Taffa® classic

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Taffa® Classic (Taffa Classic)

Composition:

Active substance: ibuprofen;

One film-coated tablet contains ibuprofen – 400 mg;

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

Film coating: hypromellose; titanium dioxide (E 171); macrogol.

Pharmaceutical form. Film-coated tablets.

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

Pharmacotherapeutic group.

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

ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with a short half-life and possesses analgesic, anti-inflammatory, and antipyretic properties necessary for effective treatment of rheumatic diseases.

Various dosage regimens allow individualized therapy.

Experimental evidence has shown that prostaglandins are responsible for the development of pain and inflammation. Ibuprofen strongly inhibits the synthesis of prostaglandins, which explains its analgesic, anti-inflammatory, and antipyretic effects. These properties provide relief from symptoms of inflammation, pain, and fever.

The same mechanism underlies the inhibition of platelet aggregation and ulcerogenic effects, as well as sodium and water retention, and bronchospastic reactions as possible adverse effects.

Although ibuprofen may affect platelet aggregation and bleeding time, clinically significant changes in prothrombin time or blood coagulation time do not occur. Ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen, when administered concomitantly, may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation. In some pharmacodynamic studies, a reduced effect of acetylsalicylic acid on thromboxane production or platelet aggregation was observed when a single 400 mg dose of ibuprofen was administered 8 hours before or 30 minutes after immediate-release acetylsalicylic acid (81 mg). Although uncertainty exists regarding the extrapolation of these data to clinical situations, it cannot be excluded that long-term treatment with ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. A clinically significant effect from occasional use of ibuprofen is unlikely (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics.

Absorption

Ibuprofen is rapidly absorbed, primarily in the small intestine. After oral administration of 200–600 mg of ibuprofen, maximum plasma concentration of 15–55 µg/mL (C_max) is reached on average within 1–2 hours (t_max). Maximum plasma concentrations are achieved within 45 minutes after oral administration on an empty stomach. This time may vary depending on the pharmaceutical formulation.

When ibuprofen is taken after food intake, absorption is significantly slower, maximum plasma concentration is lower, and peak levels are observed within 1–2 hours. After a single oral dose of 400 mg of ibuprofen, peak concentration of 8–13 µg/mL in synovial fluid is reached within 6 hours.

Distribution

Ibuprofen is 99% bound to plasma proteins. Binding is a reversible process.

Metabolism

More than 50–60% of an oral dose of ibuprofen is metabolized in the liver into two inactive metabolites. The metabolism of ibuprofen is similar in children and adults.

Elimination

The half-life in plasma is 1.5–2 hours. The short elimination half-life indicates that even with repeated administration, accumulation of ibuprofen does not occur. Ibuprofen and its metabolites are almost completely eliminated from the body within 24 hours after oral administration. It is excreted primarily by the kidneys in the form of inactive metabolites.

Preclinical data

Mutagenic and oncogenic potential

Studies on mutagenicity in vitro and in vivo (bacteria, human lymphocytes) provided no evidence of mutagenic effects of ibuprofen. Studies on oncogenic potential of ibuprofen in rats and mice showed no evidence of carcinogenic effects.

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

Clinical characteristics.

Indications.

Symptomatic treatment of headache, including migraine, toothache, pain associated with dysmenorrhea, neuralgia, back pain, muscle pain, rheumatic pain (except severe cases of arthritis), as well as symptoms of cold and flu, fever.

Contraindications.

• Hypersensitivity to ibuprofen or to any component 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 in the patient's history.
• Third trimester of pregnancy (see section "Use during pregnancy or lactation").
• Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding in the past).
• Active or previous inflammatory bowel diseases (such as Crohn’s disease, ulcerative colitis).
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Increased tendency to bleeding.
• Severe hepatic insufficiency (liver cirrhosis, ascites).
• Severe renal insufficiency (creatinine clearance <30 mL/min).
• Severe heart failure (NYHA Class III–IV).
• Postoperative pain treatment following coronary artery bypass graft (CABG) surgery (or use of cardiopulmonary bypass).

