Brufen® rapid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BRUFEN® Rapid

Composition:

Active substance: ibuprofen;

1 soft capsule contains 400 mg of ibuprofen;

Excipients: macrogols (polyethylene glycol 600), potassium hydroxide (85 % purity), purified water;

capsule shell: gelatin, sorbitol solution partially dehydrated (E 420), purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical characteristics: pale yellow, transparent, oval-shaped soft gelatin capsules with a transparent content and the mark «#» printed in white ink.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01A E01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid, which has demonstrated efficacy in inhibiting the synthesis of prostaglandins—mediators of pain and inflammation. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when these drugs are used concomitantly. Some pharmacodynamic studies have shown that administration of single doses of 400 mg ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) was associated with reduced effects of acetylsalicylic acid (aspirin) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding the extrapolation of these data to clinical situations, the possibility cannot be excluded that regular long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely.

Inside the capsule of the Brufen® Rapid medicinal product, ibuprofen is dissolved in a hydrophilic solvent. After oral administration, the gelatin capsule disintegrates under the action of gastric juice, thereby releasing pre-dissolved ibuprofen.

Pharmacokinetics.

After oral administration, ibuprofen is rapidly absorbed, partially already in the stomach, and completely in the small intestine.

Following hepatic metabolism (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are excreted predominantly in urine (90%) and also in bile. The elimination half-life in healthy volunteers, as well as in patients with liver or kidney disease, ranges from 1.8 to 3.5 hours. Plasma protein binding is approximately 99%. After oral administration of the conventional release dosage form, maximum plasma concentration is reached within 1–2 hours. In a pharmacokinetic study, the time to peak plasma levels (Tmax) under fasting conditions was 90 minutes for the tablet dosage form and 40 minutes for the soft capsule dosage form. Ibuprofen remains detectable in plasma for more than 8 hours after administration of the soft capsule dosage form.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain of various origins (headache, toothache, painful menstruation), including pain associated with colds and fever.

Contraindications.

• Hypersensitivity to ibuprofen or to any of the excipients of the medicinal product.
• Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
• Active peptic ulcer / gastrointestinal bleeding or history of recurrent episodes (two or more distinct episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with the use of NSAIDs.
• Severe impairment of liver function, severe impairment of kidney function, severe heart failure (NYHA [New York Heart Association] Class IV).
• Third trimester of pregnancy.
• Active cerebrovascular or other bleeding.
• Hemorrhagic diathesis or coagulation disorders.
• Unexplained blood dyscrasias.
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
• Patient body weight less than 40 kg or patient age under 12 years.

Interaction with other medicinal products and other forms of interaction.

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

• acetylsalicylic acid (aspirin), as this increases the risk of adverse reactions — except when aspirin (dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation. However, due to limitations in extrapolating these data to clinical practice, it is not possible to draw definitive conclusions regarding whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. For occasional use of ibuprofen, such clinically significant effects are considered unlikely;
• other NSAIDs, including selective cyclooxygenase-2 inhibitors: simultaneous use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided.

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

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

Antihypertensive agents (ACE inhibitors [angiotensin-converting enzyme inhibitors] and angiotensin II antagonists) and diuretics: NSAIDs may reduce the efficacy of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised kidney function), concomitant use of ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, particularly in elderly patients. If long-term treatment is necessary, adequate hydration should be ensured and monitoring of renal function should be considered at the start of combined therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium levels should be monitored).

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

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

Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Lithium: evidence suggests a potential increase in plasma lithium levels.

Phenytoin: concomitant use with phenytoin preparations may increase its serum concentration.

Methotrexate: administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate concentrations and enhance its toxicity.

Cyclosporine: increased risk of nephrotoxicity.

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

Tacrolimus: possible increased risk of nephrotoxicity when NSAIDs are used concomitantly with tacrolimus.

Zidovudine: increased risk of hematological toxicity is known with concomitant use of zidovudine and NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen.

Quinolone antibiotics: concurrent use with ibuprofen may increase the risk of seizures.

Sulfonylureas: blood glucose levels should be monitored as a precaution when used concomitantly.

Probenecid and sulfinpyrazone: may delay elimination of ibuprofen.

CYP2C9 inhibitors: concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in the effect of S(+)-ibuprofen. Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are used with voriconazole or fluconazole.

Special precautions for use.

