Taffa® extra

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

Composition:

Active ingredient: ibuprofen;

One film-coated tablet contains ibuprofen — 600 mg;

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

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

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex film-coated tablets of white color.

Pharmacotherapeutic group.

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

ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

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

Different dosage regimens allow individualized therapy.

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

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

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

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly. In some pharmacodynamic studies, a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed when a single 400 mg dose of ibuprofen was given 8 hours before or 30 minutes after administration of immediate-release acetylsalicylic acid (81 mg). Although there is uncertainty regarding the extrapolation of these data to the clinical setting, 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 (Cmax) is reached on average within 1–2 hours (tmax). Maximum plasma concentrations are achieved within 45 minutes after oral administration on an empty stomach. This time may vary depending on different pharmaceutical forms.

When ibuprofen is taken after food intake, absorption occurs significantly more slowly, maximum plasma concentration is lower, and peak levels are observed after 1–2 hours. After oral administration of a single 400 mg dose of ibuprofen, peak concentration of 8–13 µg/mL in synovial fluid is reached after 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 elimination half-life from plasma is 1.5–2 hours. The short 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. In carcinogenicity studies of ibuprofen in rats and mice, no evidence of carcinogenic effects of ibuprofen was found.

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

Clinical characteristics.

Indications.

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

Degenerative rheumatic conditions: arthrosis, gonarthrosis, coxarthrosis, polyarthrosis, spondylosis.

Extra-articular rheumatic conditions: myalgia, periarthritis, shoulder–arm pain syndrome, bursitis, tendinitis, tenosynovitis, back pain, neuralgia caused by intervertebral disc damage.

Soft tissue injuries such as tendon rupture and ligament sprains, postoperative pain (see "Contraindications"), dental pain and pain following dental procedures.

Relief of pain associated with dysmenorrhea.

As an adjunct in the treatment of infections with pronounced inflammatory component or high fever.

For symptomatic relief of headache, including migraine.

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.
• Third trimester of pregnancy (see section "Use during pregnancy or lactation").
• Active peptic ulcer disease of the stomach and/or duodenum or active gastrointestinal bleeding, or history of recurrence (two or more episodes of confirmed peptic ulcer or bleeding in the past).
• Acute or previous inflammatory bowel diseases (such as Crohn’s disease, ulcerative colitis).
• History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
• 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).
• Treatment of postoperative pain 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, concomitant use of ibuprofen with other NSAIDs should be avoided (see section "Special precautions for use"). Salicylic acid displaces ibuprofen from plasma protein binding sites.

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

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

Diuretics, antihypertensive agents, ß-blockers. NSAIDs may reduce the efficacy of diuretics and antihypertensive agents such as ACE inhibitors and ß-blockers. Diuretics may also increase the risk of NSAID-induced nephrotoxicity.

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 suggest that ibuprofen may competitively inhibit the antiplatelet effect of low-dose acetylsalicylic acid when administered concomitantly. Although uncertainty exists regarding extrapolation of these findings to clinical settings, it cannot be excluded that long-term ibuprofen therapy may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interaction with occasional ibuprofen use is unlikely.

Oral antidiabetic agents. The effect of oral antidiabetic agents (sulfonylurea derivatives) 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 as necessary.

H2-histamine receptor antagonists. No clinically significant interaction between ibuprofen and cimetidine or ranitidine has been established.

Digoxin. Plasma digoxin concentration may be increased.

Phenytoin. Plasma phenytoin concentration may be increased.

Lithium. NSAIDs may reduce lithium excretion, resulting in elevated plasma lithium concentrations. Monitoring of plasma lithium levels is recommended.

Methotrexate. Use of NSAIDs may lead to increased methotrexate plasma concentrations. NSAIDs may inhibit methotrexate secretion in the proximal tubules and reduce its clearance.

Baclofen. Use of NSAIDs increases baclofen toxicity.

Quinolones. Central nervous system effects are potentiated.

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

Cyclosporine. Increased risk of nephrotoxicity when used concomitantly 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 anti-prostaglandin properties of NSAIDs. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not negatively affect mifepristone or prostaglandin effects 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 coagulation, data indicate that concomitant use of zidovudine and NSAIDs increases the risk of hemarthrosis and hematoma formation.

CYP2C9 inhibitors. Concomitant administration of ibuprofen and CYP2C9 inhibitors may prolong the exposure (effect duration) of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in exposure to S(+)-ibuprofen. Consideration should be given to reducing the dose of ibuprofen when strong CYP2C9 inhibitors are used concomitantly, especially with high-dose ibuprofen 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 NSAIDs, whether selective or non-selective COX-2 inhibitors, at any time, even without warning symptoms or prior history. To reduce this risk, the lowest effective dose should be used for the shortest duration of treatment.

In placebo-controlled studies, certain selective COX-2 inhibitors have been shown to 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 trial data for 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 in patients 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.

