Caffetin® lady

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Kauffetin® LADY (CAFFETIN® LADY)

Composition:

Active substance: ibuprofen;

One tablet contains ibuprofen 200 mg (as ibuprofen lysinate 342 mg);

Excipients: microcrystalline cellulose silica, copovidone, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate, talc;

Coating: Opadry II Pink [hydroxypropylmethylcellulose (E 464), titanium dioxide (E 171), polydextrose (E 1200), talc (E 553b), maltodextrin, medium-chain triglycerides, dyes: Ponceau 4R (E 124), Sunset Yellow FCF (E 110), indigo carmine (E 132)]; Opadry FX Gray [sodium carboxymethylcellulose (E 466); maltodextrin; glucose monohydrate; pearl pigment based on titanium dioxide mica (E 555/E 171); lecithin (E 322)].

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex, film-coated tablets with a break line on one side. Pastel pink in color with a shiny effect.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. ATC code M01A E01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen inhibits cyclooxygenase (COX) enzymes and suppresses prostaglandin biosynthesis. The drug exerts analgesic, anti-inflammatory, and moderate antipyretic effects, and inhibits platelet aggregation.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation when both agents are used concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg) resulted in reduced effect of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although uncertainty exists regarding extrapolation of these data to the clinical setting, the possibility that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. With occasional, non-regular use of ibuprofen, such a clinically significant effect is considered unlikely.

In women with menstrual pain, ibuprofen reduces elevated levels of prostaglandins in menstrual fluid, decreases intrauterine pressure, and reduces the frequency of uterine contractions.

Pharmacokinetics.

Most pharmacokinetic data following ibuprofen administration also apply to ibuprofen lysinate.

Absorption and distribution

Maximum plasma concentrations are achieved within 1–2 hours after administration of ibuprofen. However, when KAFFETIN® LADY is administered, ibuprofen is absorbed more rapidly in the gastrointestinal tract, reaching peak plasma concentrations within approximately 35 minutes after administration on an empty stomach.

Ibuprofen is rapidly distributed throughout the body and is highly bound to plasma proteins.

Metabolism and excretion

Ibuprofen is metabolized in the liver into two inactive metabolites, which, together with unchanged ibuprofen, are excreted by the kidneys either unchanged or as conjugates. Renal excretion is rapid and complete. The elimination half-life of ibuprofen is approximately 2 hours.

No significant differences in pharmacokinetic profile have been observed in elderly individuals.

Clinical characteristics.

Indications.

Menstrual pain.

Contraindications.

Hypersensitivity to ibuprofen or to any of the other components of the medicinal product.

Hypersensitivity reactions (e.g. asthma, allergic rhinitis, angioedema or urticaria) previously observed after taking ibuprofen, acetylsalicylic acid (aspirin), or other non-steroidal anti-inflammatory drugs (NSAIDs).

Active peptic ulcer or gastrointestinal bleeding, or recurrence in medical history (two or more distinct episodes of peptic ulcer exacerbation or bleeding).

History of gastrointestinal bleeding or perforation associated with the use of NSAIDs.

Severe heart failure (NYHA functional class IV), severe hepatic or renal impairment.

Cerebrovascular or other bleeding; disorders of hematopoiesis or blood coagulation.

Active inflammatory bowel disease.

Last trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

In general, caution should be exercised when using NSAIDs in combination with other medicinal products that may increase the risk of gastrointestinal ulcers, gastrointestinal bleeding, or worsening of renal function.

Ibuprofen (like other NSAIDs) should not be used in combination with:

acetylsalicylic acid, as this 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 concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo data to clinical outcomes do not allow definitive conclusions about the systematic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen.

other non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors. Concomitant use of two or more NSAIDs should be avoided, as this may increase the risk of adverse effects.

Ibuprofen should be used with caution in combination with:

antihypertensives (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the therapeutic effect of these 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 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 in patients receiving coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, such combinations should be used with caution, especially in elderly patients. If treatment is necessary, adequate hydration should be ensured and monitoring of renal function should be considered at the start of combined therapy and periodically thereafter. Diuretics may increase the risk of NSAID-induced nephrotoxicity.

anticoagulants: NSAIDs may enhance the therapeutic effect of anticoagulants such as warfarin.

antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

corticosteroids: possible increased risk of gastrointestinal ulceration or bleeding.

ethanol: increases the risk of gastrointestinal bleeding.

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

cyclosporine: increased risk of nephrotoxicity.

mifepristone: NSAIDs should not be taken earlier than 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone.

