Dexpro

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXPRO (DEXPRO)

Composition:

Active substance: dexketoprofen;

1 ampoule of 2 ml solution contains dexketoprofen trometamol 73.8 mg, equivalent to dexketoprofen 50 mg;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. 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 belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs).

Mechanism of action

The mechanism of action of NSAIDs is based on reducing the synthesis of prostaglandins by inhibiting 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. In addition, 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.

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

Clinical efficacy and safety

Clinical studies of various types of pain have shown that dexketoprofen trometamol exerts pronounced analgesic effects. The analgesic effect of dexketoprofen trometamol after intramuscular or intravenous administration to patients with moderate to severe pain has been studied during surgical procedures (orthopedic and gynecological surgeries, abdominal surgeries), as well as in 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 is usually 8 hours. According to results of clinical studies, the medicinal product Dexpro allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. In patients receiving morphine administered via a patient-controlled analgesia device for postoperative pain relief, co-administration of dexketoprofen trometamol resulted in a significantly lower requirement for morphine (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics.

Absorption

After intramuscular administration of dexketoprofen trometamol to humans, maximum concentration is reached approximately within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg of the drug, the area under the AUC (concentration–time) curve is proportional to the dose.

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 is 1–2.7 hours.

Pharmacokinetic studies of repeated administration of the drug demonstrated that Cmax and AUC after the last intramuscular or intravenous dose did not differ from those after single administration, indicating absence of drug accumulation.

Biotransformation and elimination

Metabolism 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 absence of transformation of the drug into the R-(-) optical isomer in humans.

Elderly patients

After administration of single and multiple doses, the extent of exposure in elderly healthy volunteers (aged 65 years and older) participating in the study was significantly higher (up to 55%) compared to younger volunteers; however, no statistically significant differences in maximum concentration or time to reach maximum concentration were observed. The mean elimination half-life was prolonged (by up to 48%), and the total clearance was reduced.

Preclinical safety data

Standard preclinical studies—pharmacological safety, genotoxicity, and immunopharmacology—did not reveal any special 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 were fecal blood, reduced body weight gain, and at the highest dose, gastrointestinal 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 were not conducted.

Like all NSAIDs, the use of dexketoprofen may be associated with embryonic or fetal death in animals due to direct or indirect effects on development, resulting from maternal gastrointestinal tract injury.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to dexketoprofen, to any other NSAID, or to excipients of the medicinal product;
• patients in whom administration of drugs with similar action, such as acetylsalicylic acid or other NSAIDs, induces attacks of bronchial asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema;
• photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates;
• gastrointestinal bleeding or perforation in medical history associated with NSAID therapy;
• active peptic ulcer/gastrointestinal bleeding or history of gastrointestinal bleeding, ulcers, or perforations;
• chronic dyspepsia;
• active bleeding or increased bleeding tendency;
• Crohn’s disease or ulcerative colitis;
• severe heart failure;
• moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min);
• severe hepatic impairment (10–15 points on the Child–Pugh scale);
• hemorrhagic diathesis and other coagulation disorders;
• severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake);
• third trimester of pregnancy and breastfeeding period;

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use of NSAIDs with the following groups of medicinal products is not recommended:

• other NSAIDs (including selective cyclooxygenase-2 inhibitors), including salicylates in high doses (≥ 3 g/day). Concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to their mutually enhancing 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 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 relevant 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 medical supervision with careful monitoring of relevant laboratory parameters;
• corticosteroids: increased risk of gastrointestinal ulceration or gastrointestinal bleeding;
• lithium (reports exist for several NSAIDs): NSAIDs increase lithium blood levels, potentially leading to toxicity (reduced renal excretion of lithium). Therefore, lithium blood levels should be monitored at the start of dexketoprofen treatment, during dose adjustment, or upon discontinuation of the medicinal product;
• high-dose methotrexate (≥ 15 mg per week). Due to reduced renal clearance of methotrexate under NSAID therapy, its adverse effects on the blood system are generally enhanced;
• hydantoin derivatives and sulfonamides: possible increase in toxicity of these substances.

Concomitant use of NSAIDs with the following groups of medicinal products requires caution:

• diuretics, angiotensin-converting enzyme (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., due to dehydration or in elderly patients), concomitant use of cyclooxygenase-inhibiting agents with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, which is usually reversible. When using dexketoprofen together with any diuretic, ensure the patient is not dehydrated and monitor renal function at the beginning of treatment;
• low-dose methotrexate (less than 15 mg per week): due to reduced renal clearance of methotrexate under NSAID therapy, its adverse effects on the blood system are generally enhanced. During the first weeks of concomitant use, weekly blood tests are required. Even with mild renal impairment and in elderly patients, treatment should be conducted under strict medical supervision;
• pentoxifylline: increased risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently;
• zidovudine: risk of increased toxic effect on erythrocytes due to effects on reticulocytes, leading to severe anemia after one week of NSAID use. Blood tests and reticulocyte counts should be performed 1–2 weeks after initiating NSAID treatment;
• sulfonylurea drugs: NSAIDs may enhance the hypoglycemic effect of these drugs by displacing sulfonylurea drugs from plasma protein complexes.