NSAID effects on the kidneys include fluid retention with edema and/or arterial hypertension. Therefore, ibuprofen should be used cautiously in patients with cardiac impairment and other conditions associated with fluid retention. Caution is also advised in patients concurrently taking diuretics or angiotensin-converting enzyme (ACE) inhibitors, as well as in individuals at increased risk of hypovolemia.

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

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

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

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

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

The use of the medicinal product Tauffa® Extra in combination with NSAIDs, including selective cyclooxygenase-2 (COX-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, including fatal cases, have been reported with all NSAIDs. These events may occur at any time during treatment, with or without prior warning symptoms, or in patients with a history of serious gastrointestinal complications.

The risk of gastrointestinal bleeding, ulceration, or perforation is greater 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 medications that may increase gastrointestinal 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 advised 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 the event 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 cases of 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 per day), may be associated with a small increased risk of arterial thrombotic complications (e.g., myocardial infarction, stroke). Overall, epidemiological studies do not suggest that low doses of ibuprofen (e.g., <1200 mg per day) are associated with an increased risk of arterial thrombotic complications.

Patients with uncontrolled hypertension, heart failure (NYHA class 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 per day). 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 per day) are required.

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

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 of treatment.

If signs or symptoms suggestive of these reactions occur, 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 patients with 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 impairment, those concurrently taking diuretics or ACE inhibitors, and 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 the infection. This has been observed in cases of community-acquired bacterial pneumonia and bacterial complications associated with varicella. If ibuprofen is prescribed for fever or pain related to infection, the course of the infectious disease should be monitored. Outpatients should consult a physician if symptoms persist or worsen.

Aseptic meningitis, systemic lupus erythematosus, and mixed connective tissue disorders. In isolated cases, symptoms of aseptic meningitis have been observed during ibuprofen use. Patients with lupus erythematosus and collagen diseases appear to be predisposed. However, such cases have 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, medical advice should be sought.

Use during pregnancy or breastfeeding.

Pregnancy

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

In animal studies, prostaglandin synthesis inhibitors have led to increased pre- and post-implantation fetal loss and embryofetal mortality. In addition, 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 in the second trimester, most of which resolved after treatment cessation. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman trying to conceive or during the first and second trimesters 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 several days of ibuprofen exposure starting from the 20th gestational week. Treatment with Tauffa® Extra 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 to the fetus:

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

Risks to the mother near term and to 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® Extra 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

Ibuprofen use 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 difficulty conceiving 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 occasionally have adverse effects on the central nervous system, such as reduced reaction speed. This should be taken into account when high alertness is required, particularly when driving vehicles or operating machinery. This effect may be particularly pronounced when ibuprofen is taken with alcohol.

Dosage and Administration

For short-term use only. The lowest effective dose that alleviates symptoms should be used for the shortest possible duration.

Adults and children aged 12 years and older

Dosage should be adjusted according to individual patient needs. The recommended initial dose of ibuprofen is 1200–1800 mg daily, divided throughout the day. For some patients, a maintenance dose of 600–1200 mg daily may be sufficient. In certain cases, the daily dose may be increased up to 2400 mg.

Dysmenorrhea

1200–1800 mg per day, divided into several doses.

Headache, migraine

The recommended dose is 600 mg. The maximum daily dose is 2400 mg.

Administration

Most patients without gastrointestinal disturbances may take the medicinal product Tauffa® Extra on an empty stomach, which is a significant advantage when treating morning joint stiffness. The first dose can be taken daily immediately upon waking, with sufficient fluid. Subsequent doses should be taken after meals.

Morning joint stiffness may be reduced by taking the last dose immediately before bedtime. For this purpose, 400 mg of ibuprofen may be used.

Tablets should be taken with sufficient water. Tablets must be swallowed whole and not chewed, broken, crushed, or sucked to avoid oral discomfort and throat irritation.

Children

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

Overdose

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

Symptoms: In most patients who have ingested a significant amount of ibuprofen, symptoms develop within 4–6 hours. The most commonly reported overdose symptoms 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 have been co-ingested.

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

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

Adverse Reactions

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 Warnings and Precautions for Use"). Other common gastrointestinal effects include nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, and hematemesis.

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

Exacerbation of skin infections, including development of 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 daily), may be associated with a slightly increased risk of arterial thrombotic events (such as myocardial infarction or stroke) (see section "Special Warnings and Precautions for Use***").

The frequency of adverse reactions is 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 use:

Infections and parasitic diseases: Uncommon – rhinitis; rare – aseptic meningitis.

Blood and lymphatic system disorders: Rare – hematological manifestations 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, dizziness.

Cardiac disorders: Very rare – heart failure, edema, infarction; frequency not known – Couineau’s 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 transient burning sensation in the mouth or throat may occur during use.

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

Skin and subcutaneous tissue disorders: Common – exanthema; rare – urticaria, pruritus, purpura, angioneurotic edema; very rare – severe cutaneous adverse reactions (SCARs), 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 renal 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 authorization 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 per blister. 1 or 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's address and place of business.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.