INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FASPIK

Composition:

Active substance: ibuprofen;

1 tablet contains ibuprofen (as L-arginine salt) 400 mg;

Excipients: L-arginine, sodium hydrocarbonate, crospovidone, magnesium stearate, hypromellose, sucrose, titanium dioxide (E 171), polyethylene glycol (macrogol 4000).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, capsule-shaped, film-coated tablets with a break line on one side.

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

Pharmacological Properties.

Pharmacodynamics.

Ibuprofen is a synthetic analgesic and anti-inflammatory medicinal product that also exerts a pronounced antipyretic effect. Chemically, it is a derivative of phenylpropionic acid with anti-inflammatory activity.

Its analgesic activity is non-opioid in nature.

The mechanism of action of ibuprofen, as with other nonsteroidal anti-inflammatory drugs (NSAIDs), is related to the reversible inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid into cyclic endoperoxides, thereby reducing the synthesis of thromboxanes (TXA2), prostacyclin (PGI2), and prostaglandins (PGs).

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both agents are administered concomitantly. Some pharmacodynamic studies have shown that administration of a single 400 mg dose of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane production or platelet aggregation. Although uncertainty remains regarding the extrapolation of these data to clinical settings, it cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. However, such a clinically significant effect is considered unlikely with occasional, intermittent use of ibuprofen (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics.

Absorption.

Ibuprofen (a propionic acid derivative) is a racemic compound in which the S(+)-enantiomer possesses virtually all of the pharmacological activity.

The primary amino acid arginine, which is part of the medicinal product Faspic, enhances the solubility of ibuprofen in water and ensures very good and rapid absorption of the active substance after oral administration.

Human studies have demonstrated that Faspic, a new ibuprofen formulation, provides faster absorption of the active ingredient compared to traditional dosage forms (peak plasma concentrations are achieved earlier), with significantly higher plasma bioavailability during the first hour after administration.

Peak plasma concentrations are reached within approximately 15–30 minutes, and measurable plasma levels are achieved as early as 5–10 minutes after oral intake. This property is particularly important in clinical conditions (e.g., intense pain) where rapid analgesic action is essential.

Distribution.

The volume of distribution is 0.8–0.11 L/kg. Ibuprofen slowly diffuses into synovial fluid, reaching considerably lower concentrations compared to plasma levels at the same time point. Protein binding, primarily to albumin, is approximately 99%.

Metabolism.

Metabolism occurs mainly in the liver, where ibuprofen is converted into hydroxyl derivatives [(+)-2-(p-(2-hydroxypropyl-methyl-propyl)phenyl)propionic acid], carboxyl derivatives [(+)-2-(p-(2-carboxypropyl)phenyl)propionic acid], and conjugates with β-1-O-glucuronic acid, all of which are inactive.

Elimination.

Elimination of ibuprofen occurs primarily via the kidneys; the drug is excreted in the form of inactive metabolites. The elimination half-life of ibuprofen is 1.8–2 hours. No accumulation of ibuprofen or its metabolites has been observed following administration of the medicinal product Faspic, and elimination is practically complete within 24 hours.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, including migraine headache, toothache, dysmenorrhea, neuralgia, back pain, joint pain, muscle pain, as well as symptoms of cold and flu.

Contraindications.

Hypersensitivity to ibuprofen or to other chemically related substances and/or to any of the excipients of the medicinal product.
Recurrent peptic ulcer disease / gastrointestinal bleeding in medical history (at least one single episode of peptic ulcer or bleeding).
Gastrointestinal bleeding or perforation associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs) in medical history.
Active and recurrent peptic ulcer disease.
Gastrointestinal bleeding.
Ulcerative colitis and Crohn’s disease.
Hemorrhagic diathesis.
Severe impairment of liver function, kidney function impairment; heart failure (NYHA [New York Heart Association] Class IV).
Due to possible cross-allergic reactions with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, this medicinal product is contraindicated in patients in whom these agents have caused allergic reactions such as bronchospasm, asthma, urticaria, rhinitis, nasal polyps, or angioedema.
In systemic lupus erythematosus and connective tissue diseases, the use of Faspic should be evaluated by a physician.
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Cerebrovascular or other hemorrhages.
Do not use prior to or following cardiac surgery.

Interaction with other medicinal products and other forms of interaction.

