BOPHEN 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BOFEN 200 (BOFEN 200)

Composition:

Active ingredient: ibuprofen;

1 tablet contains ibuprofen 200 mg;

Excipients: lactose monohydrate; sodium lauryl sulfate; microcrystalline cellulose; sodium croscarmellose; colloidal anhydrous silicon dioxide; magnesium stearate;

Film coating: graft copolymer of polyethylene glycol with polyvinyl alcohol, talc, titanium dioxide (E 171), glycerol monocaprylocaprate, polyvinyl alcohol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex film-coated tablets.

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

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a propionic acid derivative and a non-steroidal anti-inflammatory drug (NSAID) that possesses analgesic, anti-inflammatory, and antipyretic activity. The therapeutic effects of the drug are believed to result from its inhibitory action on the enzyme cyclooxygenase, leading to a pronounced reduction in prostaglandin synthesis. These properties provide relief from inflammation, pain, and fever.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both drugs are administered simultaneously.

Some pharmacodynamic studies indicate that a single dose of ibuprofen 400 mg administered 8 hours before or 30 minutes after immediate-release acetylsallylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation.

Although there are uncertainties regarding extrapolation of these data to the clinical setting, the possibility cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interactions are unlikely with occasional, non-regular use of ibuprofen (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics.

Ibuprofen is rapidly absorbed from the gastrointestinal tract (GIT). Maximum serum concentration is reached within 1–2 hours after administration. The elimination half-life is approximately 2 hours.

Ibuprofen is metabolized in the liver into two inactive metabolites, which are excreted by the kidneys along with unchanged ibuprofen, either in free form or as conjugates. Renal excretion is rapid and complete. Ibuprofen is highly bound to plasma proteins.

Clinical characteristics.

Indications.

For relief of mild to moderate pain, such as pain associated with dysmenorrhea, dental pain, and postoperative pain, as well as for symptomatic relief of headache, including migraine.

Contraindications.

• Hypersensitivity to ibuprofen or to any of the excipients.
• Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Active or history of recurrent peptic ulcer, Crohn’s disease, recurrent gastric ulcer, or gastrointestinal bleeding (two or more distinct episodes of confirmed ulceration or bleeding).
• Gastrointestinal bleeding or perforation related to previous use of NSAIDs.
• Severe hepatic impairment, severe renal impairment, severe heart failure (NYHA Class IV).
• Active cerebrovascular or other bleeding conditions.
• Disorders of blood coagulation or hemostasis.
• Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Caution should be exercised when co-administering Bofen 200 with the following medicinal products due to possible drug interactions reported in some patients.

Antihypertensive agents, β-blockers, and diuretics. NSAIDs may reduce the antihypertensive effect of agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, β-blockers, and diuretics. Diuretics may also increase the risk of NSAID-induced nephrotoxicity.

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

Cholestyramine. Concomitant administration of ibuprofen and cholestyramine may reduce gastrointestinal absorption of ibuprofen; however, the clinical significance of this interaction is unknown.

Lithium. NSAIDs may reduce renal clearance of lithium.

Methotrexate. NSAIDs may inhibit tubular secretion of methotrexate and reduce methotrexate clearance.

Cyclosporine. Increased risk of nephrotoxicity has been observed when cyclosporine is administered with ibuprofen.

Mifepristone. A reduction in efficacy is theoretically possible due to the anti-prostaglandin properties of NSAIDs. 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, and does not reduce the clinical efficacy of medical termination of pregnancy.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use of ibuprofen and other NSAIDs, including COX-2 inhibitors, should be avoided due to the increased risk of adverse reactions (see section "Special precautions for use").

Acetylsalicylic acid. As with other NSAID-containing products, concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the 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, although the possibility of extrapolating these findings to clinical practice has not been proven, it cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interaction is unlikely with occasional use of ibuprofen (see section "Pharmacodynamics").

Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding when used concomitantly with ibuprofen (see section "Special precautions for use").

