Dexketoprofen-sofarma

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXKETOPROFEN-SOPHARMA (DEXKETOPROFEN-SOPHARMA)

Composition:

Active substance: dexketoprofen trometamol;

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

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

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

Pharmaceutical form. Solution for injection/infusion.

Main physicochemical properties: clear liquid, practically free from particles.

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

ATC code M01AE17.

Pharmacological Properties.

Pharmacodynamics.

Dexketoprofen trometamol – the tromethamine salt of S-(+)-2-(3-benzoylphenyl) propionic acid – is an analgesic, anti-inflammatory, and antipyretic medicinal product belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs).

Mechanism of action

The mechanism of action of NSAIDs is related to the reduction of prostaglandin synthesis through inhibition of the cyclooxygenase pathway.

Specifically, the conversion of arachidonic acid into cyclic endoperoxides, PGG2 and PGH2, is suppressed, which in turn produce prostaglandins PGE1, PGE2, PGF2α, and PGD2, as well as prostacyclin PGI2 and thromboxanes (TxA2 and TxB2). In addition, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the medicinal product.

Pharmacodynamic effects

It has been demonstrated that dexketoprofen is an inhibitor of COX-1 and COX-2 activity in experimental animals and humans.

Clinical efficacy and safety

Clinical studies conducted in several pain models have demonstrated effective analgesic action of dexketoprofen.

The analgesic efficacy of dexketoprofen administered intramuscularly and intravenously for the treatment of moderate to severe pain has been evaluated in several surgical pain models (orthopedic and gynecological/abdominal surgery), as well as in musculoskeletal pain (acute low back pain model) and renal colic.

In the conducted studies, onset of analgesia was rapid, with peak analgesic effect achieved within the first 45 minutes. The duration of analgesic effect after administration of 50 mg dexketoprofen typically lasts 8 hours.

Clinical studies on postoperative pain management have shown that dexketoprofen injection/infusion solution in combination with opioids significantly reduces opioid consumption. In postoperative pain studies where patients received morphine via patient-controlled analgesia, patients receiving dexketoprofen required significantly less morphine (30–45% less) than those in the placebo group.

Pharmacokinetics.

Absorption

After intramuscular administration of dexketoprofen trometamol in humans, maximum concentration is reached within 20 minutes (range from 10 to 45 minutes). It has been shown that for single doses ranging from 25 to 50 mg, the area under the concentration–time curve (AUC) is dose-proportional following both intramuscular and intravenous administration.

Distribution

As with other medicinal products exhibiting high plasma protein binding (99%), the volume of distribution has a mean value below 0.25 L/kg. The distribution half-life was approximately 0.35 hours, and the elimination half-life ranged from 1 to 2.7 hours.

In multiple-dose pharmacokinetic studies, Cmax and AUC after the last intramuscular or intravenous dose did not differ from values obtained after a single dose, indicating absence of drug accumulation.

Metabolism

Following administration of dexketoprofen trometamol, only the S-(+) enantiomer is detected in urine, indicating no in vivo conversion of the drug to the R-(–) enantiomer in humans.

Elimination

The primary route of elimination of dexketoprofen is glucuronide conjugation followed by renal excretion.

Pharmacokinetics in elderly patients (≥ 65 years)

In healthy elderly individuals (aged 65 years and older), exposure was significantly higher compared to younger volunteers after both single and repeated oral doses (up to 55%), while no statistically significant differences were observed in peak concentrations or time to reach maximum concentration. The mean elimination half-life was prolonged after both single and repeated doses (up to 48%), and apparent total clearance was reduced.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to the active substance, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product;
• in patients in whom administration of drugs with similar action (e.g., acetylsalicylic acid or other NSAIDs) triggers attacks of bronchial asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema;
• if photoallergic or phototoxic reactions occurred during treatment with ketoprofen or fibrates;
• gastrointestinal bleeding or perforation in medical history associated with NSAID therapy;
• active peptic ulcer/gastrointestinal bleeding or history of gastrointestinal bleeding, ulcers, or perforations;
• chronic dyspepsia;
• active bleeding or increased bleeding tendency;
• Crohn’s disease or ulcerative colitis;
• severe heart failure;
• moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min);
• severe hepatic impairment (10–15 points on the Child–Pugh scale);
• hemorrhagic diathesis and other coagulation disorders;
• in cases of severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake);
• third trimester of pregnancy and breastfeeding period.

