Affida max express

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT AFFFIDA MAX EXPRESS (AFFIDA MAX EXPRESS)

Composition:

Active substance: ibuprofen;

1 soft capsule contains 400 mg of ibuprofen;

Excipients: polyethylene glycol, potassium hydroxide, purified water;

Capsule shell composition: gelatin, sorbitol (E 420), purified water, soy lecithin, triglycerides.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: transparent, oval, soft gelatin capsules of pale yellow color.

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), a derivative of propionic acid, which exerts analgesic, antipyretic, and anti-inflammatory effects by inhibiting the synthesis of prostaglandins—mediators of pain and inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when these medicinal products are used concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen within 30 minutes after immediate-release acetylsalicylic acid (81 mg) was associated with reduced effects of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding 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. With occasional use of ibuprofen, such a clinically significant effect is considered unlikely.

Inside the capsule, ibuprofen is dissolved in a hydrophilic solvent. After oral administration, the gelatin capsule disintegrates under the action of gastric juice, resulting in the release of pre-dissolved ibuprofen.

Pharmacokinetics

After oral administration, ibuprofen is rapidly absorbed, partially in the stomach and completely in the small intestine.

Following metabolism in the liver (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are excreted predominantly in the urine (90%) and also in bile. The elimination half-life in healthy volunteers as well as in patients with hepatic or renal disease ranges from 1.8 to 3.5 hours. Protein binding in plasma is approximately 99%. After oral administration of the conventional release dosage form, maximum plasma concentration is reached within 1–2 hours. In a pharmacokinetic study, the time to peak plasma concentration (Tmax) on an empty stomach was 90 minutes for the tablet formulation and 40 minutes for soft capsules. Ibuprofen remains detectable in plasma for more than 8 hours after drug intake.

Clinical characteristics

Indications

Symptomatic treatment of mild to moderate pain of various origins (headache, dental pain, dysmenorrhea), including pain associated with colds and fever.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Hypersensitivity reactions (e.g., bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Active peptic ulcer disease / gastrointestinal bleeding or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
• Severe impairment of liver function, severe impairment of kidney function; heart failure (NYHA Class IV).
• Third trimester of pregnancy.
• Active cerebrovascular or other bleeding conditions.
• Hemorrhagic diathesis or coagulation disorders.
• Unexplained disturbances of blood formation.
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
• Patients with body weight less than 40 kg or patients under 12 years of age.

Interaction with other medicinal products and other forms of interaction

Concomitant use of ibuprofen with the following is not recommended:

• Acetylsalicylic acid — due to an increased risk of adverse reactions, except when acetylsalicylic acid (dose not exceeding 75 mg per day) has been prescribed by a physician.

Experimental data indicate that ibuprofen may interfere with the antiplatelet effect of low-dose acetylsalicylic acid when administered concomitantly. However, the limited ability to extrapolate these findings to clinical settings prevents definitive conclusions regarding whether regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically relevant interactions are considered unlikely with occasional, short-term use of ibuprofen.

• Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. Therefore, concomitant use of ibuprofen with other NSAIDs should be avoided.

Ibuprofen should be used with caution in combination with the following medicinal products:

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin.

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including potentially reversible acute renal failure. Therefore, such combinations should be used with caution, especially in elderly patients. Adequate hydration should be ensured, and monitoring of renal function should be considered at the start of combination therapy and periodically thereafter, particularly during long-term treatment. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Concomitant use of ibuprofen and potassium-sparing diuretics may lead to hyperkalemia (serum potassium levels should be monitored).

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): may increase the risk of gastrointestinal bleeding.

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

Lithium: evidence suggests a potential increase in plasma lithium levels.

Phenytoin: concomitant use with phenytoin may increase its serum concentration.

Methotrexate: administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate concentration and enhance its toxicity.

Cyclosporine: increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used earlier than 8–12 days after administration of mifepristone, as they may reduce its efficacy.

Tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Zidovudine: increased risk of hematological toxicity is known when zidovudine is used concomitantly with NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

Quinolone antibiotics: concomitant use with ibuprofen may increase the risk of seizures.

Sulfonylureas: blood glucose levels should be monitored as a precautionary measure during concomitant use.

Probenecid and sulfinpyrazone: may delay the elimination of ibuprofen.

CYP2C9 inhibitors: concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effects of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in the effect of S(+)-ibuprofen. Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are used with voriconazole or fluconazole.

