Dextemp

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEKSTEMP (DEKTEMP)

Composition:

Active substance: dexibuprofen;

One tablet contains 200 mg or 400 mg of dexibuprofen;

Excipients: microcrystalline cellulose, calcium carmellose, colloidal anhydrous silicon dioxide, hypromellose, talc;

Coating: Opadry II White film-coating mixture: hypromellose; lactose monohydrate; titanium dioxide (E 171); polyethylene glycol (macrogol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

200 mg tablets: white or almost white, round, biconvex film-coated tablets;

400 mg tablets: white or almost white, oblong, biconvex film-coated tablets with a breakline on both sides.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Dexibuprofen. ATC code M01A E14.

Pharmacological properties

Pharmacodynamics

Dexibuprofen (=S(+)-ibuprofen) is the pharmacologically active isomer of ibuprofen and belongs to non-selective non-steroidal anti-inflammatory drugs (NSAIDs). By inhibiting prostaglandin synthesis, dexibuprofen exerts antipyretic, analgesic, and anti-inflammatory effects and inhibits platelet aggregation.

Comparative clinical "bridging" studies evaluating the efficacy of ibuprofen and dexibuprofen in the treatment of osteoarthritis over 15 days, dysmenorrhea (including pain symptoms), and dental pain have demonstrated that dexibuprofen has equivalent efficacy to racemic ibuprofen at the recommended dose ratio of 1:2.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both agents are administered concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) was associated with reduced effects of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty exists regarding extrapolation of these findings to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. A clinically significant interaction is considered unlikely with occasional, non-regular use of ibuprofen (see section "Interaction with other medicinal products and other forms of interactions"). Despite the lack of direct data on dexibuprofen, a similar interaction between dexibuprofen (=S(+)-ibuprofen) (the pharmacologically active isomer of ibuprofen) and low-dose acetylsalicylic acid is plausible.

Pharmacokinetics

Absorption

After oral administration, dexibuprofen is rapidly and completely absorbed from the small intestine. Maximum plasma concentration (C_max) is reached approximately within 2 hours.

Distribution

Plasma protein binding of dexibuprofen is approximately 99%.

Biotransformation and elimination

Following hepatic metabolism (hydroxylation, carboxylation), inactive metabolites are primarily excreted via the kidneys (90%), with the remainder eliminated in bile. Elimination half-life ranges from 1.8 to 3.5 hours.

Effect of concomitant food intake

Administration of 400 mg dexibuprofen with a high-fat meal delays the time to reach C_max in plasma (from 2.1 hours under fasting conditions to 2.8 hours with a high-fat meal) and reduces C_max in plasma (from 20.3 to 18.1 µg/ml), which is not considered clinically significant; however, it does not affect the total extent of elimination.

Patients with impaired renal and/or hepatic function

Based on pharmacokinetic studies of ibuprofen in patients with renal impairment, dose reduction is recommended in such patients. Caution is also advised when using the medicinal product Dexemp due to inhibition of prostaglandin synthesis in the kidneys (see sections "Special precautions for use" and "Dosage and administration").

Elimination of dexibuprofen is slower in patients with liver cirrhosis.

Clinical characteristics.

Indications.

Dextemp is a non-steroidal anti-inflammatory/analgesic agent.

For symptomatic treatment of:

• pain and inflammation in osteoarthritis/arthrosis;
• menstrual pain (primary dysmenorrhea);
• mild to moderate pain, such as musculoskeletal pain, headache or toothache, painful swelling and inflammation following injuries.

For short-term symptomatic treatment of:

• rheumatoid arthritis, when other, longer-term treatment options (basic therapy: disease-modifying antirheumatic drugs (DMARDs)) are not considered.

Contraindications.

Dexibuprofen is contraindicated in patients:

• with known hypersensitivity to the active substance, other NSAIDs, or any of the excipients;
• in whom substances with a similar mechanism of action (e.g., acetylsalicylic acid and other NSAIDs) have triggered attacks of bronchial asthma, bronchospasm, acute rhinitis, or led to nasal polyps, urticaria, or angioedema;
• with a history of gastrointestinal bleeding or perforation related to previous NSAID therapy;
• with active or past history of peptic ulcer or gastrointestinal bleeding (at least two independent confirmed episodes of ulcer or bleeding);
• with active cerebrovascular or other bleeding;
• with active Crohn’s disease or active non-specific ulcerative colitis;
• with severe heart failure (NYHA class IV);
• with severe renal impairment (GFR < 30 mL/min);
• with severe hepatic impairment;
• from the sixth month of pregnancy (see section "Use in pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

The data below are based on experience with other NSAIDs. In general, NSAIDs should be used with caution in combination with other medicinal products that may increase the risk of gastrointestinal ulcers, bleeding, or adversely affect renal function.

