Deceta solution for injection 25 mg/ml ampoule 2 ml No. 6

Instructions for Deceta injection solution 25 mg/ml ampoule 2 ml No. 6

Composition

active ingredient: dexketoprofen;

1 ml of solution for injection contains 36.9 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen (1 ampoule of 2 ml contains 73.81 mg of dexketoprofen trometamol, equivalent to 50 mg of dexketoprofen);

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

Dosage form

Solution for injection.

Main physicochemical properties: transparent colorless solution.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. ATX code M01A E17.

Pharmacological properties

Pharmacodynamics.

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

Mechanism of action

The mechanism of action of NSAIDs is based on a decrease in prostaglandin synthesis by inhibiting cyclooxygenase activity. In particular, the conversion of arachidonic acid to cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2a, PGD2 are formed, as well as prostacyclin PGI2 and thromboxanes ThA2 and ThB2. In addition, inhibition of prostaglandin synthesis may affect other inflammatory mediators, such as kinins, which may also indirectly affect the main effect of the drug.

Dexketoprofen trometamol has been shown to inhibit cyclooxygenase-1 and cyclooxygenase-2 activity in laboratory animals and humans.

Clinical efficacy and safety

Clinical studies in various types of pain have demonstrated that dexketoprofen trometamol has a pronounced analgesic effect. The analgesic effect of dexketoprofen trometamol when administered intramuscularly and intravenously to patients with moderate to severe pain has been studied in various types of pain during surgical interventions (orthopedic and gynecological operations, abdominal operations), as well as in musculoskeletal pain (acute low back pain) and renal colic. During the studies, the analgesic effect of the drug began quickly and reached a maximum within the first 45 minutes. The duration of the analgesic effect after the use of 50 mg of dexketoprofen trometamol is usually 8 hours. Clinical studies have demonstrated that the use of dexketoprofen allows for a significant reduction in the dose of opiates when they are used simultaneously for the purpose of relieving postoperative pain. When patients who were given morphine for postoperative pain relief using a patient-controlled analgesia device were also given dexketoprofen trometamol, they required significantly less morphine (by 30–45%) than patients who received placebo.

Pharmacokinetics.

Absorption

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

Distribution

Similar to other drugs with a high degree of binding to plasma proteins (99%), the volume of distribution of dexketoprofen is on average 0.25 l/kg. The half-life is approximately 0.35 hours, and the half-life is 1–2.7 hours.

Pharmacokinetic studies of multiple administration of the drug have demonstrated that Cmax and AUC after the last intramuscular or intravenous administration do not differ from those after a single administration, indicating the absence of drug accumulation.

Biotransformation and excretion

Dexketoprofen is mainly metabolized by conjugation with glucuronic acid and subsequent renal excretion. After administration of dexketoprofen trometamol, only the S-(+) optical isomer is detected in the urine, indicating that there is no transformation of the drug into the R-(–) optical isomer in humans.

Elderly patients

After single and multiple doses, the extent of exposure to the drug in healthy elderly volunteers (65 years and older) participating in the study was significantly higher (up to 55%) than in young volunteers, but there was no statistically significant difference in maximum concentration and time to reach it. The mean half-life increased (up to 48%), and the determined total clearance decreased.

Standard preclinical studies — safety pharmacology, genotoxicity, and immunopharmacology studies — revealed no special hazard for humans. Chronic toxicity studies in animals revealed a maximum no-effect dose of the drug that was 2 times the recommended human dose. When higher doses were administered to monkeys, the main adverse reactions were blood in the stool, decreased body weight gain, and at the highest dose — gastrointestinal tract pathologies in the form of erosions. These reactions occurred at doses at which exposure to the drug was 14–18 times higher than at the maximum recommended human dose. Carcinogenicity studies in animals were not conducted.

Like all NSAIDs, dexketoprofen can cause embryo or fetal death in animals by directly affecting its development or indirectly by damaging the gastrointestinal tract of the mother.

Indication

The drug Deketa is indicated for the symptomatic treatment of acute pain of moderate to severe intensity in cases where oral administration of dexketoprofen is inappropriate, for example, in postoperative pain, renal colic, and low back pain.