Anticoagulants. Ibuprofen may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use").

Quinolone antibiotics. Animal studies suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving concomitant NSAIDs and quinolones have an increased risk of developing seizures.

Sulfonylureas. NSAIDs may potentiate the effects of sulfonylurea agents. Rare cases of hypoglycemia have been reported in patients receiving sulfonylureas during ibuprofen therapy.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) (e.g., clopidogrel and ticlopidine). Increased risk of gastrointestinal bleeding when administered concomitantly with ibuprofen (see section "Special precautions for use").

Tacrolimus. Increased risk of nephrotoxicity may occur when the medicinal product is administered to patients taking tacrolimus.

Zidovudine. NSAIDs increase the risk of hematological toxicity when administered concomitantly with zidovudine. Evidence suggests an increased risk of hemarthrosis and hematomas in HIV-positive patients with hemophilia receiving ibuprofen while on zidovudine therapy.

Aminoglycosides. NSAIDs may reduce the elimination of aminoglycosides.

Herbal extracts. Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.

Inhibitors of CYP2C9. Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (ibuprofen is a CYP2C9 substrate). In one study, voriconazole and fluconazole (CYP2C9 inhibitors) increased S(+)-ibuprofen exposure by approximately 80–100%. Dose reduction of ibuprofen should be considered when co-administered with CYP2C9 inhibitors, especially when high doses of ibuprofen are prescribed to patients taking voriconazole or fluconazole.

Special precautions for use

General warnings

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and gastrointestinal, cardiovascular risks below).

Prolonged use of any analgesic may lead to headache, which should not be treated with increased doses of the medicinal product.

Concomitant use of the medicinal product with alcohol may increase the risk of adverse reactions associated with the active substance, particularly gastrointestinal or central nervous system (CNS) effects, possibly due to additive effects.

Elderly patients

The incidence of adverse reactions during NSAID use is higher in elderly patients, especially gastrointestinal bleeding and perforations, which may be fatal (see section "Dosage and administration").

Paediatric population

There is a risk of impaired renal function in dehydrated children and adolescents.

Gastrointestinal bleeding, ulceration and perforation

Bofen 200 should be used with caution in patients with a history of peptic ulcer or other gastrointestinal disorders, as their condition may worsen (see section "Contraindications").

Gastrointestinal bleeding, ulceration or perforation have been reported with all NSAIDs during any period of treatment. These adverse reactions may be fatal and may occur with or without preceding symptoms, regardless of prior history of serious gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration or perforation increases with higher doses of ibuprofen, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should initiate treatment with the lowest effective dose.

For these patients, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase the risk of gastrointestinal injury, consideration should be given to co-administration of protective agents such as misoprostol or proton pump inhibitors (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use of ibuprofen with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to increased risk of ulceration or bleeding (see section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal disorders, particularly elderly patients, should be advised to report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.

Ibuprofen should be prescribed with caution to patients receiving concomitant treatment with medicinal products that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), SSRIs or antiplatelet agents, including acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in a patient taking ibuprofen, the drug should be discontinued.

Bofen 200 should be prescribed with caution to patients with a history of ulcerative colitis or Crohn’s disease due to possible exacerbation (see section "Adverse reactions").

Respiratory disorders and hypersensitivity reactions

Ibuprofen should be used with caution in patients suffering from bronchial asthma, chronic rhinitis, allergic disorders or with a history thereof, as NSAIDs have been reported to induce bronchospasm, urticaria or angioedema in such patients.

Impairment of cardiac, renal and hepatic function

Bofen 200 should be used with caution in patients with impaired renal, hepatic or cardiac function, as this may lead to worsening of renal function.

Regular concomitant use of various analgesics further increases this risk.

Systematic use of analgesics, especially combinations of different analgesic agents, further increases this risk.

Cases of Kounis syndrome have been reported in patients treated with 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.

