INSTRUCTIONS for medical use of the medicinal product SERTOFEN (SERTOFEN)

Composition:

Active substance: dexketoprofen;

One ampoule (2 ml) of solution contains dexketoprofen (as dexketoprofen trometamol) 50 mg;

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

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

Pharmaceutical form. Injectable solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives. Dexketoprofen. ATC code M01AE17.

Pharmacological Properties.

Pharmacodynamics.

Dexketoprofen trometamol is a propionic acid salt exerting analgesic, anti-inflammatory, and antipyretic effects and belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs).

The mechanism of action of NSAIDs is based on reducing the synthesis of prostaglandins by inhibiting cyclooxygenase activity. Specifically, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2α, PGD2, as well as prostacyclin PGI2 and thromboxanes TxА2 and TxВ2 are formed. In addition, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of dexketoprofen. Its inhibitory effect on the activity of cyclooxygenase-1 and cyclooxygenase-2 has been demonstrated in laboratory animals and in humans.

Clinical studies in various types of pain have demonstrated that dexketoprofen has pronounced analgesic activity. Its analgesic effect after intramuscular and 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 began rapidly and reached its maximum within the first 45 minutes. The duration of analgesic effect after administration of 50 mg dexketoprofen is typically 8 hours. The use of dexketoprofen allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. Patients receiving morphine (via a patient-controlled analgesia device) along with dexketoprofen required significantly less morphine (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics.

Absorption

After intramuscular administration of dexketoprofen, maximum plasma concentration (Cmax) is reached approximately within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg, the area under the concentration-time curve (AUC) is dose-proportional. Pharmacokinetic studies with repeated dosing have shown that AUC and Cmax (mean peak value) after the last intramuscular or intravenous dose do not differ from those after single administration, indicating no accumulation of dexketoprofen.

Distribution

Similar to other drugs highly bound to plasma proteins (99%), the volume of distribution of dexketoprofen averages 0.25 L/kg. The distribution half-life is approximately 0.35 hours.

Metabolism

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

Elimination

The elimination half-life (T1/2) of dexketoprofen ranges from 1 to 2.7 hours.

Elderly Patients

After administration of single and multiple doses, the extent of exposure to dexketoprofen 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 were observed in maximum concentration (Cmax) or time to reach Cmax (tmax). The mean T1/2 was prolonged (by up to 48%), and total clearance was reduced.

Clinical Characteristics.

Indications.

Symptomatic treatment of moderate to severe acute pain when oral administration of dexketoprofen is not appropriate, for example, 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.
Asthmatic attacks, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema associated with previous use of drugs of similar action, such as acetylsalicylic acid or other NSAIDs.
Photoallergic or phototoxic reactions associated with prior use of ketoprofen or other fibrates.
History of gastrointestinal bleeding or perforation related to previous use of NSAIDs.
Active peptic ulcer/gastrointestinal bleeding, or history of gastrointestinal bleeding, ulcers, or perforations.
Chronic dyspepsia.
Crohn’s disease or ulcerative colitis.
Active gastrointestinal bleeding, other active bleeding, or increased bleeding tendency.
Hemorrhagic diathesis and other coagulation disorders.
Severe heart failure.
Moderate to severe renal impairment (creatinine clearance ≤59 mL/min).
Severe hepatic impairment (Child-Pugh score 10–15 points).
Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).
Third trimester of pregnancy.
Breastfeeding period.
Neuraxial (intrathecal or epidural) administration of the medicinal product (due to ethanol content).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of dexketoprofen with the following agents is not recommended.

Other NSAIDs (including selective cyclooxygenase-2 inhibitors), including salicylates at high doses (≥ 3 g/day): concomitant use of dexketoprofen with these agents increases the risk of gastrointestinal ulcers and gastrointestinal bleeding due to their mutually potentiating effects.
Anticoagulants: concomitant use with dexketoprofen enhances the effect of anticoagulants such as warfarin (due to the high degree of plasma protein binding of dexketoprofen, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, careful physician monitoring and monitoring of relevant laboratory parameters are required.
Heparins: concomitant use of dexketoprofen with these agents increases the risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa by dexketoprofen). If concomitant use is necessary, careful physician monitoring and monitoring of relevant laboratory parameters are required.
Corticosteroids: concomitant use of dexketoprofen with these agents increases the risk of gastrointestinal ulcers or gastrointestinal bleeding.
Lithium: concomitant use with NSAIDs (reported for several NSAIDs) increases plasma lithium levels, potentially leading to toxicity (reduced renal excretion of lithium). At the start of dexketoprofen treatment, during dose adjustment, or upon discontinuation, plasma lithium levels should be monitored.
High-dose methotrexate (≥ 15 mg per week): concomitant use with dexketoprofen reduces renal clearance of methotrexate and generally enhances its adverse effects on the blood system.
Hydantoin derivatives and sulfonamides: concomitant use with dexketoprofen enhances the toxicity of these agents.

