Kydex inject

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KAYDEX INJECT (KEYDEXINJECT)

Composition:

Active substance: dexketoprofen trometamol;

1 ml of injectable solution contains dexketoprofen trometamol 36.9 mg, equivalent to dexketoprofen 25 mg (1 ampoule of 2 ml 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 solution.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Dexketoprofen.

ATC code M01A E17.

Pharmacological Properties

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

Mechanism of Action

The mechanism of action of NSAIDs is based on 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. Additionally, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the drug.

Pharmacodynamics

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 action of dexketoprofen trometamol following intramuscular or intravenous administration in patients with moderate to severe pain has been studied in various 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 typically 8 hours. Clinical studies have shown that the use of dexketoprofen trometamol allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. In patients receiving morphine via a patient-controlled analgesia device for postoperative pain relief, co-administration of dexketoprofen trometamol resulted in a significantly lower morphine requirement (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 proportional to the dose.

Distribution

Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen is approximately 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 with 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 the absence of drug accumulation.

Biotransformation and Elimination

The 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 the absence of in vivo conversion of the drug to the R-(-) optical isomer in humans.

Elderly Patients

After administration of single and repeated doses, the extent of drug exposure in healthy elderly 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 systemic 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 included fecal blood, reduced body weight gain, and at the highest dose, gastrointestinal lesions 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 gastrointestinal 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;
• patients in whom administration of substances with similar action, 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, Keyedex Inject is contraindicated for neuroaxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other types of interactions.

Concomitant use of the following agents with NSAIDs is not recommended:

• other NSAIDs (including selective cyclooxygenase-2 inhibitors), including salicylates at 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 platelet function inhibition and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under physician supervision with careful monitoring of relevant laboratory parameters;
• heparins: increased risk of bleeding (due to platelet function inhibition and damage to the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under physician 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 drug;
• high-dose methotrexate (≥15 mg weekly): 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 agents with NSAIDs 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 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 weekly): due to reduced renal clearance of methotrexate under NSAID therapy, its overall negative effect on the blood system is enhanced. During the first weeks of concomitant use, weekly blood tests are required. Even with mild renal impairment or in elderly patients, treatment should be under strict physician supervision;
• 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 impact on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. Blood tests and reticulocyte count should be performed within 1–2 weeks after starting NSAID treatment;
• sulfonylurea agents: NSAIDs can enhance the hypoglycemic effect of these agents by displacing sulfonylureas from plasma protein binding sites.

Potential interactions should be considered when using the following agents:

• 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 (SSRIs): increased risk of gastrointestinal bleeding;
• probenecid: possible increase in dexketoprofen plasma concentration, likely due to inhibition of renal tubular secretion and glucuronic acid 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 medical abortion agents;
• quinolone antibiotics: animal studies have shown that high-dose quinolone derivatives used in combination 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 the potential impact of concomitant use;
• deferasirox: when used concomitantly with NSAIDs, the risk of gastrointestinal toxicity may increase. Close 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. In patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), NSAID use should be avoided for two days before and two days after pemetrexed administration.

Special precautions.

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

Masking symptoms of underlying infections

Kedex Inject may mask symptoms of infectious diseases, potentially leading to delayed initiation of appropriate treatment and worsening of the disease course. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If Kedex Inject is used for fever or pain relief during infection, monitoring for infectious disease progression is recommended. When treatment is administered outside a medical facility, patients should consult a physician if symptoms persist or worsen.

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 precursor symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer (especially complicated by bleeding or perforation), and in elderly patients.

Elderly patients: Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Treatment in these patients should be initiated at the lowest possible dose. As with all NSAIDs, patients with a history of esophagitis, gastritis, and/or peptic ulcer should ensure these conditions are in remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for possible gastrointestinal complications during treatment, particularly gastrointestinal bleeding. NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), due to the risk of exacerbation. For such patients and those taking low-dose acetylsalicylic acid or other agents increasing gastrointestinal adverse reaction risk, 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 drug should be prescribed with caution to patients concurrently using agents that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents like acetylsalicylic acid.

