Moviflex® dex

for medical use of the medicinal product MOVI FLEX® DEX (MOVIFLEX® DEX)

Composition:

Active substance: dexketoprofen trometamol;

One 2 ml ampoule of injectable solution contains 73.8 mg of dexketoprofen trometamol, equivalent to 50 mg of dexketoprofen (1 ml of injectable solution contains 36.9 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen);

Excipients: ethanol 96%, sodium chloride, sodium hydroxide, water for injections.

Pharmaceutical form. Injectable solution.

Main physicochemical characteristics: almost clear, colorless solution.

Pharmacotherapeutic group.

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

Pharmacological Properties

Dexketoprofen trometamol is the tromethamine salt of (S)-(+)-2-(3-benzoylphenyl) propionic acid, exerting analgesic, anti-inflammatory, and antipyretic effects, and belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs).

Mechanism of Action.
The mechanism of action of NSAIDs is based on the reduction of prostaglandin synthesis through inhibition of cyclooxygenase activity. Specifically, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2α, PGD2, as well as prostacyclin PGI2 and thromboxanes TxА2 and TxВ2 are formed. Additionally, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the drug.

Pharmacodynamics

Studies have demonstrated the inhibitory effect of dexketoprofen trometamol on the activity of both cyclooxygenase-1 and cyclooxygenase-2 (in laboratory animals and humans).

Clinical Efficacy and Safety

Clinical studies in various types of pain have demonstrated that dexketoprofen trometamol exerts pronounced analgesic effects. The analgesic effect of dexketoprofen trometamol following intramuscular and intravenous administration to patients with moderate to severe pain has been studied in various pain conditions associated with surgical procedures (orthopedic and gynecological surgeries, abdominal surgeries), as well as musculoskeletal pain (acute low back pain) and renal colic. In these studies, the analgesic effect of the drug began rapidly and reached its maximum within the first 45 minutes. The duration of analgesic action after administration of 50 mg of dexketoprofen trometamol typically lasts 8 hours.

Clinical studies on postoperative pain relief have shown that the use of dexketoprofen trometamol in combination with opioid analgesics allows for a significant reduction in opioid use. In such studies, patients receiving morphine via a patient-controlled analgesia device and who also received dexketoprofen required significantly less morphine (by 30–45%) compared to patients in the placebo group.

Pharmacokinetics

Absorption

After intramuscular administration of dexketoprofen trometamol, maximum concentration is reached approximately within 20 minutes (10–45 minutes). When administering doses of 25–50 mg, the area under the concentration-time curve (AUC) is proportional to the administered dose for both intramuscular and intravenous routes of administration.

Distribution

Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen averages 0.25 L/kg. The distribution half-life is approximately 0.35 hours, and the elimination half-life − 1–2.7 hours.

Pharmacokinetic studies with repeated administration of the drug demonstrated that AUC and Cmax (mean maximum concentration) after the last intramuscular or intravenous dose were not different from those after single administration, indicating no accumulation of the drug.

Biotransformation and Elimination

After administration of dexketoprofen trometamol, only the S-(+) enantiomer is detected in urine, indicating no conversion of the drug into the R-(-) enantiomer in humans. The metabolism of dexketoprofen occurs mainly through conjugation with glucuronic acid, followed by renal excretion.

Elderly Patients

In healthy elderly individuals (aged 65 years and older), exposure was significantly higher compared to young volunteers after both single and multiple oral doses (up to 55%), while there was no statistically significant difference in peak concentrations or time to peak concentration. The mean elimination half-life was prolonged (by up to 48%), and the total clearance was reduced.

Preclinical Safety Data

Pharmacology safety, genotoxicity, and immunopharmacology studies revealed no particular hazard for humans. Chronic toxicity studies in animals identified the no-observed-adverse-effect level (NOAEL), which was 2 times higher than the dose recommended for humans. When higher doses were administered to monkeys, the main adverse reactions included fecal blood, reduced body weight gain, and at the highest dose, gastrointestinal tract pathology 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 trometamol may cause effects on fetal survival during the embryofetal period in animals, both indirectly via gastrointestinal toxicity in pregnant animals and directly via adverse effects on fetal development.