Potential interactions should be considered when using the following agents:

• beta-blockers: NSAIDs may attenuate 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 renal tubular secretion and conjugation of the drug with glucuronic acid, 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 products for medical termination of pregnancy;
• quinolone antibiotics: animal studies have shown that high-dose quinolone derivatives in combination with NSAIDs increase the risk of seizures;
• tenofovir: when used concomitantly with NSAIDs, plasma urea nitrogen and creatinine concentrations may increase; therefore, renal function should be monitored to assess the potential impact of concomitant use of these medicinal products;
• deferasirox: when used concomitantly with NSAIDs, the risk of gastrointestinal toxicity may increase. Careful patient monitoring is required when using this medicinal product together with deferasirox;
• pemetrexed: when used concomitantly with NSAIDs, pemetrexed excretion may be reduced; therefore, particular caution is required when using NSAIDs at high doses. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid NSAID use for two days before and two days after pemetrexed administration.

Special precautions for use

Use with caution in patients with a history of allergic conditions. Avoid using the medicinal product Dekspro 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 control symptoms.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported with all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding or ulceration occurs, the medicinal product should be discontinued. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, particularly 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, sometimes fatal. Treatment of such patients should begin with the lowest possible dose. As with all NSAIDs, patients with a history of esophagitis, gastritis, and/or peptic ulcer should be ensured to have these conditions in remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for possible gastrointestinal disturbances during treatment, particularly gastrointestinal bleeding. NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (e.g., ulcerative colitis, Crohn’s disease), as there is a risk of exacerbation. For these patients and those taking low-dose acetylsalicylic acid or other agents increasing the risk of gastrointestinal adverse reactions, combination therapy with gastroprotective agents (e.g., misoprostol or proton pump inhibitors) should be considered.

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.

The medicinal product should be used with caution in patients concurrently taking 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 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. Adequate fluid intake should be maintained during treatment to prevent dehydration, which may exacerbate renal toxicity. Like other NSAIDs, the medicinal product may increase plasma concentrations of blood urea nitrogen and creatinine. 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 used with caution in patients with impaired liver function. Similar to other NSAIDs, Dekspro 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, therapy should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with hypertension and/or mild to moderate heart failure require monitoring and medical advice. Particular caution is required in patients with a history of heart disease, especially previous episodes of heart failure (the risk of developing heart failure increases during treatment with the medicinal product), as fluid retention and edema may occur during NSAID therapy. Clinical and epidemiological data suggest that some NSAIDs (especially at high doses and prolonged use) may slightly increase the risk of arterial thrombosis (e.g., myocardial infarction or stroke). Data to exclude such risks with dexketoprofen use are insufficient. Therefore, dexketoprofen should be prescribed only after careful patient assessment in cases of uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease. A similarly careful assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking).

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The concomitant use of dexketoprofen trometamol and low-molecular-weight heparin at prophylactic doses 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 (e.g., warfarin, other coumarin derivatives, or heparins) require close medical supervision. Cardiovascular system 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 highest risk likely occurs early in treatment, with most cases appearing within the first month of therapy. If skin rashes, signs of mucosal involvement, or other hypersensitivity symptoms occur, Dekspro should be discontinued.

Masking symptoms of underlying infections

Dekspro may mask symptoms of infections, potentially delaying diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. Monitoring is recommended during Dekspro use for pain relief due to infectious processes.

In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Other information

Particular caution is required when prescribing the medicinal product to patients:

• with inherited 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.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If early signs of severe hypersensitivity reactions occur after taking Dekspro, treatment should be discontinued. Depending on symptoms, any necessary treatment should be administered under medical supervision.

Patients suffering from asthma in combination with chronic rhinitis, chronic sinusitis, and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. Prescribing this medicinal product may trigger asthma attacks or bronchospasm, especially in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications of the skin and soft tissues may occur during varicella. Data to exclude the role of NSAIDs in exacerbating this infectious process are currently lacking. Therefore, Dekspro is not recommended during varicella.

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

Like other NSAIDs, dexketoprofen trometamol may mask symptoms of infectious diseases during its use. In some cases, activation of infectious processes localized in soft tissues has been reported during NSAID use. Therefore, if symptoms of bacterial infection appear or worsen during treatment, patients are advised to seek immediate medical attention.

