Dexketoprofen

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEKSKETOPROFEN

Composition:

Active substance: dexketoprofen;

1 ml of solution contains 25 mg of dexketoprofen (as dexketoprofen trometamol);

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

Pharmaceutical form. Solution for injection.

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.

Pharmacodynamics.

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 non-steroidal anti-inflammatory drugs (NSAIDs).

Its mechanism of action is based on reducing the synthesis of prostaglandins by inhibiting cyclooxygenase activity. Specifically, it inhibits the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2, 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. Dexketoprofen has been shown to inhibit both cyclooxygenase-1 and cyclooxygenase-2 activity. It has been established that dexketoprofen produces a pronounced analgesic effect with a rapid onset, reaching its maximum within the first 45 minutes, in various types of pain, including pain associated with surgical procedures (orthopedic and gynecological surgeries, abdominal surgeries), musculoskeletal pain (acute back pain), and renal colic. The duration of analgesic effect after administration of 50 mg of dexketoprofen typically lasts 8 hours. It is known that the use of dexketoprofen allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. When patients receiving morphine for postoperative pain relief via a patient-controlled analgesia device were also given dexketoprofen, they required significantly less morphine (by 30–45%) compared to patients who received placebo alongside morphine.

Pharmacokinetics.

After intramuscular administration, maximum concentration (Cmax) of dexketoprofen is reached on average within 20 minutes (range 10–45 minutes). It has been demonstrated that following single intramuscular or intravenous administration of 25–50 mg dexketoprofen, the area under the concentration-time curve (AUC) is proportional to the dose. Multiple-dose pharmacokinetic studies have shown that AUC and Cmax after the last intramuscular or intravenous dose do not differ from those after single administration, indicating absence of accumulation. 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, while the elimination half-life ranges from 1 to 2.7 hours. Metabolism of dexketoprofen occurs mainly via conjugation with glucuronic acid, followed by renal excretion. After administration, only the S-(+) optical isomer is detected in urine, indicating no transformation of the drug into the R-(–) optical isomer. Following single and multiple dosing, exposure to the drug in elderly healthy volunteers (aged 65 years and older) was significantly higher (up to 55%) compared to younger individuals, although no statistically significant differences were observed in maximum concentration or time to reach it. The mean elimination half-life increased (by up to 48%), and total clearance decreased.

Preclinical safety data

Standard preclinical studies—including pharmacological safety, genotoxicity, and immunopharmacology assessments—did not reveal any special hazard for humans. Chronic toxicity studies in animals identified the no-observed-adverse-effect level (NOAEL), which was twice the recommended human dose. When higher doses were administered to monkeys, the main adverse reactions observed were fecal blood, reduced body weight gain, and, at the highest dose, gastrointestinal 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 development or indirectly via harmful effects on the gastrointestinal tract of the mother.

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 back (spinal) pain.

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product;
• if substances of similar action, e.g., acetylsalicylic acid or other NSAIDs, provoke in the patient an onset of bronchial asthma attacks, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria, or angioedema;
• if during treatment with ketoprofen or fibrates the patient experienced photoallergic or phototoxic reactions;
• gastrointestinal bleeding or perforation in history related to previous NSAID therapy;
• active phase of peptic ulcer or gastrointestinal bleeding, or any gastrointestinal bleeding, ulcer, or perforation in history;
• chronic dyspepsia;
• other active bleeding or coagulation disorders;
• 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;
• severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake);
• third trimester of pregnancy and breastfeeding period.

Due to ethanol content, the medicinal product must not be used for neuroaxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other forms of interaction.

The following combinations with dexketoprofen are not recommended:

Other NSAIDs. Concurrent use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to mutual potentiation of their effects. Concomitant use of other NSAIDs, including high-dose salicylates (≥ 3 g per day), with dexketoprofen is not recommended.

Anticoagulants. NSAIDs enhance the effect of anticoagulants such as warfarin due to high plasma protein binding of dexketoprofen, as well as inhibition of platelet function and damage to gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under strict medical supervision and with appropriate laboratory monitoring.