Clinical characteristics.

Indications.

Symptomatic treatment of moderate to severe acute pain when oral administration of a medicinal product is inappropriate, for example, in postoperative pain, renal colic, and back pain.

Contraindications.

• Third trimester of pregnancy and breastfeeding period.
• Hypersensitivity to dexketoprofen, any other NSAID, or to excipients of the medicinal product.
• NSAIDs are contraindicated in patients with a history of hypersensitivity reactions (e.g., bronchospasm, bronchial asthma, acute rhinitis, or development of nasal polyps, angioedema, or urticaria) following the use of ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Known photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.
• Active phase or history of peptic ulcer, gastrointestinal bleeding, or perforations.
• History of gastrointestinal bleeding or perforation associated with previous NSAID therapy.
• Active gastrointestinal bleeding, other active bleeding, or increased bleeding tendency.
• Hemorrhagic diathesis and other coagulation disorders.
• Chronic dyspepsia.
• Crohn’s disease or ulcerative colitis.
• Marked dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
• Severe heart failure.
• Moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min).
• Severe hepatic impairment (Child–Pugh score 10–15 points).

Due to the ethanol content, the medicinal product is contraindicated for neuraxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other types of interactions.

The following drug interactions are generally typical for NSAIDs.

Concomitant use not recommended with the following medicinal products:

• Other NSAIDs, including selective cyclooxygenase-2 inhibitors, salicylates in high doses (≥ 3 g/day): concurrent use of multiple NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to synergistic effects.
• Anticoagulants: NSAIDs enhance the effect of anticoagulants, such as warfarin, due to the high degree of plasma protein binding of dexketoprofen, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under physician supervision with careful monitoring of appropriate laboratory parameters.
• Heparins: 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 physician supervision with careful monitoring of appropriate laboratory parameters.
• Corticosteroids: increased risk of peptic ulcers and gastrointestinal bleeding.
• Lithium preparations: (reports exist for several NSAIDs) NSAIDs increase lithium blood levels, potentially leading to toxicity, due to reduced renal excretion. Therefore, lithium blood levels should be monitored at the start of dexketoprofen therapy, during dose adjustments, or upon discontinuation of the medicinal product.
• Methotrexate when administered in high doses (≥ 15 mg/week): due to reduced renal clearance of methotrexate in the context of NSAID use, its negative effects on the blood system are generally intensified.
• Hydantoin derivatives and sulfonamides: possible increase in toxicity of these substances.

Concomitant use of the following agents with NSAIDs requires caution:

• Diuretics, ACE inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the effectiveness of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., in dehydrated patients or elderly individuals), concomitant use of NSAIDs with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, which is usually a reversible process. When using dexketoprofen concomitantly with any diuretic, ensure the patient is not dehydrated, and monitor renal function at the beginning of treatment.
• Methotrexate when administered in low doses (< 15 mg/week): due to reduced renal clearance of methotrexate under NSAID therapy, its negative effects on the blood system are intensified. If such combination use is necessary, weekly blood monitoring is required, especially in the presence of even slight renal impairment, as well as in elderly patients.
• Pentoxifylline: risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently.
• Zidovudine: risk of increased toxic effects on erythrocytes due to effects on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. A blood test with reticulocyte count should be performed within 1–2 weeks after starting NSAID therapy.
• Sulfonylurea derivatives: NSAIDs may enhance the hypoglycemic effect of sulfonylurea drugs due to their displacement from plasma protein binding sites.