Special precautions for use

Adverse effects can be minimized by using the lowest effective dose required to control symptoms for the shortest duration necessary.

Caution should be exercised when treating patients with:

• systemic lupus erythematosus and mixed connective tissue disease – increased risk of aseptic meningitis (see section "Adverse reactions");
• congenital disorders of porphyrin metabolism (e.g., acute intermittent porphyria);
• gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) (see section "Adverse reactions");
• arterial hypertension and/or heart failure (see sections "Contraindications" and "Adverse reactions");
• renal impairment, as renal function may deteriorate (see sections "Contraindications" and "Adverse reactions");
• hepatic impairment (see sections "Contraindications" and "Adverse reactions");
• following major surgical procedures;
• hypersensitivity to other substances, as they are also at increased risk of hypersensitivity reactions when using the drug;
• patients suffering from hay fever, nasal polyps, chronic obstructive respiratory diseases, or with a history of allergic conditions, as they are at increased risk of allergic reactions. They may experience asthma attacks (so-called analgesic-induced asthma), angioedema, or urticaria.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal.

Respiratory effects. Bronchospasm may occur in patients with bronchial asthma or allergic conditions, or with a history of such diseases.

Other NSAIDs. Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should be avoided.

Systemic lupus erythematosus and mixed connective tissue diseases. Ibuprofen should be used with caution in patients with manifestations of systemic lupus erythematosus or mixed connective tissue diseases due to an increased risk of aseptic meningitis.

Porphyrin metabolism. Caution is advised in patients with congenital disorders of porphyrin metabolism (e.g., acute intermittent porphyria).

Cardiovascular and cerebrovascular effects. Patients with a history of arterial hypertension and/or heart failure should begin treatment with caution (medical consultation is required), as fluid retention, hypertension, and edema have been reported during ibuprofen therapy, as with other NSAIDs.

Clinical trial data and epidemiological evidence 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 complications (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g., ≤ 1200 mg per day) increases the risk of arterial thrombotic complications.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful clinical assessment. High doses (2400 mg per day) should be avoided.

Careful clinical evaluation should also be performed before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, 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.

Renal effects. Ibuprofen should be used with caution in patients with renal impairment, as renal function may deteriorate.

Hepatic effects. Impairment of liver function may occur.

Surgical procedures. Caution should be exercised immediately after major surgical procedures.

Effect on female fertility. Limited data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis, when used long-term (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days), may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Gastrointestinal effects. NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. Cases of gastrointestinal bleeding, perforation, and ulcers, possibly fatal, have been reported during NSAID therapy at any stage, regardless of prior warning symptoms or history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, perforation, and ulcers increases with higher NSAID doses, in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. Such patients should start treatment with the lowest doses. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, consideration should be given to combined therapy with gastroprotective agents (e.g., misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal disorders, particularly elderly patients, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.

Caution should be exercised when treating patients receiving concomitant 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 (e.g., acetylsalicylic acid).

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

Serious skin adverse reactions (SSARs). Serious skin adverse reactions (SSARs), including exfoliative dermatitis, erythema multiforme, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month. If signs or symptoms suggestive of these reactions occur, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

Hypersensitivity. Caution should be exercised in patients with hypersensitivity to other substances, as they are also at increased risk of hypersensitivity reactions with ibuprofen.

Patients with hay fever, nasal polyps, chronic obstructive respiratory diseases, or a history of allergic conditions are at increased risk of allergic reactions, which may manifest as asthma attacks (so-called analgesic-induced asthma), angioedema, or urticaria.

This medicinal product contains sorbitol. If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

NSAIDs may mask symptoms of infection and fever.

Other. Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. If the first signs of hypersensitivity occur after drug administration, treatment must be discontinued. Symptomatic and specialized therapy should be initiated in such cases.

Ibuprofen may temporarily inhibit platelet function (affect platelet aggregation); therefore, careful monitoring is recommended in patients with coagulation disorders.

Masking symptoms of underlying infections. Affida Max Express may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of the disease. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If the medicinal product 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.

During long-term use of the medicinal product, liver and kidney function tests and blood counts should be monitored regularly.

Prolonged use of any analgesic for headache treatment may worsen the condition. In suspected or confirmed cases, medical advice should be sought and treatment discontinued. Medication-overuse headache should be suspected in patients with frequent or daily headaches despite (or because of) regular use of headache medications.

