in patients with hepatic insufficiency, NSAIDs should be used with caution in such patients. Patients with mild to moderate hepatic insufficiency should start treatment with low doses and be closely monitored. Ibuprofen should not be used in patients with severe hepatic insufficiency (see section "Contraindications").

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

In case of exceeding the recommended dose, immediate medical advice should be sought.

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

Overdose

In pediatric patients, symptoms of overdose may occur following ingestion of ibuprofen doses exceeding 400 mg/kg. In adults, reactions to overdose are 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 frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, including vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may sometimes occur. Prolonged use of doses higher than recommended or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, hypothermia and prolonged prothrombin time/international normalized ratio [INR] may occur (likely due to interaction with circulating blood coagulation factors). Acute renal failure, liver damage, hypotension, respiratory depression, and cyanosis may also develop. In patients with bronchial asthma, an exacerbation of asthma may occur. Nystagmus, visual disturbances, and loss of consciousness may also occur.

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 oral activated charcoal or gastric lavage if less than 1 hour has passed since ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be used to enhance urinary excretion of acidic ibuprofen. In cases of frequent or prolonged seizures, intravenous administration of anticonvulsant agents (e.g., diazepam or lorazepam) should be administered. Bronchodilators should be used in cases of bronchial asthma. Immediate medical attention should be sought.

Adverse Reactions

The list of adverse reactions includes all undesirable effects reported during treatment with ibuprofen, particularly those observed during long-term use of high doses in patients with rheumatism. The frequencies exceeding very rare reports refer to short-term use of oral dosage forms (maximum 1200 mg of ibuprofen per day).

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

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

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

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

There are case reports of infection-related inflammation exacerbations, such as necrotizing fasciitis, temporally associated with NSAID use. This may be related to the mechanism of action of NSAIDs.

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

Blood tests should be performed regularly during long-term therapy.

Patients should immediately consult a physician and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even upon first use 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.

Eye disorders:

Frequency not known: Visual disturbances and optic neuritis may occur during prolonged treatment.

Ear and labyrinth disorders:

Frequency not known: Dizziness may occur during prolonged treatment;
Rare: Tinnitus.

Respiratory, thoracic and mediastinal disorders:

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

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 or Crohn’s disease;
Very rare: Esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders:

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

Renal and urinary disorders:

Rare: Acute renal function impairment, especially with prolonged NSAID use, associated with increased serum urea levels and edema; papillary necrosis;
Very rare: Edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Nervous system disorders:

Uncommon: Headache, dizziness, insomnia, restlessness, irritability, or fatigue;
Very rare: Aseptic meningitis².

Psychiatric disorders:

Very rare: Psychotic reactions, depression; hallucinations, confusion (only with prolonged use).

Cardiovascular disorders:

Very rare: Heart failure, tachycardia, edema, myocardial infarction, arterial hypertension, vasculitis;
Frequency not known: Coats’ syndrome.

Blood and lymphatic system disorders:

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

Immune system disorders:

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

Skin and subcutaneous tissue disorders:

Uncommon: Various skin rashes¹;
Very rare: Severe skin adverse reactions (including erythema multiforme, exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis¹), alopecia;
Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis, photosensitivity reactions.

General disorders and administration site conditions:

Frequency not known: Malaise and fatigue.

Investigations:

Rare: Decreased hemoglobin levels.

Infections and infestations:

Very rare: Exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis); in rare cases, varicella may lead to severe skin and soft tissue infections.

¹ Hypersensitivity reactions have been reported following ibuprofen treatment. These include:

− Non-specific allergic reactions and anaphylaxis;
− Respiratory tract reactions, including bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea;
− Various skin disorders, including rashes of different types, pruritus, urticaria, purpura, angioedema, 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 is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug intake and symptom resolution after drug discontinuation). In particular, isolated symptoms of aseptic meningitis (such as nuchal rigidity, headache, nausea, vomiting, malaise, or disorientation) have been observed during ibuprofen treatment in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus or mixed connective tissue disease).

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and/or lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life: 3 years. After first opening of the bottle — 6 months.

Storage conditions

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

Packaging
100 ml in a bottle; 1 bottle with a dosing syringe in a carton.

Availability
Over-the-counter.

Manufacturer

Delpharm Bladel B.V. / Delpharm Bladel B.V.
Edefarm, S.L. / Edefarm, S.L.
Farmalider S.A. / Farmalider S.A.

Manufacturer's address and site of operations

Industrieweg 1, Bladel, 5531 AD, Netherlands
Polígono Industrial Enchilagar del Rullo, 117, C.P. 46191 Villamarchante, Valencia, Spain
Calle De Los Aragoneses 2, Poligono Industrial Calabozos, Alcobendas, 28108, Spain

Marketing Authorization Holder
JSC "Pharmaceutical Company "Darnytsia"

Address of Marketing Authorization Holder
13 Boryspylska Street, Kyiv, 02093, Ukraine