Potential interactions should be considered when using the following agents:

• Beta-blockers: NSAIDs may reduce their antihypertensive effect due to inhibition of prostaglandin synthesis.
• Cyclosporine and tacrolimus: possible increase in nephrotoxicity due to the effect of NSAIDs on renal prostaglandins. Renal function should be monitored during combination therapy.
• Thrombolytic agents: increased risk of bleeding.
• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
• Probenecid: possible increase in dexketoprofen plasma concentration, likely due to inhibition of its renal tubular secretion and glucuronidation, requiring dose adjustment of dexketoprofen.
• Cardiac glycosides: NSAIDs may increase glycoside plasma concentrations.
• Mifepristone: theoretically, there is a risk of altered mifepristone efficacy under the influence of prostaglandin synthetase inhibitors. Limited data suggest that concomitant administration of NSAIDs on the same day as prostaglandin does not adversely affect the efficacy of mifepristone or prostaglandin regarding cervical ripening or contractility, nor does it reduce the clinical efficacy of medicinal abortion agents.
• Quinolone antibiotics: animal studies have shown that administration of quinolone derivatives in high doses in combination with NSAIDs increases the risk of seizures.
• Tenofovir: when used concomitantly with NSAIDs, plasma concentrations of blood urea nitrogen and creatinine may increase; therefore, renal function should be monitored to assess the potential impact of concomitant use of these medicinal products.
• Deferasirox: concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Careful patient monitoring is required when using this medicinal product concomitantly with deferasirox.
• Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using NSAIDs at high doses. Patients with mild to moderate renal impairment (creatinine clearance from 45 to 79 mL/min) should avoid concomitant use of pemetrexed and NSAIDs for two days before and two days after pemetrexed administration.

Special precautions for use.

Use the medicinal product with caution in patients with a history of allergic conditions. Avoid using the medicinal product in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to improve the condition.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, in some cases fatal, have been observed 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, 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 complicated by bleeding or perforation, and in elderly patients.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Treatment in such patients should be initiated with the lowest possible dose.

Before starting treatment with dexketoprofen trometamol in patients with a history of esophagitis, gastritis, and/or peptic ulcer disease, ensure that these conditions are in remission.

Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders require monitoring of gastrointestinal status during treatment for possible adverse events, particularly gastrointestinal bleeding.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. For such patients and for patients taking low-dose acetylsalicylic acid or other agents increasing the risk of gastrointestinal adverse reactions, consider combination therapy with gastroprotective agents, such as misoprostol or proton pump inhibitors.

Patients, especially elderly ones, with a history of gastrointestinal adverse reactions should inform their physician about any unusual gastrointestinal symptoms, including gastrointestinal bleeding, particularly during the initial stages of treatment.

Exercise caution when prescribing the drug to patients who are concurrently using agents that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents like acetylsalicylic acid.

Renal safety

The medicinal product should be administered with caution to patients with impaired renal function, as NSAID use may lead to worsening renal function, fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients undergoing diuretic therapy 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, the medicinal product may increase plasma urea nitrogen and creatinine concentrations. 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 medicinal product should be administered with caution in patients with impaired liver function. Like other NSAIDs, the drug may cause transient and mild elevations in certain liver function parameters, as well as marked increases in AST and ALT activity. If such increases occur, treatment should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with 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 cardiac disease, especially those with prior episodes of heart failure (the risk of heart failure increases during treatment), as NSAIDs may cause fluid retention and edema. Clinical studies and epidemiological data suggest 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 (e.g., myocardial infarction or stroke). Data to exclude such a risk with dexketoprofen trometamol are insufficient.

Therefore, in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, dexketoprofen should be prescribed only after careful patient assessment. Similarly, careful evaluation is required before initiating long-term treatment in patients with cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, or smoking).

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The concomitant use of dexketoprofen trometamol and prophylactic doses of low-molecular-weight heparin in the postoperative period has been studied in clinical trials, with no effect on coagulation parameters observed. However, patients receiving dexketoprofen trometamol concurrently with agents affecting hemostasis, such as warfarin, other coumarins, or heparins, require close medical supervision. Cardiovascular function disturbances occur most frequently in elderly patients.

Skin reactions

There have been reports of very rare cases of serious skin reactions (some fatal) associated with NSAID use, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The risk of such reactions is likely highest at the beginning of treatment, with most cases occurring within the first month of therapy. If skin rashes, signs of mucosal involvement, or other symptoms of hypersensitivity occur, the medicinal product should be discontinued.

