Auxilien®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AUCSILEN® (AUXILEN®)

Composition:

Active substance: dexketoprofen;

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

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

Pharmaceutical form. Injection 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

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

Mechanism of Action

The mechanism of action of NSAIDs is based on reducing the synthesis of prostaglandins by inhibiting the activity of cyclooxygenase. 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 the drug.

Pharmacodynamics

Inhibitory effects of dexketoprofen trometamol on the activity of cyclooxygenase-1 and cyclooxygenase-2 have been demonstrated in laboratory animals and in humans.

Clinical Efficacy and Safety

Clinical studies in various types of pain have demonstrated that dexketoprofen trometamol exerts a pronounced analgesic effect. The analgesic effect of dexketoprofen trometamol administered intramuscularly or intravenously to 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 of the drug began rapidly and reached its maximum within the first 45 minutes. The duration of analgesic action after administration of 50 mg dexketoprofen trometamol is typically 8 hours. Clinical studies have demonstrated that the use of dexketoprofen trometamol allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain. When patients receiving morphine via a patient-controlled analgesia device for postoperative pain relief were also administered dexketoprofen trometamol, they required significantly less morphine (30–45% less) compared to patients receiving placebo.

Pharmacokinetics

Absorption

After intramuscular administration of dexketoprofen trometamol in humans, maximum concentration (Cmax) is achieved approximately within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg of the drug, the area under the concentration-time curve (AUC) is dose-proportional.

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, and the elimination half-life is 1–2.7 hours. Pharmacokinetic studies of repeated administration of the drug demonstrated that Cmax and AUC after the last intramuscular or intravenous dose were not different from those after single administration, indicating absence of drug accumulation.

Biotransformation and Elimination

Metabolism of dexketoprofen occurs mainly via conjugation with glucuronic acid followed by renal excretion. After administration of dexketoprofen trometamol, only the S-(+) optical isomer is detected in urine, indicating absence of interconversion of the drug to the R-(-) optical isomer in humans.

Elderly Patients

After administration of single and multiple doses, the extent of drug exposure in elderly healthy volunteers (aged 65 years and older) participating in the study was significantly higher (up to 55%) compared to younger volunteers; however, no statistically significant differences in maximum concentration or time to reach maximum concentration were observed. The mean elimination half-life 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), which was 2 times higher than 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 lesions such as erosions. These effects occurred at doses where drug exposure was 14–18 times higher than at the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Like all NSAIDs, dexketoprofen may lead to embryonic or fetal death in animals, either directly due to its effects on development or indirectly via maternal gastrointestinal toxicity.

Clinical Characteristics

Indications

Symptomatic treatment of moderate to severe acute pain when oral administration of the drug is inappropriate, such as 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;
• Patients in whom the use of substances with similar action, for example acetylsalicylic acid or other NSAIDs, triggers the development of bronchial asthma attacks, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioedema;
• If photoallergic or phototoxic reactions occurred during treatment with ketoprofen or fibrates;
• History of gastrointestinal bleeding or perforation related to previous 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 or 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 marked dehydration (due to vomiting, diarrhea, or insufficient fluid intake);
• Third trimester of pregnancy and breastfeeding period.

Due to the ethanol content, the medicinal product Aucelen® is contraindicated for neuraxial (intrathecal or epidural) administration.

Interaction with Other Medicinal Products and Other Types of Interactions

Concomitant use of the following medicinal products with NSAIDs is not recommended:

• Other NSAIDs (including selective cyclooxygenase-2 inhibitors), as well as high-dose salicylates (≥ 3 g/day). Concurrent use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to their mutually enhancing effects.
• Anticoagulants: NSAIDs enhance the effects of anticoagulants, such as warfarin, due to the high degree of plasma protein binding of dexketoprofen and due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under physician supervision with careful monitoring of relevant laboratory parameters.
• Heparin: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under physician supervision with careful monitoring of relevant laboratory parameters.
• Corticosteroids: increased risk of gastrointestinal ulceration or gastrointestinal bleeding.
• Lithium (reports exist for several NSAIDs): NSAIDs increase lithium blood levels, potentially leading to toxicity (due to reduced renal elimination of lithium). Therefore, lithium blood levels should be monitored at the initiation of dexketoprofen therapy, during dose adjustments, or upon discontinuation of the drug.
• High-dose methotrexate (≥ 15 mg weekly): NSAIDs in general reduce renal methotrexate clearance, thereby enhancing its adverse effects on the blood system.
• Hydantoin derivatives and sulfonamides: possible enhancement of toxicity of these agents.