Dexketoprofen-Sofarma, solution for injection/infusion, is contraindicated for neuraxial (intrathecal or epidural) administration due to the presence of ethanol.

Interaction with other medicinal products and other forms of interaction.

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

Other NSAIDs (including selective COX-2 inhibitors) and high-dose salicylates (≥ 3 g/day): concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to synergistic effects.

Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin due to high plasma protein binding of dexketoprofen, platelet function inhibition, and damage to gastric and duodenal mucosa. If combination cannot be avoided, careful clinical monitoring and laboratory parameter surveillance are required.

Heparins: increased risk of bleeding (due to platelet function inhibition and damage to gastric and duodenal mucosa). If combination cannot be avoided, careful clinical monitoring and laboratory surveillance are required.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.

Lithium (reported with several NSAIDs): NSAIDs may increase lithium blood levels to potentially toxic concentrations (reduced renal lithium excretion). Therefore, serum lithium levels should be monitored at the start of dexketoprofen treatment, during dose adjustments, and upon discontinuation.

High-dose methotrexate (≥ 15 mg/week): increased hematological toxicity of methotrexate due to reduced renal clearance caused by anti-inflammatory agents in general.

Hydantoins and sulfonamides: toxic effects of these agents may be enhanced.

Concomitant use of the following agents with NSAIDs requires caution:

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists: dexketoprofen may reduce the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of cyclooxygenase-inhibiting agents and ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may lead to further deterioration of renal function, which is usually reversible. When combining dexketoprofen with a diuretic, adequate hydration must be ensured and renal function monitored at the beginning of treatment.

Low-dose methotrexate (< 15 mg/week): increased hematological toxicity of methotrexate due to reduced renal clearance by anti-inflammatory agents in general. Weekly blood monitoring during the first weeks of combination therapy. Enhanced monitoring is required in patients with even mild renal impairment and in elderly patients.

Pentoxifylline: increased risk of bleeding. Intensify clinical monitoring and more frequent bleeding time checks.

Zidovudine: risk of enhanced erythrocyte toxicity due to effects on reticulocytes, leading to severe anemia appearing about one week after starting NSAID therapy. Perform complete blood count and reticulocyte count one to two weeks after initiation of NSAID treatment.

Sulfonylurea derivatives: NSAIDs may enhance the hypoglycemic effect of sulfonylurea derivatives by displacing them from plasma protein binding sites.

Potential interactions should be considered when using the following agents:

Beta-blockers: NSAID treatment may reduce their antihypertensive effect by inhibiting prostaglandin synthesis.

Cyclosporine and tacrolimus: nephrotoxicity may be potentiated by NSAIDs due to effects on renal prostaglandins. Renal function should be monitored during combination therapy.

Thrombolytics: increased risk of bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

Probenecid: plasma concentration of dexketoprofen may increase; this interaction may be due to inhibition at the site of tubular secretion and glucuronidation in the kidneys, requiring dose adjustment of dexketoprofen.

Cardiac glycosides: NSAIDs may increase plasma concentrations of glycosides.

Mifepristone: there is a theoretical risk that prostaglandin synthesis inhibitors may alter the efficacy of mifepristone. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not negatively affect the ripening of the cervix or uterine contractility induced by mifepristone or prostaglandin, and does not reduce the clinical efficacy of medical termination of pregnancy.

Quinolone antibiotics: animal studies indicate that high doses of quinolones in combination with NSAIDs may increase the risk of seizures.

Tenofovir: concomitant use with NSAIDs may increase blood urea nitrogen and creatinine levels. Renal function should be monitored to control potential synergistic effects on kidney function.