Contraindication

- Hypersensitivity to dexketoprofen, any other non-steroidal anti-inflammatory drug (NSAID) or to the excipients of the drug;

- if substances with a similar effect, such as acetylsalicylic acid or other NSAIDs, provoke the development of asthma attacks, bronchospasm, acute rhinitis or cause the development of nasal polyps, the appearance of urticaria or angioedema;

- if photoallergic or phototoxic reactions occurred during treatment with ketoprofen or fibrates;

- history of gastrointestinal bleeding or perforation associated with NSAID therapy;

- active peptic ulcer/gastrointestinal bleeding or history of gastrointestinal bleeding, ulcers or perforations;

- chronic dyspepsia;

- bleeding in the active phase or increased bleeding;

- Crohn's disease or nonspecific ulcerative colitis;

- severe heart failure;

- moderate or severe renal impairment (creatinine clearance ≤ 59 ml/min);

- severe liver dysfunction (10–15 points on the Child-Pugh scale);

- hemorrhagic diathesis and other blood clotting disorders;

- severe dehydration (due to vomiting, diarrhea or insufficient fluid intake);

- 3rd trimester of pregnancy and breastfeeding period.

Due to its ethanol content, the drug Deketa is contraindicated for neuraxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other types of interactions

The simultaneous use of the following drugs with NSAIDs is not recommended:

- other NSAIDs (including selective cyclooxygenase-2 inhibitors), including salicylates in high doses (≥ 3 g/day). The simultaneous use of several NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to mutual potentiation of the effect;

- anticoagulants: NSAIDs enhance the effect of anticoagulants, such as warfarin, due to the high degree of binding of dexketoprofen to blood plasma proteins, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be carried out under the supervision of a physician and with 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 carried out under the supervision of a physician and with monitoring of relevant laboratory parameters;

- corticosteroids: the risk of developing ulcers in the digestive tract and gastrointestinal bleeding increases;

- lithium (reported for several NSAIDs): NSAIDs increase the level of lithium in the blood, which can lead to intoxication (reduced renal excretion of lithium). Therefore, when starting dexketoprofen, when adjusting the dose or discontinuing the drug, it is necessary to monitor the level of lithium in the blood;

- methotrexate in high doses (at least 15 mg per week): due to the decrease in renal clearance of methotrexate against the background of the use of NSAIDs, its negative effect on the blood system is generally increased;

- hydantoin derivatives and sulfonamides: possible increase in the toxicity of these substances.

The simultaneous use of such agents with NSAIDs requires caution:

- methotrexate in low doses (less than 15 mg per week): due to the decrease in renal clearance of methotrexate against the background of the use of NSAIDs, its negative effect on the blood system in general is increased. In the first weeks of simultaneous use, it is necessary to conduct a blood test every week. Even with a slight impairment of renal function, as well as in elderly patients, treatment should be carried out under strict medical supervision;

- pentoxifylline: there is a risk of bleeding. It is necessary to increase monitoring and check the bleeding time more often;

- zidovudine: there is a risk of increased toxicity to erythrocytes due to the effect on reticulocytes, which leads to severe anemia after the 1st week of NSAID use. Within 1-2 weeks after starting NSAID use, a blood test should be performed and the reticulocyte count checked;

- sulfonylureas: NSAIDs can enhance the hypoglycemic effect of these agents by displacing sulfonylureas in their binding to plasma proteins.

Possible interactions should be considered when using the following agents:

- beta-blockers: NSAIDs can weaken their antihypertensive effect by inhibiting prostaglandin synthesis;

- cyclosporine and tacrolimus: possible increase in nephrotoxicity due to the effect of NSAIDs on renal prostaglandins. In combination therapy, renal function should be monitored;

- thrombolytic agents: increased risk of bleeding;

- antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding;

- probenecid: an increase in the concentration of dexketoprofen in the blood plasma is possible, which is probably due to inhibition of tubular secretion and conjugation of the drug with glucuronic acid and requires correction of the dose of dexketoprofen;

- cardiac glycosides: NSAIDs can increase the concentration of glycosides in blood plasma;