Renal safety

The drug should be used with caution in patients with impaired renal function, as NSAIDs may worsen renal function, cause fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or those at risk of hypovolemia. Adequate fluid intake should be maintained during treatment to prevent dehydration, which may exacerbate renal toxicity. Like other NSAIDs, the drug 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 safety

The drug should be used with caution in patients with impaired liver function. As with other NSAIDs, the drug may cause transient and mild elevations in certain liver parameters, as well as marked increases in AST and ALT activity. If such elevations occur, treatment should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with arterial hypertension and/or mild to moderate heart failure require monitoring and medical advice. Particular caution is required in patients with a history of heart disease, especially those with prior episodes of heart failure (as the drug increases the risk of heart failure development), due to fluid retention and edema associated with NSAID use. Clinical studies and epidemiological data suggest a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) with some NSAIDs, particularly at high doses and prolonged use. Data to rule out such risk with dexketoprofen are insufficient. Therefore, dexketoprofen should be prescribed only after careful patient assessment in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease. Similarly careful assessment is required before initiating long-term treatment in patients with cardiovascular risk factors (e.g., 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 prophylactic doses of low-molecular-weight heparin in the postoperative period has been studied in clinical trials, with no effect on coagulation parameters observed. However, patients receiving dexketoprofen trometamol concurrently with agents affecting hemostasis (e.g., warfarin, other coumarins, 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 NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk appears to occur early in treatment, with most cases developing within the first month of therapy. If skin rashes, signs of mucosal involvement, or other signs of hypersensitivity occur, Kedex Inject should be discontinued.

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 long-term 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 Kedex Inject, treatment should be discontinued. 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 compared to other patients. This drug 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 to exclude the role of NSAIDs in exacerbating this infectious process are currently lacking. Therefore, Kedex Inject is not recommended during varicella.

Kedex Inject 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 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.

Each ampoule of Kedex Inject 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. The drug may have adverse effects in individuals with alcoholism. Ethanol content should be considered when using the drug in pregnant women, breastfeeding women, children, and patients at risk, such as those with liver disease or 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 Kedex Inject 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 the use of drugs inhibiting prostaglandin synthesis in early pregnancy increases the risk of miscarriage and fetal congenital abnormalities, including cardiac defects and abdominal wall defects. The absolute risk of cardiovascular malformations increases from <1% to approximately 1.5%. The risk is considered to increase with higher drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors have caused increased pre- and post-implantation losses and elevated embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal developmental abnormalities, including cardiovascular anomalies, has been 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 treatment initiation 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 treatment cessation. Therefore, dexketoprofen trometamol may be prescribed during the first and second trimesters only if absolutely necessary. When prescribing dexketoprofen trometamol to women planning pregnancy or during the first and second trimesters, the lowest effective dose for the shortest possible duration should be used. Prenatal monitoring for oligohydramnios and fetal arterial duct 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 fetal arterial duct constriction is detected.

During the third trimester, all prostaglandin synthesis inhibitors cause:

Risks for the fetus:

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

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

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

Breastfeeding

There are no data on the passage of dexketoprofen into breast milk. Kedex Inject 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 Kedex Inject. In such cases, the ability to react quickly, orient in traffic situations, and drive vehicles or operate machinery may be impaired.

Method of Administration and Dosage

Adults. The recommended dose is 50 mg administered at 8–12 hour intervals. If necessary, the next dose may be given after 6 hours. The maximum daily dose should not exceed 150 mg. Kaidex Inject is intended for short-term use only and should be administered only during the period of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible, if feasible. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use"). In 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 is recommended: the maximum daily dose should be limited to 50 mg 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 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 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, avoiding exposure to natural daylight. The prepared solution should be clear. The infusion should be administered intravenously slowly over 10–30 minutes.

Kaidex Inject 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 injection (bolus administration).

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.

Kaidex Inject 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.

When administered intramuscularly or by intravenous bolus, the drug should be administered immediately after being drawn from the ampoule.

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 ethyl vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

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

Adverse reactions.

The table below lists the adverse reactions by organ systems 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 after the marketing of the medicinal product Kedex Inject.

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, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may develop during treatment with the drug. Gastritis has been observed less frequently. Edema, arterial hypertension, and heart failure, possibly related to the use of NSAIDs, have also been reported. 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; agranulocytosis and bone marrow hypoplasia are rare). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are also possible.

According to results of clinical trials 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 drug registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product.

Healthcare professionals should report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions. Store protected from light in the original packaging at a temperature not exceeding 25 °C. After dilution, the solution may be stored for 24 hours at a temperature of 2 to 8 °C. Keep out of reach and sight of children.

Incompatibilities.

Kedex Inject 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 "Administration 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. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of manufacturing activities.

36 Severin Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.