Dexodev®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXODEV®

Composition:

Active substance: dexketoprofen trometamol;

1 ampoule (2 ml) contains 73.8 mg of dexketoprofen trometamol equivalent to 50 mg of dexketoprofen;

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

Pharmaceutical form. Solution for injection/infusion.

Main physico-chemical properties: clear, colorless solution.

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

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 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. In addition, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of dexketoprofen.

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 in various types of pain have demonstrated that dexketoprofen trometamol exerts a pronounced analgesic effect. 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 dexketoprofen 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 typically 8 hours. Clinical studies have shown that the use of dexketoprofen allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. When patients receiving morphine via a patient-controlled analgesia device for postoperative pain relief were also administered dexketoprofen trometamol, they required significantly less morphine (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics

Absorption

After intramuscular administration of dexketoprofen trometamol in 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 concentration-time curve (AUC) is dose-proportional.

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 drug administration demonstrated that maximum concentration (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 drug conversion to the R-(-) optical isomer in humans.

Elderly patients

After administration of single and multiple doses, the extent of drug 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 it 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—revealed no 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 included fecal blood, reduced body weight gain, and at the highest dose, gastrointestinal tract (GIT) pathologies such as erosions. These effects 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 lead to embryonic or fetal death in animals, either directly by affecting embryonic/fetal development or indirectly via maternal GIT toxicity.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the drug;
• in patients in whom administration of substances with similar activity, such as acetylsalicylic acid or other NSAIDs, triggers attacks of bronchial asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema;
• if photoallergic or phototoxic reactions occurred 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 (Child-Pugh score 10–15 points);
• hemorrhagic diathesis and other coagulation disorders;
• in case of pronounced 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, the drug is contraindicated for neuroaxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other forms of interaction.

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

• Other NSAIDs (including selective cyclooxygenase-2 inhibitors), including high-dose salicylates (≥ 3 g/day). Concurrent use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to their mutually enhancing effects.
• Anticoagulants. NSAIDs enhance the effects 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 appropriate laboratory parameters.
• Heparins. Increased risk of bleeding (due to inhibition of platelet function and damage to 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 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 initiation of dexketoprofen therapy, during dose adjustments, or upon discontinuation.
• High-dose methotrexate (≥ 15 mg per week). NSAIDs in general reduce renal clearance of methotrexate, thereby enhancing its adverse effects on the blood system.
• Hydantoin derivatives and sulfonamides. Possible increase in toxicity of these substances.

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

• Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydration or elderly patients), concomitant use of cyclooxygenase inhibitors with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, although this is usually reversible. When using dexketoprofen with any diuretic, ensure the patient is not dehydrated, and monitor renal function at the beginning of treatment.
• Low-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. During the first weeks of concomitant use, weekly blood tests are required. Treatment should be closely monitored by a physician, even in cases of mild renal impairment and 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 one week of NSAID use may lead to severe anemia. Blood tests and reticulocyte counts should be performed within 1–2 weeks after starting dexketoprofen.
• Sulfonylurea preparations. NSAIDs may enhance the hypoglycemic effect of these drugs by displacing sulfonylureas from plasma protein binding sites.

Potential interactions should be considered when using the following medicinal products:

• Beta-blockers. NSAIDs may reduce their antihypertensive effect due to inhibition of prostaglandin synthesis.
• Cyclosporine and tacrolimus. Possible increase in nephrotoxicity due to NSAID effects 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 glucuronide conjugation of the drug, 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 mifepristone or prostaglandin efficacy regarding cervical ripening or contractility, nor does it reduce the clinical efficacy of drugs used 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 potential effects of combined use.
• Deferasirox. Concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Close patient monitoring is required when using this drug with deferasirox.
• Pemetrexed. Concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using high-dose NSAIDs. In patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), dexketoprofen should be avoided for two days before and two days after pemetrexed administration.

Special precautions.

Dexketoprofen should be used with caution in patients with a history of allergic conditions. Avoid using dexketoprofen 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 relieve symptoms.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported during treatment with all NSAIDs at any stage of therapy, regardless of the presence of precursor 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, particularly in patients with a history of peptic ulcer, especially 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 pathology, including history of such conditions, require monitoring of gastrointestinal status during treatment for possible complications, particularly gastrointestinal bleeding. NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation. For such patients and those taking low-dose acetylsalicylic acid or other drugs increasing gastrointestinal adverse risk, consider combination therapy with gastroprotective agents, such as misoprostol or proton pump inhibitors.

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

Dexketoprofen should be prescribed with caution to patients concurrently using medications that may increase the risk of ulceration or bleeding: oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

Renal function impairment

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 treated with 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, dexketoprofen may increase plasma urea nitrogen and creatinine concentrations. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, leading to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function disturbances occur most frequently in elderly patients.

Hepatic function impairment

The drug should be used with caution in patients with impaired liver function. Similar to other NSAIDs, dexketoprofen may cause transient and mild elevation of certain liver parameters, as well as marked increases in AST and ALT activity. Therapy should be discontinued if such elevations occur.

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 advice. Particular caution is required when treating patients with a history of heart disease, especially previous episodes of heart failure (the risk of heart failure increases during treatment), as fluid retention and edema may occur with NSAID therapy. Clinical studies and epidemiological data suggest that some NSAIDs (especially at high doses and prolonged use) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Data to exclude this risk with dexketoprofen 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, smoking). Nonselective 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 drugs affecting hemostasis, such as warfarin, other coumarins, or heparins, require close medical supervision. Cardiovascular 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, the drug should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask symptoms of infections, potentially interfering with diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. When dexketoprofen is administered to relieve pain associated with an infectious process, monitoring of the 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 is recommended.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. Treatment should be discontinued at the first signs of severe hypersensitivity reactions after dexketoprofen intake. Depending on symptoms, any necessary treatment should be administered under medical supervision. Patients suffering from asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. Dexketoprofen may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

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

Dexketoprofen should be administered with caution to patients with blood dyscrasias, 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 infections 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.