Acetylsalicylic acid: concomitant use of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased adverse effects.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. Despite uncertainty regarding the clinical relevance of these data, a potential reduction in the cardioprotective effect of low-dose acetylsalicylic acid due to regular, long-term use of ibuprofen cannot be excluded. In the case of occasional ibuprofen use, clinically significant effects are considered unlikely (see section "Pharmacodynamics").

Other NSAIDs, including selective cyclooxygenase-2 inhibitors: ibuprofen should be used with caution in combination with other NSAIDs, as this may increase the risk of gastrointestinal adverse reactions.

Anticoagulants: NSAIDs may enhance the therapeutic effect of anticoagulants such as warfarin (see section "Special precautions for use"). Prothrombin time should be carefully monitored during the first weeks of combined therapy—dose adjustment of anticoagulants may be required.

Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of an ACE inhibitor or angiotensin II receptor antagonist with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered when treating patients receiving Faspic concomitantly with ACE inhibitors or angiotensin II receptor antagonists. Such combinations should be prescribed with caution, especially in elderly patients. Adequate hydration should be ensured, and monitoring of renal function should be considered at the initiation of combined therapy.

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding (see section "Special precautions for use").

Digoxin, phenytoin, and lithium: scientific publications report isolated cases of increased plasma levels of digoxin, phenytoin, and lithium with combined therapy using ibuprofen.

Methotrexate: ibuprofen may cause an increase in methotrexate plasma levels.

Zidovudine: evidence exists of increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant zidovudine and ibuprofen.

Tacrolimus: concomitant use of ibuprofen and tacrolimus may increase the risk of nephrotoxicity due to reduced renal prostaglandin synthesis.

Hypoglycemic agents: ibuprofen potentiates the hypoglycemic effect of oral hypoglycemic agents and insulin. Dose adjustment may be required.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section "Special precautions for use").

Furosemide and thiazide diuretics: the efficacy of furosemide and thiazide diuretics may be reduced, likely due to sodium retention associated with inhibition of renal prostaglandin synthase.

Beta-blockers: the antihypertensive effect of beta-blockers may be diminished. Concomitant use of NSAIDs and beta-blockers is associated with a risk of acute kidney injury.

Cyclosporine: concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of cyclosporine-associated nephrotoxicity.

Voriconazole or fluconazole: concomitant use with ibuprofen may lead to increased exposure to ibuprofen and elevated plasma concentrations.

Mifepristone: concomitant use with nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to increased exposure to NSAIDs.

Theoretically, a reduction in mifepristone efficacy may occur due to the anti-prostaglandin properties of NSAIDs. However, some studies investigating the effect of single or multiple doses of ibuprofen, starting on the day of prostaglandin administration (or as needed), have not demonstrated any evidence of negative impact on mifepristone action or on the overall clinical efficacy of pregnancy termination.

Quinolone antibiotics: concomitant use with NSAIDs increases the risk of seizures.

Herbal extracts: Ginkgo biloba may increase the risk of bleeding when used with NSAIDs.

Alcohol, bisphosphonates, and pentoxifylline: these agents may potentiate gastrointestinal adverse effects and increase the risk of bleeding and ulcer formation.

Baclofen: high toxicity of baclofen.

Aminoglycosides: NSAIDs may reduce the elimination of aminoglycosides.

Effect on diagnostic test results:

Bleeding time (the medicinal product may prolong bleeding time up to 1 day after discontinuation of therapy);
Serum glucose concentration (may decrease);
Creatinine clearance (may decrease);
Hematocrit or hemoglobin (may decrease);
Azotemia, serum creatinine and potassium concentrations (may increase);
Liver function tests (elevated transaminase activity may occur).

Special precautions for use.

The adverse effects of ibuprofen can generally be minimized by using the lowest effective dose required to control symptoms for the shortest duration possible (see section "Dosage and administration" and information below regarding gastrointestinal and cardiovascular risks).

Appropriate monitoring and appropriate recommendations are necessary for patients with hypertension and/or a history of moderate to severe congestive heart failure, as fluid retention and edema have been reported during NSAID therapy.

Clinical trial data indicate that the use of ibuprofen, especially at high doses (2400 mg daily), is associated with a small increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or 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 hypertension, congestive heart failure (NYHA classes II–III), established ischemic cardiomyopathy, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful clinical assessment. High doses (2400 mg daily) should be avoided. Clinical evaluation should also be carefully performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg daily) are required.

