Deprorilgin® is

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEPROLGIN® IS

Composition:

Active substance: dexketoprofen trometamol;

1 sachet contains dexketoprofen trometamol 36.9 mg (equivalent to 25 mg of dexketoprofen);

Excipients: sucrose, natural lemon flavor, colloidal anhydrous silicon dioxide, ammonium glycyrrhizinate, neohesperidin dihydrochalcone, food color Yellow FCF (E 110).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: white powder, with possible specks of pale yellow and/or orange color.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Dexketoprofen. ATC code M01AE17.

Pharmacological Properties

Pharmacodynamics

Dexketoprofen trometamol is the tromethamine salt of (S)-(+)-2-(3-benzoylphenyl)propionic acid. It is an analgesic, anti-inflammatory, and antipyretic medicinal product belonging to the group of nonsteroidal anti-inflammatory drugs (NSAIDs).

Mechanism of action

The mechanism of action of NSAIDs is related to the reduction of prostaglandin synthesis through inhibition of the cyclooxygenase pathway. Specifically, NSAIDs inhibit the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2, which produce prostaglandins PGE1, PGE2, PGF2α, and PGD2, as well as prostacyclin PGI2 and thromboxanes (TXA2 and TXB2). In addition, inhibition of prostaglandin synthesis may affect other inflammatory mediators such as kinins, thereby providing not only direct but also indirect effects.

Pharmacodynamic effects

The inhibitory effect of dexketoprofen on the activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) has been demonstrated in laboratory animals and in humans.

Clinical efficacy and safety

Clinical studies using dexketoprofen in several pain models have shown that the medicinal product has pronounced analgesic activity. According to data from some studies, analgesic effect begins 30 minutes after administration of dexketoprofen. The duration of analgesic action is 4–6 hours.

Pharmacokinetics

Absorption

Dexketoprofen is rapidly absorbed after oral administration. When administered as granules for oral solution, the time to reach maximum plasma concentration (tmax) is 0.25–0.33 hours. In a comparative study of two oral formulations of dexketoprofen—immediate-release tablets and granules for oral solution—administered at doses of 12.5 mg and 25 mg, both formulations were shown to be bioequivalent in terms of bioavailability [AUC (area under the concentration-time curve)]. After administration of the granules for oral solution, the maximum concentration (Cmax) of dexketoprofen was approximately 30% higher than after administration of the tablet formulation. When taken with food, AUC remains unchanged, but Cmax of dexketoprofen in plasma decreases and the rate of absorption slows (tmax increases).

Distribution

The distribution half-life of dexketoprofen is 0.35 hours. Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen averages less than 0.25 L/kg.

Pharmacokinetic studies following multiple doses of dexketoprofen show that AUC values after the last dose do not differ from those after a single dose, indicating no accumulation of the active substance.

Metabolism and elimination

After administration of dexketoprofen, only the S-(+) enantiomer is found in urine, indicating no transformation into the R-(–) enantiomer in humans.

The main pathway of metabolism and elimination of dexketoprofen is conjugation with glucuronic acid, followed by renal excretion.

The elimination half-life (T1/2) of dexketoprofen is 1.65 hours.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of mild to moderate acute pain, including musculoskeletal pain, dysmenorrhea (menstrual pain), and dental pain.

Contraindications.

Hypersensitivity to dexketoprofen or to any other component of the medicinal product, or to any other NSAID.

Dexketoprofen should not be used in patients in whom substances with a similar mechanism of action, such as acetylsalicylic acid or other NSAIDs, have previously triggered attacks of bronchial asthma, bronchospasm, acute rhinitis, or led to the development of nasal polyps, urticaria, or angioedema.

History of photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.

History of gastrointestinal bleeding or gastrointestinal tract (GIT) perforation associated with previous NSAID therapy.

Active peptic ulcer/GIT bleeding, or history of GIT bleeding, ulcer, or perforation.

