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

Composition:

Active substance: ibuprofen;

1 soft capsule contains 200 mg of ibuprofen;

Excipients: polyethylene glycol 600, potassium hydroxide (85% purity), purified water;

Capsule shell composition: gelatin, partially dehydrated liquid sorbitol (E 420), purified water, soy lecithin, medium-chain triglycerides.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: transparent, oval, soft gelatin capsules of pale yellow color with a clear filling.

Pharmacotherapeutic group.

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

ATC code M01A E01.

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) resulted in reduced effects of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding the extrapolation of these data to clinical settings, the possibility cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional, non-regular 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, thereby releasing the pre-dissolved ibuprofen.

Pharmacokinetics

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

Following hepatic metabolism (hydroxylation, carboxylation, conjugation), pharmacologically inactive metabolites are excreted predominantly in 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. Plasma protein binding 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 levels (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/gastrointestinal hemorrhage or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Severe impairment of liver function; severe impairment of kidney function; heart failure (NYHA class IV).
Third trimester of pregnancy.
Active cerebrovascular or other bleeding.
Hemorrhagic diathesis or coagulation disorders.
Unexplained disturbances of blood formation.
Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
Children with body weight less than 20 kg.

Interaction with other medicinal products and other forms of interactions

Concomitant use of ibuprofen with the following is not recommended:

Acetylsalicylic acid: coadministration may increase the 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 inhibit the antiplatelet effect of low-dose acetylsalicylic acid when administered concomitantly. However, due to limitations in extrapolating these data to clinical settings, definitive conclusions cannot be drawn regarding whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant interactions are considered unlikely with occasional, short-term use of ibuprofen.

Other NSAIDs, including selective cyclooxygenase-2 inhibitors: concomitant use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, concomitant administration of ibuprofen with other NSAIDs should be avoided.

Ibuprofen should be used with caution when coadministered 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 possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, particularly in elderly patients. Adequate hydration should be ensured if long-term treatment is necessary, and monitoring of renal function should be considered at the initiation of combination therapy and periodically thereafter. 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.

MTX (methotrexate): administration of ibuprofen within 24 hours before or after methotrexate may increase methotrexate plasma concentrations and enhance its toxicity.

Cyclosporine: increased risk of nephrotoxicity.

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

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

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 enhance the effects of ibuprofen (a CYP2C9 substrate). In studies with voriconazole and fluconazole (CYP2C9 inhibitors), the effect of S(+)-ibuprofen was increased by approximately 80–100%. Dose reduction of ibuprofen should be considered when potent CYP2C9 inhibitors are used concomitantly, especially when high doses of ibuprofen are administered with voriconazole or fluconazole.

Special precautions for use

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

Caution is advised when treating patients with:

systemic lupus erythematosus or mixed connective tissue disease – increased risk of aseptic meningitis (see section "Adverse reactions");
congenital porphyrin metabolism disorders (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");
impaired renal function, as kidney function may deteriorate (see sections "Contraindications" and "Adverse reactions");
impaired liver function (see sections "Contraindications" and "Adverse reactions");
following major surgical procedures;
allergic reactions to other substances, as they may also be 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 are at increased risk of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal.

Respiratory system 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 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 porphyrin metabolism disorders (e.g., acute intermittent porphyria).

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

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, especially at high doses (2400 mg daily), may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low-dose ibuprofen (e.g., ≤ 1200 mg daily) 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 daily) should be avoided.

Careful clinical evaluation is also required before initiating long-term treatment in patients with cardiovascular risk factors (e.g., 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 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 impaired renal function, as kidney function may worsen.

Hepatic effects. Impaired liver function may occur.

Surgical procedures. Caution is advised immediately after major surgical interventions.

Effect on female fertility. Limited data suggest that drugs inhibiting cyclooxygenase/prostaglandin synthesis, when used long-term (doses of 2400 mg daily 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 cautiously in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as these conditions may worsen. Cases of gastrointestinal bleeding, perforation, and ulcers, some fatal, have been reported during NSAID therapy at any stage, regardless of prior warning symptoms or history of severe gastrointestinal disorders (GI).

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 possible dose. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase GI risk, consideration should be given to combination 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 is advised 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, or antiplatelet agents (e.g., acetylsalicylic acid).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Severe skin adverse reactions. Severe 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), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen (see section "Adverse reactions"). Most such reactions occurred within the first month of therapy. If signs or symptoms suggestive of these reactions occur, ibuprofen should be discontinued immediately and alternative therapy considered (if necessary).

In rare cases, varicella may lead to severe skin and soft tissue infections. The potential influence of NSAIDs on worsening the course of such infections cannot be excluded; therefore, the use of ibuprofen in varicella is not recommended.

Allergy. Caution is advised in patients with allergic reactions to other substances, as they may also be 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 early signs of hypersensitivity occur after drug administration, therapy should be discontinued. Symptomatic and specialized treatment should be initiated in such cases.