Concomitant use of the following medicinal products with NSAIDs requires caution:

• Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the effectiveness of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., due to dehydration or in elderly patients), the use of cyclooxygenase-inhibiting agents together with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, although this is usually reversible. When using dexketoprofen concomitantly with any diuretic, ensure the patient is not dehydrated, and monitor renal function at the beginning of treatment.
• Low-dose methotrexate (< 15 mg weekly): due to reduced renal clearance of methotrexate under NSAID therapy, its adverse effects on the blood system are generally enhanced. During the first weeks of concomitant use, weekly blood counts should be performed. Treatment should be conducted under strict medical supervision, even in cases of mild renal impairment and in elderly patients.
• Pentoxifylline: risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently.
• Zidovudine: risk of increased toxic effects on erythrocytes due to effects on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. Blood tests and reticulocyte counts should be performed within 1–2 weeks after initiating NSAID therapy.
• Sulfonylurea agents: NSAIDs may enhance the hypoglycemic effect of these drugs by displacing sulfonylureas from plasma protein binding sites.

Potential interactions should be considered when using the following medicinal products:

• Beta-blockers: NSAIDs may attenuate their antihypertensive effect by inhibiting prostaglandin synthesis.
• Cyclosporine and tacrolimus: possible increase in nephrotoxicity due to the effect of NSAIDs on renal prostaglandins. Renal function should be monitored during combination therapy.
• Thrombolytic agents: increased risk of bleeding.
• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
• Probenecid: possible increase in dexketoprofen plasma concentration, likely due to inhibition of renal tubular secretion and glucuronidation of the drug, requiring dose adjustment of dexketoprofen.
• Cardiac glycosides: NSAIDs may increase glycoside plasma concentrations.
• Mifepristone: theoretically, there is a risk of altered mifepristone efficacy due to prostaglandin synthetase inhibitors. Limited data suggest that concomitant administration 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 medicinal products for medical termination of pregnancy.
• Quinolone antibiotics: animal studies have shown that high-dose quinolone derivatives in combination with NSAIDs increase the risk of seizures.
• Tenofovir: when used concomitantly with NSAIDs, plasma concentrations of blood urea nitrogen and creatinine may increase; therefore, renal function should be monitored to assess the potential impact of concomitant use.
• Deferasirox: concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Close patient monitoring is required when using this medicinal product together with deferasirox.
• Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using high-dose NSAIDs. In patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), NSAID use should be avoided for two days before and two days after pemetrexed administration.

Special precautions for use

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

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported with all NSAIDs at any stage of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, and in elderly patients.

Elderly patients

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Treatment in these patients should begin with the lowest possible dose. As with all NSAIDs, patients with a history of esophagitis, gastritis, and/or peptic ulcer should be ensured to have these conditions in remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for possible gastrointestinal complications during treatment, particularly gastrointestinal bleeding. NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation. For such patients and those taking low-dose acetylsalicylic acid or other drugs increasing gastrointestinal adverse reaction risk, consider combination therapy with protective agents, such as misoprostol or proton pump inhibitors.

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

Use with caution in patients concurrently taking medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents like acetylsalicylic acid.

Renal safety

Use with caution in patients with impaired renal function, as NSAIDs may worsen renal function, cause fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or those at risk of hypovolemia. Adequate fluid intake should be maintained during treatment to prevent dehydration, which may exacerbate renal toxicity. Like other NSAIDs, the drug may increase plasma urea nitrogen and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function disturbances occur most frequently in elderly patients.