Deferasirox: concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Careful clinical monitoring is required when deferasirox is used in combination with these agents.

Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, caution is required when prescribing higher NSAID doses. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid concomitant use of pemetrexed and NSAIDs for 2 days before and 2 days after pemetrexed administration.

Special precautions for use.

Use with caution in patients with a history of allergic diseases.

Concomitant use of dexketoprofen with NSAIDs, including selective COX-2 inhibitors, should be avoided.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration").

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, which may be fatal, have been reported with all NSAIDs at any time during therapy, regardless of the presence or absence of prior warning symptoms or serious gastrointestinal history. If gastrointestinal bleeding or ulceration occurs in patients receiving Dexketoprofen-Sofarma, treatment 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: Elderly individuals have an increased incidence of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal. These patients should start treatment with the lowest available dose.

Patients with a history of gastrointestinal adverse reactions, especially elderly individuals, should inform their physician about any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

As with other NSAIDs, prior to initiating dexketoprofen therapy, it is necessary to assess for a history of esophagitis, gastritis, and/or peptic ulcer—ensuring these conditions are in remission to ensure adequate treatment. Patients with gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for digestive disturbances, particularly gastrointestinal bleeding.

NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as their condition may worsen.

Combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered for these patients, as well as for patients requiring concomitant low-dose acetylsalicylic acid or other medications that may increase gastrointestinal risk.

Caution is advised when patients are receiving concomitant medications that 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 safety

Use with caution in patients with impaired renal function. In such patients, NSAID use may lead to worsening renal function, fluid retention, and edema. Caution is also advised in patients receiving diuretic therapy or those who may develop hypovolemia, due to an increased risk of nephrotoxicity.

During treatment, adequate fluid intake should be ensured to prevent dehydration and associated increased renal toxicity.

Like all NSAIDs, dexketoprofen may increase plasma urea and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may negatively affect the renal system and may lead to glomerulonephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome, and acute renal failure.

Elderly patients are more likely to experience impaired renal function.

Hepatic safety

Use with caution in patients with impaired liver function. Like other NSAIDs, dexketoprofen may cause transient, mild elevations in some liver function parameters, as well as significant increases in ALT and AST. If substantial increases in these parameters occur, therapy should be discontinued.

Elderly patients are more likely to experience impaired liver function.

Cardiovascular and cerebrovascular safety

Patients with a history of arterial hypertension and/or mild to moderate heart failure require appropriate monitoring and consultation. The drug should be prescribed with particular caution in patients with a history of heart disease, especially those with prior episodes of heart failure, due to an increased risk of developing heart failure, as fluid retention and edema have been reported with NSAID therapy.

Cases of Kounis syndrome have been reported in patients receiving dexketoprofen therapy. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may potentially lead to myocardial infarction.

Clinical trial data and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and during prolonged treatment) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with dexketoprofen use.

Therefore, patients with uncontrolled arterial hypertension, congestive heart failure, established ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease should only be treated with dexketoprofen after careful risk assessment. A similar assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

All NSAIDs may inhibit platelet aggregation and prolong bleeding time by suppressing prostaglandin synthesis. Concomitant use of dexketoprofen and prophylactic doses of low-molecular-weight heparin in the postoperative period has been evaluated in controlled clinical trials, with no observed effect on blood coagulation parameters. Nevertheless, patients receiving anticoagulant therapy, such as warfarin or other coumarins or heparins, should be closely monitored when using dexketoprofen.

Elderly patients are more likely to experience impaired cardiovascular function.

Skin reactions

Serious skin reactions (some of which are fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported in association with NSAID use. The highest risk of these reactions occurs early in the course of therapy, with most cases appearing within the first month of treatment. Administration of Dexketoprofen-Sofarma injection/infusion solution should be discontinued at the first sign of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Masking symptoms of underlying infections

Like other NSAIDs, dexketoprofen may mask symptoms of infectious diseases, potentially interfering with diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. When dexketoprofen is administered to relieve pain associated with an infectious process, monitoring of the infection is recommended. In isolated cases, worsening of soft tissue infections has been described in temporal association with NSAID use. Therefore, in outpatient settings, patients are advised to seek immediate medical consultation if signs of bacterial infection appear or worsen during therapy.