Masking symptoms of underlying infections

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

In rare cases, varicella may lead to serious skin and soft tissue infections. At present, a potential role of NSAIDs in exacerbating these infections cannot be excluded. Therefore, it is advisable to avoid using dexketoprofen trometamol in cases of varicella.

Other information

Particular caution is required when prescribing the medicinal product 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, liver and kidney function should be monitored regularly.

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

Patients with bronchial asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps are more prone to allergic reactions when using acetylsalicylic acid and/or NSAIDs than other patients. The use of this medicinal product may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

The medicinal product should be administered with caution to patients with coagulation disorders, systemic lupus erythematosus, and mixed connective tissue diseases.

Each ampoule of the medicinal product contains 12.35 vol.% ethanol, i.e., 200 mg per dose, equivalent to 5 ml of beer or 2.08 ml of wine per dose. The medicinal product may have adverse effects in individuals suffering from alcoholism. The ethanol content should be considered when using the product in pregnant women, breastfeeding women, children, and patients at risk, such as those with liver disease or epilepsy.

The medicinal product contains less than 1 mmol sodium (23 mg) per dose and is therefore practically sodium-free.

Use during pregnancy or breastfeeding.

The use of the medicinal product is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. According to epidemiological studies, the use of drugs that inhibit prostaglandin synthesis in early pregnancy increases the risk of miscarriage and fetal congenital heart defects and abdominal wall defects. The absolute risk of cardiovascular malformations increases from <1% to approximately 1.5%. The risk of such events is considered to increase with higher drug doses and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors 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 developmental abnormalities, including cardiovascular malformations, was observed. However, animal studies with dexketoprofen trometamol did not reveal reproductive toxicity.

From the 20th week of pregnancy, the use of dexketoprofen trometamol may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation.

Additionally, there are reports of arterial duct constriction after treatment during the second trimester, most of which resolved after stopping treatment. Therefore, dexketoprofen trometamol should not be prescribed during the first and second trimesters of pregnancy, except in cases of extreme necessity. When prescribing dexketoprofen trometamol to women planning pregnancy or during the first and second trimesters, the lowest possible effective dose should be used for the shortest possible duration.

Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of exposure to the drug, starting from the 20th gestational week. The use of the medicinal product should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks:

Risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• renal dysfunction (see above).

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

• possible prolongation of bleeding time, antiplatelet effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, the medicinal product is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period.

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

Fertility.

Like all other NSAIDs, dexketoprofen trometamol may reduce female fertility and therefore is not recommended for women planning pregnancy. For women experiencing fertility problems or undergoing infertility evaluation, discontinuation of the medicinal product should be considered.

Ability to affect reaction speed when driving or operating machinery.

Dizziness, visual disturbances, or drowsiness may occur during treatment with the medicinal product. In such cases, the ability to react quickly, orient in traffic situations, and drive or operate machinery may be impaired.

Method of Administration and Dosage.

Solution for intramuscular and intravenous administration.

To minimize adverse reactions, the lowest effective dose for the shortest duration should be used (see section "Special Warnings and Precautions for Use").

Adults. The recommended dose is 50 mg administered every 8–12 hours. If necessary, the next dose may be given after 6 hours. The maximum daily dose should not exceed 150 mg. This medicinal product is intended for short-term use only and should be administered solely during episodes of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible. For moderate to severe postoperative pain, the medicinal product may be used as indicated at the same recommended doses in combination with opioid analgesics.

Elderly patients. Dose adjustment is generally not required. However, due to physiological decline in renal function, a lower dose is recommended: maximum daily dose of 50 mg in patients with mild renal impairment.

Hepatic impairment. In patients with mild or moderate hepatic disease (5–9 points on the Child–Pugh scale), the maximum daily dose should be reduced to 50 mg, and liver function should be closely monitored. The medicinal product is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Renal impairment. In patients with mild renal impairment (creatinine clearance 60–89 mL/min), the maximum daily dose should be reduced to 50 mg. The medicinal product is contraindicated in patients with moderate or severe renal impairment (creatinine clearance <59 mL/min).