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

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

methotrexate: there is a possibility of increased methotrexate plasma levels.

phenytoin: increased plasma concentration and consequently toxicity.

zidovudine: increased risk of hematologic toxicity when NSAIDs are used concomitantly with zidovudine. Evidence indicates an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia who are receiving zidovudine and ibuprofen concomitantly.

quinolone antibiotics: animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Concomitant use of NSAIDs and quinolone antibiotics may increase the risk of seizures.

probenecid and sulfinpyrazone: prolong the elimination time of ibuprofen. The uricosuric effect of these agents is reduced when used concomitantly with ibuprofen.

aminoglycosides: concomitant use may increase their nephrotoxic and ototoxic effects.

Medicinal products of the sulfonylurea group and phenytoin: possible potentiation of effect.

Special precautions for use.

Adverse effects associated with ibuprofen can be minimized by using the lowest effective dose required to relieve symptoms for the shortest possible duration.

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

Cardiovascular and cerebrovascular effects

Caution should be exercised when initiating long-term treatment in patients with a history of arterial hypertension and/or heart failure (medical consultation is required), as fluid retention, arterial hypertension, and edema have been reported during therapy with ibuprofen and other NSAIDs.

Clinical trials and epidemiological data indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and prolonged use, may lead to a slight increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low doses of ibuprofen (e.g., ≤1200 mg per day) increase the risk of arterial thrombotic complications. Treatment may be prescribed by a physician only after careful assessment for patients with uncontrolled arterial hypertension, congestive heart failure (NYHA functional class II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. High doses (2400 mg per day) should be avoided. Long-term NSAID treatment, particularly at high doses (2400 mg per day), should be prescribed only after careful consideration in patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Respiratory effects.

Bronchospasm may occur in patients suffering from 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, should be avoided, as this increases the risk of adverse reactions.

Systemic lupus erythematosus and systemic connective tissue diseases.

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

Cases of aseptic meningitis have been reported during ibuprofen use. Although this effect is more likely in patients with systemic lupus erythematosus and other connective tissue disorders, such cases have also been reported in some patients without chronic diseases; therefore, this should be considered when using this medicinal product.

Effects on kidneys/liver.

Prolonged use of NSAIDs may lead to dose-dependent reduction in prostaglandin synthesis and provoke the development of renal failure. Patients with impaired kidney function, cardiac disorders, hepatic dysfunction, and those taking diuretics are at higher risk of this reaction, as prostaglandin inhibition may lead to fluid retention and further deterioration of kidney function. These patients should use the lowest possible dose of ibuprofen and have their kidney function monitored regularly. Adequate fluid intake should be ensured in cases of dehydration. There is a risk of renal failure in children (aged 6 years and older) and adolescents who are dehydrated.

Renal tubular acidosis and hypokalemia may occur after acute overdose and in patients taking high doses of ibuprofen over a prolonged period (usually longer than 4 weeks), including doses exceeding the recommended daily dose.

In general, chronic use of analgesics, especially combinations of different painkillers, may lead to long-term kidney damage with a risk of renal failure (analgesic nephropathy). The highest risk of this reaction exists in elderly patients, patients with renal, cardiac, or hepatic insufficiency, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID treatment, recovery to the pre-treatment state is usually achieved.

Like other NSAIDs, ibuprofen may cause a slight, temporary increase in certain liver function parameters, as well as significant elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Treatment should be discontinued if substantial increases in these parameters occur.

During prolonged use of ibuprofen, liver function, kidney function, and hematological parameters/blood counts should be monitored regularly.

Effect on female fertility.

Limited data suggest that medicinal products inhibiting cyclooxygenase/prostaglandin synthesis may impair female reproductive function due to effects on ovulation. This effect is reversible upon discontinuation of treatment. Prolonged use (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days) of ibuprofen may impair female fertility and is not recommended for women attempting to conceive. This medication should be discontinued in women experiencing difficulty conceiving or undergoing infertility investigations.

Gastrointestinal tract effects.

NSAIDs should be prescribed with caution to patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated. Cases of gastrointestinal ulcers, bleeding, or perforation have been reported with various NSAIDs, which may be fatal, 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 in patients with a history of peptic ulcer disease, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest doses. Caution is necessary for patients receiving concomitant therapy with drugs that may increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid). Combined therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered, especially in patients requiring long-term low-dose acetylsalicylic acid.

Patients who experience gastrointestinal disturbances, particularly elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially at the beginning of treatment.

Prolonged use of any analgesic for headache treatment may worsen this condition. In such cases, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients suffering from frequent or daily headaches despite (or because of) regular use of headache medications.

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

Skin and subcutaneous tissue.