Adverse effects of ibuprofen, as with all other NSAIDs, can be minimized by using the lowest effective dose required to treat symptoms for the shortest possible duration.

Caution is necessary when treating patients:

• with systemic lupus erythematosus or mixed connective tissue disease — increased risk of aseptic meningitis (see section "Adverse reactions");
• with congenital porphyrin metabolism disorders (e.g., acute intermittent porphyria);
• with gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) (see section "Adverse reactions");
• with arterial hypertension and/or heart failure (see sections "Contraindications" and "Adverse reactions");
• with impaired renal function — as kidney function may deteriorate (see sections "Contraindications" and "Adverse reactions");
• with impaired hepatic function (see sections "Contraindications" and "Adverse reactions");
• following major surgical procedures;
• with allergic reactions to other substances — as they also have an increased risk of hypersensitivity reactions when using the medicinal product;
• suffering from hay fever, nasal polyps, chronic obstructive respiratory diseases, or with a history of allergic diseases — as they have an increased risk of allergic reactions. In such patients, asthma attacks (so-called analgesic-induced asthma), Quincke's edema, or urticaria may occur.

Elderly patients

In elderly patients, there is an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal.

Respiratory effects

Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with a history of such conditions.

Other NSAIDs

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

Systemic lupus erythematosus and mixed connective tissue diseases

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

Porphyrin metabolism

Caution should be exercised in patients with congenital porphyrin metabolism disorders (e.g., acute intermittent porphyria).

Cardiovascular and cerebrovascular effects

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

Renal tubular acidosis and hypokalemia may develop after acute overdose or with prolonged use of high doses of ibuprofen (usually longer than 4 weeks), including doses exceeding the recommended daily dose.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg per day), may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g., ≤1200 mg per day) increases the risk of arterial thrombotic complications.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful assessment of the clinical condition. High doses (2400 mg per day) should be avoided.

A careful clinical evaluation should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may potentially lead to myocardial infarction.

Renal effects

Ibuprofen should be used with caution in patients with impaired renal function, as renal function may deteriorate.

Hepatic effects

Ibuprofen may impair liver function.

Surgical procedures

Caution should be exercised when using ibuprofen immediately after major surgical procedures.

Effects on female fertility

Limited data suggest that medicinal products which inhibit cyclooxygenase/prostaglandin synthesis, when used long-term (doses of 2400 mg daily and treatment duration exceeding 10 days), may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Gastrointestinal (GI) effects

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may worsen. Cases of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, have been reported at any stage of NSAID therapy, regardless of prior warning symptoms or history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, and ulcers increases with higher NSAID doses, in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment at the lowest possible dose. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase gastrointestinal risk, consideration should be given to concomitant protective therapy (e.g., misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal disorders, particularly elderly patients, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

Caution is required when treating patients receiving 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 (e.g., aspirin).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Severe cutaneous adverse reactions

Severe skin adverse reactions have been reported with ibuprofen, 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 (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment. If signs or symptoms suggestive of these reactions occur, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In rare cases, varicella may lead to severe skin and soft tissue infections. At present, a potential negative influence of NSAIDs on such infections cannot be excluded; therefore, it is recommended to avoid the use of ibuprofen in cases of varicella.

Allergy

Caution should be exercised in patients with allergic reactions to other substances, as such patients have an increased risk of hypersensitivity reactions when using ibuprofen.

Patients suffering from hay fever, nasal polyps, chronic obstructive respiratory diseases, or with a history of allergic diseases have an increased risk of allergic reactions, which 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 diseases, potentially delaying appropriate treatment and thereby worsening the course of the illness. Such symptom masking has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Excipients

Brufen® Rapid contains sorbitol. If the patient has known intolerance to certain sugars, consultation with a physician is required before taking this medicinal product.

Other

Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. If any signs of hypersensitivity occur after taking Brufen® Rapid, treatment must be discontinued immediately. Symptomatic and specialized treatment should be initiated in such cases.

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

During prolonged use of Brufen® Rapid, liver and kidney function tests, as well as blood counts, should be monitored regularly.

Prolonged use of any analgesic for headache treatment may worsen the condition. If suspected or confirmed, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients with frequent or daily headaches despite (or because of) regular use of headache medications.

Chronic use of analgesics, especially combinations of multiple analgesics, may lead to persistent kidney dysfunction with risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration.

The risk of adverse effects related to the active substance, particularly gastrointestinal or central nervous system (CNS) effects, may increase when NSAIDs are used concomitantly with alcohol.

