Bofen 600

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BOFEN 600 (BOFEN600)

Composition:

Active substance: ibuprofen;

1 tablet contains 600 mg of ibuprofen;

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 characteristics: white, oval-shaped, biconvex film-coated tablets.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

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

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

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

Although there are uncertainties regarding extrapolation of these findings to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid/aspirin. Clinically significant interactions are unlikely with occasional use of ibuprofen (see section "Interaction with other medicinal products and other types of interactions").

Pharmacokinetics.

Ibuprofen is rapidly absorbed from the gastrointestinal tract (GIT). Peak plasma concentrations are 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.

Rheumatoid arthritis, ankylosing spondylitis (including juvenile rheumatoid arthritis or Still's disease), osteoarthritis, and other non-rheumatoid (seronegative) arthropathies.

Extra-articular rheumatic and periarticular disorders such as periarthritis of the shoulder (capsulitis), bursitis, tendinitis, tenosynovitis, and low back pain; soft tissue injuries, for example sprains and strains of ligaments.

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

Contraindications.

Known hypersensitivity to the active substance or to any of the excipients.

Asthma, urticaria, or allergic reactions after taking acetylsalicylic acid/aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) in medical history.

Severe heart failure (NYHA functional class IV).

Severe hepatic impairment.

Severe renal impairment (glomerular filtration rate < 30 mL/min).

History of gastrointestinal bleeding or perforation related to previous NSAID therapy.

Conditions associated with increased risk of bleeding or active bleeding.

Acute or previously experienced ulcerative colitis, Crohn’s disease, recurrent peptic ulcer, or gastrointestinal bleeding (two or more episodes of confirmed ulcer formation or bleeding).

Third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

Caution should be exercised when co-administering the following drugs due to possible drug interactions observed in some patients.

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

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 lithium excretion.

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

Cyclosporine. Increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Mifepristone. A theoretical reduction in efficacy is 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, nor does it reduce the clinical efficacy of medical termination of pregnancy.

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

Acetylsalicylic acid/aspirin. As with other NSAID-containing products, concomitant use of ibuprofen and acetylsalicylic acid/aspirin is generally not recommended due to the risk of increased adverse reactions.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid/aspirin on platelet aggregation when administered concomitantly.

However, despite uncertainties regarding the extrapolation of these data to clinical practice, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant effects are unlikely with occasional ibuprofen use (see section "Pharmacodynamics").

Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding when co-administered with NSAIDs (see section "Special precautions for use").

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

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

Sulfonylureas. NSAIDs may potentiate the effects of sulfonylurea drugs. 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 taken concomitantly with NSAIDs (see section "Special precautions for use").

Tacrolimus. Possible increased risk of nephrotoxicity when NSAIDs are administered to patients taking tacrolimus.

Zidovudine. NSAIDs increase the risk of hematological toxicity when administered concomitantly with zidovudine. Evidence exists for an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia who receive ibuprofen while taking zidovudine.

Aminoglycosides. NSAIDs may reduce the elimination of aminoglycosides.

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

CYP2C9 inhibitors. Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase ibuprofen exposure (ibuprofen is a CYP2C9 substrate). In one study, voriconazole and fluconazole (CYP2C9 inhibitors) increased S(+)-ibuprofen exposure by approximately 80–100%. 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 effects 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).

As with other NSAIDs, ibuprofen may mask the symptoms of infection, which could lead to delayed initiation of appropriate treatment and thereby worsen 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 during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

With prolonged use of any analgesic, headache may develop, which should not be treated with increased doses of the drug.

Concomitant use of NSAIDs with alcohol may increase adverse effects related to the active substance, particularly those affecting the gastrointestinal tract or the central nervous system (CNS).

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

The product contains sodium. This should be taken into account by patients who need to restrict sodium intake.

Elderly patients.

In elderly patients, the frequency of adverse reactions during NSAID use is higher, particularly gastrointestinal bleeding and perforation, 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.

NSAIDs 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 at any time during treatment. These adverse reactions may be fatal and may occur with or without warning symptoms, regardless of prior serious gastrointestinal pathology.

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 start treatment with the lowest effective dose.

Concomitant use of protective agents (e.g., misoprostol or proton pump inhibitors) should be considered for these patients, as well as for patients taking low-dose acetylsalicylic acid/aspirin or other drugs that increase the risk of gastrointestinal tract (GIT) injury (see section "Interaction with other medicinal products and other forms of interaction").

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

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

Ibuprofen should be prescribed with caution to patients receiving concomitant therapy with drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents (including aspirin) (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.

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

Impairment of cardiac, renal, and hepatic function.

NSAIDs 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 similar 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 receiving ibuprofen treatment. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic reaction 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 long-term 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 associated with NSAID therapy have been reported.