Masking symptoms of underlying infections. The medicinal product Affida Express may mask symptoms of infectious disease, potentially delaying appropriate treatment and thereby worsening the course of illness. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When the medicinal product is used for fever or pain relief during infection, monitoring of the infectious condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

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

With long-term use of the medicinal product, regular monitoring of liver and kidney function tests and blood counts is advised.

Long-term use of any analgesic for headache treatment may worsen the condition. If suspected or confirmed, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients with frequent or daily headaches despite (or because of) regular use of headache medications.

Regular 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 kidney function in dehydrated adolescents.

If intolerance to certain sugars is diagnosed, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy. Inhibition of prostaglandin synthesis may negatively 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 Express may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after second-trimester treatment, most of which resolved after stopping therapy. NSAIDs should not be used during the first two trimesters of pregnancy unless the expected benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose for the shortest duration should be used. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of exposure to Affida Express starting from the 20th gestational week. Use of Affida 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:

cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
renal dysfunction (see above);
for the mother near term and for the newborn: prolonged bleeding time, anti-aggregatory 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.

Breastfeeding period. In limited studies, ibuprofen has been detected in breast milk at very low concentrations, making it unlikely to adversely affect the breastfed infant. However, NSAIDs are not recommended during breastfeeding.

Fertility. Ibuprofen may affect female fertility. This effect is reversible upon discontinuation of treatment. Therefore, ibuprofen is not recommended for women experiencing difficulty conceiving.

Ability to affect reaction speed when driving or operating machinery

Patients experiencing dizziness, drowsiness, or visual disturbances during ibuprofen use 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 with alcohol.

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

Method of Administration and Dosage

For short-term use only. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Precautions").

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

Adults and children with body weight ≥ 40 kg. The recommended initial dose is 1–2 capsules. If necessary, 1–2 capsules (200–400 mg of ibuprofen) may be taken every 4–6 hours. Do not exceed 6 capsules (1200 mg) within 24 hours.

Children with body weight ≤ 39 kg. The medicinal product may be used in children with body weight of at least 20 kg. The maximum daily dose of ibuprofen is 20–30 mg per kilogram of body weight, divided into 3–4 doses administered at 6–8 hour intervals. Do not exceed the maximum recommended daily dose.

Children with body weight from 20 to 29 kg. The recommended initial dose is 1 capsule (200 mg of ibuprofen). The maximum daily dose is 3 capsules (600 mg of ibuprofen).

Children with body weight from 30 to 39 kg. The recommended initial dose is 1 capsule (200 mg of ibuprofen). The maximum daily dose is 4 capsules (800 mg of ibuprofen).

If symptoms persist for more than 3 days, or more than 4 days when used for pain relief, consult a physician for diagnosis clarification and treatment adjustment.

The duration of treatment is determined individually by a physician depending 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 increased risk of adverse reactions, elderly patients should be monitored particularly carefully.

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

Dose reduction is not necessary for patients with mild or moderate hepatic impairment (for patients with severe hepatic impairment, see section "Special Precautions").

Children

Do not administer to children with body weight < 20 kg.

Overdose

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

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

Treatment. Management should be symptomatic and supportive, including ensuring airway patency and monitoring cardiac and vital functions until stabilization. Oral administration of activated charcoal or gastric lavage is recommended within one hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalinizing agents may be administered to enhance renal excretion of the acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators are required for the treatment of bronchial asthma exacerbation.

There is no specific antidote.

Side effects

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 after ibuprofen administration primarily depends on the dose and individual patient characteristics.

The most commonly observed adverse reactions are gastrointestinal (GI) in nature. Peptic ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. During drug use, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease have been reported. Gastritis has been observed 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, especially at high doses (2400 mg per day), slightly increases the 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, dyspnea; and various skin reactions such as pruritus, urticaria, angioedema, and less frequently, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

The patient should immediately discontinue the drug and inform their physician if any of the above symptoms occur.

Adverse reactions associated with ibuprofen use 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), 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 drug use, patients are advised to seek immediate medical attention. It is necessary to determine whether antimicrobial/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, thrombocytopen, pancytopenia, agranulocytosis). Initial symptoms include fever, 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 should consult a physician.

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 edema, dyspnea, tachycardia, and 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. Frequency not known – photosensitivity reactions.

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

Cardiovascular disorders. Very rare – heart failure, myocardial infarction (see section "Special 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 structures.

Patients must immediately discontinue the drug and seek medical advice if upper abdominal pain, melena, or hematemesis occur.

Hepatobiliary disorders. Very rare – liver 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 reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acute generalized exanthematous pustulosis (AGEP).

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

Renal and urinary disorders. Rare – acute renal dysfunction (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 suspected adverse reactions

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report suspected adverse reactions and lack of drug efficacy to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 30 °C. Store in the original packaging. Keep out of reach of children.

Packaging

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

Dispensing category

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

Ottenbachstrasse 26, Zurich CH-8001, Switzerland.

Affido express