Dexketoprofen abril

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXKETOPROFEN ABRYL (DEXKETOPROFENABRYL)

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 physicochemical properties: clear, colorless solution.

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 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. 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

Inhibitory effects of dexketoprofen trometamol on the activity of cyclooxygenase-1 and cyclooxygenase-2 have 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 pronounced analgesic effects. The analgesic effect of dexketoprofen trometamol following intramuscular or intravenous administration in patients with moderate to severe pain intensity 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 analgesia following administration of 50 mg of dexketoprofen trometamol typically lasts 8 hours. Clinical studies have shown that the use of dexketoprofen allows a significant reduction in opioid dosage when used concomitantly for postoperative pain management. When patients receiving morphine via a patient-controlled analgesia device for postoperative pain relief were also administered dexketoprofen trometamol, their morphine requirements were significantly lower (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics

Absorption

Following 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 ranges from 1 to 2.7 hours.

Pharmacokinetic studies with repeated administration of the drug demonstrated that maximum concentration (Cmax) and AUC after the last intramuscular or intravenous dose did not differ from those observed 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 conversion of the drug into the R-(-) optical isomer in humans.

Elderly Patients

Following administration of single and repeated 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 total systemic clearance was reduced.

Preclinical Safety Data

Standard preclinical studies—including pharmacological safety, genotoxicity, and immunopharmacology assessments—did not reveal any special hazard to humans. Chronic toxicity studies in animals identified a no-observed-adverse-effect level (NOAEL) that was twice 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 (GI) tract pathologies such as erosions. These reactions occurred at doses where drug exposure was 14–18 times higher than the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Like all NSAIDs, dexketoprofen may cause embryonic or fetal death in animals, either directly by affecting embryofetal development or indirectly via maternal gastrointestinal toxicity.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product;
• in patients in whom administration of substances with similar activity, for example acetylsalicylic acid or other NSAIDs, induces 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 (10–15 points on the Child-Pugh scale);
• 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 salicylates in high doses (≥ 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 effect of anticoagulants, such as warfarin, due to the high degree of plasma protein binding of dexketoprofen and 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 the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under medical supervision with careful monitoring of appropriate laboratory parameters.
• Corticosteroids. Increased risk of 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 therapy, during dose adjustments, or upon discontinuation.
• High-dose methotrexate (≥ 15 mg per week). Due to reduced renal clearance of methotrexate under NSAID therapy, its overall negative effect on the blood system is enhanced.
• 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., due to dehydration or in 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 overall negative effect on the blood system is enhanced. Weekly blood tests are required during the first weeks of concomitant use. Treatment should be closely supervised by a physician, even in cases of mild renal impairment or in elderly patients.
• Pentoxifylline. 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 within 1–2 weeks after starting dexketoprofen.
• Sulfonylurea agents. 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 by inhibiting 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. Increased risk of gastrointestinal bleeding.
• Probenecid. Possible increase in plasma concentration of dexketoprofen, 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 due to 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 for medical termination of pregnancy.
• Quinolone antibiotics. Animal studies indicate that high-dose quinolone derivatives combined with NSAIDs increase 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 potential effects of combined use.
• Deferasirox. Risk of increased gastrointestinal toxicity when used concomitantly with NSAIDs. 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. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid using dexketoprofen for two days before and two days after pemetrexed administration.

Special precautions for use.

The drug should be used with caution in patients with a history of allergic conditions. Avoid using dexketoprofen in combination with other NSAIDs, including selective COX-2 inhibitors. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to improve symptoms.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, in some cases fatal, have been reported with the use of 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 develops, 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, particularly complicated by bleeding or perforation, as well as in elderly patients.

Elderly patients. Elderly patients have a higher 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 disease should ensure these conditions are in remission before starting therapy. Patients with existing gastrointestinal pathology, including history, require monitoring of gastrointestinal status during treatment for possible complications, particularly gastrointestinal bleeding. NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders (e.g., 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 risk, consider concomitant 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 initial stages of treatment.

Dexketoprofen should be prescribed with caution to patients concurrently using drugs 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 increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or those at risk of hypovolemia. During treatment, adequate fluid intake should be maintained to avoid dehydration, which may exacerbate renal toxicity. Like other NSAIDs, dexketoprofen may increase plasma urea nitrogen and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function disturbances occur most frequently in elderly patients.