Chronic use of analgesics, especially combinations of multiple analgesics, may lead to persistent kidney dysfunction with risk of renal failure (analgesic nephropathy). This risk may be increased by salt loss and dehydration.

The risk of adverse effects related to the active substance, particularly gastrointestinal or CNS effects, may increase when NSAIDs are used concomitantly with alcohol.

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

Use during pregnancy or breastfeeding

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

From the 20th week of pregnancy, use of Affida Max Express 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 following treatment in the second trimester, most of which resolved after stopping treatment.

NSAIDs should not be used during the first two trimesters of pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman attempting to conceive or during the first or second trimester of pregnancy, the lowest possible dose should be used for the shortest possible duration. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to Affida Max Express for several days, starting from the 20th gestational week. Treatment with Affida Max Express should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

• to the fetus: cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension); renal dysfunction (see above);
• to the mother and newborn near term: prolonged bleeding time, antiplatelet effect (which may occur even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor. Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding period. In limited studies, ibuprofen has been detected in breast milk at very low concentrations; thus, it is unlikely to have a negative effect on the breastfed infant. However, NSAIDs are not recommended during breastfeeding.

Fertility. Use of ibuprofen may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, ibuprofen is not recommended for women with fertility difficulties.

Ability to influence reaction speed when driving or operating machinery

Patients who experience dizziness, drowsiness, or visual disturbances while taking ibuprofen should avoid driving or operating machinery. Single-dose administration or short-term use of ibuprofen generally does not require special precautions. This primarily applies to concomitant use of the drug with alcohol.

When used according to recommended doses and treatment duration, the drug does not affect reaction speed when driving or operating machinery.

Dosage and Administration

For oral use in adults and children aged 12 years and older with body weight >40 kg. For short-term use only. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").

Capsules should be taken preferably with or after food, without chewing, and swallowed with water.

The single dose for children aged 12 years and older with body weight >40 kg and for adults is 1 capsule (400 mg of ibuprofen). If necessary, 1 capsule may be administered every 6 hours. The maximum daily dose is 1200 mg (3 capsules per day). Use the lowest effective dose required to treat symptoms for the shortest possible duration.

If symptoms worsen or persist for more than 3 days in adolescents, medical advice should be sought for diagnosis clarification and treatment adjustment.

If fever symptoms persist for more than 3 days in adults, or if pain treatment lasts 4 days, or if symptoms worsen, medical advice should be sought for diagnosis clarification and treatment adjustment.

The duration of treatment should be determined individually by a physician based on the course of the disease and the patient's condition.

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment. Due to the potential for adverse effects, elderly patients should be monitored particularly carefully.

Patients with mild to moderate renal impairment do not require dose reduction (patients with severe renal impairment, see section "Special Warnings and Precautions for Use").

Dose reduction is not required in patients with mild or moderate hepatic impairment (patients with severe hepatic impairment, see section "Special Warnings and Precautions for Use").

Children

Do not administer to children under 12 years of age or with body weight <40 kg.

Overdose

Administration of doses exceeding 400 mg/kg in children may lead to intoxication symptoms. In adults, the effect of overdose is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients who have ingested clinically significant amounts of NSAIDs, symptoms include nausea, vomiting, epigastric pain, and very rarely diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic CNS effects may develop, presenting as vertigo, drowsiness, occasionally agitation, disorientation, or coma. Seizures may occasionally be observed. Severe intoxication may lead to hyperkalemia and metabolic acidosis. Prolongation of prothrombin time / increase in prothrombin index may occur, possibly due to effects on circulating blood coagulation factors. Acute renal failure, hepatic injury, arterial hypotension, respiratory depression, and cyanosis may develop. In patients with bronchial asthma, disease exacerbation is possible.

Treatment. Treatment should be symptomatic and supportive, including maintenance of airway patency and continuous monitoring of cardiac and vital functions until stabilization. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalinizing agents may be administered to enhance urinary excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators should be used to manage bronchial asthma exacerbations.

There is no specific antidote.

Adverse Reactions

The list of adverse reactions observed after treatment with ibuprofen includes all side effects reported during short-term use as well as those observed during long-term high-dose therapy in patients with rheumatism. The specified frequencies, even for very rare reports, refer to short-term use of daily doses of ibuprofen up to 1200 mg in oral dosage forms and up to 1800 mg for suppositories.