Very rarely, severe skin reactions that may be fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (see section "Adverse reactions"), may occur during NSAID use. The highest risk of such reactions occurs early in the treatment course, with most cases appearing within the first month of therapy. Cases of acute generalized exanthematous pustulosis (AGEP) have also been reported after administration of medicinal products containing ibuprofen. Ibuprofen should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Masking symptoms of underlying infections

Like other NSAIDs, ibuprofen may mask symptoms of infectious diseases, potentially delaying the initiation of appropriate treatment and thereby complicating the course of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief in infectious diseases, monitoring of the condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

In rare cases, varicella may lead to severe skin and soft tissue infections. At present, the influence of NSAIDs on the complications of these infections cannot be excluded; therefore, the use of the medicinal product Kauffetin® Lady is not recommended in cases of varicella.

The tablets contain colorants (E 110 and E 124), which may cause allergic reactions.

The tablets contain glucose. Patients with rare hereditary glucose-galactose malabsorption should not take this medicinal product.

The tablets contain soy lecithin. Patients with peanut or soy allergy should not use this medicinal product.

Use during pregnancy or breastfeeding.

The medicinal product is used for menstrual pain.

Ibuprofen should be avoided during the first and second trimesters of pregnancy. Ibuprofen is contraindicated during the third trimester of 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 the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

In animal studies, prostaglandin synthesis inhibitors caused increased rates of pre- and post-implantation loss and embryonic/fetal mortality. In addition, increased incidences of various developmental abnormalities, including cardiovascular defects, were reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after the start of 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. Therefore, ibuprofen should not be taken during the first two trimesters of pregnancy or during labor unless the potential 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 exposure to ibuprofen for several days starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

• to the fetus: cardiopulmonary toxicity (premature constriction/closure of the fetal arterial duct with pulmonary hypertension); renal dysfunction, which may progress to renal failure associated with oligohydramnios;
• to the mother and newborn at the end of pregnancy: prolonged bleeding time, antiplatelet effect (which may occur even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

In limited studies, ibuprofen was detected in breast milk at very low concentrations; therefore, it is unlikely to adversely affect the breastfed infant.

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

No effect, provided the recommended dosage and treatment duration are followed. Patients who experience dizziness, drowsiness, disorientation, or visual disturbances while taking NSAIDs should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage.

For short-term oral use only. Tablets should be swallowed with water, not chewed.

The lowest effective dose required to treat symptoms should be used for the shortest possible duration.

Adults and children aged 12 years and older: administer 1–2 tablets, preferably during or after meals.

The interval between two doses should be 4–6 hours. Regular administration at fixed time intervals eliminates fluctuations in pain intensity.

The total daily dose (within 24 hours) must not exceed 6 tablets, corresponding to 1200 mg of ibuprofen.

Patients with gastrointestinal disorders are advised to take the tablets with food.

If pain persists beyond 3 days, treatment with this medication should not be continued without consulting a physician.

Children.

The medicinal product may be used in children aged 12 years and older.

Overdose.

Most reported cases of overdose were asymptomatic. Symptoms may occur at ibuprofen doses exceeding 80–100 mg/kg. Doses exceeding 400 mg/kg in children may cause intoxication symptoms. In adults, the dose effect is less pronounced. The half-life during overdose is 1.5–3 hours.

Symptoms of overdose typically appear within 4 hours after ingestion. In most patients participating in clinical trials, ingestion of large amounts of NSAIDs caused only nausea, vomiting, epigastric pain, or very rarely diarrhea. Other possible symptoms include tinnitus, headache, and gastrointestinal bleeding. In more severe poisoning, toxic effects on the central nervous system may occur, such as vertigo, dizziness, lethargy, somnolence, nystagmus, visual disturbances, occasionally nervous excitation and disorientation, ataxia, or coma. Seizures may occasionally occur. Severe poisoning may lead to hyperkalemia and metabolic acidosis; prothrombin time/international normalized ratio (INR) may increase, likely due to interaction with circulating coagulation factors. Acute renal failure, liver damage, hypothermia, arterial hypotension, respiratory insufficiency, and cyanosis may occur; transient apnea episodes may occur in children after ingestion of large amounts of the drug. In patients with bronchial asthma, disease exacerbation may occur. Serious poisoning may result in metabolic acidosis. Nystagmus, visual acuity disturbances, and loss of consciousness may also occur.

Prolonged use at doses higher than recommended may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and general weakness (see section “Special precautions for use” and “Adverse reactions”).

Treatment: There is no specific antidote. Treatment should be symptomatic and supportive, ensuring airway patency and monitoring cardiac and vital signs until condition stabilizes. After ingestion of small amounts of the drug (less than 50 mg/kg ibuprofen), drinking water is recommended to minimize gastrointestinal disturbances. After ingestion of larger amounts, oral activated charcoal or gastric lavage is recommended if less than 1 hour has passed since ingestion of a potentially toxic (but not life-threatening) dose. If ibuprofen has already been absorbed, alkalizing agents may be used to promote urinary excretion of acidic ibuprofen. The benefit of measures such as forced diuresis, hemodialysis, and hemoperfusion has not been proven, as ibuprofen has a high degree of plasma protein binding. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. Bronchodilators should be used to treat bronchial asthma. Medical help should be sought immediately.