Other information

Special attention is required in patients:

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

If prolonged treatment with dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function, as well as blood tests, should be performed.

In very rare cases, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. Treatment should be discontinued at the first signs of severe hypersensitivity reactions following dexketoprofen administration. Medical procedures should be initiated by healthcare professionals depending on symptoms.

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 than the general population. Use of this medicinal product may trigger asthma attacks or bronchospasm, particularly in patients with allergy to acetylsalicylic acid or NSAIDs (see section "Contraindications").

In exceptional cases, varicella may lead to serious skin and soft tissue infections. Currently, the influence of NSAIDs on the exacerbation of these infections cannot be excluded. Therefore, in cases of varicella, the use of dexketoprofen should be avoided.

Dexketoprofen-Sofarma injection/infusion solution should be used with caution in patients with coagulation disorders, systemic lupus erythematosus, or mixed connective tissue disease.

The medicinal product contains 12.35% v/v ethanol (alcohol), i.e., up to 200 mg per dose (in 2 mL of injection/infusion solution), equivalent to 5 mL of beer or 2.08 mL of wine per dose. Harmful in patients with alcoholism. Caution is advised in pregnant and breastfeeding women, children, patients with liver disease, and patients with epilepsy.

The medicinal product contains less than 1 mmol (23 mg)/dose (2 mL of injection/infusion solution) of sodium, i.e., practically sodium-free.

Pediatric population

Safety of use in children and adolescents has not been established.

Use during pregnancy or breastfeeding.

Dexketoprofen-Sofarma 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 embryonic/fetal development. Epidemiological data raise concerns about an increased risk of miscarriage, cardiac malformations, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. Animal studies with prostaglandin synthesis inhibitors have shown increased pre- and post-implantation losses and embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during the organogenetic period, an increased incidence of various developmental abnormalities, including cardiovascular defects, has been observed. However, animal studies with dexketoprofen did not reveal toxicity to reproductive organs.

From the 20th week of pregnancy, the use of dexketoprofen may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible upon discontinuation of therapy. Dexketoprofen should not be used during the first and second trimesters of pregnancy except in cases of extreme necessity. If dexketoprofen is administered to 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. Prenatal monitoring for oligohydramnios may be advisable after several days of dexketoprofen exposure starting from the 20th week of pregnancy. If oligohydramnios is detected, dexketoprofen should be discontinued.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• impaired renal function, which may progress to renal failure with oligohydramnios.

and the mother at the end of pregnancy and the newborn:

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

Breastfeeding. It is unknown whether dexketoprofen is excreted in breast milk. Dexketoprofen is contraindicated in women during breastfeeding (see section "Contraindications").

Fertility. Like other NSAIDs, dexketoprofen may impair female fertility and therefore is not recommended for women attempting to conceive. If a woman experiences difficulties with conception or is undergoing infertility evaluation, discontinuation of dexketoprofen should be considered.

Ability to influence reaction speed when driving or operating machinery.

Dexketoprofen-Sofarma injection/infusion solution may cause adverse effects such as dizziness, visual disturbances, or somnolence. In such cases, the ability to react and actively participate in traffic or operate machinery may be impaired.

Method of Administration and Dosage

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Adults

The recommended dose is 50 mg every 8–12 hours. Administration may be repeated every 6 hours if necessary. The maximum daily dose should not exceed 150 mg.

Dexketoprofen-Sofarma, solution for injection/infusion, is intended for short-term use: treatment should be limited to the acute symptomatic period (no more than two days). Patients should be switched to oral analgesics as soon as possible.

In cases of moderate to severe postoperative pain, Dexketoprofen-Sofarma, solution for injection/infusion, may be used in combination with opioid analgesics when indicated, at the same recommended doses for adults.