Other active bleeding or increased bleeding tendency.

Hemorrhagic diathesis and other coagulation disorders.

Chronic dyspepsia.

Crohn’s disease or non-specific ulcerative colitis.

Severe heart failure.

Moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min).

Severe hepatic impairment (Child–Pugh score 10–15 points).

Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).

Third trimester of pregnancy and breastfeeding period (see section "Use in pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

The drug interactions listed below are typical for all NSAIDs.

Undesirable combinations

Other NSAIDs (including selective COX-2 inhibitors) and high-dose salicylates (≥ 3 g per day). Concurrent use of multiple NSAIDs may increase the risk of gastrointestinal ulcers and GIT bleeding due to synergistic effects of the drugs.

Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use") due to the high degree of plasma protein binding of dexketoprofen, inhibition of platelet function, and damage to the gastric and duodenal mucosa. If concomitant use is necessary, careful monitoring of the patient and appropriate laboratory parameters is required.

Heparin. Increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, careful monitoring of the patient and appropriate laboratory parameters is required.

Corticosteroids. Increased risk of gastrointestinal ulceration or GIT bleeding (see section "Special precautions for use").

Lithium preparations (reports with several NSAIDs). NSAIDs increase plasma lithium concentrations up to toxic levels (reduced renal elimination of lithium). Therefore, plasma lithium concentrations should be monitored at the start of dexketoprofen treatment, during dose adjustments, and upon discontinuation of therapy.

Methotrexate [when used at high doses (≥ 15 mg per week)]. Increased hematological toxicity of methotrexate due to reduced renal clearance when used concomitantly with NSAIDs.

Hydantoin derivatives and sulfonamides. Potentiation of toxic effects of these substances is possible.

Combinations requiring caution

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the efficacy of diuretics and antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of drugs that inhibit cyclooxygenase with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may lead to further deterioration of renal function, which is usually reversible. When prescribing dexketoprofen in combination with diuretics, ensure adequate fluid intake by the patient; monitor renal function at the beginning and during combination therapy (periodically). Concomitant use of dexketoprofen with potassium-sparing diuretics may lead to hyperkalemia. Serum potassium levels should be monitored (see section "Special precautions for use").

Methotrexate [when used at low doses (< 15 mg per week)]. Increased hematological toxicity of methotrexate due to reduced renal clearance when used concomitantly with NSAIDs. Weekly monitoring of complete blood count parameters is required during the first weeks of such combination therapy. Close monitoring is required in patients with even mild renal impairment and in elderly patients.

Pentoxifylline. Increased risk of bleeding. Careful clinical monitoring and regular assessment of bleeding time are required.

Zidovudine. Risk of enhanced toxic effects on erythropoiesis due to effects on reticulocytes, leading to severe anemia within one week after initiation of NSAID therapy. Complete blood count and reticulocyte count should be monitored 1–2 weeks after starting NSAID treatment.

Sulfonylurea preparations. NSAIDs may enhance the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding sites.

Combinations to be considered

β-Adrenergic blockers. When used concomitantly with NSAIDs, the antihypertensive effect of β-blockers may be reduced due to inhibition of prostaglandin synthesis.

Cyclosporine and tacrolimus. NSAIDs may enhance nephrotoxicity by affecting renal prostaglandin-mediated effects. Renal function should be monitored when using such combinations.

Thrombolytics. Increased risk of bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal ulceration or GIT bleeding (see section "Special precautions for use").

Probenecid. Increased plasma concentration of dexketoprofen. This interaction may be due to inhibition of renal tubular secretion and glucuronidation and may require dose adjustment of dexketoprofen.

Cardiac glycosides. NSAIDs may increase plasma levels of cardiac glycosides.

Mifepristone. There is a theoretical risk that prostaglandin synthesis inhibitors may alter the efficacy of mifepristone. Limited data suggest that NSAID use on the day of prostaglandin administration does not adversely affect the action of mifepristone or prostaglandin, specifically cervical ripening or uterine contractility, and does not reduce the clinical efficacy of medical termination of pregnancy.