Hepatic function impairment

The drug should be used with caution in patients with impaired liver function. As with 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 significant increases in these parameters occur.

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 supervision. Particular caution is advised in patients with a history of heart disease, especially previous episodes of heart failure (the drug increases the risk of heart failure), as NSAID treatment may lead to fluid retention and edema. Clinical studies and epidemiological data suggest that some NSAIDs (especially at high doses and long-term 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, dexketoprofen should be prescribed only after careful patient assessment in cases of uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Similarly careful assessment is required 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 concomitantly with drugs affecting hemostasis, such as warfarin, other coumarins, or heparins, require close medical supervision. Cardiovascular adverse events occur most frequently in elderly patients.

Skin reactions

There have been reports of very rare cases of serious skin reactions (some fatal) with NSAID use, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk appears to be during the initial stages of treatment, with most cases occurring within the first month. 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 delaying diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. When dexketoprofen is used 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 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, 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 with 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, especially in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications of skin and soft tissues may occur during varicella. Data excluding a role of NSAIDs in exacerbating this infection are lacking. Therefore, dexketoprofen is not recommended in varicella.

Dexketoprofen should be administered with caution in 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 soft tissue infections 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 drug 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 with alcoholism. Ethanol content should be considered when using in pregnant women, breastfeeding women, children, and patients at risk, e.g., with liver disease, as well as in patients with epilepsy.

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

Use during pregnancy or breastfeeding.

The use of the drug 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 malformations 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 lead to increased embryonic loss before and after implantation and embryonic/fetal mortality. Additionally, in animals receiving prostaglandin synthesis inhibitors during organogenesis, increased incidence of various anomalies, including cardiovascular, has been 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. Additionally, cases of fetal ductus arteriosus constriction have been reported after maternal use in the second trimester, most of which resolved after stopping treatment. Therefore, dexketoprofen trometamol may be prescribed during the first and second trimesters only if absolutely necessary. Women planning pregnancy or in the first and second trimesters should use the lowest effective dose of dexketoprofen trometamol for the shortest possible duration. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered if dexketoprofen is used for several days starting from the 20th gestational week. Pregnant women should discontinue dexketoprofen if oligohydramnios or 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 and 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 infertility or undergoing fertility investigations 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 Warnings and Precautions for Use").

Adults. The recommended dose is 50 mg every 8–12 hours. If necessary, the next dose may be administered after 6 hours. The maximum daily dose should not exceed 150 mg. The drug 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 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 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 drug 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 drug is contraindicated in patients with moderate or 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 slowly injected deeply into the muscle.

Intravenous infusion

For intravenous infusion, the contents of one ampoule (2 mL) should be diluted in 30–100 mL of 0.9% sodium chloride solution, glucose solution, or Ringer-lactate solution. The infusion solution must be prepared under aseptic conditions, avoiding exposure to natural daylight. The prepared solution should 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 dopamine, promethazine, pentazocine, pethidine, or hydroxyzine solutions, as precipitation may occur.

Diluted infusion solutions must not be mixed with promethazine or pentazocine. The drug may only be mixed with the medicinal products listed above. After drawing into a syringe from the ampoule, the drug should be administered immediately.

No changes in active substance content due to adsorption have 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 symptoms of overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (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 dexketoprofen 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 related to dexketoprofen trometamol, as well as adverse reactions reported during the post-marketing period.

Gastrointestinal disorders were observed most frequently.

The development of peptic ulcer, perforation, or gastrointestinal bleeding, sometimes with fatal outcome, 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 treatment with dexketoprofen. Gastritis is observed less frequently. Edema, arterial hypertension, and heart failure, which may be caused by NSAID use, 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 disorders (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), may also occur.

According to clinical studies 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 arterial thrombotic events such as myocardial infarction and stroke.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives, should report any 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.

Storage conditions.

Store at a temperature 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, meperidine, or hydroxyzine solutions, as precipitation may occur.

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

Packaging.

2 ml in an ampoule. 5 ampoules in a blister pack and cardboard box.

Prescription status. Prescription only.

Manufacturer.

Abhil Labortories Private Limited.

Manufacturer's address and location of its business operations.

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