Heparin. The risk of bleeding increases (due to inhibition of platelet function and damage to gastric and duodenal mucosa) when NSAIDs are used concomitantly with heparin. If concomitant use is necessary, it should be performed under strict medical supervision and with appropriate laboratory monitoring.

Corticosteroids. Concomitant use of the medicinal product with corticosteroids increases the risk of gastrointestinal ulceration and gastrointestinal bleeding.

Lithium. Some NSAIDs increase lithium blood levels, potentially leading to toxicity (due to reduced renal excretion of lithium). Therefore, lithium blood levels should be monitored at the initiation of dexketoprofen therapy, during dose adjustments, and upon discontinuation.

High-dose methotrexate (more than 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. The toxicity of these substances may be increased when used concomitantly with the medicinal product Dexketoprofen.

Dexketoprofen should be used with caution in combination with the following medicinal products:

• Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycosides, 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 drugs that inhibit cyclooxygenase with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycosides may worsen renal function, although this is usually reversible. When using dexketoprofen concomitantly with any diuretic, ensure the patient is not dehydrated and monitor renal function at the beginning of treatment.
• Low-dose methotrexate (less than 15 mg per week): due to reduced renal clearance of methotrexate under NSAID therapy, its overall negative effect on the blood system is enhanced. During the first weeks of concomitant use, weekly blood tests are required. Treatment should be closely supervised by a physician, even in cases of mild renal impairment and in elderly patients.
• Pentoxifylline: there is a risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently.
• Zidovudine: there is a risk of increased toxic effect on erythrocytes due to effects on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. A blood test and reticulocyte count should be performed 1–2 weeks after starting treatment with 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: increased nephrotoxicity may occur due to NSAID effects on renal prostaglandins. Renal function should be monitored during combination therapy.
• Thrombolytic agents: the risk of bleeding is increased.
• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): the risk of gastrointestinal bleeding is increased.
• Probenecid: increased plasma concentration of dexketoprofen is possible, likely due to inhibition of renal tubular secretion and glucuronidation of the drug, requiring dose adjustment of dexketoprofen.
• Cardiac glycosides: NSAIDs may increase glycoside plasma concentrations.
• Mifepristone: there is a theoretical risk of altered mifepristone efficacy under the influence of prostaglandin synthetase inhibitors. Limited data suggest that concomitant use of the medicinal product on the day of prostaglandin administration does not negatively affect mifepristone or prostaglandin efficacy regarding cervical ripening or uterine contractility, nor does it reduce the clinical effectiveness of medical abortion.
• Quinolones: animal studies indicate that high-dose quinolone derivatives used in combination with dexketoprofen increase the risk of seizures.
• Tenofovir: concomitant use with dexketoprofen may increase plasma urea nitrogen and creatinine concentrations; therefore, renal function should be monitored to assess potential synergistic effects of these medicinal products.
• Deferasirox: concomitant use with dexketoprofen increases the risk of gastrointestinal toxicity. Close patient monitoring is required when using these drugs together.
• Pemetrexed: concomitant use with dexketoprofen may reduce pemetrexed elimination; therefore, particular caution is required when using high-dose dexketoprofen. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid using the medicinal product for two days before and two days after pemetrexed administration.

Special precautions for use.

Use with caution in patients with a history of allergic conditions. Avoid concomitant use of this medicinal product 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 control symptoms.

Gastrointestinal effects

Gastrointestinal bleeding, ulceration, and perforation, sometimes fatal, have been reported during NSAID therapy at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events. If gastrointestinal bleeding 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, particularly if complicated by bleeding or perforation, and in elderly patients.

The incidence of adverse reactions associated with NSAID use, particularly gastrointestinal bleeding and perforation, sometimes fatal, is higher in elderly patients. Treatment in such patients should be initiated with the lowest effective dose. The medicinal product Dexketoprofen should be prescribed with caution in patients with a history of gastrointestinal disorders, as there is a risk of exacerbation.