Cases of Kounis syndrome have been reported in patients receiving Faspic. Kounis syndrome is defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction associated with coronary artery spasm, potentially leading to myocardial infarction.

The medicinal product Faspic should not be used concomitantly with NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors.

Dehydrated children are at risk of impaired kidney function.

In elderly patients, there is an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal (see section "Dosage and administration").

Gastrointestinal bleeding, perforations, and ulcers. Cases of gastrointestinal bleeding, perforation, and ulcers, including fatal outcomes, have been reported during NSAID therapy at any stage of treatment, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, and ulcers increases with higher NSAID doses, particularly 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 doses. For such patients, as well as for those taking low-dose aspirin or other drugs that increase the risk of gastrointestinal complications, the concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered (see below and section "Interaction with other medicinal products and other forms of interaction"). Caution should be exercised when treating patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin or heparin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., aspirin) (see section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal disorders, particularly elderly patients, should report any unusual gastrointestinal symptoms, especially gastrointestinal bleeding, at the beginning of treatment. If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued.

Ibuprofen at doses exceeding 1000 mg may prolong bleeding time.

Severe cutaneous adverse reactions (SCARs). Severe cutaneous adverse reactions (SCARs) have been reported with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

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

Hepatotoxic reactions may occur as part of generalized hypersensitivity reactions.

Caution should be exercised when treating patients with a history of bronchospasm, particularly if it occurred after taking other medications, as well as patients with coagulation disorders or impaired renal and/or hepatic or cardiac function. Clinical and laboratory parameters of such patients should be monitored periodically, especially during long-term treatment (see section "Dosage and administration").

In patients with bronchial asthma or allergic diseases, or a history thereof, bronchospasm may be exacerbated.

Systemic lupus erythematosus or other connective tissue diseases are risk factors for severe generalized hypersensitivity reactions. Therefore, caution should be exercised when treating patients with these conditions.

Since there are (although very rare) reports of visual disturbances during ibuprofen therapy, treatment should be discontinued and an ophthalmological consultation sought if visual disturbances occur.

The use of Faspic, as with any other medicinal product that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended for women planning pregnancy, as it may negatively affect female fertility by disrupting ovulation. Women with fertility problems or undergoing fertility investigations should discontinue Faspic (see section "Use during pregnancy or lactation").

Treatment with ibuprofen should be initiated cautiously in patients with severe dehydration.

Masking symptoms of underlying infections. Faspic may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating the course of the illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. Isolated cases of worsening of infectious inflammation (e.g., development of necrotizing fasciitis) have been reported with concomitant NSAID use. Therefore, ibuprofen therapy should be prescribed cautiously in patients with infections. When Faspic 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.

NSAIDs may cause elevated liver function test parameters.

Alcohol consumption should be avoided, as it may exacerbate NSAID side effects, particularly gastrointestinal or central nervous system effects.

Medical care should be initiated by specialized healthcare personnel, depending on symptoms.

Acidic ibuprofen may increase bleeding time, as it causes reversible inhibition of platelet aggregation.

The medicinal product Faspic contains sucrose. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or deficiencies of sucrase or isomaltase enzymes should not take this product.

One tablet contains 82.98 mg of sodium, equivalent to 4.15% of the maximum daily sodium intake recommended by WHO for adults (2 g). This should be considered when prescribing the product to patients on a low-sodium diet.

Use during pregnancy or lactation.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage, congenital heart defects, and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The overall risk of congenital heart defects increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. Animal studies have shown that prostaglandin synthesis inhibitors increase the incidence of pre- and post-implantation losses and embryonic/fetal mortality. In addition, increased frequency of various developmental abnormalities, including cardiovascular malformations, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, the use of Faspic may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, cases of arterial duct constriction have been reported after second-trimester treatment, which mostly resolved after stopping the drug. Therefore, Faspic should not be taken during the first two trimesters of pregnancy, except when absolutely necessary.

If Faspic is prescribed to women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible duration. After the 20th week of pregnancy, if Faspic is used for several days, antenatal monitoring for oligohydramnios and arterial duct constriction should be considered. If oligohydramnios or arterial duct constriction is detected, Faspic should be discontinued.

