INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Decpro® (Dexpro)

Composition:

Active substance: dexketoprofen;

1 single-dose sachet contains 36.90 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen;

Excipients: ammonium glycyrrhizinate, acesulfame potassium, lemon flavor, sucrose, silicon dioxide anhydrous colloidal.

Pharmaceutical form. Granules for oral solution.

Main physicochemical properties: white or almost white granules.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives. Dexketoprofen. ATC code M01A E17.

Pharmacological properties.

Pharmacodynamics.

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

Mechanism of action.

The action of nonsteroidal anti-inflammatory drugs (NSAIDs) is based on reducing the synthesis of prostaglandins by inhibiting the activity of cyclooxygenase. Specifically, NSAIDs inhibit the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2, which form prostaglandins PGE1, PGE2, PGF2α, PGD2, and PGI2 (prostacyclin), as well as thromboxanes TxA2 and TxB2. In addition, inhibition of prostaglandin synthesis may affect other mediators of inflammation, such as kinins, thereby producing an additional indirect effect.

Pharmacodynamic action.

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

Clinical efficacy and safety.

Clinical studies in various types of pain have shown that dexketoprofen has pronounced analgesic activity. According to data from some studies, analgesic effect begins within 30 minutes after administration. The duration of analgesic action is 4–6 hours.

Pharmacokinetics.

Absorption.

Dexketoprofen trometamol is rapidly absorbed after oral administration; when administered in granule form, maximum plasma concentration is achieved within 0.25–0.33 hours. Comparison of dexketoprofen tablets with standard release and granules at doses of 12.5 and 25 mg showed that these two formulations are biologically equivalent in terms of bioavailability (AUC). Peak concentrations (Cmax) after administration of granules were approximately 30% higher than after administration of tablets.

When administered with food, AUC is not altered, but Cmax of dexketoprofen trometamol is reduced and the rate of absorption decreases (tmax is prolonged).

Distribution.

The half-life of distribution and elimination half-life of dexketoprofen trometamol are 0.35 and 1.65 hours, respectively. 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.

Biotransformation and elimination.

Elimination of dexketoprofen occurs mainly via conjugation with glucuronic acid followed by renal excretion.

After administration of dexketoprofen trometamol, only the S-(+)-optical isomer is detected in urine, indicating the absence of transformation of dexketoprofen into the R-(–) optical isomer in humans.

Pharmacokinetic studies indicate that AUC values after repeated administration of dexketoprofen do not differ from those after single dosing, indicating no accumulation of the active substance.

Preclinical safety data.

Standard preclinical studies — including pharmacological safety, genotoxicity, and immunopharmacology assessments — revealed no special risk for humans. Chronic toxicity studies in mice and monkeys allowed determination of the no-observed-adverse-effect level (NOAEL), which was found to be twice the maximum recommended human dose. When higher doses were administered to monkeys, the main adverse reactions were fecal blood, reduced body weight gain, and, at the highest dose, gastrointestinal tract (GIT) pathologies such as erosions. These reactions occurred at doses where drug exposure was 14–18 times higher than at the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Like all NSAIDs, dexketoprofen may cause embryonic or fetal death in animals due to a direct effect on development or indirectly — as a result of maternal gastrointestinal tract damage.

Clinical characteristics.

Indications.

For short-term symptomatic treatment of mild to moderate acute pain, such as musculoskeletal pain, dysmenorrhea, and dental pain.

Contraindications.

Hypersensitivity to the active substance or to any other NSAID, or to any of the excipients.
Use in patients in whom substances with a similar mechanism of action, e.g., acetylsalicylic acid and other NSAIDs, induce asthma attacks, bronchospasm, acute rhinitis, or lead to the development of nasal polyps, urticaria, or angioedema.
Known photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.
Bleeding or perforation in the gastrointestinal tract in medical history associated with the use of NSAIDs.
Active phase of peptic ulcer/gastrointestinal bleeding, bleeding, ulcer, or perforation in the gastrointestinal tract in medical history.
Chronic dyspepsia.
Active bleeding or increased bleeding tendency.
Crohn’s disease or ulcerative colitis.
Severe heart failure.
Moderate or severe renal impairment (creatinine clearance ≤ 59 mL/min).
Severe hepatic impairment (10–15 points on the Child–Pugh scale).
Hemorrhagic diathesis or other coagulation disorders.
Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
Third trimester of pregnancy and breastfeeding period (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction.

The drug interactions listed below generally apply to the class of NSAIDs.