Before initiating treatment with dexketoprofen trometamol, patients with a history of esophagitis, gastritis, and/or peptic ulcer should be evaluated to ensure these conditions are in remission. Patients with symptoms of gastrointestinal pathology, including those with a history of such disorders, require monitoring of gastrointestinal status during treatment for possible complications, particularly gastrointestinal bleeding. Dexketoprofen should be prescribed with caution in patients with a history of inflammatory bowel disease (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 that increase gastrointestinal risk, consider concomitant therapy with gastroprotective agents, such as misoprostol or proton pump inhibitors.

Patients, especially elderly individuals, with a history of gastrointestinal adverse reactions should be advised to inform their physician about any unusual gastrointestinal symptoms, particularly gastrointestinal bleeding, especially at the beginning of treatment.

Renal effects

Dexketoprofen should be prescribed with caution in patients with impaired renal function, as the drug may cause worsening renal function, fluid retention, and peripheral edema. Due to the increased risk of nephrotoxicity, dexketoprofen should be used cautiously in patients receiving diuretic therapy or those at risk of hypovolemia. Adequate fluid intake should be maintained during treatment to prevent dehydration and associated increased toxicity.

Like all NSAIDs, dexketoprofen may increase blood urea nitrogen and creatinine levels. Similar to other inhibitors of prostaglandin synthesis, 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 effects

The medicinal product should be used with caution in patients with impaired liver function. Like other NSAIDs, dexketoprofen may cause transient, mild elevations in liver function tests, as well as significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). If such increases occur, the drug should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular effects

Patients with arterial hypertension and/or mild to moderate congestive heart failure should be closely monitored due to possible fluid retention and development of peripheral edema.

Particular caution is required when treating patients with a history of heart disease, especially those with prior episodes of heart failure, as dexketoprofen use may increase the risk of heart failure (fluid retention and edema associated with NSAID use have been reported).

Clinical and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and over prolonged periods, may slightly increase the risk of thrombotic events such as myocardial infarction or stroke. Data are insufficient to exclude this risk with dexketoprofen. Therefore, dexketoprofen should be prescribed only after careful evaluation in patients with uncontrolled arterial hypertension, congestive heart failure, confirmed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Careful assessment is also recommended before initiating long-term treatment in patients with cardiovascular risk factors such as arterial hypertension, hyperlipidemia, diabetes mellitus, or smoking.

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. It is known that concomitant use of dexketoprofen trometamol and low-molecular-weight heparin at prophylactic doses in the postoperative period does not affect coagulation parameters. However, patients receiving dexketoprofen trometamol concomitantly with agents affecting hemostasis, such as warfarin, other coumarins, or heparins, should be closely monitored.

Cardiovascular system disturbances occur most frequently in elderly patients.

Skin reactions

Very rare cases of serious skin reactions (some fatal) have been reported during NSAID therapy, including exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis. The highest risk occurs early in treatment, particularly during the first month. If skin rashes, signs of mucosal involvement, or other signs of hypersensitivity occur, the drug should be discontinued.

Other information

Special caution is required when prescribing the drug to patients:

• with hereditary disorders of porphyrin metabolism (e.g., acute intermittent porphyria);
• with dehydration;
• immediately after major surgical procedures.

If prolonged use of dexketoprofen is considered necessary by the physician, liver and kidney function should be monitored regularly.

Very rare cases of severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If signs of severe hypersensitivity reactions occur after drug administration, 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 have a higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to other patients. This medicinal product may trigger asthma attacks or bronchospasm, especially in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications of the skin and soft tissues may occur during varicella. Currently, a contributory role of dexketoprofen in exacerbating this infectious process cannot be excluded. Therefore, its use is not recommended in varicella.

The drug should be administered with caution in patients with blood dyscrasias, systemic lupus erythematosus, and mixed connective tissue diseases.