- mifepristone: there is a theoretical risk that the efficacy of mifepristone may be altered by prostaglandin synthetase inhibitors. Limited data suggest that co-administration of NSAIDs on the same day as a prostaglandin does not adversely affect the efficacy of mifepristone or prostaglandin in cervical ripening or contractility, nor does it reduce the clinical efficacy of medical abortion;

- quinoline antibiotics: results of animal studies have shown that the use of quinolone derivatives in high doses in combination with NSAIDs increases the risk of seizures;

- tenofovir: when used together with NSAIDs, the concentration of urea nitrogen and creatinine in the blood plasma may increase, therefore, to assess the possible effect of the combined use of these drugs, it is necessary to monitor renal function;

- deferasirox: when used together with NSAIDs, the risk of gastrointestinal toxicity increases. When using this drug together with deferasirox, careful monitoring of the patient's condition is necessary;

- pemetrexed: Pemetrexed excretion may be reduced when used concomitantly with NSAIDs, therefore special caution should be exercised when using NSAIDs at high doses. Patients with mild to moderate renal impairment (creatinine clearance 45 to 79 ml/min) should avoid NSAIDs for two days before and two days after taking pemetrexed.

Application features

Use with caution in patients with a history of allergic conditions. Avoid using Deketa in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors. The occurrence of adverse reactions can be reduced by using the lowest effective dose for the shortest time necessary to improve the condition.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration or perforation, in some cases fatal, have been reported with all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disease. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued.

Elderly patients. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, sometimes fatal. Treatment of such patients should be started with the lowest possible dose. NSAIDs should be prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as there is a risk of their exacerbation. In the case of the use of any NSAID, if the patient has a history of esophagitis, gastritis and/or peptic ulcer disease, it should be ensured that these diseases are in remission. In patients with existing symptoms of gastrointestinal pathology and with a history of gastrointestinal diseases, it is necessary to monitor the condition of the gastrointestinal tract for possible disorders during the use of the drug, especially gastrointestinal bleeding. For such patients and patients taking low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal adverse reactions, combination therapy with protective agents, such as misoprostol or proton pump inhibitors, should be considered.

Patients, especially the elderly, who have a history of adverse reactions from the digestive tract should report to their doctor any unusual symptoms related to the digestive system, including gastrointestinal bleeding, especially in the initial stages of treatment.

Caution should be exercised when prescribing the drug to patients who are concomitantly taking agents 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.

Kidney safety

Patients with impaired renal function should be prescribed the drug with caution, since against the background of the use of NSAIDs, deterioration of renal function, fluid retention in the body and edema are possible. Due to the increased risk of nephrotoxicity, the drug should be prescribed with caution in treatment with diuretics, as well as in those patients who may develop hypovolemia. During treatment, the body should receive a sufficient amount of fluid to avoid dehydration, which can lead to increased toxic effects on the kidneys. Like other NSAIDs, the drug may increase the concentration of urea nitrogen and creatinine in the blood plasma. Like other prostaglandin synthesis inhibitors, its use may be accompanied by adverse reactions from the kidneys, leading to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Most impaired renal function occurs in elderly patients.

Liver safety

Patients with impaired liver function should be prescribed the drug with caution. As with other NSAIDs, dexketoprofen may cause a temporary and slight increase in the values of some liver parameters, as well as a pronounced increase in the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). If these parameters increase, therapy should be discontinued.

Most liver dysfunction occurs in elderly patients.

Cardiovascular and cerebrovascular safety

Non-selective NSAIDs can reduce platelet aggregation and increase bleeding time by inhibiting prostaglandin synthesis. The simultaneous use of dexketoprofen trometamol and low molecular weight heparin in prophylactic doses in the postoperative period was studied in clinical studies and no effect on coagulation parameters was found. However, patients who use dexketoprofen trometamol simultaneously with drugs that affect hemostasis, such as warfarin, other coumarin drugs or heparins, should be under close medical supervision. The greatest number of cardiovascular system disorders occurs in elderly patients.

Skin reactions

There have been very rare reports of serious skin reactions (some fatal) with NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of these reactions appears to be greatest at the start of treatment, with most patients experiencing them within the first month of treatment. If skin rash, signs of mucosal involvement or other signs of hypersensitivity occur, Deceta should be discontinued.

