INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ROTALFEN (ROTALFEN)

Composition:

Active substance: dexketoprofen;

1 ampoule (2 mL of solution) contains dexketoprofen (as dexketoprofen trometamol) 50 mg;

Excipients: sodium chloride, sodium hydroxide, ethanol 96%, 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 M01AE17.

Pharmacological Properties

Pharmacodynamics

Dexketoprofen trometamol is a propionic acid salt that exerts analgesic, anti-inflammatory, and antipyretic effects and belongs 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. Inhibitory effects on the activity of both cyclooxygenase-1 and cyclooxygenase-2 have 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 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 action after administration of 50 mg dexketoprofen is typically 8 hours. The use of dexketoprofen allows for a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. Patients receiving morphine (via a patient-controlled analgesia device) and 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 proportional to the dose. Multiple-dose pharmacokinetic studies have shown that AUC and Cmax (mean maximum value) after the last intramuscular or intravenous administration do not differ from those after single administration, indicating the absence of dexketoprofen accumulation.

Distribution

Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen averages 0.25 L/kg. The distribution half-life is approximately 0.35 hours.

Metabolism

Dexketoprofen is primarily metabolized 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 is 1–2.7 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 or time to reach it. The mean T1/2 was prolonged (by up to 48%), and total 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) of dexketoprofen as being twice the dose recommended for humans. When higher doses were administered to monkeys, the main adverse reactions were fecal blood, reduced body weight gain, and, at the highest dose, gastrointestinal tract lesions such as erosions. These effects occurred at doses where dexketoprofen 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 cause embryonic or fetal death in animals either directly by affecting embryofetal development or indirectly via adverse effects on the gastrointestinal tract of the mother.

Clinical characteristics.

Indications.

Symptomatic treatment of acute moderate to severe pain when oral administration of dexketoprofen is inappropriate, e.g., in postoperative pain, renal colic, and lumbar pain.

Contraindications.

Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product.
Asthma attacks, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema associated with previous use of drugs of similar action, e.g., 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.
Gastrointestinal bleeding, other active bleeding, or increased bleeding tendency.
Haemorrhagic diathesis and other coagulation disorders.
Severe heart failure.
Moderate or severe renal impairment (creatinine clearance ≤59 mL/min).
Severe hepatic impairment (10–15 points on the Child–Pugh scale).
Marked dehydration (due to vomiting, diarrhoea, or insufficient fluid intake).
Third trimester of pregnancy.
Breastfeeding period.
Neuraxial (intrathecal or epidural) administration of dexketoprofen (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 in high doses (≥ 3 g/day): concomitant use of dexketoprofen with these agents increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to their mutually enhancing effects.
Anticoagulants: concomitant use with dexketoprofen enhances the effect of anticoagulants, e.g., 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, careful physician monitoring and laboratory parameter surveillance are required.
Heparins: concomitant use of dexketoprofen with these agents increases the risk of bleeding (due to inhibition of platelet function and damage to gastric and duodenal mucosa by dexketoprofen). If concomitant use is necessary, careful physician monitoring and laboratory parameter surveillance are required.
Corticosteroids: concomitant use of dexketoprofen with these agents increases the risk of gastrointestinal ulceration or gastrointestinal bleeding.
Lithium: concomitant use with NSAIDs (reports exist for several NSAIDs) increases plasma lithium levels, potentially leading to toxicity (reduced renal excretion of lithium). Plasma lithium levels should be monitored at the beginning of dexketoprofen treatment, during dose adjustments, or upon discontinuation.
High-dose methotrexate (≥ 15 mg/week): concomitant use with dexketoprofen reduces renal clearance of methotrexate and generally enhances its adverse effects on the blood system.
Hydantoin derivatives and sulphonamides: concomitant use with dexketoprofen increases 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 cyclooxygenase inhibitors (including dexketoprofen) with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, which is usually reversible. When using these agents together, ensure the patient is not dehydrated and monitor renal function at the start of treatment.
Low-dose methotrexate (< 15 mg/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. Careful physician monitoring is required for patients with even mild renal impairment and in elderly patients.
Pentoxifylline: concomitant use of dexketoprofen with pentoxifylline increases the risk of bleeding. Enhanced monitoring and more frequent bleeding time tests are recommended.
Zidovudine: concomitant use of dexketoprofen with zidovudine increases the risk of toxic effects on erythrocytes due to effects on reticulocytes, leading to severe anaemia after one week of NSAID use. Blood tests and reticulocyte counts should be performed after 1–2 weeks of concomitant use.
Sulphonylurea agents: concomitant use with dexketoprofen enhances the hypoglycaemic effect of these agents due to displacement of sulphonylureas 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 the nephrotoxicity of these agents (due to the effect of dexketoprofen on renal prostaglandins). Renal function should be monitored when these agents are used together.
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.
Cardiac glycosides: concomitant use with dexketoprofen may increase plasma levels of cardiac glycosides.
Mifepristone: theoretically, there is a risk of altered mifepristone efficacy due to prostaglandin synthetase inhibitors. Limited data suggest that concomitant use 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 regimens.
Quinolone antibiotics: animal studies indicate that concomitant use of high-dose quinolones with NSAIDs increases the risk of seizures.
Tenofovir: concomitant use with dexketoprofen may increase blood urea nitrogen and creatinine levels. Renal function should be monitored.
Deferasirox: concomitant use of dexketoprofen with deferasirox may increase the risk of gastrointestinal toxicity. Close patient monitoring is required.
Pemetrexed: concomitant use with dexketoprofen may reduce pemetrexed elimination. Extreme caution is required, especially with high-dose dexketoprofen. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid concomitant use of pemetrexed and dexketoprofen 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 the 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 achieve symptom relief.