Masking of infectious disease symptoms

Dexketoprofen may mask symptoms of infectious diseases, potentially delaying appropriate treatment and worsening infection outcomes. This has been observed in bacterial pneumonia and bacterial complications of varicella. When using this medicinal product to relieve pain associated with infection, the course of the infectious disease should be monitored. In outpatient settings, patients should consult a physician if infection symptoms persist or worsen.

In rare cases, varicella may lead to serious infectious complications of the skin and soft tissues. Currently, the influence of dexketoprofen on the exacerbation of these infections cannot be excluded. Therefore, it is advisable to avoid using the drug in varicella.

Each ampoule of the medicinal product Dexketoprofen contains 200 mg of ethanol (per dose), equivalent to 5 mL of beer or 2.08 mL of wine. The product may have adverse effects in individuals with alcoholism. The ethanol content should be considered when using the drug during the first and second trimesters of pregnancy, in high-risk patients (e.g., those with liver disease), and in patients with epilepsy. Dexketoprofen contains less than 1 mmol of sodium (23 mg) per dose, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

The use of this medicinal product is contraindicated during the third trimester of pregnancy and during breastfeeding (see section "Contraindications").

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. It is known that drugs inhibiting prostaglandin synthesis, when used in early pregnancy, increase the risk of miscarriage and fetal congenital heart defects and abdominal wall defects. For example, 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 duration of therapy.

In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and elevated embryofetal mortality. In addition, when administered during organogenesis, prostaglandin synthesis inhibitors increased the incidence of fetal developmental abnormalities, including cardiovascular malformations. However, animal studies with dexketoprofen trometamol did not reveal toxicity to reproductive organs.

From the 20th week of pregnancy, dexketoprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction during the second trimester associated with dexketoprofen use, most of which were reversible after stopping treatment.

Dexketoprofen should not be prescribed during the first and second trimesters of pregnancy except in cases of extreme necessity. If dexketoprofen is used in women attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of dexketoprofen exposure, starting from the 20th week of pregnancy. The drug should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors cause:

Risks to the fetus:

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

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

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

Dexketoprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period

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

Fertility

Like all other NSAIDs, dexketoprofen may impair female fertility; therefore, it is not recommended for use in women attempting to conceive. If a woman experiences infertility or is undergoing fertility investigations, discontinuation of the drug should be considered.

Ability to influence reaction speed when driving or operating machinery.

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

Method of Administration and Dosage.

Adults

The recommended dose is 50 mg every 8–12 hours. If necessary, the repeat dose may be administered after 6 hours. The maximum daily dose should not exceed 150 mg. Dexketoprofen is intended for short-term treatment and should only be used 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.

For moderate to severe postoperative pain, dexketoprofen 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 reduction in renal function, a lower maximum daily dose of 50 mg is recommended in patients with mild renal impairment.

Patients with 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. Dexketoprofen is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Patients with Renal Impairment

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

Children and Adolescents

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

Intramuscular Administration

The contents of one ampoule (2 mL) should be administered slowly and 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’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 over 10–30 minutes. Avoid exposure of the prepared solution to natural daylight.

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

Dexketoprofen must not be mixed in the infusion solution with promethazine or pentazocine.

Intravenous Injection (Bolus Administration)

If necessary, the contents of one ampoule (2 mL of injection solution) may be administered intravenously over at least 15 seconds.

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

Dexketoprofen must not be mixed in small volumes (e.g., in a syringe) with dopamine, promethazine, pentazocine, pethidine, or hydrocortisone solutions due to the formation of a white precipitate.

When administered intramuscularly or intravenously by injection, the medicinal product should be administered immediately after being drawn from the ampoule. The solution for intravenous infusion should be used immediately after preparation.

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

Children.

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

Overdose.

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

Adverse Reactions

The following frequency categories are used to classify adverse reactions:

Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), or frequency not known (cannot be estimated from available data).

The adverse reactions listed below are classified by system organ class and frequency of occurrence. These reactions have been associated with dexketoprofen trometamol in clinical trials, at least possibly, as well as adverse reactions reported after marketing of dexketoprofen trometamol products.