Interaction with other medicinal products and other forms of interaction.

Other NSAIDs, including salicylates. Concomitant use of multiple NSAIDs, including selective cyclooxygenase-2 inhibitors, may increase the risk of gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, simultaneous use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions for use"). Salicylic acid displaces ibuprofen during protein binding in blood.

Glucocorticoids. Increased risk of gastrointestinal adverse effects, including gastrointestinal bleeding and ulceration (see section "Special precautions for use").

Alcohol. Enhanced gastrointestinal adverse effects, increased risk of gastrointestinal bleeding.

Diuretics, antihypertensives, ß-blockers. NSAIDs may reduce the effectiveness of diuretics and antihypertensive agents such as ACE inhibitors and ß-blockers. Diuretics may also increase the risk of nephrotoxicity associated with NSAIDs.

Probenecid, sulfinpyrazone. Slowed elimination of ibuprofen; the uricosuric effect of probenecid and sulfinpyrazone is diminished.

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

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding when NSAIDs are used concomitantly (see section "Special precautions for use").

Aminoglycosides. NSAIDs may reduce the excretion of aminoglycosides.

Acetylsalicylic acid. Experimental data indicate that ibuprofen may competitively inhibit the antiplatelet effect of low-dose acetylsalicylic acid when administered concomitantly. Although uncertainty exists regarding extrapolation of these data to clinical settings, it cannot be excluded that long-term ibuprofen therapy may reduce the cardioprotective effect of low-dose acetylsalicylic acid. A clinically significant effect from occasional ibuprofen use is unlikely.

Oral antidiabetic agents. The effect of oral antidiabetic agents (sulfonylureas) may be enhanced by ibuprofen, as with other NSAIDs. Rare cases of hypoglycemia have been reported in patients receiving ibuprofen during sulfonylurea therapy. Blood glucose levels should be monitored regularly and the dose of antidiabetic agent adjusted if necessary.

H2-histamine receptor antagonists. Clinically significant interaction between ibuprofen and cimetidine or ranitidine has not been established.

Digoxin. Plasma digoxin concentration may be increased.

Phenytoin. Plasma phenytoin concentration may be increased.

Lithium. NSAIDs may reduce lithium excretion, leading to increased plasma lithium concentrations. Monitoring of plasma lithium levels is recommended.

Metotrexate. NSAID use may lead to increased plasma concentrations of methotrexate. NSAIDs may inhibit methotrexate secretion in proximal tubules and reduce its clearance.

Baclofen. NSAID use may increase baclofen toxicity.

Quinolones. Central nervous system effects may be enhanced.

Cholestyramine. Concomitant use of ibuprofen with cholestyramine may reduce ibuprofen absorption in the gastrointestinal tract. However, clinical significance is unknown.

Cyclosporine. Increased risk of nephrotoxicity when used with NSAIDs.

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

Mifepristone. Theoretically, the efficacy of mifepristone may be reduced due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that combined administration of NSAIDs on the day of prostaglandin administration does not negatively affect the effect of mifepristone or prostaglandins on cervical ripening or uterine contractility, and does not reduce the clinical efficacy of pregnancy termination.

Quinolone antibiotics. Animal experimental studies have shown that seizures associated with quinolones may be potentiated by NSAIDs. Patients receiving quinolones and NSAIDs concomitantly have an increased risk of seizures.

Tacrolimus. Risk of nephrotoxicity may be increased when tacrolimus is used concomitantly with NSAIDs.

Zidovudine. Concomitant use of zidovudine and NSAIDs increases the risk of hematological toxicity. In HIV-positive individuals with poor blood clotting, data indicate that concomitant use of zidovudine and NSAIDs increases the risk of hemarthrosis and hematoma.

CYP2C9 inhibitors. Concomitant administration of ibuprofen and CYP2C9 inhibitors may prolong the exposure (time under the effect curve) of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in S(+)-ibuprofen exposure. Dose reduction of ibuprofen should be considered when co-administered with strong CYP2C9 inhibitors, especially when high doses of ibuprofen are used or when combined with voriconazole or fluconazole.