Concomitant use of dexketoprofen with the following agents should be performed with caution.

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists: concomitant use with dexketoprofen reduces the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydration or elderly patients), concomitant use of agents that inhibit cyclooxygenase (including dexketoprofen) with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, which is usually reversible. When these agents are used concomitantly, ensure the patient is not dehydrated, and monitor renal function at the beginning of treatment.
Low-dose methotrexate (< 15 mg per week): concomitant use with dexketoprofen reduces renal clearance of methotrexate and generally enhances its adverse effects on the blood system. During the first weeks of concomitant use, weekly blood tests should be performed. Close physician monitoring is required for patients with even mild renal impairment and for elderly patients.
Pentoxifylline: concomitant use of dexketoprofen with pentoxifylline increases the risk of bleeding. When these agents are used concomitantly, monitoring should be intensified, and bleeding time should be checked more frequently.
Zidovudine: concomitant use of dexketoprofen with zidovudine increases the risk of toxic effects on erythrocytes due to effects on reticulocytes, leading to severe anemia after one week of NSAID use. If these agents are used concomitantly for 1–2 weeks, a blood test and reticulocyte count should be performed.
Sulfonylurea preparations: concomitant use with dexketoprofen enhances the hypoglycemic effect of sulfonylureas due to displacement of sulfonylureas from plasma protein binding sites.

When using dexketoprofen concomitantly with the following agents, potential interactions should be considered.

Beta-blockers: concomitant use with dexketoprofen may reduce the antihypertensive effect of beta-blockers (due to inhibition of prostaglandin synthesis).
Cyclosporine, tacrolimus: concomitant use with dexketoprofen may increase nephrotoxicity of these agents (due to the effect of dexketoprofen on renal prostaglandins). Renal function should be monitored when these agents are used concomitantly.
Thrombolytic agents: concomitant use of dexketoprofen with these agents increases the risk of bleeding.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): concomitant use of dexketoprofen with these agents increases the risk of gastrointestinal bleeding.
Probenecid: concomitant use with probenecid may increase plasma levels of dexketoprofen, likely due to inhibition of its renal tubular secretion and glucuronidation. Dose adjustment of dexketoprofen may be necessary when used concomitantly.
Cardiac glycosides: concomitant use with dexketoprofen may increase plasma levels of glycosides.
Mifepristone: theoretically, there is a risk of altered efficacy of mifepristone due to prostaglandin synthetase inhibitors. Limited data suggest that concomitant use of NSAIDs on the same day as prostaglandin does not adversely affect the efficacy of mifepristone or prostaglandin regarding cervical ripening or contractility, nor does it reduce the clinical efficacy of drugs for medical termination of pregnancy.
Quinolone antibiotics: animal studies have shown that concomitant use of high-dose quinolone derivatives with NSAIDs increases the risk of seizures.
Tenofovir: concomitant use with dexketoprofen may increase plasma levels of urea nitrogen and creatinine. Renal function should be monitored when these agents are used concomitantly.
Deferasirox: concomitant use of dexketoprofen with deferasirox may increase the risk of gastrointestinal toxicity. Close patient monitoring is required when these agents are used concomitantly.
Pemetrexed: concomitant use with dexketoprofen may reduce pemetrexed elimination. Particular caution is required when these agents are used concomitantly (especially with high-dose dexketoprofen). In patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), concomitant use of pemetrexed and dexketoprofen should be avoided for 2 days before and 2 days after pemetrexed administration.

Special precautions for use.

The medicinal product should be used with caution in patients with a history of allergic conditions.

Concomitant use of this medicinal product with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Adverse reactions of the medicinal product can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Gastrointestinal effects

Gastrointestinal bleeding, ulceration, or perforation, in some cases fatal, have been reported with all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders.

If gastrointestinal bleeding or ulceration occurs, administration of the medicinal product 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 if complicated by bleeding or perforation, and in elderly patients.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Treatment of such patients should begin with the lowest possible dose of the medicinal product.

As with all NSAIDs, patients with a history of esophagitis, gastritis, and/or peptic ulcer should ensure that these conditions are in remission before starting treatment.

During treatment with the medicinal product, patients with existing gastrointestinal symptoms or gastrointestinal disorders in their medical history should be monitored for possible gastrointestinal complications, particularly gastrointestinal bleeding.