Blood and lymphatic system disorders

Uncommon: anaemia.
Very rare: neutropenia, thrombocytopenia.

Immune system disorders

Rare: laryngeal oedema.
Very rare: anaphylactic reactions, including anaphylactic shock.

Metabolism and nutrition disorders

Rare: hyperglycaemia, hypoglycaemia, hypertriglyceridaemia, anorexia, loss of appetite.

Psychiatric disorders

Uncommon: insomnia, restlessness.

Nervous system disorders

Uncommon: headache, dizziness, somnolence.
Rare: paraesthesia, loss of consciousness.

Eye disorders

Uncommon: blurred vision.

Ear and labyrinth disorders

Uncommon: vertigo.
Rare: tinnitus.

Cardiac disorders

Uncommon: palpitations.
Rare: extrasystoles, tachycardia.

Vascular disorders

Uncommon: arterial hypotension, flushing.
Rare: arterial hypertension, superficial thrombophlebitis.

Respiratory, thoracic and mediastinal disorders

Rare: bradypnoea.
Very rare: bronchospasm, dyspnoea.

Gastrointestinal disorders

Common: nausea, vomiting.
Uncommon: abdominal pain, dyspepsia, diarrhoea, constipation, vomiting with blood, dry mouth.
Rare: peptic ulcer, gastrointestinal bleeding or perforation.
Very rare: pancreatitis.

Hepatobiliary disorders

Rare: hepatocellular injury.
Very rare: hepatocellular pathology.

Skin and subcutaneous tissue disorders

Uncommon: dermatitis, pruritus, rash, increased sweating.
Rare: urticaria, acne.
Very rare: Stevens–Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), angioneurotic oedema, facial swelling, photosensitisation.

Musculoskeletal and connective tissue disorders

Rare: muscle rigidity, joint stiffness, muscle cramps, back pain.

Renal and urinary disorders

Rare: acute renal failure, polyuria, renal pain, ketonuria, proteinuria.
Very rare: nephritis, nephrotic syndrome.

Reproductive system and breast disorders

Rare: menstrual disorders, prostate function disorders.

General disorders and administration site conditions

Common: injection site pain, injection site reactions including inflammation, haematoma, bleeding.
Uncommon: chills, fatigue, pain, shivering, asthenia, malaise.
Rare: tremor, peripheral oedema.

Investigations

Rare: liver function test abnormalities.

The most frequently reported adverse reactions were gastrointestinal disorders.

Peptic ulceration, gastrointestinal perforation or bleeding, sometimes fatal, may occur, particularly in the elderly. Available data indicate that nausea, vomiting, diarrhoea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melaena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn’s disease may occur during treatment. Gastritis has been reported less frequently. Oedema, arterial hypertension, and heart failure may also occur and may be related to the use of dexketoprofen. As with other NSAIDs, adverse reactions such as aseptic meningitis (generally in patients with systemic lupus erythematosus or mixed connective tissue disorders) and blood disorders (purpura, aplastic and haemolytic anaemia, rarely agranulocytosis and bone marrow hypoplasia) may occur. Bullous reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis (very rare), have also been reported.

Clinical trial results and epidemiological data indicate that the use of certain NSAIDs, particularly at high doses and over long durations, may slightly increase the risk of thrombotic events such as myocardial infarction and stroke.

Reporting of Adverse Reactions

Reporting suspected adverse reactions after a medicinal product is authorised is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

After dilution, the solution should be stored for up to 24 hours at 2–8 °C.

Incompatibilities

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

Diluted infusion solutions, as prepared according to the section "Method of administration and dosage. Intravenous infusion", 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 cardboard box.

Prescription status

Prescription only.

Manufacturer

Steril-Djen Life Sciences (P) Ltd.

Manufacturer's address and place of business

No. 45, Mangalam Main Road, Villianur Commune, Puducherry, 605110, India.