Quinolone antibiotics. Animal studies have shown that high-dose quinolones in combination with NSAIDs increase the risk of seizures.

Tenofovir. Concomitant use with NSAIDs may increase plasma concentrations of creatinine and blood urea nitrogen; therefore, monitoring of renal function is required to control for possible synergistic effects of these drugs on the kidneys.

Deferasirox. Concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity and requires careful clinical monitoring.

Pemetrexed. Concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, caution is advised when using high-dose NSAIDs. In patients with mild renal impairment (creatinine clearance 89–60 mL/min), NSAID use should be avoided for 2 days before and 2 days after pemetrexed administration.

Special precautions for use.

Use with caution in patients with a history of allergic reactions.

Concomitant use of dexketoprofen with other NSAIDs, including selective COX-2 inhibitors, should be avoided.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and the gastrointestinal and cardiovascular risks described below).

Gastrointestinal disorders

Cases of potentially fatal gastrointestinal bleeding, ulcers, or gastrointestinal perforation have been reported with NSAID therapy at any time during treatment, regardless of the presence of prior gastrointestinal symptoms or history of severe gastrointestinal disorders. If gastrointestinal bleeding or ulcers occur during treatment with dexketoprofen, the drug should be discontinued.

The risk of gastrointestinal bleeding, ulceration, 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"), and in elderly patients.

Use in elderly patients. Adverse reactions associated with NSAID use occur more frequently in elderly patients, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "Dosage and administration"). Treatment of elderly patients should be initiated with the lowest possible dose.

Prior to initiating dexketoprofen therapy in patients with a history of esophagitis, gastritis, and/or peptic ulcer, as with other NSAIDs, it should be confirmed that these conditions are in complete remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for possible complications during treatment with dexketoprofen, particularly gastrointestinal bleeding.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as their condition may worsen (see section "Side effects"). For such patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase the risk of gastrointestinal adverse reactions (see section "Interaction with other medicinal products and other forms of interaction"), consideration should be given to concomitant use of protective agents (such as misoprostol or proton pump inhibitors).

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed about the need to report any unusual abdominal symptoms (especially those indicating possible gastrointestinal bleeding), particularly at the beginning of treatment.

Dexketoprofen should be used with caution in patients who are concurrently taking medicinal products that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (including warfarin), SSRIs, or antiplatelet agents (including acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").

Renal function disorders

Dexketoprofen should be used with caution in patients with impaired renal function (see section "Contraindications"), as NSAID use may lead to worsening of renal function, fluid retention, and edema. Due to the increased risk of nephrotoxicity, dexketoprofen should be used cautiously in patients taking diuretics and in those who may develop hypovolemia.

Patients should be advised to maintain adequate fluid intake during treatment with dexketoprofen to prevent dehydration and, possibly, the associated increase in nephrotoxic effects.

Like other NSAIDs, dexketoprofen may increase plasma creatinine and blood urea nitrogen levels. Adverse effects on the urinary system associated with dexketoprofen and other prostaglandin synthesis inhibitors may include glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure.

Renal function disorders occur more frequently in elderly patients (see section "Dosage and administration").

Hepatic function disorders

Dexketoprofen should be used with caution in patients with impaired liver function.

Like other NSAIDs, dexketoprofen may cause transient, mild increases in certain liver function parameters, as well as marked elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. If marked increases in these parameters occur, treatment with dexketoprofen should be discontinued.

Hepatic function disorders occur more frequently in elderly patients (see section "Dosage and administration").

Cardiovascular disorders and cerebrovascular events

Appropriate monitoring and medical advice are required when prescribing dexketoprofen to patients with a history of arterial hypertension and/or mild to moderate heart failure. Particular caution is necessary when treating patients with a history of heart disease, especially previous episodes of heart failure, due to reports of fluid retention and edema associated with NSAID use, which may increase the risk of heart failure.