There is a risk of impaired renal function in adolescents with dehydration.

Use during pregnancy or breastfeeding

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

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction following second-trimester treatment, which in most cases resolved after treatment cessation. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman trying to conceive or during the first and second trimesters, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to ibuprofen for several days starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

• to the fetus: cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension); renal dysfunction (see above);
• to the mother near term and to the newborn: prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses; inhibition of uterine contractions, leading to delayed or prolonged labor. Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

In a limited number of studies, ibuprofen has been detected in breast milk at very low concentrations, making it unlikely to adversely affect the breastfed infant. However, NSAIDs are not recommended during breastfeeding.

Fertility

Ibuprofen use may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, ibuprofen use is not recommended for women experiencing difficulty conceiving.

Ability to influence reaction rate while driving or operating machinery

Patients who experience dizziness, drowsiness, or visual disturbances while taking ibuprofen should avoid driving or operating machinery. Single-dose administration or short-term use of ibuprofen generally does not require special precautions. This primarily applies to concomitant use of the drug with alcohol.

When used according to recommended doses and treatment duration, the drug does not affect reaction speed while driving or operating machinery.

Method of Administration and Dosage

To minimize adverse effects of the medicinal product, the lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Instructions").

Brufen® Rapid is intended for oral administration to adults and children aged 12 years and older with body weight > 40 kg. For short-term use only.

Capsules should preferably be taken during or after meals, without chewing, and swallowed with water.

The single dose for children aged 12 years and older with body weight > 40 kg and for adults is 1 capsule (400 mg of ibuprofen). If necessary, 1 capsule may be administered every 6 hours. The maximum daily dose is 1200 mg (3 capsules per day). Use the lowest effective dose required to treat symptoms for the shortest possible duration (see section "Special Instructions").

If symptoms worsen or persist for more than 3 days in adolescents, medical advice should be sought to confirm diagnosis and adjust treatment regimen.

If elevated body temperature persists for more than 3 days in adults, or if pain does not resolve within 4 days, or if symptoms worsen, medical advice should be sought to confirm diagnosis and adjust treatment regimen.

The duration of treatment should be determined individually by a physician, depending on the course of the disease and the patient's condition.

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment. Due to the potential for adverse effects, elderly patients require careful monitoring.

Patients with mild to moderate renal impairment do not require dose reduction (for patients with severe renal impairment, see section "Contraindications").

Patients with mild to moderate hepatic impairment do not require dose reduction (for patients with severe hepatic impairment, see section "Contraindications").

Children

Do not administer to children under 12 years of age or with body weight < 40 kg.

Overdose

Administration of the medicinal product in doses exceeding 400 mg/kg in children may cause symptoms of intoxication. In adults, the dose-effect relationship is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients who have ingested clinically significant amounts of NSAIDs, only nausea, vomiting, epigastric pain, or very rarely diarrhea occur. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system (CNS) may develop, manifesting as dizziness, drowsiness, occasionally agitation, disorientation, or coma. Seizures may occasionally occur. Severe intoxication may lead to hyperkalemia and metabolic acidosis; prothrombin time / international normalized ratio (INR) may increase, likely due to interaction with circulating coagulation factors. Acute renal failure, liver damage, arterial hypotension, respiratory failure, and cyanosis may develop. In patients with bronchial asthma, disease exacerbation is possible.

Prolonged use at doses higher than recommended may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and generalized weakness (see sections "Special Instructions" and "Adverse Reactions").

Treatment. Treatment should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac and vital functions until condition stabilizes. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalinizing agents may be administered to enhance urinary excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators are required to treat exacerbations of bronchial asthma. Serum electrolyte imbalances should be corrected as needed. There is no specific antidote.

Side effects.

Below is a list of ibuprofen side effects observed during short-term use, as well as those reported during long-term high-dose therapy in patients with rheumatism. The specified frequencies exceeding very rare reports refer to short-term use of doses up to 1200 mg ibuprofen per day for oral dosage forms and up to 1800 mg per day for suppositories.

The development of adverse drug reactions primarily depends on dose and individual patient characteristics.

The most commonly observed side effects are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes with fatal outcomes, may occur, particularly in elderly patients. During treatment, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis or Crohn’s disease have been reported. Gastritis has been observed less frequently. The risk of gastrointestinal bleeding mainly depends on dose and duration of treatment. Cases of edema, arterial hypertension, and heart failure associated with NSAID therapy have been reported.