Patients with Hepatic Impairment

For patients with mild to moderate hepatic impairment (Child-Pugh score 5–9), the maximum daily dose should be reduced to 50 mg, and liver function should be closely monitored (see section "Special Warnings and Precautions for Use"). Dexketoprofen-Sofarma, solution for injection/infusion, is contraindicated in patients with severe hepatic impairment (Child-Pugh score 10–15) (see section "Contraindications").

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 (see section "Special Warnings and Precautions for Use"). Dexketoprofen-Sofarma, solution for injection/infusion, should not be used in patients with moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min) (see section "Contraindications").

Elderly Patients

Dose adjustment in elderly patients is generally not required. However, due to the physiological decline in renal function in elderly patients, a lower dose is recommended in case of mild renal impairment: maximum daily dose of 50 mg.

Paediatric Population

Safety and efficacy in children and adolescents have not been established; therefore, the medicinal product should not be used in children and adolescents.

Method of Administration

Dexketoprofen-Sofarma, solution for injection/infusion, can be administered either intramuscularly or intravenously:

• Intramuscular administration: The contents of one ampoule (2 mL) of Dexketoprofen-Sofarma solution for injection/infusion should be injected slowly and deeply into the muscle.
• Intravenous administration:
  • Intravenous infusion: The diluted solution, prepared as described below, should be administered as a slow intravenous infusion lasting from 10 to 30 minutes. The solution must always be protected from natural daylight.
  • Intravenous bolus injection: If necessary, the contents of one ampoule (2 mL) of Dexketoprofen-Sofarma solution for injection/infusion may be administered slowly as an intravenous bolus over at least 15 seconds.

Dexketoprofen-Sofarma, solution for injection/infusion, has been shown to be compatible when mixed in small volumes (e.g., in a syringe) with injectable solutions of heparin, lidocaine, morphine, and theophylline.

Dexketoprofen-Sofarma, solution for injection/infusion, 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.

Dexketoprofen-Sofarma, solution for injection/infusion, is compatible with the following materials: polypropylene, high-density polyethylene (HDPE), and low-density polyethylene (LDPE).

For intravenous administration, the contents of one ampoule (2 mL) of Dexketoprofen-Sofarma solution for injection/infusion should be diluted in 30 mL of 0.9% sodium chloride solution, 5% glucose solution, or Ringer's lactate. The solution should be diluted under aseptic conditions and protected from natural daylight (see section "Storage Conditions"). The diluted solution is a clear solution.

No changes in active ingredient content due to adsorption have been observed during storage of diluted solutions in polyethylene bags or in administration devices made of ethyl vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

Dexketoprofen-Sofarma, solution for injection/infusion, is intended for single use only; any unused solution should be discarded. The solution should be visually inspected before administration to ensure it is clear and colourless; it must not be used if particulate matter is observed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Handling of the Medicinal Product

When Dexketoprofen-Sofarma solution for injection/infusion is administered intramuscularly or as an intravenous bolus injection, the solution should be administered immediately after being drawn from the ampoule.

For intravenous infusion, the solution should be diluted under aseptic conditions and protected from natural daylight (see section "Storage Conditions").

Children

The effect of the medicinal product Dexketoprofen-Sofarma has not been studied in children and adolescents. Therefore, safety and efficacy in children and adolescents have not been established, and the product should not be used in this patient population.

Overdose

Symptoms: The clinical picture of overdose is unknown. Similar medicinal products have caused gastrointestinal (vomiting, anorexia, abdominal pain) and neurological (drowsiness, dizziness, disorientation, headache) disturbances.

Treatment: In case of accidental or excessive ingestion or administration, symptomatic therapy should be initiated immediately. Dexketoprofen trometamol may be removed by dialysis.

Adverse Reactions

Below is a list of adverse events considered at least possible in relation to dexketoprofen trometamol based on clinical trial data, as well as adverse reactions reported during the post-marketing period. Adverse reactions are classified by system organ class and are listed in order of frequency: 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); not known (cannot be estimated from available data).