Clinical and epidemiological data indicate that the use of certain NSAIDs (particularly at high doses and for prolonged periods) may be associated with a small increased risk of arterial thrombotic events (such as myocardial infarction or stroke). Data are insufficient to exclude the risk of arterial thrombotic events with dexketoprofen. Therefore, therapy with dexketoprofen should be prescribed to patients with uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease only after careful benefit-risk assessment. Similarly, long-term treatment with dexketoprofen in patients with risk factors for cardiovascular complications (such as arterial hypertension, hyperlipidemia, diabetes, smoking) should be considered only after careful evaluation.

Non-selective NSAIDs may reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. Therefore, dexketoprofen is not recommended for patients taking medicinal products affecting hemostasis (e.g., warfarin and other coumarins; heparins) (see section "Interaction with other medicinal products and other forms of interaction").

Cardiovascular disorders occur more frequently in elderly patients (see section "Dosage and administration").

Skin reactions

Very rare cases of serious skin reactions (some with fatal outcome), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with NSAID use. The risk of such reactions is likely highest at the beginning of treatment, as most cases occur within the first month of therapy. If early signs of skin rash, mucosal lesions, or any other signs of hypersensitivity reactions appear, dexketoprofen should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask symptoms of infectious diseases, potentially delaying appropriate treatment and worsening the course of the illness. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When dexketoprofen is used to relieve pain associated with an infectious disease, monitoring of the disease course is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Other information

Particular caution should be exercised when prescribing the medicinal product to patients:

‒ with inherited disorders of porphyrin metabolism (e.g., acute intermittent porphyria);

‒ with dehydration (see section "Contraindications");

‒ immediately after major surgical procedures.

If prolonged use of dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function, as well as complete blood count, is recommended.

In very rare cases, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If signs of severe hypersensitivity reactions occur after taking dexketoprofen, treatment should be discontinued. Depending on symptoms, appropriate treatment should be administered under medical supervision.

Patients suffering from bronchial asthma in combination with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of allergic reactions to acetylsalicylic acid and/or NSAIDs than other patients. Dexketoprofen may trigger asthma attacks or bronchospasm, particularly in patients with allergic reactions to acetylsalicylic acid or NSAIDs (see section "Contraindications").

Dexketoprofen should be used with caution in patients with coagulation disorders, systemic lupus erythematosus, or mixed connective tissue diseases.

In rare cases, varicella may lead to severe skin and soft tissue infections. Current data do not fully exclude a role of NSAIDs in exacerbating this infectious process. Therefore, the use of dexketoprofen should be avoided in varicella.

The medicinal product contains the dye tartrazine (E 110), which may cause allergic reactions.

The medicinal product contains sucrose. This should be taken into account in patients with diabetes. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency should not use this medicinal product.

Children

The safety of dexketoprofen use in children (under 18 years of age) has not been established.

Use during pregnancy or breastfeeding.

The use of this medicinal product is contraindicated during the third trimester of pregnancy and during breastfeeding (see section "Contraindications").

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryofetal mortality (due to both direct effects on embryonic/fetal development and indirect effects—maternal gastrointestinal toxicity). Furthermore, administration of prostaglandin synthesis inhibitors to animals during organogenesis has been associated with increased incidence of various developmental abnormalities, including cardiovascular malformations. However, animal studies with dexketoprofen did not reveal signs of reproductive toxicity. According to epidemiological data, the use of medicinal products that inhibit prostaglandin synthesis during early pregnancy increases the risk of spontaneous abortion, congenital heart defects, and gastroschisis. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. It is believed that the risk of such events increases with higher drug doses and longer duration of therapy.