Undesirable combinations:

Other NSAIDs, including selective cyclooxygenase-2 inhibitors and high-dose salicylates (≥ 3 g/day): concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to synergistic effects.
Anticoagulants: NSAIDs enhance the effect of anticoagulants, e.g., warfarin, due to high plasma protein binding, as well as due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under medical supervision with careful monitoring of appropriate laboratory parameters.
Heparin: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under medical supervision with careful monitoring of appropriate laboratory parameters.
Corticosteroids: increased risk of peptic ulcers and gastrointestinal bleeding.
Lithium preparations: NSAIDs (reports exist regarding concomitant use with several NSAIDs) increase lithium blood levels up to toxic values due to reduced renal excretion. Therefore, monitoring of this parameter is required at the beginning of treatment, during dose adjustment, and upon discontinuation of dexketoprofen.
Methotrexate when administered at high doses (15 mg/week or more): increased methotrexate blood levels due to reduced renal excretion, leading to hematological toxicity.
Hydantoin derivatives and sulfonamides: possible increase in toxicity of these substances.

Combinations requiring cautious use:

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists: dexketoprofen reduces the effect of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., in dehydrated patients or elderly patients with renal impairment), the condition may worsen when used concomitantly with agents that inhibit cyclooxygenase activity, such as ACE inhibitors, angiotensin II receptor antagonists, and aminoglycoside antibiotics. This deterioration is usually reversible. When dexketoprofen is used concomitantly with any diuretic, ensure the patient receives adequate fluid intake, and monitor renal function at the start and periodically after treatment initiation. Concomitant use of dexketoprofen and potassium-sparing diuretics may lead to hyperkalemia. Serum potassium levels should be monitored.
Methotrexate when administered at low doses (< 15 mg/week): possible increase in hematological toxicity due to reduced renal clearance during anti-inflammatory therapy; weekly blood count monitoring is required during the first weeks of such combination therapy, especially in the presence of even slight renal impairment or in elderly patients.
Pentoxifylline: increased risk of bleeding; therefore, patient monitoring and bleeding time assessment are necessary.
Zidovudine: risk of increased zidovudine toxicity on erythropoiesis (toxic effect on reticulocytes) up to severe anemia one week after NSAID administration; therefore, blood analysis with reticulocyte count should be performed during the first 1–2 weeks after initiation of NSAID therapy.
Sulfonylurea derivatives: NSAIDs may enhance the hypoglycemic effect of sulfonylurea drugs due to their displacement from plasma protein binding sites.

Combinations to be considered:

β-blockers: their antihypertensive effect may be reduced due to inhibition of prostaglandin synthesis.
Cyclosporine and tacrolimus: enhanced nephrotoxic effects of these drugs due to NSAID effects on prostaglandin synthesis; regular monitoring of renal function is required when using this combination.
Thrombolytic agents: increased risk of bleeding.
Platelet aggregation inhibitors and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.
Probenecid: increased plasma concentration of dexketoprofen due to reduced renal tubular secretion and glucuronidation; dose adjustment of dexketoprofen may be necessary in such cases.
Cardiac glycosides: their plasma concentration may increase.
Mifepristone: there is a theoretical risk that prostaglandin synthesis inhibitors may alter the efficacy of mifepristone. Some data suggest that concomitant use of NSAIDs and prostaglandins does not affect mifepristone or prostaglandin action—specifically cervical ripening or uterine contractility—and does not reduce the clinical efficacy of medical abortion.
Quinolone antibiotics: animal studies have shown that high-dose quinolone antibiotics in combination with NSAIDs increase the risk of seizures.
Tenofovir: concomitant use with NSAIDs may increase blood urea nitrogen and creatinine levels; therefore, renal function should be monitored to control potential synergistic effects on kidney function.
Deferasirox: concomitant use with NSAIDs may increase gastrointestinal toxicity and requires careful clinical monitoring.
Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, caution should be exercised when administering higher NSAID doses. Patients with mild to moderate renal impairment (creatinine clearance of 45–79 mL/min) should avoid NSAID use 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, particularly selective COX-2 inhibitors, should be avoided.

Adverse reactions can be minimized by using the lowest effective dose for the shortest possible duration needed to control symptoms (see further information on gastrointestinal and cardiovascular risks below).

Gastrointestinal safety.

Gastrointestinal bleeding, ulceration, or perforation have been reported with all NSAIDs at various stages of treatment, regardless of the presence of preceding symptoms or a history of serious gastrointestinal pathology. If gastrointestinal bleeding or ulceration occurs 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, and in elderly patients.

Elderly patients: Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be life-threatening. Treatment in these patients should begin with the lowest possible dose.

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

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease) due to the risk of disease exacerbation.