Clinical studies indicate that the use of ibuprofen, especially at high doses (2400 mg daily), may be associated with a small increase in the risk of arterial thrombotic events such as myocardial infarction or stroke. Overall, epidemiological data do not suggest an association between low-dose ibuprofen use (≤ 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 doses of 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 (such as 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, especially 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. Administration of NSAIDs to 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, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and elderly patients. Discontinuation of NSAIDs is usually followed by recovery to the pre-treatment state.

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 suggesting these reactions appear, ibuprofen should be discontinued immediately and alternative treatment should be considered (if necessary).

In rare cases, serious skin and soft tissue infections may occur during varicella. The role of NSAIDs in worsening these infections is not fully established; therefore, it is recommended to avoid ibuprofen use in varicella.

Haematological effects.

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

Aseptic meningitis.

Aseptic meningitis has been rarely observed in patients receiving ibuprofen therapy. Although aseptic meningitis is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, cases have also been reported in patients without these chronic conditions.

Use during pregnancy or breastfeeding.

Fertility.

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

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed to increase with higher doses and longer duration of therapy. Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryo/fetal mortality. In addition, increased incidence of various malformations, including cardiovascular, has 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 starting treatment and is usually reversible upon discontinuation of the drug. Additionally, cases of fetal ductus arteriosus constriction have been reported after treatment in the second trimester, most of which resolved after stopping treatment. 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 ductus arteriosus constriction should be considered if ibuprofen exposure occurs for several days starting from the 20th gestational week. Treatment with BoFen 600 should be discontinued if oligohydramnios or ductus arteriosus constriction is detected in the fetus.

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

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

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

Towards the end of pregnancy, prostaglandin synthesis inhibitors 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, which may lead 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 in both mother and child increased.

Breastfeeding.

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

Ability to affect reaction speed when driving vehicles or operating machinery.

Ibuprofen may affect patients' reaction speed, which should be considered when engaging in activities requiring high concentration, such as driving vehicles or operating machinery. The effect on reaction speed 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 NSAID use, patients should not drive vehicles or operate machinery.

Method of Administration and Dosage.

Doses.

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

Adults and children aged 12 years and older.

The recommended daily dose of the drug is 1200–1800 mg, administered in 2–3 divided doses. Some patients may respond adequately to 600–1200 mg daily. The maximum daily dose generally should not exceed 2400 mg, which should be taken in divided doses.

Children.

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

In juvenile rheumatoid arthritis, the drug may be used at up to 40 mg/kg body weight per day, divided into several doses.

Elderly patients.

There is an increased risk of serious adverse reactions when administering the drug to elderly patients. If nonsteroidal anti-inflammatory drugs (NSAIDs) are required, the lowest effective dose should be prescribed for the shortest possible duration. Regular monitoring for gastrointestinal bleeding during NSAID therapy is essential. Dosage must be individually adjusted in cases of hepatic or renal impairment.

Method of administration.

For oral use.

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

Children.

Not recommended for children under 12 years of age.

More suitable dosage forms are available for young children.

Overdose.

Toxicity.

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

Symptoms.

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

The most common symptoms of overdose 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, coma, apnea, CNS depression, and respiratory depression.

In severe poisoning, metabolic acidosis may occur. Cases of disorientation, agitation, unconsciousness, and cardiovascular toxicity, including arterial hypotension, bradycardia, and tachycardia, have been reported. With significant overdose, renal failure and hepatic injury are possible. Overdose with large doses of the drug is generally well tolerated, provided other medications are not co-ingested.

Treatment.

There is no specific antidote for ibuprofen overdose. If the ingested amount exceeds 400 mg/kg, gastric lavage/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 maintenance of airway patency and monitoring of cardiac function and vital signs until the patient's condition stabilizes.

Ensure adequate diuresis.

Renal and hepatic function 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 based on the patient's clinical condition.

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

Side effects.

The side effects of ibuprofen are similar to those observed with other NSAIDs.

Gastrointestinal system. Adverse reactions affecting the gastrointestinal tract are the most commonly observed. Peptic ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions").

During ibuprofen 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 (see section "Contraindications"). Gastritis, gastric ulcer, duodenal ulcer, gastrointestinal perforation, and pancreatitis have been observed less frequently.

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

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

Clinical trial data indicate that ibuprofen use, particularly at high doses (2400 mg daily), may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions").

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 precautions").

Exacerbations of infectious inflammation coinciding with NSAID use have been described. If signs of infection develop or worsen during ibuprofen treatment, patients should seek medical advice immediately.

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 reported during ibuprofen use are classified by organ systems and frequency of occurrence according to MedDRA.

Frequency of adverse reactions is 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 order of decreasing severity.

Infections and infestations: uncommon – rhinitis; rare – aseptic meningitis (see section "Special precautions").

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

Immune system disorders: 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 – colitis, 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 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 precautions"); frequency not known – Kounis syndrome.

Vascular disorders: very rare – arterial hypertension.

Reporting suspected adverse reactions. Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister, 2 blisters per carton.

Prescription category.

Prescription only.

Manufacturer.

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

Manufacturer's address and location of business activity.

17 Myru Street, Kyiv, 03134, Ukraine.