Adverse reactions.

The adverse reactions listed below have been observed in patients taking NSAIDs as analgesics for short-term treatment, including ibuprofen at doses not exceeding 1200 mg/day. Other adverse reactions may occur during treatment of chronic conditions or with prolonged use.

Adverse reactions are listed according to MEDDRA organ system and frequency of occurrence: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders.

Very rare: blood disorders (aplastic anemia, hemolytic anemia, eosinophilia, decreased hematocrit and hemoglobin levels, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial signs include high fever, sore throat, development of superficial ulcers in the oral cavity, flu-like symptoms, severe exhaustion, bleeding, and unexplained hematomas.

Immune system disorders.

Uncommon: hypersensitivity reactions accompanied by urticaria and pruritus^1.

Very rare: severe hypersensitivity reactions, which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, decreased blood pressure (anaphylaxis, angioedema, or severe shock), hepatorenal syndrome, exacerbation of bronchial asthma, and bronchospasm^1.

Nervous system disorders.

Uncommon: headache, dizziness, irritability, nervousness, depression, somnolence, insomnia, anxiety, psychomotor agitation, emotional instability, seizures.

Very rare: aseptic meningitis^2.

Frequency not known: paresthesia, optic neuritis.

Cardiovascular system disorders.

Frequency not known: edema, arterial hypertension, and heart failure may be associated with treatment with nonsteroidal anti-inflammatory drugs.

Clinical studies and epidemiological data indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and prolonged treatment, may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Respiratory, thoracic and mediastinal disorders.

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea^1.

Gastrointestinal disorders.

Uncommon: abdominal pain, nausea, dyspepsia, heartburn (most commonly observed gastrointestinal adverse reactions).

Rare: diarrhea, flatulence, constipation, vomiting, pancreatitis, duodenitis, esophagitis.

Very rare: peptic ulcer, gastrointestinal perforation or gastrointestinal bleeding, melena, vomiting with blood (in some cases may be fatal, especially in elderly individuals), ulcerative stomatitis, gastritis.

Frequency not known: exacerbation of ulcerative colitis and Crohn’s disease (see section “Special precautions for use”).

Hepatobiliary disorders.

Very rare: liver function abnormalities, hepatitis, jaundice, hepatonecrosis, liver failure.

Skin and subcutaneous tissue disorders.

Uncommon: various types of skin rashes^1, purpura, skin desquamation, alopecia.

Very rare: severe skin reactions, such as bullous reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis^1.

Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

Metabolism and nutrition disorders.

Frequency not known: decreased appetite, hypokalemia*.

Renal and urinary system disorders.

Very rare: acute kidney function impairment (especially with prolonged NSAID use, combined with increased serum urea levels and edema; also includes papillary necrosis); cystitis, hematuria, interstitial nephritis, nephrotic syndrome, oliguria, polyuria, tubular necrosis, glomerulonephritis.

Frequency not known: nephrotoxicity, ureteric colic, dysuria, renal tubular acidosis*.

Laboratory investigations.

Very rare: decreased hemoglobin levels.

Ear and labyrinth disorders.

Uncommon: hearing disturbances, hearing loss, tinnitus.

Eye disorders.

Uncommon: blurred vision, color vision disturbances, toxic amblyopia.

Frequency not known: visual disturbances.

Psychiatric disorders.

Frequency not known: hallucinations, confusion, irritability.

General disorders.

Frequency not known: malaise, increased fatigue.

Other adverse effects. Endocrine system and metabolism changes. Very rare: decreased appetite, dryness of eye and oral mucous membranes, rhinitis.

^1 Hypersensitivity reactions may include: (a) nonspecific allergic reactions, anaphylaxis; (b) respiratory tract reactivity, e.g., bronchial asthma, asthma exacerbation, bronchospasm, dyspnea; or (c) various skin reactions, e.g., pruritus, urticaria, purpura, Quincke’s edema; exfoliative and bullous dermatoses (including toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) have been very rarely reported.

^2 The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal relationship to drug intake and symptom resolution after drug discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as neck stiffness, headache, nausea, vomiting, chills, or disorientation) have been observed during ibuprofen treatment in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

* Renal tubular acidosis and hypokalemia have been reported during the post-marketing period, usually after prolonged use of ibuprofen at doses higher than recommended.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25°C. Keep out of reach of children.

Packaging. 10 tablets per blister; 1 or 2 blisters per cardboard box.

Prescription status. Over-the-counter.

Manufacturer. Alkaloid AD Skopje.

Manufacturer’s address.
Boulevard Aleksandar Makedonski 12, Skopje, 1000, North Macedonia.