Hepatic safety

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

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with arterial hypertension and/or mild to moderate heart failure require monitoring and medical advice. Particular caution is required in patients with a history of heart disease, especially previous episodes of heart failure (the risk of heart failure increases during treatment), as NSAIDs may cause fluid retention and edema. Clinical and epidemiological data suggest a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) with some NSAIDs, particularly at high doses and during prolonged use. Data to exclude such risk with dexketoprofen are insufficient. Therefore, dexketoprofen should be prescribed only after careful patient assessment in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. A similarly careful assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (e.g., 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 trometamol and low-molecular-weight heparin at prophylactic doses in the postoperative period has been studied in clinical trials, with no effect on coagulation parameters observed. However, patients receiving dexketoprofen trometamol concurrently with agents affecting hemostasis, such as warfarin, other coumarins, or heparins, require close medical supervision. Cardiovascular function disturbances occur most frequently in elderly patients.

Cases of Kounis syndrome have been reported in patients receiving dexketoprofen. Kounis syndrome manifests as cardiovascular symptoms due to coronary artery spasm caused by an allergic or hypersensitivity reaction, potentially leading to myocardial infarction.

Skin reactions

Rare cases of serious skin reactions (some fatal) have been reported with NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk appears to be 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 hypersensitivity symptoms occur, Auxilen® should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask infection symptoms, 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 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 information

Particular caution is required when prescribing the drug to patients:

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

If prolonged use of dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function is recommended.

Very rare cases of severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. Treatment should be discontinued at the first signs of severe hypersensitivity reactions after taking Auxilen®. Any necessary treatment should be administered under medical supervision, depending on symptoms.

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. This drug may trigger asthma attacks or bronchospasm, especially in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications of the skin and soft tissues may occur during varicella. Data to exclude a role of NSAIDs in exacerbating this infection are lacking. Therefore, the use of Auxilen® is not recommended in varicella.

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

Like other NSAIDs, dexketoprofen trometamol may mask symptoms of infectious diseases during its use. In some cases, NSAIDs have been associated with the activation of soft tissue infections. Therefore, if symptoms of bacterial infection appear or worsen during treatment, patients are advised to seek immediate medical attention.

One ampoule of Auxilen® contains 200 mg of ethanol, equivalent to 5 ml of beer or 2.08 ml of wine per dose. The product may adversely affect individuals with alcoholism.

Ethanol content should be considered when using the drug in pregnant women, breastfeeding women, children, and patients at risk, such as those with liver disease or epilepsy. The product contains less than 1 mmol of sodium (23 mg) per dose and is practically sodium-free.

Use during pregnancy or breastfeeding

The use of Auxilen® is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological studies indicate that using drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage and fetal congenital heart 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 drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation losses and elevated embryofetal mortality. Additionally, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the frequency of fetal developmental abnormalities, including cardiovascular anomalies, increased. However, animal studies with dexketoprofen trometamol did not reveal reproductive toxicity. Starting from the 20th week of pregnancy, using Auxilen® may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, cases of fetal arterial duct constriction have been reported after maternal use of the drug during the second trimester, most of which resolved after treatment cessation. Therefore, prescribing dexketoprofen trometamol during the first and second trimesters should only occur if absolutely necessary. When prescribing dexketoprofen trometamol to women planning pregnancy or during the first and second trimesters, the lowest effective dose should be used for the shortest possible duration. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to Auxilen® for several days starting from the 20th week of pregnancy. Treatment with Auxilen® should be discontinued if oligohydramnios or fetal arterial duct constriction is detected.

During the third trimester, all prostaglandin synthesis inhibitors cause:

Risks to the fetus:

• cardiopulmonary toxic syndrome (ductus arteriosus constriction/occlusion and pulmonary hypertension);
• impaired renal function (see above).

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

• prolonged bleeding time (due to platelet aggregation inhibition), which may occur even with low doses;
• delayed uterine contractions, leading to delayed labor and prolonged delivery.

Breastfeeding

There are no data on the passage of dexketoprofen into breast milk. Auxilen® is contraindicated during breastfeeding.

Fertility

Like all other NSAIDs, dexketoprofen trometamol may reduce female fertility and is therefore not recommended for women planning pregnancy. Women experiencing infertility or undergoing fertility investigations should consider discontinuing the drug.