Children and adolescents. The medicinal product should not be used in children and adolescents due to lack of data on safety and efficacy.

Method of Administration.

Intramuscular administration. The injection solution should be administered slowly as a deep intramuscular injection.

Intravenous infusion. For intravenous infusion, the contents of a 2 mL ampoule should be diluted in 30–100 mL of 0.9% sodium chloride solution, 5% glucose solution, or Ringer's lactate solution. The infusion solution should be prepared under aseptic conditions and protected from exposure to natural daylight. The prepared solution should be clear and free from particles. The infusion should be administered slowly over 10–30 minutes.

The medicinal product diluted in 100 mL of 0.9% sodium chloride solution or 5% glucose solution is compatible with the following medicinal products: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

The medicinal product must not be mixed in the infusion solution with promethazine or pentazocine.

Intravenous injection (bolus administration). If necessary, the contents of one ampoule (2 mL of injection solution) should be administered intravenously slowly over at least 15 seconds.

The medicinal product may be mixed in small volumes (e.g., in a syringe) with injection solutions of heparin, lidocaine, morphine, and theophylline.

The medicinal product must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, pethidine, or hydroxyzine, as precipitation may occur.

The medicinal product may only be mixed with the medicinal products listed above.

After drawing the medicinal product from the ampoule, it should be administered immediately when administered by intramuscular or intravenous injection.

No changes in active substance concentration due to adsorption have been observed during storage of diluted solutions of the medicinal product in polyethylene bags or in administration devices made of ethylene-vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

The medicinal product is intended for single use only; any unused portion of the prepared solution should be discarded. Before administration, ensure that the solution is clear and colorless. The solution must not be used if it contains particulate matter.

Children.

The medicinal product should not be used in children and adolescents due to lack of data on efficacy and safety.

Overdose.

Symptoms of overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, dizziness, disorientation, headache). In case of accidental overdose, symptomatic treatment appropriate to the patient's condition should be initiated immediately. Dexketoprofen trometamol is eliminated from the body by dialysis.

Adverse reactions.

The table below lists adverse reactions by organ systems and frequency of occurrence, which, according to clinical trial data, are considered at least possible in relation to dexketoprofen trometamol, as well as adverse reactions for which reports have been received.

Gastrointestinal disorders were observed most frequently.

Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. According to available data, nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, vomiting of blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may develop during treatment. Gastritis has been reported less frequently.

Edema, arterial hypertension, and heart failure have also been reported, which may be associated with the use of NSAIDs.

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

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

According to results of clinical trials and epidemiological data, the use of certain NSAIDs, particularly at high doses and over prolonged periods, may be associated with a small increased risk of thrombotic events such as myocardial infarction and stroke.

Reporting suspected adverse reactions

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

Shelf life. 3 years.

After reconstitution, the solution should be stored in a light-protected container at 2 °C to 8 °C for up to 24 hours.

Storage conditions.

Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25°C. Storage conditions after reconstitution are specified in the section «Shelf life».

Incompatibilities.

The medicinal product must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydroxyzine, as precipitation may occur.

Diluted infusion solutions prepared as described in the section «Method of administration and dosage» must not be mixed with promethazine or pentazocine.

The medicinal product should not be mixed with other medicinal products except those specified in the section «Method of administration and dosage».

Packaging.

2 ml in a vial; 6 vials in a blister pack, 1 blister pack in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Deva Holding A.Ş.

Manufacturer's address and location of its business operations.

Dumlupınar Mahallesi, Ankara Caddesi No: 2, Kartepe, Kocaeli, Turkey.

Marketing Authorization Holder.

LLC "Movi Health"

Address of the Marketing Authorization Holder.

162 A, Shevchenka Street, Shevchenkove village, Kyiv-Sviatoshyn district, Kyiv region, 08140, Ukraine