The development of adverse reactions following ibuprofen intake primarily depends on the dose and individual patient characteristics.

The most commonly observed adverse reactions are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. During the use of the medicinal product, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease have been reported. Gastritis occurs less frequently. The risk of gastrointestinal bleeding mainly depends on the dose and duration of treatment. Cases of edema, arterial hypertension, and heart failure have been reported.

Clinical studies indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), is associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Hypersensitivity reactions have been reported, which may manifest as non-specific allergic reactions and anaphylaxis; respiratory tract reactivity such as asthma, asthma exacerbation, bronchospasm, and dyspnea; and various skin reactions such as pruritus, urticaria, angioedema, and less frequently, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Patients should immediately discontinue the use of the medicinal product if any of the above symptoms occur and inform their physician.

Adverse reactions associated with the use of ibuprofen are classified by organ systems and frequency of occurrence: very common (> 1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated due to limited available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and parasitic diseases. Very rare: exacerbation of inflammation associated with infection (e.g., development of necrotizing fasciitis), which may coincide with the use of NSAIDs. If signs of infection occur or worsen during treatment with the drug, patients are advised to seek immediate medical attention. It is necessary to determine whether antimicrobial or antibacterial therapy is indicated.

Aseptic meningitis symptoms, including nuchal rigidity, headache, nausea, vomiting, fever, or altered consciousness, have been observed in patients with pre-existing autoimmune diseases such as systemic lupus erythematosus or mixed connective tissue disease during ibuprofen use.

Blood and lymphatic system disorders. Very rare: blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include malaise, sore throat, oral ulcerations, flu-like symptoms, severe fatigue, unexplained bleeding, and bruising. In such cases, patients should be advised to discontinue the drug to avoid self-medication with analgesics or antipyretics and to consult a physician immediately.

Regular blood monitoring is recommended during prolonged therapy.

Immune system disorders. Uncommon: hypersensitivity reactions including urticaria, pruritus, and asthma attacks. Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal swelling, dyspnea, tachycardia, arterial hypotension (anaphylactic reactions, angioedema, or severe shock); asthma exacerbation, bronchospasm.

Psychiatric disorders. Very rare: psychotic reactions, depression.

Nervous system disorders. Uncommon: headache, dizziness, insomnia, anxiety, irritability, or fatigue.

Eye disorders. Uncommon: visual disturbances.

Ear and labyrinth disorders. Rare: tinnitus, hearing loss.

Cardiovascular system disorders. Very rare: heart failure, myocardial infarction (see section "Special Warnings and Precautions for Use"), arterial hypertension. Frequency not known: Kounis syndrome.

Gastrointestinal disorders. Common: dyspepsia, heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation. Minor gastrointestinal blood loss, which may lead to anemia in rare cases. Uncommon: peptic ulcer, perforations, or gastrointestinal hemorrhage, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease, gastritis. Very rare: esophagitis, pancreatitis, intestinal diaphragm-like structure formation.

Patients should immediately discontinue the drug and consult a physician if upper abdominal pain, melena, or hematemesis occurs.

Hepatic disorders. Very rare: hepatic function abnormalities, liver damage (especially with long-term therapy), liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders. Uncommon: various skin rashes. Very rare: severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis). Frequency not known: drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

In some cases, varicella may be a source of serious skin and soft tissue infections.

Renal and urinary system disorders. Rare: acute renal function impairment (papillary necrosis), increased blood uric acid concentration, increased blood urea concentration. Very rare: edema, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure. Therefore, regular monitoring of renal function is recommended.

Laboratory investigations. Rare: decreased hemoglobin levels.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous 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 through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf Life

3 years.

Storage Conditions

Store at a temperature not exceeding 30 °C in the original packaging, in a place inaccessible to children.

Packaging

10 soft capsules in a blister; 1, 2, 3, or 10 blisters in a cardboard box.

Prescription Status

Over-the-counter (without prescription).

Manufacturer

Jeltex Private Limited.

Manufacturer's Address and Place of Business

Plot No. 24, 26/3, 27/2, Yadavanahalli Attibele, Bangalore-Hosur Road, Bangalore, Karnataka 562 107, India.

Marketing Authorization Holder

Delta Medical Promotions AG.

Address of the Marketing Authorization Holder

Othenbachstrasse 26, Zurich CH-8001, Switzerland.