Ability to affect reaction speed when driving or operating machinery

Dizziness, visual disturbances, or drowsiness may occur during treatment with Auxilen®. In such cases, the ability to react quickly, orient in traffic situations, and drive or operate machinery may be impaired.

Dosage and Administration

To minimize adverse reactions, the lowest effective dose for the shortest duration should be used (see section "Special Warnings and Precautions for Use").

Adults. The recommended dose is 50 mg every 8–12 hours. If necessary, the dose may be repeated after 6 hours. The maximum daily dose should not exceed 150 mg. The medicinal product Aucelen® is intended for short-term use and should only be administered during episodes of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible. For moderate to severe postoperative pain, the drug may be used as indicated at the same recommended doses in combination with opioid analgesics.

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

Hepatic impairment. In patients with mild or 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 drug is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

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

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

Administration method

Intramuscular injection

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

Intravenous infusion

For intravenous infusion, the contents of a 2 mL ampoule should be diluted in 30–100 mL of 0.9% sodium chloride solution, glucose solution, or Ringer’s lactate solution. The infusion solution should be prepared under aseptic conditions, avoiding exposure to natural daylight. The prepared solution should be clear. The infusion should be administered intravenously slowly over 10–30 minutes.

Aucelen® diluted in 100 mL of 0.9% sodium chloride solution or glucose solution may be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

Intravenous bolus injection

If necessary, the contents of one ampoule (2 mL of injection solution) may be administered intravenously slowly over at least 15 seconds. The drug may be mixed in small volumes (e.g., in a syringe) with injection solutions of heparin, lidocaine, morphine, and theophylline.

Aucelen® must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, pethidine, or hydroxyzine, as precipitation may occur.

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

The drug may only be mixed with medicinal products listed above.

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

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

Aucelen® is intended for single use only; any unused portion of the prepared solution should be discarded. The solution should be visually inspected before administration to ensure it is clear and colorless. Solutions containing particulate matter must not be used.

How to open the ampoule:

1. Turn the ampoule so that the colored dot faces you. Gently tap the top of the ampoule with your finger to ensure the solution is in the lower part.
2. Open the ampoule with both hands: hold the lower part of the ampoule with one hand and press the top part away from the colored dot with the other hand (see figures below).

Children

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

Overdose

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

Adverse reactions

The table below lists adverse reactions by organ systems and frequency, which are considered at least possible in relation to dexketoprofen trometamol based on clinical trial data, as well as adverse reactions reported after the marketing of the drug Aucelen®.

Gastrointestinal disorders were the most frequently observed.

Peptic ulcer, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. According to available data, nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may develop during treatment with the drug. Gastritis has been observed less frequently. Edema, arterial hypertension, and heart failure, which may be caused by the use of NSAIDs, have also been reported. As with other NSAIDs, the following adverse reactions are possible: aseptic meningitis, which generally occurs in patients with systemic lupus erythematosus or mixed connective tissue diseases, and blood disorders (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), may also occur.

Based on clinical trial results and epidemiological data, the use of certain NSAIDs, especially at high doses and for prolonged periods, may be associated with a small increase in the risk of thrombotic events such as myocardial infarction and stroke.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows ongoing monitoring of the benefit-risk balance of the drug. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

5 years.

Do not use the drug after the expiry date stated on the packaging.

Storage conditions

No special storage conditions required. Store in the original packaging to protect from light. Do not freeze.

Keep out of reach and sight of children.

Incompatibilities

Auxilen® must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydroxyzine, as precipitation may occur.

Diluted infusion solutions prepared as described in the section "Administration and dosage" must not be mixed with promethazine or pentazocine.

Packaging

2 ml in a vial made of brown light-protective glass of hydrolytic class I with score marks and a break point.

5 vials in a blister pack (cavity) made of polyvinyl chloride film.

1 blister pack (cavity) in a cardboard box.

Prescription status: Prescription only.

Manufacturer

Manufacturer responsible for batch release:

JSC "Kalceks".

Manufacturer's address and location of manufacturing site

71E Krustpils Street, Riga, LV-1057, Latvia.

Marketing Authorization Holder

JSC "Kalceks".

Address of the Marketing Authorization Holder

71E Krustpils Street, Riga, LV-1057, Latvia.