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

For the fetus: cardiopulmonary toxicity (characterized by premature closure/constriction of the arterial duct and pulmonary hypertension); impaired renal function (see above);
For the mother near term and the newborn: possible prolonged bleeding time, antiplatelet effect (which may occur even at very low doses), and inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

This medicinal product should not be used by women during breastfeeding or administered to infants.

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

The medicinal product Faspic may affect the ability to drive vehicles or operate machinery due to possible occurrence of somnolence, vertigo, headache, and depression.

Patients whose activities require high attention should exercise caution if they experience somnolence, vertigo, headache, or depression during ibuprofen treatment.

Method of Administration and Dosage.

For oral use, for short-term use only.

Adults and children aged 12 years and older. The drug is administered one tablet two to three times daily. Tablets should be taken with a small amount of water. Patients with more sensitive stomachs should take this medicinal product during meals. Do not exceed 3 tablets within 24 hours. The maximum daily dose is 1200 mg.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Precautions"). If symptoms persist for more than 3 days after initiation of treatment or worsen, medical advice should be sought.

Elderly patients. The lowest doses indicated above should be used.

Dosage in elderly patients should be carefully determined by a physician, who must assess whether the above-mentioned doses need to be reduced.

Dosages should be reduced in patients with impaired renal, hepatic, or cardiac function.

Hepatic impairment. Caution is required when treating patients with hepatic impairment. Clinical and laboratory parameters in such patients should be monitored periodically, especially during prolonged treatment (see section "Special Precautions"). The use of the medicinal product Faspik is contraindicated in patients with hepatic insufficiency (see section "Contraindications").

Renal impairment. Caution is required when treating patients with renal impairment. Clinical and laboratory parameters in such patients should be monitored periodically, especially during prolonged treatment (see section "Special Precautions"). The use of the medicinal product Faspik is contraindicated in patients with renal insufficiency (see section "Contraindications").

Children. Not recommended for children under 12 years of age.

Overdose

Toxicity. Signs and symptoms of intoxication have generally not been observed with doses below 100 mg/kg in children or adults. However, supportive treatment may be required in some cases. Signs and symptoms of intoxication in children have been reported following ibuprofen doses of 400 mg/kg or higher.

Symptoms. In most patients who have taken a significant overdose of ibuprofen, symptoms appear within 4–6 hours.

The most commonly reported symptoms of overdose include: nausea, vomiting, epigastric pain, abdominal pain, marked lethargy, and drowsiness.

Central nervous system (CNS) effects include headache, tinnitus, vertigo, diplopia, spasms, ataxia, rhabdomyolysis, epileptic seizures, convulsions, and loss of consciousness.

Rare cases have been reported of nystagmus, hypothermia, renal impairment, gastrointestinal bleeding, coma, apnea, diarrhea, and CNS and respiratory depression.

Cases of disorientation, agitation, stupor, and signs of toxic effects on the cardiovascular system, including arterial hypotension, bradycardia, and tachycardia, have been reported. Severe overdose may lead to renal failure and hepatic injury.

In cases of severe poisoning, metabolic acidosis may develop.

Treatment. There is no specific antidote for ibuprofen overdose.

In case of overdose, symptomatic and supportive therapy is recommended.

Particular attention should be paid to monitoring blood pressure, acid-base balance, and gastrointestinal bleeding (if present).

Activated charcoal should be considered within one hour after ingestion of a potentially toxic dose. As an alternative, gastric lavage and correction of severe electrolyte disturbances may be performed in adults within one hour after ingestion of a potentially lethal dose.

Due to the high degree of plasma protein binding of ibuprofen (up to 99%), dialysis is unlikely to be beneficial in cases of overdose.

Adequate diuresis should be maintained, and renal and hepatic functions should be closely monitored.

Patients should remain under observation for at least four hours after ingestion of a potentially toxic dose.

In case of frequent or prolonged seizures, intravenous diazepam should be administered.

Other supportive measures may be required depending on the patient's clinical condition.

For additional information, contact the local toxicology center.

Adverse Reactions

Unwanted effects are mainly related to the pharmacological action of ibuprofen on prostaglandin synthesis.

Gastrointestinal disorders: Adverse effects involving the gastrointestinal tract are the most commonly observed. These include peptic ulcers, gastrointestinal perforation or hemorrhage, which may sometimes be fatal, especially in elderly patients (see section "Special precautions for use").