The medicinal product should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation. NSAID use may trigger relapses of ulcerative colitis or Crohn's disease in patients in remission. For such patients and patients taking low-dose acetylsalicylic acid or other agents increasing the risk of gastrointestinal adverse reactions, concomitant therapy with protective agents such as misoprostol or proton pump inhibitors should be considered.

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

The medicinal product should be used with caution in patients who are concurrently taking agents that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

Renal effects

The medicinal product should be used with caution in patients with impaired renal function, as NSAIDs may cause deterioration of kidney function, fluid retention, and edema. Due to the increased risk of nephrotoxicity, the medicinal product should be used with caution in patients taking diuretics and in those in whom hypovolemia may develop.

During treatment with the medicinal product, patients should receive adequate fluid intake to avoid dehydration, which may exacerbate renal toxicity.

Like all NSAIDs, dexketoprofen may increase plasma concentrations of blood urea nitrogen and creatinine.

Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, leading to 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 and mild elevations in certain liver function parameters, as well as marked increases in AST and ALT activity. If significant elevations in these parameters occur, the medicinal product should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebral circulation effects

Patients with arterial hypertension and/or mild to moderate heart failure should be under close medical supervision during treatment with the medicinal product.

The medicinal product should be used with particular caution in patients with a history of heart disease, particularly those with previous episodes of heart failure (the risk of developing heart failure increases with dexketoprofen use), as fluid retention and edema may occur during NSAID treatment. Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for prolonged periods) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Data to exclude such risk with dexketoprofen use are insufficient.

The medicinal product may be used only after careful assessment of the patient's condition in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Similarly careful assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The concomitant use of dexketoprofen and low-molecular-weight heparin at prophylactic doses in the postoperative period has been studied in clinical trials, and no effect on coagulation parameters was observed.

However, patients receiving agents affecting hemostasis, such as warfarin, other coumarin derivatives, or heparins, should be under close medical supervision during treatment with the medicinal product. Cardiovascular system disturbances occur most frequently in elderly patients.

Skin effects

Serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported rarely during NSAID use. The highest risk is likely during the initial stages of treatment, with most cases occurring within the first month of therapy. If skin rashes, signs of mucosal involvement, or other symptoms of hypersensitivity occur, the medicinal product should be discontinued.

Other warnings

The medicinal product should be used with particular caution in patients with hereditary porphyrin metabolism disorders (e.g., acute intermittent porphyria), dehydration, or immediately after major surgical procedures.

With prolonged use of the medicinal product, liver and kidney function and blood cell counts should be monitored regularly.

Severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed very rarely during dexketoprofen use. If early signs of severe hypersensitivity reactions occur, the medicinal product should be discontinued. Depending on symptoms, any necessary treatment should be administered under medical supervision.

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

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

The medicinal product should be used with caution in patients with blood dyscrasias, systemic lupus erythematosus, and mixed connective tissue diseases.

Like other NSAIDs, dexketoprofen may mask symptoms of infectious diseases during its use. In isolated cases, activation of soft tissue infections has been reported during NSAID use. If bacterial infection symptoms develop or worsen, immediate medical attention should be sought.

Each ampoule of the medicinal product contains 12.35 vol.% ethanol, i.e., up to 200 mg per dose, equivalent to 5 ml of beer or 2.08 ml of wine per dose. The medicinal product may have a negative effect on individuals suffering from alcoholism. The ethanol content should be considered when using the product in pregnant women, breastfeeding women, children, patients at risk (e.g., liver disease), and patients with epilepsy.

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

Use during pregnancy or breastfeeding.

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

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. According to epidemiological studies, the use of drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage and congenital heart defects and abdominal wall defects in the fetus. The absolute risk of cardiovascular malformations increases from <1% to approximately 1.5%. The risk of such events is considered to increase with higher doses of dexketoprofen and longer duration of therapy. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and increased embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the incidence of fetal developmental abnormalities, including cardiovascular anomalies, increased. 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 after discontinuation of the drug.

During the first and second trimesters of pregnancy, the use of the medicinal product is possible only if absolutely necessary.

When used in women planning pregnancy or during the first and second trimesters of pregnancy, the lowest effective dose for the shortest possible duration should be used.

Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to dexketoprofen for several days starting from the 20th gestational week. The medicinal product should be discontinued if oligohydramnios is detected.

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

Risks for the fetus:

Cardio-pulmonary toxic syndrome (with closure of the ductus arteriosus and pulmonary hypertension);
Impaired renal function, which may progress to renal failure with oliguria (see above);

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

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

Breastfeeding period

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

Fertility

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

Ability to affect reaction speed when driving or operating machinery.