Combinations not recommended:

Anticoagulants:

NSAIDs may enhance the effects of anticoagulants such as warfarin. At the beginning of treatment with dexibuprofen, coagulation parameters (international normalized ratio, coagulation time) should be monitored and the anticoagulant dose adjusted if necessary (see section "Special precautions for use").

Methotrexate at doses of 15 mg/week or higher:

Administration of NSAIDs within 24 hours before or after methotrexate may increase methotrexate plasma concentration due to reduced renal clearance, potentially increasing methotrexate toxicity. Therefore, concomitant use of dexibuprofen during high-dose methotrexate therapy is not recommended.

Lithium:

NSAIDs may increase plasma lithium levels by reducing its renal clearance. Combination is not recommended. If concomitant use is necessary, regular monitoring of lithium levels is required. Dose reduction of lithium may be considered if needed.

Other NSAIDs and salicylates (acetylsalicylic acid as an analgesic):

Concomitant use of Dextemp with other NSAIDs, including selective COX-2 inhibitors, should be avoided, as combined use of different NSAIDs may increase the risk of gastrointestinal ulceration and bleeding (see section "Special precautions for use").

Acetylsalicylic acid:

Concomitant use of dexibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased adverse reactions.

Experimental data indicate that ibuprofen may competitively inhibit the antiplatelet effect of low-dose acetylsalicylic acid when used concomitantly. Although uncertainty exists regarding extrapolation of these data to clinical settings, it cannot be ruled out 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 (see section "Pharmacodynamics"). Despite the lack of data on dexibuprofen, a similar interaction between dexibuprofen (=S(+)-ibuprofen) (the pharmacologically active isomer of ibuprofen) and low-dose acetylsalicylic acid is plausible.

Combinations requiring caution:

Thrombolytics, ticlopidine, and antiplatelet agents:

Dexibuprofen inhibits platelet aggregation by inhibiting platelet cyclooxygenase. Therefore, due to the risk of enhanced antithrombotic effect, concomitant use of dexibuprofen with thrombolytics, ticlopidine, and antiplatelet agents should be used with caution.

Antihypertensive agents:

NSAIDs may reduce the effectiveness of beta-blockers, possibly by inhibiting the synthesis of vasodilatory prostaglandins. Concomitant use of NSAIDs with ACE inhibitors and angiotensin II receptor antagonists may increase the risk of acute renal failure, especially in patients with pre-existing renal impairment. Such combinations may lead to acute renal failure in elderly patients and/or dehydrated patients due to direct effects on glomerular filtration. Careful monitoring of renal function is recommended at the beginning of treatment. Moreover, long-term use of NSAIDs may theoretically reduce the antihypertensive effect of angiotensin II receptor antagonists, similar to ACE inhibitors. Therefore, such combinations should be used with caution, with careful monitoring of renal function at the start of treatment and advice to patients to maintain adequate fluid intake (see section "Special precautions for use").

Cyclosporine, tacrolimus, sirolimus, and aminoglycoside antibiotics:

Concomitant use with NSAIDs may increase the risk of nephrotoxicity due to reduced renal prostaglandin synthesis. Continuous monitoring of renal function is recommended, especially in elderly patients.

Corticosteroids:

Concomitant use of NSAIDs with corticosteroids may increase the risk of gastrointestinal bleeding and ulcers (see section "Special precautions for use").

Digoxin:

NSAIDs may increase digoxin plasma levels and increase the risk of digoxin toxicity.

Methotrexate at doses less than 15 mg/week:

Dexibuprofen may increase methotrexate plasma levels. When dexibuprofen is used concomitantly with low-dose methotrexate, careful monitoring of blood parameters is required, especially during the first weeks of combination therapy. Enhanced monitoring is indicated even with minor renal impairment, particularly in elderly patients. Renal function should also be monitored to prevent reduced methotrexate excretion.

Phenytoin:

Some NSAIDs may displace phenytoin from protein-binding sites, potentially increasing plasma phenytoin concentration and thereby enhancing its toxicity. As clinical confirmation of this interaction is limited, phenytoin dosage should be adjusted based on plasma phenytoin levels and/or observed signs of toxicity.