Clinical studies indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), is associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Hypersensitivity reactions have been reported, which may manifest as:

• Non-specific allergic reactions and anaphylaxis;
• Respiratory tract reactivity, such as asthma, asthma exacerbation, bronchospasm, dyspnea;
• Various skin reactions, such as pruritus, urticaria, angioedema, and less frequently, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Patients should immediately discontinue the medication and inform their physician if any of the above symptoms occur.

The adverse reactions associated with ibuprofen use are listed below by organ system and frequency of occurrence. Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), and frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in decreasing order of severity.

Infections and parasitic diseases.

Uncommon: rhinitis;
Very rare: exacerbation of infection-related inflammation.

If signs of infection occur or worsen during treatment, patients should seek immediate medical attention. The need for anti-infective or antibacterial therapy should be assessed.

Aseptic meningitis with nuchal rigidity, headache, nausea, vomiting, fever, or altered consciousness has been observed in patients with autoimmune diseases such as systemic lupus erythematosus or mixed connective tissue disease during ibuprofen use.

Blood and lymphatic system disorders.

Very rare: blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, neutropenia, agranulocytosis). Initial symptoms may include sore throat, oral ulceration, flu-like symptoms, severe fatigue, unexplained bleeding, or bruising.

In such cases, patients should be advised to discontinue the medication and consult a physician.

Regular blood monitoring is recommended during prolonged therapy.

Immune system disorders.

Uncommon: hypersensitivity reactions, including urticaria and pruritus;
Very rare: severe hypersensitivity reactions, which may include facial, tongue, or laryngeal swelling, dyspnea, tachycardia, hypotension, anaphylactic reactions, angioedema, or severe shock; asthma exacerbation, bronchospasm.

Psychiatric disorders.

Very rare: psychotic reactions, depression.

Nervous system disorders.

Uncommon: headache, dizziness, insomnia, anxiety, irritability, fatigue, paresthesia, somnolence;
Rare: optic neuritis.

Eye disorders.

Uncommon: visual disturbances;
Rare: toxic optic neuropathy.

Ear and labyrinth disorders.

Rare: tinnitus, hearing loss, vertigo.

Cardiac disorders.

Very rare: palpitations, heart failure, myocardial infarction;
Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: arterial hypertension, vasculitis;
Frequency not known: edema.

Gastrointestinal disorders.

Common: dyspepsia, heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, minor gastrointestinal bleeding (including melena and hematemesis), which may rarely lead to anemia;
Uncommon: peptic ulcer, gastrointestinal perforation or bleeding, ulcerative stomatitis, exacerbations of colitis or Crohn’s disease, gastritis;
Very rare: esophagitis, pancreatitis, intestinal diaphragm-like stricture formation.

Patients should immediately discontinue the medication and seek medical attention if they experience upper abdominal pain, melena, or hematemesis.

Hepatobiliary disorders.

Uncommon: jaundice;
Very rare: hepatic dysfunction, liver damage (especially with long-term use), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders.

Uncommon: various skin rashes;
Very rare: severe skin reactions, such as bullous reactions, severe cutaneous adverse reactions [including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell’s syndrome)], alopecia.

In some cases, varicella may lead to serious skin and soft tissue infections;
Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis, photosensitivity reactions.

Metabolism and nutrition disorders.

Frequency not known: decreased appetite, hypokalemia*.

Renal and urinary disorders.

Rare: acute renal impairment, papillary necrosis (especially with prolonged use), associated with increased serum urea levels;
Very rare: edema (particularly in patients with hypertension or renal insufficiency), nephrotic syndrome, interstitial nephritis, which may lead to acute renal failure. Renal function should therefore be monitored regularly;
Frequency not known: ureteric colic, dysuria, renal tubular acidosis*.

Investigations.

Rare: decreased hemoglobin levels.

* Reports of renal tubular acidosis and hypokalemia have occurred during the post-marketing period, typically after prolonged use of ibuprofen at doses exceeding the recommended levels.

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

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C, in a place inaccessible to children.

Packaging.

10 capsules in a blister pack, 1 blister pack in a cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Geltec Private Limited, India.

Manufacturer’s address and place of business.

Sr No 24, 26/3, 27/2 Yadavanahalli Attibele, Bangalore-Hosur Road, Bangalore, Karnataka, 562107, India.