Gastrointestinal effects

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

If gastrointestinal bleeding 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, particularly 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 be initiated with the lowest possible dose of the medicinal product.

Prior to initiating treatment with the medicinal product, patients with a history of esophagitis, gastritis, and/or peptic ulcer disease should be evaluated to ensure these conditions are in remission.

During treatment with the medicinal product, patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders 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 for patients taking low-dose acetylsalicylic acid or other agents increasing the risk of gastrointestinal adverse reactions, 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 be advised to inform their physician of 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 (SSRIs), or antiplatelet agents such as acetylsalicylic acid.

Renal effects

The medicinal product should be used with caution in patients with impaired renal function, as NSAID use may lead to worsening renal function, fluid retention, and edema. Due to the increased risk of nephrotoxicity, the medicinal product should be used with caution in patients concurrently taking diuretics and in patients 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, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function disturbances are most commonly observed 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 such elevations occur, the use of the medicinal product should be discontinued.

Hepatic function disturbances are most commonly observed in elderly patients.

Cardiovascular and cerebrovascular effects

Patients with arterial hypertension and/or mild to moderate heart failure should be closely monitored during treatment with the medicinal product.

The medicinal product should be used with particular caution in patients with a history of heart disease, particularly previous episodes of heart failure (as dexketoprofen use increases the risk of heart failure development), due to fluid retention and edema associated with NSAID therapy. Clinical studies and epidemiological data suggest that use of certain 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 are insufficient.

The medicinal product may be used only after careful assessment in patients with 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 risk factors for cardiovascular disease (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

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

However, patients taking agents affecting hemostasis, such as warfarin, other coumarins, or heparins, should be closely monitored during treatment with the medicinal product.

Cardiovascular system disturbances are most commonly observed in elderly patients.

Skin effects

Rare cases of serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported during NSAID therapy. The highest risk appears to occur early in treatment, with most cases developing within the first month. If skin rashes, signs of mucosal involvement, or other symptoms of hypersensitivity occur, the medicinal product should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask symptoms of infections, potentially interfering with diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. If the medicinal product is used to relieve pain associated with an infectious process, monitoring of the infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Other warnings

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

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

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

Patients suffering from asthma associated 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. Use of the medicinal product may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Severe skin and soft tissue infections may develop during varicella. Data to exclude a role of NSAIDs in exacerbating this infectious process are lacking. Therefore, use of the medicinal product is not recommended in varicella.

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

Like other NSAIDs, dexketoprofen may mask symptoms of infectious diseases during its use. In isolated cases, NSAID use has been associated with exacerbation of soft tissue infections. If bacterial infection symptoms develop or worsen, immediate medical consultation is required.