Following administration of the medicinal product Faspic, the following effects have been reported: nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, heartburn, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn’s disease (see section "Special precautions for use").

Gastritis has been observed less frequently.

Skin and subcutaneous tissue disorders: Bullous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Cardiac and vascular disorders: Edema, arterial hypertension, and heart failure have been reported in association with NSAID therapy.

Clinical trial data indicate that the use of ibuprofen, particularly at high doses (2400 mg/day), is associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions for use").

Adverse reactions are classified by system organ class and frequency of occurrence: 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; frequency not known (cannot be estimated due to limited available data).

Cardiac disorders

Frequency not known — heart failure, Coumadin syndrome.

Gastrointestinal disorders

Very common — dyspepsia, diarrhea; common — abdominal pain, heartburn, nausea, flatulence, abdominal tenderness; uncommon — peptic ulcer, gastrointestinal hemorrhage, vomiting, melena, gastritis, stomatitis; rare — gastrointestinal perforation, constipation, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease; frequency not known — anorexia.

Nervous system disorders

Common — headache, dizziness; uncommon — confusion, somnolence; rare — stroke*; very rare — lethargy (obnubilation); frequency not known — depression, psychotic reactions, aseptic meningitis.

Renal and urinary disorders

Rare — hematuria, dysuria; very rare — interstitial nephritis, papillary necrosis, renal failure, acute kidney injury.

Hepatic disorders

Rare — hepatotoxicity; frequency not known — liver injury, hepatitis, jaundice.

Vascular disorders

Frequency not known — arterial hypertension, arterial thrombosis, arterial hypotension.

Skin and subcutaneous tissue disorders

Common — skin disorders and rash; uncommon — pruritus, urticaria, purpura, angioneurotic edema, exanthema; very rare — severe cutaneous adverse reactions (SCARs) (including Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, and toxic epidermal necrolysis), allergic vasculitis; frequency not known — photosensitivity reactions, worsening of skin reactions, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Blood and lymphatic system disorders

Rare — aplastic anemia, thrombocytopenia, agranulocytosis, granulocytopenia, hemolytic anemia; frequency not known — anemia.

Eye disorders

Rare — blurred vision, amblyopia, color vision disturbances; frequency not known — optic disc edema.

Ear and labyrinth disorders

Rare — tinnitus and hearing disturbances.

Immune system disorders

Uncommon — allergic reactions; rare — anaphylaxis; frequency not known — anaphylactic shock.

General disorders

Frequency not known — edema, fever.

Investigations

Rare — liver function test abnormalities (elevated transaminase activity), elevated alkaline phosphatase activity, decreased hematocrit, prolonged bleeding time, decreased blood calcium level*, increased uric acid level*; very rare — decreased hemoglobin level; frequency not known — renal function test abnormalities.

Respiratory, thoracic and mediastinal disorders

Uncommon — asthma, worsening of asthma severity, bronchospasm, dyspnea; frequency not known — throat irritation.

Musculoskeletal and connective tissue disorders

Frequency not known — musculoskeletal stiffness.

Metabolism and nutrition disorders

Frequency not known — increased uricemia, sodium and water retention, or edema.

Reproductive system and breast disorders

Frequency not known — menstrual cycle disturbances.

*Class effect of NSAIDs.

The occurrence of adverse effects during treatment requires immediate discontinuation of therapy and medical consultation.

Children

Overall clinical experience indicates no clinically significant differences in the nature, frequency, severity, or reversibility of adverse reactions between the safety profile in adults and in the pediatric age group for which the medicinal product is approved (age ≥ 12 years).

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and 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. 3 years.

Storage conditions. Store in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 6 tablets per blister. 1 blister per cardboard box.

Prescription status. Over-the-counter (without prescription).

Manufacturer.

Zambon S.P.A. / Zambon S.P.A.

Manufacturer's address and place of business.

Via della Chimica, 9 - 36100 Vicenza (VI), Italy / Via della Chimica, 9 - 36100 Vicenza (VI), Italy.

Marketing authorization holder.

Zambon S.P.A. / Zambon S.P.A.

Address of marketing authorization holder.

Via Lillo del Duca, 10 - 20091 Bresso, Milan, Italy / Via Lillo del Duca, 10 - 20091 Bresso, Milan, Italy.