Phenytoin, phenobarbital, rifampicin:

Concomitant use with inhibitors of CYP2C8 and CYP2C9 may reduce the efficacy of dexibuprofen.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs):

Concomitant use of NSAIDs with these agents may increase the risk of gastrointestinal bleeding.

Thiazides, thiazide-like agents, loop diuretics, and potassium-sparing diuretics:

Concomitant use of NSAIDs with these agents may reduce their diuretic effect or increase the risk of renal failure.

Antihypertensive effects may be reduced (see section "Special precautions for use").

Medicinal products that increase plasma potassium concentration:

NSAIDs may increase plasma potassium levels. Therefore, Dextemp should be used with caution concomitantly with medicinal products that increase plasma potassium concentration, such as potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, immunosuppressants (e.g., cyclosporine or tacrolimus), trimethoprim, and heparin. Monitoring of blood pressure and plasma potassium concentration is recommended, and patients should be advised to maintain adequate fluid intake.

Oral antidiabetic agents:

Concomitant use of NSAIDs with sulfonylureas may lead to fluctuations in plasma glucose levels; appropriate monitoring may be required.

Zidovudine (azidothymidine, AZT):

According to available data, concomitant use of NSAIDs and zidovudine increases the risk of hemarthrosis and hematoma in patients with hemophilia.

Pemetrexed:

High doses of NSAIDs may increase pemetrexed plasma concentration and its efficacy. Patients with renal impairment should avoid concomitant use of high-dose dexibuprofen within 2 days before and 2 days after pemetrexed administration.

Alcohol:

Excessive alcohol consumption during NSAID use may increase the risk of gastrointestinal adverse reactions.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose required to control symptoms for the shortest possible duration (see section "Dosage and administration").

Concomitant use of dexibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section "Interaction with other medicinal products and other forms of interaction").

Gastrointestinal risks

Elderly patients are more likely to experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal under certain circumstances (see section "Dosage and administration").

Cases of gastrointestinal bleeding, perforation, and ulcers, sometimes fatal, have been reported with NSAID therapy at any stage of treatment, regardless of the presence of prior warning symptoms or a history of serious gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulcers, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), in patients with alcoholism, and in elderly patients. Such patients should initiate treatment with the lowest possible doses. For these patients, the possibility of combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered, as well as for patients receiving concomitant therapy with low-dose acetylsalicylic acid or other medicinal products that may increase gastrointestinal risk (see below and section "Interaction with other medicinal products and other forms of interaction").

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

Dexibuprofen (Dekstemp) should be used with caution in patients receiving concomitant medications that 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) (see section "Interaction with other medicinal products and other forms of interaction").

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

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 (see section "Adverse reactions").

Hypersensitivity

As with other NSAIDs, allergic reactions, including anaphylactic or anaphylactoid reactions, may occur even without prior exposure to the active substance.

Dexibuprofen (Dekstemp) should be used with caution in patients with bronchial asthma (active or in history), seasonal allergic rhinitis, nasal mucosal edema (e.g., nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory tract infections, as NSAID use in such patients may trigger bronchospasm (see section "Contraindications"). Severe acute hypersensitivity reactions (e.g., anaphylactic shock) are very rare. At the first signs of hypersensitivity following dexibuprofen intake, treatment should be discontinued. The physician should take appropriate medical measures based on the patient's symptoms.

Effects on the cardiovascular and cerebrovascular systems

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and advice, as fluid retention and edema have been reported with NSAID use.

Clinical trial data indicate that ibuprofen use, particularly at high doses (2400 mg daily), may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., <1200 mg daily) is associated with an increased risk of arterial thrombotic events. Despite limited data on the risk of arterial thrombotic complications with dexibuprofen, the risk with high-dose dexibuprofen (1200 mg daily) is expected to be similar to that with high-dose ibuprofen (2400 mg daily).

Dexibuprofen may be used in patients with uncontrolled arterial hypertension, heart failure (NYHA class II–III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease only after careful consideration and avoidance of high doses (1200 mg daily).

Patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should only receive long-term NSAID therapy, especially if high-dose dexibuprofen (1200 mg daily) is required, after careful consideration.

Cases of Kounis syndrome (frequency unknown) have been reported in patients treated with 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.

Effects on the kidneys

Dexibuprofen (Dekstemp) should be used with caution in patients with renal disease, arterial hypertension, elderly patients, and those receiving concomitant therapy with diuretics or other medicinal products that significantly affect renal function; the risk of fluid retention, edema, and impaired renal function should be considered. If dexibuprofen is used in such patients, the lowest possible doses should be used, and renal function should be monitored regularly.