Each ampoule of the medicinal product contains 200 mg of ethanol, equivalent to 5 mL of beer or 2.08 mL of wine per dose. The medicinal product may adversely affect individuals suffering from alcoholism. The ethanol content should be taken into account when using the medicinal product in:

the first and second trimesters of pregnancy, children, and patients at risk, e.g., those with liver disease or 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, use of drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage and congenital malformations, including cardiac defects and abdominal wall defects. The absolute risk of cardiovascular abnormalities increases from <1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of dexketoprofen therapy. In animal studies, prostaglandin synthesis inhibitors have caused increased pre- and post-implantation loss and elevated embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal developmental abnormalities, including cardiovascular malformations, has been observed. However, animal studies with dexketoprofen trometamol did not reveal toxicity to reproductive organs.

Starting from the 20th week of pregnancy, dexketoprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after treatment initiation and is usually reversible upon discontinuation.

During the first and second trimesters of pregnancy, dexketoprofen should not be prescribed except in cases of extreme necessity.

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 applied.

Fetal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after several days of dexketoprofen exposure 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 may cause:

risks to the fetus:

cardiopulmonary toxic syndrome (with closure of the ductus arteriosus and pulmonary hypertension);
impaired renal function, which may progress to renal failure with oligohydramnios (see above);

risks to the mother and neonate 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 prolonged labor.

Breastfeeding period

There are no data on the excretion 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 and therefore is not recommended for women planning pregnancy. Women experiencing infertility or undergoing fertility investigations should consider discontinuing the medicinal product.

Ability to affect reaction speed when driving or operating machinery.

During dexketoprofen use, dizziness, visual disturbances, or somnolence may occur. In such cases, the ability to react quickly, orient in traffic situations, or operate vehicles or 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 only and should be administered solely 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 this patient group. 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 one ampoule (2 mL of injection solution) should be administered slowly and deeply into the muscle.

Intravenous Infusion

The contents of one 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 must be prepared under aseptic conditions, avoiding exposure to natural daylight. The prepared solution must be clear and transparent.

The infusion should be administered over 10–30 minutes.

Avoid exposure of the prepared solution to natural daylight.

The diluted medicinal product 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 one ampoule (2 mL of injection solution) should be administered intravenously over no less than 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 solutions of dopamine, promethazine, pentazocine, pethidine, or hydrocortisone, as a white precipitate may form.

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

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 of the medicinal product 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 must be discarded.

Before administration, ensure that the solution is clear and colorless. Do not use solutions containing 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

Below are the adverse reactions listed by organ systems and frequency of occurrence, which are considered at least possible in relation to dexketoprofen, based on available clinical data, as well as adverse reactions reported during the post-marketing period. Frequency categories: 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 edema; very rare – anaphylactic reactions, including anaphylactic shock.

Metabolism and nutrition disorders:

Rare – hyperglycemia, hypoglycemia, hypertriglyceridemia, 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 edema, facial swelling, photosensitivity.

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 gland function disorders.

General disorders and administration site conditions:

Common – injection site pain, injection site reactions including inflammation, hematoma, bleeding; uncommon – chills, fatigue, pain, shivering, asthenia, malaise; rare – tremor, peripheral edema.

Investigations:

Rare – liver function test abnormalities.

Gastrointestinal disorders were the most frequently observed.

Peptic ulcer, perforation, or gastrointestinal hemorrhage, sometimes fatal, may occur, particularly in elderly patients.

Available data indicate that 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 observed less frequently.

Edema, arterial hypertension, and heart failure may also occur, which may be associated with the use of NSAIDs.

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

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

Reporting of suspected adverse reactions

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

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 25°C, in the original packaging, 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, meperidine, or hydrocortisone, as a white precipitate may form.

The diluted infusion solution, as prepared according to the section "Administration and dosage. Intravenous infusion", 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. /
PharmaVision San. ve Tic. A.S.

Manufacturer's address and place of business

Davutpasa Cad. No:145 Zeytinburnu Istanbul, Turkey /
Davutpasa Cad. No:145 Zeytinburnu Istanbul, Turkey.

Marketing Authorization Holder

WORLD MEDICINE, LLC, Ukraine /
WORLD MEDICINE, LLC, Ukraine.

Rotaphen