Patients with impaired renal, hepatic or cardiac function should be prescribed the lowest effective dose for the shortest possible duration, and renal function should be monitored, especially during prolonged treatment (see section "Contraindications").

Cardiovascular and cerebrovascular effects

Ibuprofen should be used with caution in patients with a history of arterial hypertension and/or heart failure, as fluid retention and oedema have been reported with NSAID therapy.

Clinical studies indicate that the use of ibuprofen, especially at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. Overall, epidemiological data do not suggest an association between low-dose ibuprofen (≤ 1200 mg daily) and increased risk of arterial thrombotic events.

Ibuprofen should only be prescribed to patients with uncontrolled arterial hypertension, congestive heart failure (NYHA functional class II–III), diagnosed ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease after careful consideration, and high-dose ibuprofen (2400 mg daily) should be avoided.

Careful consideration is also required before initiating long-term ibuprofen therapy in patients with risk factors for cardiovascular disease (arterial hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high-dose ibuprofen (2400 mg daily) is required.

Renal effects

Treatment with ibuprofen should be initiated with caution in patients with significant dehydration. There is a risk of impaired renal function, particularly in dehydrated children, adolescents and elderly patients.

As with other NSAIDs, prolonged use of ibuprofen may lead to renal papillary necrosis and other pathological changes in the kidneys. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. Use of the medicinal product in such patients may cause dose-dependent reduction in prostaglandin synthesis and, secondarily, reduced renal blood flow, potentially leading to renal failure.

Patients at high risk of such reactions include those with impaired renal function, heart failure, hepatic dysfunction, patients taking diuretics and ACE inhibitors, and elderly patients. Discontinuation of the medicinal product is usually followed by recovery to the pre-treatment condition.

Systemic lupus erythematosus and mixed connective tissue disease

Ibuprofen should be used with caution in patients with systemic lupus erythematosus or mixed connective tissue disease due to an increased risk of aseptic meningitis (see section "Adverse reactions" and aseptic meningitis below).

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 during ibuprofen use (see section "Adverse reactions"). Most of these 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 occur during varicella. The role of NSAIDs in worsening these infections cannot currently be excluded; therefore, use of the medicinal product is not recommended in patients with varicella.

As with other NSAIDs, ibuprofen may mask signs of infection, potentially delaying appropriate treatment and thereby worsening the course of the disease. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If ibuprofen is used for fever or pain relief in infectious conditions, monitoring of the infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Haematological effects

Ibuprofen, like other NSAIDs, may inhibit platelet aggregation and prolong bleeding time.

Aseptic meningitis

Rarely, aseptic meningitis has been observed in patients during treatment with ibuprofen. Although aseptic meningitis occurs more frequently in patients with systemic lupus erythematosus and related connective tissue disorders, cases have also been reported in patients without these chronic conditions.

Masking symptoms of underlying infections

As with other NSAIDs, ibuprofen may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby worsening the course of infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief in infectious diseases, monitoring of the condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Excipients

Patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

The medicinal product contains < 1 mmol sodium per dose, i.e. essentially "sodium-free".

Use during pregnancy or breastfeeding

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and congenital malformations, particularly cardiac defects and gastroschisis, following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with dose and duration of therapy. Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryo/fetal mortality. Furthermore, increased incidences of various malformations, including cardiovascular defects, have been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

Use of ibuprofen from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation of the drug. Additionally, cases of fetal arterial duct constriction have been reported after treatment during the second trimester, most of which resolved after discontinuation of therapy. Therefore, during the first and second trimesters of pregnancy, ibuprofen should not be used except when clearly necessary. When ibuprofen is used in women planning pregnancy or during the first or second trimester, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and fetal arterial duct constriction should be considered if exposure to ibuprofen occurs for several days starting from the 20th gestational week. Bofen 200 should be discontinued if oligohydramn游戏副本 or fetal arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus by causing:

− cardiopulmonary toxicity (with premature constriction/closure of the arterial duct and pulmonary hypertension);

− impaired renal function, which may progress to renal failure with oligohydramnios.