For such patients and those taking low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal adverse reactions, consideration should be given to combination therapy with protective agents, such as misoprostol or proton pump inhibitors.

Patients, especially elderly ones, with a history of gastrointestinal adverse reactions should report any unusual gastrointestinal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

The drug should be prescribed with caution to patients who are concurrently taking agents that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

Renal safety.

The drug should be used with caution in patients with impaired renal function, as NSAIDs may worsen renal function, cause fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or those at risk of hypovolemia.

During treatment, patients should receive adequate fluid intake to prevent dehydration, which may exacerbate renal toxicity.

Like all NSAIDs, dexketoprofen may increase plasma urea and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure.

Renal function disturbances occur most frequently in elderly patients.

Hepatic safety.

The drug should be used with caution in patients with impaired liver function. Similar to other NSAIDs, dexketoprofen may cause transient and minor elevations in some liver parameters, as well as marked increases in aspartate aminotransferase and alanine aminotransferase activity. If such increases occur, treatment should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety.

Patients with a history of arterial hypertension and/or mild to moderate heart failure require monitoring and medical supervision. Particular caution is required when treating patients with a history of heart disease, especially those with prior episodes of heart failure, as the use of dexketoprofen may increase the risk of heart failure due to fluid retention and edema. Clinical studies and epidemiological data suggest a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) with some NSAIDs, particularly at high doses and with prolonged use. Data are insufficient to exclude this risk with dexketoprofen. Therefore, dexketoprofen should be prescribed only after careful patient assessment in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease. Similarly, careful evaluation is required before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

All non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time due to inhibition of prostaglandin synthesis. Therefore, dexketoprofen trometamol is not recommended in patients taking medications affecting hemostasis, such as warfarin, other coumarin derivatives, or heparins. Cardiovascular function disturbances occur most frequently in elderly patients.

Skin reactions.

Very rare cases of serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported during NSAID use. The highest risk appears to be during the initial stages of treatment, with most cases occurring within the first month.

If signs of skin rash, mucosal lesions, or other hypersensitivity symptoms appear, the drug should be discontinued.

Masking symptoms of underlying infections.

Dexketoprofen may mask symptoms of infectious diseases, potentially delaying diagnosis and treatment and thereby complicating the disease course. Such masking has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When dexketoprofen is used to relieve pain associated with infection, monitoring for infection 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 drug to patients:

with hereditary porphyrin metabolism disorders (e.g., acute intermittent porphyria);
with dehydration;
immediately after major surgical procedures.

If prolonged use of dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function and blood counts should be performed.

In very rare cases, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. Treatment should be discontinued at the first signs of severe hypersensitivity reactions. Depending on symptoms, appropriate treatment should be administered under medical supervision.

Patients suffering from asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to other patients. Use of this drug may trigger asthma attacks or bronchospasm, especially in patients allergic to acetylsalicylic acid or NSAIDs.

In rare cases, severe skin and soft tissue infections may develop during varicella. Currently, there are insufficient data to fully exclude the role of NSAIDs in exacerbating this infectious process. Therefore, the use of dexketoprofen should be avoided during varicella.

The drug should be used with caution in patients with blood dyscrasias, systemic lupus erythematosus, and mixed connective tissue diseases.

Children.

Safety and efficacy in children and adolescents have not been established.

Important information on excipients.

This medicinal product contains sucrose. This should be considered in diabetic patients.

Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency should not take this medicinal product.

Use during pregnancy or breastfeeding.

The drug is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic and fetal development. According to epidemiological studies, the use of drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage and congenital heart defects and abdominal wall defects in the fetus.

The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase with higher drug doses and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors have caused increased pre- and post-implantation losses and increased embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal malformations, particularly cardiovascular abnormalities, was observed. However, animal studies with dexketoprofen did not reveal toxic effects on reproductive organs. Starting from the 20th week of pregnancy, the use of dexketoprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after starting treatment and is usually reversible upon discontinuation of the drug. There have also been reports of ductus arteriosus constriction after treatment in the second trimester, most of which resolved after stopping treatment. Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to dexketoprofen for several days starting from the 20th gestational week. The use of the drug DEXPRO should be discontinued if these fetal abnormalities are detected. The use of dexketoprofen during the first and second trimesters of pregnancy is possible only if absolutely necessary. When prescribing dexketoprofen to women planning pregnancy or during the first and second trimesters, the lowest effective dose for the shortest possible duration should be used.

During the third trimester, all prostaglandin synthesis inhibitors cause:

Risks to the fetus:

cardiopulmonary toxicity, e.g., premature constriction/closure of the ductus arteriosus and pulmonary hypertension;
renal dysfunction, which may progress to renal failure and lead to oligohydramnios (see above).