Special precautions for use.

To minimize risks, the lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

Gastrointestinal ulcers, bleeding, or perforation may occur during treatment with non-selective or selective COX-2 NSAIDs at any time, even without preceding symptoms or relevant medical history. To reduce this risk, the lowest effective dose should be used for the shortest possible treatment duration.

Placebo-controlled studies have shown that certain selective COX-2 inhibitors increase the risk of thrombotic cardiovascular and cerebrovascular complications. It is not yet known whether this risk is directly correlated with the COX-1/COX-2 selectivity of individual NSAIDs. Since comparable clinical data on ibuprofen at maximum doses and long-term therapy are currently lacking, such an increased risk cannot be excluded. Until appropriate information becomes available, ibuprofen should be used in patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial occlusion, or those with significant risk factors (e.g., high blood pressure, hyperlipidemia, diabetes, smoking) only after careful assessment of the benefit-risk ratio. Due to this risk, the lowest effective dose should be used for the shortest possible treatment duration.

The effect of NSAIDs on the kidneys includes fluid retention with edema and/or arterial hypertension. Therefore, ibuprofen should be used with caution in patients with cardiac impairment and other conditions associated with fluid retention. Caution is also advised in patients concurrently taking diuretics or ACE inhibitors, as well as in individuals at increased risk of hypovolemia.

Concomitant alcohol consumption may enhance adverse effects of NSAIDs, particularly those affecting the gastrointestinal tract or central nervous system.

With prolonged use of analgesics, headache may occur, which should not be treated with increased doses of the drug.

Respiratory disorders. Ibuprofen may cause bronchospasm, urticaria, or angioedema in patients with or with a history of bronchial asthma, chronic rhinitis, or allergic disease.

Impaired cardiac, renal, or hepatic function. Caution is required in patients with impaired liver, kidney, or heart function, as NSAID use may worsen renal function. The concomitant regular use of other analgesics further increases this risk. In such high-risk patients, the lowest possible dose should be selected, and renal function should be monitored regularly, especially during long-term therapy.

NSAIDs may worsen heart failure and glomerular filtration rate and increase plasma concentrations of cardiac glycosides.

Concomitant use of the medicinal product Tauffa® Classic with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see section "Interaction with other medicinal products and other forms of interaction").

Elderly patients. In elderly patients, adverse effects occur more frequently during NSAID therapy, particularly gastrointestinal bleeding and perforation, which may be fatal.

Gastrointestinal bleeding, ulcers, and perforation. Gastrointestinal bleeding, ulcers, and perforation, sometimes fatal, have been reported with all NSAIDs, occurring with or without warning symptoms or a history of serious gastrointestinal complications at any time during therapy.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should start treatment with the lowest dose. For such patients, as well as for those requiring concomitant therapy with low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal tract injury risk, consideration should be given to concomitant protective therapy (e.g., misoprostol or proton pump inhibitors) (see section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should report any unusual abdominal symptoms (including gastrointestinal bleeding), especially at the beginning of therapy.

Caution is required when patients are concurrently receiving medications 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 such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

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

Ibuprofen should be prescribed only under strict indications and under medical supervision in patients with gastrointestinal complications or impaired liver function, as the condition of internal organs may worsen (see "Adverse reactions").

Cardiovascular and cerebrovascular effects. Patients with a history of hypertension and/or decompensated heart failure should be appropriately monitored and advised, as fluid retention and edema 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 slight increase in the risk of arterial thrombotic complications (e.g., myocardial infarction and stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g., <1200 mg daily) is associated with an increased risk of arterial thrombotic complications.

Patients with uncontrolled arterial hypertension, heart failure (NYHA II), established ischemic heart disease, peripheral arterial occlusion, and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration and should avoid high doses (2400 mg daily). The clinical picture should also be carefully evaluated before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., high blood pressure, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg daily) 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.