This medicinal product contains up to 200 mg of ethanol per 2 ml ampoule (3 mg/kg/dose (10% w/v)), equivalent to 5 ml of beer or 2 ml of wine. The small amount of alcohol contained in this medicinal product will not have a noticeable effect.

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

Use during pregnancy or breastfeeding

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

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological studies indicate that using drugs that inhibit prostaglandin synthesis early in 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 believed to increase with higher drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation losses and higher embryofetal mortality. Additionally, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal developmental abnormalities, particularly cardiovascular malformations, was observed. However, animal studies with dexketoprofen trometamol did not reveal reproductive toxicity. The use of dexketoprofen from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation of the drug. Additionally, cases of fetal arterial duct constriction have been reported after maternal use of the drug in the second trimester, most of which resolved after discontinuation of treatment. Therefore, prescribing dexketoprofen trometamol in the first and second trimesters of pregnancy is possible only if absolutely necessary. When prescribing dexketoprofen trometamol to women planning pregnancy or during the first and second trimesters of pregnancy, the lowest effective dose should be used for the shortest possible duration. Prenatal monitoring for oligohydramnios and fetal arterial duct constriction should be considered if exposure to dexketoprofen occurs over several days starting from the 20th gestational week. Pregnant women should discontinue dexketoprofen if oligohydramnios or fetal arterial duct constriction is detected.

During the third trimester, all prostaglandin synthesis inhibitors cause:

Risks for the fetus:

• cardiopulmonary toxic syndrome (narrowing/occlusion of the arterial duct and pulmonary hypertension);
• impaired renal function (see above);

Risks for the mother and child near the end of pregnancy:

• prolonged bleeding time (due to inhibition of platelet aggregation), which may occur even with low-dose use;
• delayed uterine contractions, leading to prolonged labor.

Breastfeeding

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

Fertility

Like all other NSAIDs, dexketoprofen trometamol may reduce female fertility and therefore is not recommended for women planning pregnancy. Women experiencing fertility problems or undergoing infertility evaluation should consider discontinuing the drug.

Ability to affect reaction speed when driving or operating machinery

Dizziness, visual disturbances, or somnolence may occur during treatment with Dekspro. 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

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

Adults. The recommended dose is 50 mg every 8–12 hours. If necessary, the dose may be repeated after 6 hours. The maximum daily dose should not exceed 150 mg. Dexpro is intended for short-term use and should only be administered 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—specifically, the maximum daily dose should be limited to 50 mg in patients with mild renal impairment.

Hepatic impairment. For patients with mild to moderate liver 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. For 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 to 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 efficacy and safety.

Method of Administration

Intramuscular injection.

The contents of one ampoule (2 mL) should be administered slowly by deep intramuscular injection.

Intravenous infusion.

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

Dexpro diluted in 100 mL of 0.9% sodium chloride solution or glucose solution may be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

Intravenous bolus injection.

If necessary, the contents of one ampoule (2 mL of injection solution) may 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.

Dexpro 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.

Diluted infusion solutions must not be mixed with promethazine or pentazocine.

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

After reconstitution, the medicinal product should be administered immediately following withdrawal from the ampoule when administered intramuscularly or as an intravenous bolus.

No changes in active substance content 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 Dexpro is intended for single use only; any unused portion of the prepared solution must be discarded. Prior to administration, the solution should be visually inspected to ensure it is clear and colorless. Solutions containing particulate matter must not be used.

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 following table lists adverse reactions by organ systems and frequency of occurrence:

Gastrointestinal disorders were observed most frequently.

The development of peptic ulcer, perforation, or gastrointestinal bleeding, sometimes fatal, is possible, especially in elderly patients. According to available data, nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may occur during the use of the medicinal product. Gastritis is observed less frequently. Edema, arterial hypertension, and heart failure, which may be caused by the use of NSAIDs, have also been reported. As with other NSAIDs, the following adverse reactions are possible: aseptic meningitis, which generally occurs in patients with systemic lupus erythematosus or mixed connective tissue diseases, and blood-related reactions (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions may occur, including Stevens–Johnson syndrome and toxic epidermal necrolysis (very rare).

According to the results of clinical studies and epidemiological data, the use of certain NSAIDs, especially at high doses and for prolonged periods, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction and stroke.

Reporting of suspected adverse reactions.

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

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. After reconstitution, the solution should be stored for 24 hours at a temperature between 2 °C and 8 °C, protected from light. Keep out of reach of children.

Incompatibilities.

Dexpro 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 "Instructions for use and dosage" must not be mixed with promethazine or pentazocine.

Packaging.

2 ml in an ampoule; 5 ampoules in a blister pack; 1 blister pack in a carton.

Prescription status. By prescription only.

Manufacturer.

JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activities.

13, Boryspilska Street, Kyiv, 02093, Ukraine.