Risks to the mother at the end of pregnancy and to the newborn:

prolonged bleeding time due to inhibition of platelet aggregation, even with low-dose administration;
inhibition of uterine contractility, leading to prolonged labor and delayed delivery.

Breastfeeding.

There are no data on the passage of dexketoprofen into breast milk. Dexketoprofen is contraindicated during breastfeeding.

Fertility.

Like all other NSAIDs, dexketoprofen may reduce female fertility and therefore is not recommended for women attempting to conceive. If a woman experiences fertility problems or is undergoing infertility investigations, discontinuation of dexketoprofen should be considered.

Ability to affect reaction speed when driving or operating machinery.

During treatment with dexketoprofen, adverse effects such as dizziness, visual disturbances, or somnolence may occur. In such cases, the ability to drive or operate machinery may be impaired.

Method of Administration and Dosage.

Dosing.

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

Adults.

Depending on the type 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 use necessary to relieve symptoms.

Elderly patients. It is recommended to initiate treatment with low doses. The daily dose is 50 mg. If the medicinal product is well tolerated, the dose may be increased to the usual level. Due to the risk of adverse reactions of a certain profile, elderly patients should remain under close medical supervision.

Hepatic impairment.

For patients with mild to moderate hepatic impairment, treatment should be initiated at the lowest recommended dose and under strict medical supervision. The daily dose is 50 mg. Dexketoprofen is contraindicated in patients with severe hepatic dysfunction.

Renal impairment.

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

Method of Administration.

Before use, dissolve the entire contents of 1 sachet in a glass of water and mix thoroughly for better dissolution. The resulting solution should be taken immediately after preparation.

Concomitant administration with food slows the absorption rate of the medicinal product (see section "Pharmacokinetics"); therefore, in the case of acute pain, it is recommended to take the medicinal product at least 15 minutes before food intake.

Children.

The use of dexketoprofen in children has not been studied; therefore, safety and efficacy in children and adolescents have not been established. The medicinal product should not be administered to children and adolescents.

Overdose.

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

In case of accidental overdose or excessive use, symptomatic therapy should be initiated immediately according to the patient's clinical condition. If the ingested dose exceeds 5 mg/kg in an adult or child, activated charcoal should be administered within one hour. Dexketoprofen trometamol is eliminated from the body by dialysis.

Adverse Reactions

The adverse reactions listed below are considered at least possibly related to the use of dexketoprofen (in tablet form) based on clinical trial data, as well as adverse reactions reported during the post-marketing period.

Since the plasma Cmax level of dexketoprofen in granule form is higher than in tablet form, an increased risk of adverse reactions (particularly gastrointestinal) cannot be excluded.

All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), 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), frequency not known (cannot be estimated from available data).

Eye disorders: very rare – blurred vision.

Aural and vestibular disorders: uncommon – dizziness; very rare – tinnitus.

Respiratory, thoracic and mediastinal disorders: rare – bradypnea; very rare – bronchospasm, dyspnea.

Gastrointestinal disorders: common – nausea and/or vomiting, abdominal pain, diarrhea, dyspepsia; uncommon – gastritis, constipation, dry mouth, flatulence; rare – peptic ulcer, gastrointestinal bleeding or perforation; very rare – pancreatitis.

Hepatobiliary disorders: rare – liver cell damage.

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

Metabolism and nutrition disorders: rare – anorexia.

Nervous system disorders: uncommon – headache, dizziness, somnolence; rare – paresthesia, loss of consciousness.

Psychiatric disorders: uncommon – insomnia, anxiety.

Cardiac disorders: uncommon – palpitations; very rare – tachycardia.

Vascular disorders: uncommon – flushing; rare – hypertension; very rare – arterial hypotension.

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

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

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

Musculoskeletal and connective tissue disorders: rare – back pain.

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

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

Investigations: rare – liver function test abnormalities.

Gastrointestinal adverse effects are the most commonly observed. Peptic ulceration, gastrointestinal perforation, or bleeding may occur and, in some cases, may be fatal, particularly in elderly patients. Nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported. Gastritis is less frequently observed. Edema, arterial hypertension, and heart failure have also been reported during treatment with NSAIDs.

According to clinical trial results and epidemiological data, the use of certain NSAIDs, particularly at high doses and over prolonged periods, is associated with a small increase in the risk of thrombotic events (e.g., myocardial infarction or stroke).

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

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life. 1.5 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of the reach of children.

Packaging.

10 single-dose sachets per pack.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspilska Street, Kyiv, 02093, Ukraine.