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

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

In rare cases, varicella may lead to serious skin infections and soft tissue complications. The involvement of NSAIDs in exacerbating these infections has not been ruled out. Therefore, it is recommended to avoid prescribing ibuprofen in cases of varicella.

Renal effects. Patients with severe dehydration or postoperative fluid volume changes should be rehydrated before starting ibuprofen therapy and then closely monitored. There is a risk of impaired renal function, particularly in children, adolescents, and elderly patients with dehydration.

During long-term therapy, as with other NSAIDs, renal papillary necrosis and other kidney tissue damage may occur. Toxic kidney injury may also occur in patients in whom renal prostaglandins play a supportive role in renal perfusion. In these patients, NSAID administration may cause dose-dependent reduction in renal prostaglandin production, decreased renal blood flow, and overt renal decompensation. These reactions occur primarily in patients with renal, cardiac, or hepatic insufficiency, those concurrently taking diuretics or ACE inhibitors, and in elderly patients.

Hematological effects. Like other NSAIDs, ibuprofen reduces platelet aggregation and prolongs bleeding time.

Masking symptoms of underlying infection. Ibuprofen may mask symptoms of infection, potentially leading to delayed appropriate treatment and thus worsening of the infection. This has been observed in cases of bacterial community-acquired pneumonia and bacterial complications associated with varicella. If ibuprofen is prescribed for the treatment of fever or pain associated with infection, monitoring of the infection's course is recommended. Outpatients should consult a physician if symptoms persist or worsen.

Aseptic meningitis, systemic lupus erythematosus, and mixed connective tissue diseases. In isolated cases, symptoms of aseptic meningitis have been observed during ibuprofen use. This appears to be more common in patients with lupus and collagen diseases. However, it has also been observed in patients without these chronic conditions.

This medicinal product contains lactose monohydrate. If the patient has been diagnosed with intolerance to certain sugars, they should consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological data suggest an increased risk of miscarriage, as well as congenital heart defects and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed to increase with higher doses and longer duration of treatment.

In animal studies, prostaglandin synthesis inhibitors have led to increased pre- and post-implantation embryo-fetal loss and embryofetal mortality. Additionally, increased incidences of various developmental abnormalities, including cardiac defects, have been reported in animals treated with prostaglandin synthesis inhibitors during the organogenesis phase.

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

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

Risks for the fetus:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• Renal dysfunction (see above);

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

• Possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, the medicinal product Tauffa® Classic is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding

NSAIDs pass into breast milk. For safety reasons, ibuprofen is not recommended for breastfeeding women. If treatment is essential, the infant should be switched to artificial feeding.

Fertility

The use of ibuprofen may negatively affect female fertility; therefore, it is not recommended for women attempting to conceive. Consideration should be given to discontinuing ibuprofen in women experiencing difficulties with conception or undergoing infertility investigations.

Ability to influence reaction speed when driving or operating machinery.

No specific studies have been conducted. However, it is known that ibuprofen may sometimes have adverse effects on the central nervous system, such as reduced reaction speed. This should be considered when high alertness is required, especially when driving vehicles or operating machinery. This effect may be particularly pronounced when taken with alcohol.

Method of Administration and Dosage

For short-term use only. Use the lowest effective dose required to relieve symptoms for the shortest possible duration.

Most patients can take the medicinal product Taffa® Classic on an empty stomach without gastrointestinal discomfort.

Adults and children aged 12 years and older: Take 1 tablet every 6 hours. Tablets should be taken with water. Do not exceed 3 tablets within 24 hours. The maximum daily dose is 1200 mg.

Children

The medicinal product Taffa® Classic must not be used in children under 12 years of age.

Overdose

Signs of toxicity are generally not observed in children or adults at doses below 100 mg/kg body weight. However, supportive measures may be necessary in some cases. In children, symptoms of toxicity have been observed after ingestion of 400 mg/kg or more.