Near the end of pregnancy, prostaglandin synthesis inhibitors may expose both mother and newborn to the following risks:

− prolonged bleeding time, antiplatelet effect, which may occur even at very low doses;

− inhibition of uterine contractions, potentially leading to delayed or prolonged labour.

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

Labour and delivery

Ibuprofen is not recommended during labour and delivery.

Onset of labour may be delayed, its duration prolonged, and the risk of bleeding increased in both mother and child.

Breastfeeding

Limited available data show that NSAIDs, including ibuprofen, pass into breast milk in very low concentrations. Ibuprofen is not recommended for use in women during breastfeeding.

Fertility

Ibuprofen use may impair female fertility and is therefore not recommended for women attempting to conceive. For women experiencing infertility or undergoing fertility investigations, discontinuation of ibuprofen should be considered.

Ability to affect reaction speed when driving or operating machinery

Ibuprofen may affect patients' reaction speed, which should be considered when engaging in activities requiring heightened attention, such as driving or operating machinery. This effect is significantly enhanced when combined with alcohol.

After taking NSAIDs, adverse effects such as dizziness, somnolence, fatigue and visual disturbances may occur. If such effects occur during treatment, patients should not drive or operate machinery.

Method of Administration and Dosage

Doses

For short-term use only.

Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control disease symptoms (see section "Special precautions for use***"***).

During short-term use, if symptoms persist or worsen, the patient should consult a physician.

Adults and children aged 12 years and older

The recommended daily dose is 1200 mg, divided into several doses. Some patients may require only 600–1200 mg per day.

Children

The daily dose is 20 mg/kg of body weight, divided into several doses.

Elderly patients

There is an increased risk of serious adverse reactions when using the drug in elderly patients. If treatment is necessary, the lowest effective dose for the shortest possible duration should be prescribed. Regular monitoring for gastrointestinal bleeding should be performed during drug therapy. In case of impaired liver and/or kidney function, dosage should be individually adjusted.

Patients with renal impairment

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

Patients with hepatic impairment

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

Method of administration

For oral use.

The medication should preferably be taken during or after food, with a large amount of liquid. Tablets should be swallowed whole, without chewing, splitting, crushing, or dissolving, to avoid oral discomfort and throat irritation.

Children

Do not use in children with body weight less than 20 kg or under 6 years of age.

More convenient dosage forms are available for young children.

Overdose

Toxicity

Toxicity symptoms are generally not observed at doses below 100 mg/kg in children and adults. However, supportive measures may be required in some cases. In children, toxicity symptoms have been reported after ibuprofen ingestion at doses of 400 mg/kg.

Symptoms

In most patients, symptoms of overdose develop within 4–6 hours after ingestion of a significant amount of ibuprofen.

The most common overdose symptoms include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) manifestations: headache, tinnitus, dizziness, seizures, and loss of consciousness. Rarely reported: nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, diarrhea, coma, apnea, CNS depression, and respiratory depression.

Metabolic acidosis may occur in severe poisoning. Disorientation, agitation, unconsciousness, and cardiovascular toxicity—including arterial hypotension, bradycardia, and tachycardia—have been reported. Significant overdose may lead to renal failure and liver damage. Overdose with large doses of the drug is generally well tolerated unless other medications are co-ingested.

Treatment

There is no specific antidote for ibuprofen overdose. If the ingested amount exceeds 400 mg/kg, gastric lavage or stomach emptying is recommended within 1 hour of ingestion, followed by symptomatic treatment. Activated charcoal should be administered within 1 hour after ingestion of a potentially toxic amount. Treatment should include ensuring airway patency and monitoring cardiac function and vital signs until the patient's condition stabilizes.

Adequate diuresis should be maintained.

Renal and hepatic functions should be closely monitored.

Patients should be observed for at least 4 hours after ingestion of a potentially toxic amount.