During treatment with dexketoprofen, dizziness, visual disturbances, or somnolence may occur. 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

Dosage

Adults

The recommended dose is 50 mg every 8–12 hours.

If necessary, a repeat dose may be administered after 6 hours.

The maximum daily dose should not exceed 150 mg.

The medicinal product is intended for short-term use and should only be administered 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, the medicinal product may be used, as indicated, at the same recommended doses in combination with opioid analgesics.

Elderly Patients

Dose adjustment is generally not required in elderly patients. However, due to physiological decline in renal function, a lower dose is recommended—specifically, the maximum daily dose should be limited to 50 mg in patients with mild renal impairment.

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. The use of the medicinal product is contraindicated in patients with moderate or severe renal impairment (creatinine clearance <59 mL/min).

Patients with Hepatic Impairment

In patients with mild to moderate hepatic impairment (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 use of the medicinal product is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Method of Administration

Intramuscular Injection

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

Intravenous Infusion

The contents of the ampoule (2 mL of injection solution) should be diluted in 30–100 mL of 0.9% sodium chloride solution, glucose solution, or Ringer’s lactate solution.

The infusion solution should be prepared under aseptic conditions and protected from exposure to natural daylight. The prepared solution must be clear and transparent.

The infusion should be administered intravenously over 10–30 minutes at a slow rate.

The prepared solution must be protected from exposure to natural daylight.

The medicinal product, when 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.

The medicinal product must not be mixed in the infusion solution with promethazine or pentazocine.

Intravenous Injection (Bolus Administration)

The contents of the ampoule (2 mL of injection solution) should be administered intravenously slowly over at least 15 seconds.

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

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

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

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

After intramuscular or intravenous bolus administration, 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 remaining solution should be discarded.

Before administration, the solution should be visually inspected to ensure it is clear and colorless. The solution must not be used if it contains particulate matter.

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 can be removed from the body by dialysis.

Adverse Reactions

The adverse reactions listed below are classified by organ systems and frequency of occurrence, and are considered at least possible in relation to dexketoprofen based on available clinical trial data. Also included are adverse reactions reported during the post-marketing period. Frequency categories are defined as follows:
Common (≥ 1/100 to < 1/10);
Uncommon (≥ 1/1,000 to < 1/100);
Rare (≥ 1/10,000 to < 1/1,000);
Very rare (< 1/10,000).

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, syncope.

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, thrombophlebitis of superficial veins.

Respiratory, thoracic and mediastinal disorders:

Rare – bradypnoea; very rare – bronchospasm, dyspnoea.

Gastrointestinal disorders:

Common – nausea, vomiting; uncommon – abdominal pain, dyspepsia, diarrhoea, constipation, haematemesis, dry mouth; rare – peptic ulcer, gastrointestinal bleeding or perforation; very rare – pancreatitis.

Hepatobiliary disorders:

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 oedema, photosensitivity.

Musculoskeletal and connective tissue disorders:

Rare – muscle rigidity, joint stiffness, muscle spasms, 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 – abnormalities in liver function tests.

Gastrointestinal disorders were the most frequently observed.

Peptic ulceration, perforation, or gastrointestinal bleeding (sometimes fatal), particularly in elderly patients, may occur.

Based on available data, nausea, vomiting, diarrhoea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may occur during treatment with dexketoprofen. Gastritis is less commonly observed.

Oedema, arterial hypertension, and heart failure have also been reported, which may be associated with NSAID use.

As with other NSAIDs, the following adverse reactions may occur: aseptic meningitis, generally in patients with systemic lupus erythematosus or mixed connective tissue disorders; blood disorders (purpura, aplastic and haemolytic anaemia; rarely agranulocytosis and bone marrow hypoplasia). Bullous skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), may also occur.

According to clinical trial results 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 or stroke.

Suspected adverse reaction reporting

Reporting of suspected adverse reactions after product authorization is important. It allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions via the national reporting system.

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 25 °C, protected from light and out of reach of children.

Incompatibilities

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

The diluted infusion solution, prepared as described in the section "Intravenous infusions", must not be mixed with promethazine or pentazocine.

Packaging

2 ml in a vial, 5 vials in a blister pack, 1 or 2 blister packs in a cardboard box.

Prescription status

Prescription only.

Manufacturer

PharmaVision San. ve Tic. A.S.

Manufacturer's address

Davutpasa Cad. No:145 Zeytinburnu Istanbul, Turkey

Marketing Authorisation Holder

WORLD MEDICINE, LLC, Ukraine

Sertofen