Dexibuprofen (Dekstemp) should be used with caution in patients with reduced extracellular fluid volume for any reason, e.g., before or after major surgery, due to the risk of complications such as bleeding, electrolyte imbalance, or fluid volume disturbances. In such cases, monitoring of renal function is recommended as a precautionary measure.

Like other NSAIDs, dexibuprofen may increase plasma concentrations of urea and creatinine. Like other NSAIDs, dexibuprofen may adversely affect renal function, potentially leading to glomerular or interstitial nephritis, renal papillary necrosis, nephrotic syndrome, and acute renal failure (see sections "Contraindications", "Dosage and administration", and "Adverse reactions").

Prolonged use of analgesics, particularly combinations of different painkillers, may lead to persistent renal dysfunction with a risk of renal failure (analgesic nephropathy). Therefore, concomitant use of dexibuprofen with other NSAIDs (including over-the-counter products and selective cyclooxygenase-2 inhibitors) should be avoided.

Liver

As with other NSAIDs, dexibuprofen may cause transient, mild increases in certain liver parameters, as well as significant increases in AST and ALT levels. If substantial increases in ALT and AST levels occur, treatment should be discontinued (see sections "Contraindications" and "Dosage and administration").

Serious skin adverse reactions (SSARs)

Very rare cases of serious skin adverse reactions, 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 during dexibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

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

Blood coagulation

Like other NSAIDs, dexibuprofen may reversibly inhibit platelet aggregation and prolong bleeding time. Therefore, Dexibuprofen (Dekstemp) should be used with caution in patients with hemorrhagic diathesis or other coagulation disorders and when used concomitantly with oral anticoagulants (see section "Interaction with other medicinal products and other forms of interaction").

Preclinical data indicate that NSAIDs, such as dexibuprofen, may inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. This interaction may reduce the cardioprotective effect. If concomitant use of low-dose acetylsalicylic acid is indicated, Dexibuprofen (Dekstemp) should be used with particular caution, especially if treatment duration exceeds short-term use (see sections "Pharmacodynamics" and "Interaction with other medicinal products and other forms of interaction").

Masking symptoms of underlying infections

Dexibuprofen may mask symptoms of infections, potentially delaying appropriate treatment and thereby complicating the course of the disease. This has been observed in bacterial, non-hospitalized pneumonias and bacterial complications of varicella. If Dexibuprofen (Dekstemp) 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.

Special warnings and precautions for use of dexibuprofen

For patient safety, regular monitoring (renal, hepatic, and hematological functions) should be performed in patients receiving long-term dexibuprofen therapy.

Dexibuprofen should be used with caution in patients with systemic lupus erythematosus or mixed connective tissue diseases due to an increased risk of renal and central nervous system adverse reactions (including aseptic meningitis) associated with NSAID use (see section "Adverse reactions").

Prolonged, unsupervised use of high-dose analgesics may lead to medication-overuse headache, which cannot be treated by increasing the dose of the drug.

Medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may reversibly affect fertility and are therefore not recommended for women attempting to conceive. Women experiencing difficulties in becoming pregnant or undergoing infertility investigations should consider discontinuing dexibuprofen (see section "Use during pregnancy or breastfeeding").

Lactose. The medicinal product contains lactose; therefore, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not use this medicinal product.

If intolerance to certain sugars is diagnosed, consultation with a physician is necessary before taking this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and embryonic/fetal development.

Epidemiological data suggest an increased risk of miscarriage and congenital malformations, including cardiac defects and gastroschisis, following use of prostaglandin synthesis inhibitors in early pregnancy. The overall risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase proportionally with dose and duration of therapy.

Animal studies have shown that prostaglandin synthesis inhibitors cause pre- and post-implantation loss and embryonic/fetal death. Furthermore, administration of prostaglandin synthesis inhibitors during organogenesis in animals has been associated with increased incidence of various congenital abnormalities, including cardiovascular defects.

From the 20th week of pregnancy, dexibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. Additionally, cases of ductus arteriosus constriction after second-trimester treatment have been reported, most of which resolved after stopping treatment. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after several days of dexibuprofen exposure starting from the 20th gestational week. Treatment should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

Therefore, during the first and second trimesters of pregnancy, dexibuprofen should be prescribed only if absolutely necessary. If a woman attempting to conceive or pregnant in the first or second trimester uses Dexibuprofen (Dekstemp), the dose should be as low as possible and the duration of treatment as short as possible.