Important information about excipients

Each ampoule of the medicinal product contains 12.35 vol. % ethanol, i.e., up to 200 mg per dose, equivalent to 5 ml of beer or 2.08 ml of wine per dose. Dexketoprofen may adversely affect individuals suffering from alcoholism. Ethanol content should be considered when using in pregnant women, breastfeeding women, children, and patients at risk, e.g., those with liver disease, as well as patients with 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 in the third trimester of pregnancy and during breastfeeding (see section "Contraindications").

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. According to epidemiological studies, the use of drugs inhibiting prostaglandin synthesis in early pregnancy increases the risk of miscarriage, congenital heart defects, and gastroschisis. The absolute risk of cardiovascular anomalies increases from <1% to approximately 1.5%. The risk is believed to increase with higher drug doses and longer treatment duration. Animal studies have shown that prostaglandin synthesis inhibitors increase embryonic loss before and after implantation and embryonic/fetal mortality. Furthermore, in animals receiving prostaglandin synthesis inhibitors during organogenesis, increased incidences of various anomalies, including cardiovascular, were observed. However, animal studies did not show reproductive toxicity of dexketoprofen trometamol. 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 ductus arteriosus constriction have been reported after maternal use of the drug in the second trimester, most of which resolved after discontinuation of treatment. Therefore, dexketoprofen trometamol may be prescribed during the first and second trimesters of pregnancy only if absolutely necessary. Women planning pregnancy or in the first and second trimesters of pregnancy should use the lowest effective dose of dexketoprofen trometamol for the shortest possible duration. Prenatal monitoring for oligohydramnios and fetal ductus arteriosus 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 ductus arteriosus constriction is detected.

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

• cardiopulmonary toxic syndrome (constriction/occlusion of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above);
• at the end of pregnancy for both mother and child;
• prolonged bleeding time (due to inhibition of platelet aggregation), which may occur even with low doses;
• delayed uterine contractions, leading to delayed or prolonged labor.

Breastfeeding period

There are no data on the passage of dexketoprofen into breast milk. The drug is contraindicated during breastfeeding (see section "Contraindications").

Fertility

Like other NSAIDs, dexketoprofen trometamol may reduce female fertility and is therefore 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 drowsiness may occur during dexketoprofen use. 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").

Adults. The recommended dose is 50 mg administered at 8–12 hour intervals. If necessary, the repeat dose may be given after 6 hours. The maximum daily dose should not exceed 150 mg. The drug 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 drug 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 of dexketoprofen (maximum daily dose of 50 mg) is recommended in patients with mild renal impairment.

Hepatic impairment. In patients with mild to 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 drug is contraindicated in patients with severe hepatic disease (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 drug is contraindicated in patients with moderate to severe renal impairment (creatinine clearance < 59 mL/min).

Children and adolescents. The drug 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 should be prepared under aseptic conditions and protected from exposure to natural daylight. The prepared solution must be clear. The infusion should be administered intravenously slowly over 10–30 minutes.

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

Dexketoprofen 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 drug may only be mixed with medicinal products specified above. After drawing the drug from the ampoule, it should be administered immediately when used intramuscularly or as an intravenous bolus.

No change in active ingredient content due to adsorption has been observed during storage of diluted solutions in polyethylene bags or in administration devices made of ethylene-vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

The drug is intended for single use only; any unused portion of the prepared solution should be discarded. Before administration, the solution should be visually inspected to ensure it is clear and colorless. Solutions containing particulate matter must not be used.

Children.

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

Overdose.

Symptoms. The clinical picture of overdose is not well known. Similar medicinal products may cause gastrointestinal disorders (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, dizziness, disorientation, headache).

Treatment. In case of accidental overdose, symptomatic treatment appropriate to the patient’s condition should be initiated immediately. Trometamol salt of dexketoprofen is eliminated from the body by dialysis.

Adverse reactions.

The table below lists adverse reactions by system organ class and frequency of occurrence, which are considered at least possible in relation to dexketoprofen trometamol based on clinical trial data, as well as adverse reactions reported during the post-marketing period.

Gastrointestinal disorders were observed most frequently.

Peptic ulcer, 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, hematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may occur during treatment with dexketoprofen. Gastritis has been reported less frequently. Edema, arterial hypertension, and heart failure, which may be caused by NSAID use, have also been observed. As with other NSAIDs, the following adverse reactions may occur: aseptic meningitis, which generally occurs in patients with systemic lupus erythematosus or mixed connective tissue diseases, and blood disorders (purpura, aplastic and hemolytic anemia; rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are possible.

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Incompatibilities.

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

Diluted infusion solutions prepared as described in the section "Dosage and administration" must not be mixed with promethazine or pentazocine.

Packaging.

2 mL in a vial. 5 vials in a blister pack and cardboard box.

Prescription status. Prescription only.

Manufacturer.

Abhil Laboratories Private Limited.

Manufacturer's address and location of its business operations.

Village Bhagwanpur, Tehsil Dera Bassi, District Sahibzada Ajit Singh Nagar, Punjab – 140507, India.