Frequent or prolonged seizures should be treated with intravenous diazepam. Other interventions may be indicated depending on the patient's clinical condition.

For the most up-to-date information, contact the local toxicology center.

Adverse Reactions

Adverse reactions to ibuprofen are similar to those observed with other NSAIDs.

Gastrointestinal system. Adverse reactions affecting the gastrointestinal system are the most commonly observed. Peptic ulcers, perforation, or gastrointestinal bleeding may occur, sometimes resulting in fatal outcomes, particularly in elderly patients (see section "Special Warnings and Precautions for Use").

Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, gastrointestinal bleeding, and exacerbations of colitis and Crohn’s disease have been reported during ibuprofen treatment (see section "Special Warnings and Precautions for Use"). Gastritis, gastric ulcer, duodenal ulcer, gastrointestinal perforation, and pancreatitis have been observed less frequently.

Immune system. Hypersensitivity reactions have been reported with NSAIDs, including ibuprofen. These include nonspecific allergic reactions and anaphylaxis; respiratory tract reactivity, including asthma, worsening of asthma, bronchospasm, or dyspnea; and various skin manifestations, such as rashes of different types, pruritus, urticaria, purpura, angioedema, and very rarely, erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

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

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 Warnings and Precautions for Use").

Infections and infestations. Rhinitis and aseptic meningitis (particularly in patients with autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue diseases) have been reported, with symptoms including neck stiffness, headache, nausea, vomiting, fever, or disorientation (see section "Special Warnings and Precautions for Use").

Exacerbations of infectious diseases coinciding with NSAID use have been described. If signs of infection appear or worsen during treatment, patients should seek immediate medical attention.

Skin and subcutaneous tissue disorders. In rare cases, severe skin infections and soft tissue complications may occur during varicella (chickenpox) (see also "Infections and infestations").

Adverse reactions associated with ibuprofen use are classified by organ systems and frequency according to MedDRA.

Frequency of adverse reactions is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and frequency not known (cannot be estimated from available data).

Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations: uncommon – rhinitis; rare – aseptic meningitis (see section "Special Warnings and Precautions for Use").

Blood and lymphatic system disorders: rare – leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Immune system disorders: uncommon – hypersensitivity reactions; rare – anaphylactic reaction.

Psychiatric disorders: uncommon – insomnia, anxiety disorders; rare – depression, confusion.

Nervous system disorders: common – headache, dizziness; uncommon – paresthesia, somnolence; rare – optic neuritis.

Eye disorders: uncommon – visual disturbances; rare – toxic optic neuropathy.

Ear and labyrinth disorders: uncommon – hearing impairment, tinnitus, vertigo.

Respiratory system 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 – exacerbation of colitis and Crohn’s disease.

Hepatobiliary disorders: uncommon – hepatitis, jaundice, liver function abnormalities; very rare – liver failure.

Skin and subcutaneous tissue disorders: common – rash; uncommon – urticaria, pruritus, purpura, angioedema, photosensitivity reactions; very rare – serious skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis); frequency not known – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis (AGEP).

Renal and urinary system disorders: uncommon – toxic nephropathy in various forms, including tubulointerstitial nephritis, nephrotic syndrome, and renal failure.

General disorders and administration site conditions: common – fatigue; rare – edema.

Cardiac disorders: very rare – heart failure, myocardial infarction (see section "Special Warnings and Precautions for Use"); frequency not known – Kounis syndrome.

Vascular disorders: very rare – arterial hypertension.

Reporting suspected adverse reactions. Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua/.

Shelf life.

4 years.

Storage conditions.

No special storage conditions required.

Keep out of reach of children.

Packaging.

10 tablets per blister, 2 blisters per carton.

Prescription status.

Over-the-counter (without prescription).

Manufacturer. Public Joint-Stock Company "Scientific and Production Center "Borshchahivskiy Chemical and Pharmaceutical Plant".

Manufacturer's address and location of operations.

17 Myru Street, Kyiv, 03134, Ukraine.