Starting from the 20th week of pregnancy, the use of dexketoprofen may cause oligohydramnios due to fetal renal dysfunction. This condition may develop shortly after initiation of treatment, is usually reversible, and resolves after discontinuation of therapy. Prescribing dexketoprofen during the first and second trimesters of pregnancy is possible only if clearly necessary. If dexketoprofen is required for women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible effective dose should be used for the shortest possible duration. If treatment with dexketoprofen beyond the 20th gestational week lasts more than a few days, monitoring of amniotic fluid volume for pathological reduction should be considered. If oligohydramnios is detected, dexketoprofen therapy should be discontinued.

The use of any prostaglandin synthesis inhibitor during the third trimester of pregnancy may cause

in the fetus:

‒ cardiovascular and pulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

‒ renal dysfunction (see above);

in the mother and newborn, and at the end of pregnancy:

‒ prolonged bleeding time due to inhibition of platelet aggregation, even with low-dose dexketoprofen;

‒ inhibition of uterine contractility, leading to delayed onset of labor or prolonged labor.

Lactation

It is unknown whether dexketoprofen passes into breast milk. The use of dexketoprofen is contraindicated during breastfeeding.

Fertility

Like other NSAIDs, dexketoprofen may reduce female fertility and therefore is not recommended for women attempting to conceive. In women experiencing infertility or undergoing fertility investigations, discontinuation of dexketoprofen should be considered.

Ability to affect reaction speed when driving or operating machinery.

The medicinal product may cause adverse effects such as dizziness, visual disturbances, or somnolence. In such cases, the ability to react quickly, orient in traffic situations, and operate machinery may be impaired.

Method of Administration and Dosage

Dosage

The lowest effective dose of the medicinal product should be used for the shortest duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use").

Adults

Depending on the etiology and intensity of pain, the recommended dose is 25 mg every 8 hours. The daily dose should not exceed 75 mg.

The medicinal product is intended only for short-term therapy; treatment duration should be limited to the period of symptom manifestation.

Elderly Patients

Treatment should be initiated at the lower end of the recommended dosage range. The daily dose is 50 mg. The dose may be increased to that recommended for the general patient population only if treatment is well tolerated.

Given that elderly patients have an increased risk of developing adverse effects, including potentially life-threatening ones (see section "Special Warnings and Precautions for Use"), careful monitoring of these patients during treatment is required.

Patients with Renal Impairment

For patients with mild renal impairment (creatinine clearance 89–60 mL/min), the initial maximum daily dose should be reduced to 50 mg. Use of dexketoprofen in patients with moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min) is contraindicated.

Patients with Hepatic Impairment

For patients with mild to moderate hepatic impairment, treatment should be initiated at the minimum recommended dose. The daily dose is 50 mg. Close monitoring of these patients during treatment is required. Use of dexketoprofen in patients with severe hepatic impairment is contraindicated.

Method of Administration

The medicinal product is administered orally as a solution.

Before use, dissolve the entire contents of one sachet in a glass of water, stirring to ensure complete dissolution. The resulting solution should be taken immediately after preparation.

Concomitant intake with food slows the absorption rate of dexketoprofen (see section "Pharmacological Properties"). Therefore, in cases of acute pain, the medicinal product should be taken at least 15 minutes before a meal.

Children

The safety and efficacy of dexketoprofen in children (under 18 years of age) have not been established. Use of dexketoprofen in the pediatric population is contraindicated.

Overdose

Symptoms of dexketoprofen overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (nausea, vomiting, loss of appetite, abdominal pain) and nervous system effects (drowsiness, vertigo, disorientation, headache).

In case of accidental overdose or ingestion of an excessive amount of dexketoprofen, symptomatic treatment appropriate to the patient's clinical condition should be initiated immediately. If less than 1 hour has passed since ingestion of dexketoprofen at a dose exceeding 5 mg/kg body weight in an adult or child, activated charcoal should be administered. Dexketoprofen trometamol may be removed by dialysis.