Symptoms: In most patients who have ingested a significant amount of ibuprofen, symptoms develop within 4 to 6 hours. The most commonly reported symptoms of overdose include nausea, vomiting, abdominal pain, drowsiness, and lethargy. Central nervous system (CNS) effects include headache, tinnitus, dizziness, seizures, and loss of consciousness. Rarely reported effects include nystagmus, metabolic acidosis, hypothermia, renal impairment, gastrointestinal bleeding, coma, apnea, and CNS and respiratory depression. Cardiovascular toxicity has also been reported, including hypotension, bradycardia, and tachycardia. In cases of significant overdose, renal failure and hepatic injury may occur. Significant overdose is generally well tolerated if no other drugs are co-ingested.

Treatment: There is no specific antidote for ibuprofen overdose. Patients should be treated symptomatically as needed. After ingestion of a potentially toxic amount, activated charcoal should be administered within one hour. If necessary, serum electrolyte imbalances should be corrected.

If the drug has already been absorbed, alkalizing agents should be given to promote urinary excretion of ibuprofen.

Side effects.

The most commonly observed adverse reactions associated with the use of NSAIDs affect the gastrointestinal tract. Peptic ulcers, perforations, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions for use"). Other gastrointestinal side effects include nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, and hematemesis.

Ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported following administration. Gastritis occurs less frequently. Rare cases of gastrointestinal tract perforation have been reported with ibuprofen use.

Exacerbation of skin infections, including serious infections such as necrotizing fasciitis, has been described during concomitant use of NSAIDs. If any signs of infection appear or worsen during treatment with ibuprofen, the patient should seek immediate medical attention.

Clinical studies 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 (such as myocardial infarction or stroke) (see section "Special precautions for use***").

Adverse reaction frequencies are defined as follows: "very common" (>1/10), "common" (>1/100, <1/10), "uncommon" (>1/1000, <1/100), "rare" (>1/10,000, <1/1000), "very rare" (<1/10,000), and "frequency not known" (cannot be estimated from available data). The following adverse reactions have been observed with ibuprofen:

Infections and infestations: uncommon – rhinitis; rare – aseptic meningitis.

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

Immune system disorders: uncommon – hypersensitivity; rare – anaphylactic reaction, lupus-like syndrome, autoimmune hemolytic anemia.

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

Nervous system disorders: common – central nervous system effects such as reduced reaction speed (especially when combined with alcohol), headache, dizziness; uncommon – paresthesia, somnolence.

Eye disorders: uncommon – visual disturbances (usually reversible upon discontinuation of treatment); rare – toxic amblyopia, toxic optic neuropathy, optic neuritis.

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

Cardiac disorders: very rare – heart failure, edema, infarction; frequency not known – Kounis syndrome.

Vascular disorders: very rare – arterial hypertension.

Respiratory, thoracic and mediastinal disorders: uncommon – bronchial asthma, bronchospasm, dyspnea, risk of acute pulmonary edema in patients with heart failure.

Gastrointestinal disorders: common – dyspepsia, diarrhea, nausea, vomiting, constipation, abdominal pain, flatulence, melena, hematemesis, gastrointestinal bleeding; rare – gastritis, gastrointestinal ulcers, ulcerative stomatitis, gastrointestinal perforation; very rare – pancreatitis; frequency not known – exacerbation of colitis or Crohn’s disease. A temporary burning sensation in the mouth or throat may occur during treatment.

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

Skin and subcutaneous tissue disorders: common – exanthema; rare – urticaria, pruritus, purpura, angioedema; very rare – severe 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), photosensitivity reactions.

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

Renal and urinary disorders: rare – toxic nephropathy in various forms, including renal papillary necrosis, interstitial nephritis, impaired kidney function with edema progressing to renal failure.

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

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

No special storage conditions required.

Keep out of reach and sight of children.

Packaging. 10 tablets in a blister. 1 or 5 blisters per carton.

Prescription status. Over-the-counter.

Manufacturer.

JSC "Farmak".

Manufacturer's address.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.