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 ductus arteriosus and pulmonary hypertension);
  • impaired renal function (see above), which may progress to renal failure manifesting as oligohydramnios;
• pose the following risks to the mother and newborn:
  • possible prolongation of bleeding time, reduced platelet aggregation, even with very low doses;
  • inhibition of uterine contractility, which may lead to delayed or prolonged labor.

From the beginning of the 6th month of pregnancy, dexibuprofen use is contraindicated (see section "Contraindications").

Lactation. Dexibuprofen passes into breast milk in small amounts. Use during lactation is possible only at low doses for a short duration. If long-term treatment or higher doses are required, breastfeeding should be discontinued.

Fertility. NSAIDs may reversibly affect fertility; therefore, Dexibuprofen (Dekstemp) is not recommended for women attempting to conceive (see section "Special precautions for use").

Ability to influence reaction speed when driving or operating machinery.

During dexibuprofen treatment, a patient's ability to react may be impaired if adverse reactions such as dizziness, confusion, fatigue, or visual disturbances occur. This should be considered when performing tasks requiring high attention (e.g., participation in traffic or operating machinery).

With single-dose or short-term use, special precautions are usually not required.

Method of Administration and Dosage

The dose should be adjusted according to the severity of the disease and the patient's symptoms. Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use").

For adults, the usual dose is 1–2 tablets (200–400 mg of dexibuprofen) three times daily after meals.

The recommended initial dose is 200 mg of dexibuprofen.

The recommended daily dose is 600–900 mg of dexibuprofen, divided into three doses.

The maximum single dose is 400 mg, and the maximum daily dose for adults is 1200 mg of dexibuprofen.

Osteoarthritis/arthritis and rheumatoid arthritis

The recommended dose is 600 to 900* mg of dexibuprofen daily, divided into three doses. The dose may be temporarily increased to 1200 mg of dexibuprofen daily in patients with acute symptoms.

Primary dysmenorrhea

The recommended dose is 600 to 900* mg of dexibuprofen daily, divided into three doses.

Mild or moderate pain

The recommended dose is 600 mg of dexibuprofen daily, divided into three doses. It is advisable to take the medication with food. If necessary, the daily dose may be temporarily increased to 1200 mg in patients with acute pain (e.g., following surgical tooth extraction).

This medicinal product is intended for symptomatic relief of pain. However, if symptoms persist for more than 3 days, are accompanied by high fever, headache, or other signs, the diagnosis should be re-evaluated and the treatment regimen adjusted accordingly.

Elderly patients (aged 65 years and older)

No specific dose adjustment is required. However, due to the increased susceptibility of elderly patients to gastrointestinal adverse reactions, individual dose reduction should be considered (see section "Special Warnings and Precautions for Use").

Hepatic impairment

Patients with mild to moderate hepatic impairment should start treatment with reduced doses and be closely monitored. Dexibuprofen is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

Renal impairment

The initial dose should be reduced in patients with mild to moderate renal impairment. Dexibuprofen is contraindicated in patients with severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min) (see section "Contraindications").

*Dexibuprofen should be administered at the appropriate dosage.

Method of Administration

For oral use.

The medicinal product Dexemp, film-coated tablets, can be taken independently of food intake (see section "Pharmacokinetics"). Generally, NSAIDs are taken with food to reduce gastrointestinal irritation, especially during prolonged use. However, when film-coated tablets are taken with or immediately after food, the onset of effect may be delayed in some patients.

Children

This medicinal product should not be used in pediatric practice.

Overdose

Dexibuprofen is characterized by low acute toxicity. High single doses equivalent to 54 g of ibuprofen (approximately equivalent to 27 g of dexibuprofen) have been tolerated. In most cases, overdose is asymptomatic. The risk of developing symptoms arises when doses exceeding 80–100 mg/kg of ibuprofen (equivalent to 40–50 mg/kg of dexibuprofen) are administered.

Symptoms. Symptoms usually appear within 4 hours. They are primarily mild and include abdominal pain, nausea, vomiting, lethargy, confusion, headache, nystagmus, tinnitus, delirium, and ataxia. Moderately severe and serious symptoms occur rarely, such as gastrointestinal bleeding, hypotension, hypothermia, metabolic acidosis, seizures, renal dysfunction, coma, adult respiratory distress syndrome, and transient apnea episodes (in young children after ingestion of a large dose). In severe poisoning, metabolic acidosis may occur.