Adverse Reactions

Preclinical Safety Data

Standard preclinical studies—safety pharmacology, genotoxicity, and immunopharmacology—revealed no special hazard for humans. In chronic toxicity studies in mice and monkeys, the no-observed-adverse-effect level (NOAEL) of dexketoprofen was twice the maximum recommended human dose. When higher doses of dexketoprofen were administered to monkeys, the main adverse effects observed were fecal blood, reduced body weight gain, and at the highest dose, gastrointestinal erosions. These effects occurred at doses 14–18 times higher than the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Below is a list of adverse reactions considered at least possibly related to dexketoprofen (in tablet form) and reported during clinical trials, as well as adverse reactions reported during post-marketing use of dexketoprofen in the form of granules for oral solution. Adverse reactions are classified by organ system and frequency. Frequencies are defined as follows: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000).

Since the Cmax of dexketoprofen in plasma is higher when administered as granules for oral solution than with tablets, an increased risk of adverse reactions (particularly gastrointestinal) cannot be excluded.

Psychiatric disorders: uncommon – insomnia, anxiety.

Nervous system disorders: uncommon – headache, dizziness, somnolence; rare – paraesthesia, loss of consciousness (syncope).

Eye disorders: very rare – blurred vision.

Ear and labyrinth disorders: uncommon – vertigo; very rare – tinnitus.

Skin and subcutaneous tissue disorders: uncommon – rash; rare – urticaria, acne, increased sweating; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioedema, facial swelling, photosensitivity reactions, pruritus.

Musculoskeletal and connective tissue disorders: rare – back pain.

Renal and urinary disorders: rare – polyuria, acute renal failure; very rare – nephritis or nephrotic syndrome.

Reproductive system and breast disorders: rare – menstrual disorders, prostate gland dysfunction.

Cardiovascular disorders: uncommon – palpitations, flushing; rare – increased blood pressure; very rare – tachycardia, decreased blood pressure.

Blood and lymphatic system disorders: very rare – neutropenia, thrombocytopenia.

Immune system disorders: rare – laryngeal edema; very rare – anaphylactic reactions, including anaphylactic shock.

Gastrointestinal disorders: common – nausea and/or vomiting, abdominal pain, diarrhea, dyspepsia; uncommon – gastritis, constipation, dry mouth, flatulence; rare – peptic ulcer, ulcer bleeding or perforation (see section "Special precautions"); very rare – pancreatitis.

Hepatobiliary disorders: rare – hepatocellular injury.

Metabolism and nutrition disorders: rare – loss of appetite.

Respiratory, thoracic and mediastinal disorders: rare – bradypnea; very rare – bronchospasm, dyspnea (shortness of breath).

General disorders and administration site conditions: uncommon – fatigue, pain, asthenia, chills, malaise; rare – peripheral edema.

Investigations: rare – abnormal liver function test values.

The most commonly observed adverse effects are gastrointestinal. Peptic ulceration, gastrointestinal perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions"). After administration of dexketoprofen, adverse effects such as nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis and Crohn's disease have been reported (see section "Special precautions"). Gastritis has been reported less frequently. Adverse reactions associated with NSAID use such as edema, increased blood pressure, and heart failure have also been reported.

Clinical trial data and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and over prolonged periods) may be associated with a small increase in the risk of arterial thrombotic events (such as myocardial infarction or stroke; see section "Special precautions").

As with other NSAIDs, the following adverse effects may occur: aseptic meningitis, occurring predominantly in patients with systemic lupus erythematosus or mixed connective tissue diseases; hematological disorders (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia).

Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are possible.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2.5 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

Powder 2.5 g per sachet; 10 sachets per pack.

Prescription status. Prescription only.

Manufacturer.

Limited liability company "INTERKHIM".

Manufacturer's location and address of place of business.

40-A, 21st km, Starokyivska Road, Odesa, Ukraine, 65025.