Blood and lymphatic system disorders: uncommon – anaemia; very rare – neutropenia, thrombocytopenia.

Immune system disorders: rare – laryngeal edema; very rare – anaphylactic reaction, including anaphylactic shock.

Metabolism and nutrition disorders: rare – hyperglycemia, hypoglycemia, hypertriglyceridemia, anorexia, loss of appetite.

Psychiatric disorders: uncommon – insomnia, anxiety.

Nervous system disorders: uncommon – headache, dizziness, somnolence; rare – paresthesia, syncope (fainting).

Eye disorders: uncommon – blurred vision.

Ear and labyrinth disorders: uncommon – vertigo; rare – tinnitus.

Cardiac disorders: uncommon – palpitations; rare – extrasystoles, tachycardia; not known – Kounis syndrome.

Vascular disorders: uncommon – arterial hypotension, flushing; rare – arterial hypertension, superficial thrombophlebitis.

Respiratory, thoracic and mediastinal disorders: rare – bradypnea; very rare – bronchospasm, dyspnea.

Gastrointestinal disorders: common – nausea, vomiting; uncommon – abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth; rare – peptic ulcer, gastrointestinal bleeding or perforation of peptic ulcer; very rare – pancreatitis.

Hepatobiliary disorders: rare – hepatocellular injury.

Skin and subcutaneous tissue disorders: uncommon – dermatitis, pruritus, rash, increased sweating; rare – urticaria, acne; very rare – bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), angioneurotic edema, facial swelling, photosensitivity reaction; not known – fixed drug eruption.

Musculoskeletal and connective tissue disorders: rare – muscle stiffness, joint stiffness, muscle spasms, back pain.

Renal and urinary disorders: rare – acute renal failure, polyuria, renal pain, ketonuria, proteinuria; very rare – nephritis or nephrotic syndrome.

Reproductive system and breast disorders: rare – menstrual cycle disturbances, prostate function disorders.

General disorders and administration site conditions: common – injection site pain, injection site reaction, including inflammation, bruising or bleeding; uncommon – fever, fatigue, pain, feeling cold, asthenia, malaise; rare – tremor, peripheral edema.

Investigations: rare – liver function test abnormalities.

The most commonly reported adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported (see section "Special precautions"). Gastritis has been reported less frequently.

Edema, arterial hypertension, and heart failure have been reported in association with NSAID therapy.

As with other NSAIDs, the following adverse effects may occur: aseptic meningitis, which may occur predominantly in patients with systemic lupus erythematosus or mixed connective tissue disease; hematological reactions (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia).

Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

Clinical trial data and epidemiological evidence suggest that the use of certain NSAIDs (particularly at high doses and with long-term treatment) may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua/.

Shelf life. 4 years.

Storage conditions.

Keep out of the reach of children.

This medicinal product does not require special storage temperature conditions. Store in the original packaging to protect from light.

After dilution, the solution remains stable for 24 hours at 25 °C and for 24 hours at temperatures from 2 to 8 °C.

From a microbiological standpoint, the prepared solution should be used immediately. If not used immediately, the responsibility for storage duration and conditions prior to use lies with the user. The solution should always be protected from light.

Incompatibilities.

Dexketoprofen-Sofarma, solution for injection/infusion, must not be mixed in a small volume (e.g., in a syringe) with dopamine, promethazine, pentazocine, pethidine, or hydroxyzine solutions, as this may result in precipitation.

Diluted infusion solutions, prepared as described in the section "Dosage and method of administration", must not be mixed with promethazine or pentazocine.

This medicinal product must not be mixed with other medicinal products except those specified in the section "Dosage and method of administration".

Packaging.

2 ml of solution in a vial made of brown glass; 5 or 10 vials in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

JSC "Sofarma".

Manufacturer's address and place of business.

16 Iliensko Shose Str., Sofia, 1220, Bulgaria.