Treatment. Symptomatic treatment; there is no specific antidote. Ingestion of less than 50 mg/kg of dexibuprofen is unlikely to cause symptoms of overdose and should be diluted with water to minimize gastrointestinal disturbances. In cases of ingestion of larger amounts of dexibuprofen, activated charcoal should be administered.

Gastric emptying by inducing emesis should only be considered within 60 minutes of drug intake. Gastric lavage is indicated only in cases of potentially life-threatening dexibuprofen overdose (gastric lavage may be performed within 60 minutes of ingestion). Forced diuresis, hemodialysis, or hemoperfusion are ineffective due to the high degree of plasma protein binding of dexibuprofen.

Side effects

Available data from clinical studies indicate that the risk of adverse reactions associated with dexibuprofen is comparable to that of racemic ibuprofen. Adverse reactions most commonly affect the gastrointestinal tract. Peptic ulcers, gastrointestinal perforations, or gastrointestinal bleeding may occur, occasionally resulting in fatal outcomes, particularly in elderly patients (see section "Special precautions").

Results from clinical "bridging" studies and other studies of approximately 2 weeks' duration have shown mainly mild gastrointestinal adverse reactions occurring in 8–20% of patients. In patient groups at substantially lower risk, for example during short-term treatment or intermittent use of dexibuprofen, these adverse reactions occur much less frequently.

Assessment of the frequency of adverse reactions is based on the following criteria:

Infections and parasitic diseases

Very rare: exacerbation of inflammatory infectious processes (necrotizing fasciitis).

Blood and lymphatic system disorders

Prolonged blood clotting time is possible.

Rare: blood disorders, including thrombocytopenia, leukopenia, granulocytopenia, pancytopenia, agranulocytosis, aplastic anemia, or hemolytic anemia.

Immune system disorders

Uncommon: purpura (including allergic purpura), angioneurotic edema.

Rare: anaphylactic reaction.

Very rare: generalized hypersensitivity reactions, including symptoms such as fever with rash, abdominal pain, headache, nausea and vomiting, signs of impaired liver function, and aseptic meningitis. In most cases where aseptic meningitis occurred during ibuprofen use, an underlying autoimmune disease (e.g., systemic lupus erythematosus or other collagenoses) was present as a risk factor. In cases of generalized hypersensitivity reactions, swelling of the face, tongue, and larynx, bronchospasm, bronchial asthma, tachycardia, arterial hypotension, and shock may occur.

Psychiatric disorders

Uncommon: anxiety.

Rare: psychotic reactions, depression, irritability.

Nervous system disorders

Common: confusion, headache, dizziness, vertigo.

Uncommon: insomnia, restlessness.

Rare: disorientation, mental confusion, excitement.

Very rare: aseptic meningitis (see immune system disorders).

Eye disorders

Uncommon: blurred vision.

Rare: reversible toxic amblyopia.

Ear and labyrinth disorders

Uncommon: tinnitus.

Rare: hearing disturbances.

Cardiovascular system disorders

Frequency unknown: Kounis syndrome.

Edema, arterial hypertension, and heart failure have been reported during NSAID use.

Clinical trial data indicate 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) (see section "Special precautions"). Despite limited data on the risk of arterial thrombotic complications with dexibuprofen, it can be assumed that the risk with high-dose dexibuprofen (1200 mg per day) is similar to that with high-dose ibuprofen (2400 mg per day).

Gastrointestinal disorders

Very common: dyspepsia, abdominal pain.

Common: diarrhea, nausea, vomiting.

Uncommon: gastrointestinal ulcers and bleeding, gastritis, ulcerative stomatitis, melena.

Rare: gastrointestinal perforations, flatulence, constipation, esophagitis, esophageal strictures, exacerbation of diverticulitis, nonspecific hemorrhagic colitis, ulcerative colitis, or Crohn's disease.

In the event of gastrointestinal bleeding, anemia and hematemesis may occur.

Skin and subcutaneous tissue disorders

Common: skin rash.

Uncommon: urticaria, pruritus.

Very rare: severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis).

Frequency unknown: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

Respiratory, thoracic and mediastinal disorders

Uncommon: rhinitis, bronchospasm.

Renal and urinary disorders

Very rare: interstitial nephritis, nephrotic syndrome, or acute renal failure, renal papillary necrosis.

Hepatobiliary disorders

Rare: liver function abnormalities, hepatitis, jaundice.

General disorders

Common: fatigue.

Fluid retention: may occur in patients with arterial hypertension or impaired renal function.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister per pack.

Prescription status. Over-the-counter.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of operations.

38 Kopilivska Street, Kyiv, 04073, Ukraine.