Other information

Particular caution is required when prescribing the drug to patients:

- with hereditary disorders of porphyrin metabolism (for example, with acute intermittent porphyria);

- with dehydration;

- immediately after major surgical interventions.

If the doctor considers that long-term use of dexketoprofen is necessary, liver and kidney function should be monitored regularly.

In very rare cases, severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed. At the first signs of severe hypersensitivity reactions after administration of Deceta, treatment should be discontinued. Depending on the symptoms, any necessary treatment in such cases should be carried out under medical supervision.

Patients with asthma in combination with chronic rhinitis, chronic sinusitis and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. Administration of dexketoprofen may cause asthma attacks or bronchospasm, especially in patients with allergy to acetylsalicylic acid or NSAIDs.

Severe infectious complications of the skin and soft tissues may develop in the setting of chickenpox. To date, there is no data to rule out the role of NSAIDs in the exacerbation of this infectious process. Therefore, the use of Deceta in chickenpox is not recommended.

Deketa should be administered with caution to patients with hematopoietic disorders, systemic lupus erythematosus, and mixed connective tissue diseases.

Masking of symptoms of underlying infections. Dexketoprofen may mask the symptoms of infection, which may delay the initiation of appropriate treatment and thereby worsen the consequences of the infection. Masking of symptoms has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When this medicinal product is administered for the relief of pain associated with an infection, it is recommended to monitor the infection. In the community setting, the patient should seek medical advice if symptoms persist or worsen.

Excipients

Deceta contains up to 200 mg of ethanol per dose (2 ml of solution) which is equivalent to 5 ml of beer or 2.08 ml of wine per dose.

Harmful for patients with alcoholism. Caution should be exercised when used in pregnant and breastfeeding women, children, and patients with liver disease and epilepsy.

This medicinal product contains less than 1 mmol sodium (23 mg) per (2 ml solution), i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

The use of the drug Deketa is contraindicated in the third trimester of pregnancy and during breastfeeding.

Pregnancy

The use of Deceta from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible upon discontinuation of the drug. In addition, cases of narrowing of the ductus arteriosus have been reported after treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment. Therefore, Deceta should not be administered during the first and second trimesters of pregnancy unless clearly necessary. If Deceta is used in a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose should be kept as low and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be considered in case of exposure to Deceta for several days starting from the 20th week of pregnancy. Deceta should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.

During the third trimester, all prostaglandin synthesis inhibitors can cause:

risks to the fetus:

- cardiopulmonary toxic syndrome (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);

- impaired renal function (see above), which may progress to renal failure with the development of oligohydramnios;

Risks at the end of pregnancy for mother and child:

- prolongation of bleeding time (effect of inhibiting platelet aggregation), which is possible even when using low doses;

- delayed uterine contractions with corresponding delayed labor and prolonged labor.

Breast-feeding

There is no data on the penetration of dexketoprofen into breast milk. The drug Deketa is contraindicated during breastfeeding.

Fertility

As with all NSAIDs, dexketoprofen trometamol may impair female fertility and is therefore not recommended in women attempting to conceive. If a woman has difficulty conceiving or is undergoing investigation of infertility, discontinuation of the drug should be considered.

Ability to influence reaction speed when driving vehicles or other mechanisms

While using the drug Deketa, dizziness, visual disturbances, or drowsiness may occur. In such cases, the ability to react quickly, navigate the road situation, and drive vehicles or other mechanisms may deteriorate.

Method of administration and doses

Adults. The recommended dose is 50 mg every 8–12 hours. If necessary, a second dose is administered after 6 hours. The maximum daily dose should not exceed 150 mg. The drug is intended for short-term use, therefore it should be used only during the period of acute pain (no more than 2 days). Patients should be transferred to oral analgesics when possible. The lowest effective dose should be used for the shortest possible period necessary to relieve symptoms. In moderate to severe postoperative pain, dexketoprofen can be used according to indications in the same recommended doses in combination with opioid analgesics.

Elderly patients: Dose adjustment is usually not required. However, due to physiologically decreased renal function, a lower dose of dexketoprofen is recommended, namely: the maximum daily dose is 50 mg in mild renal impairment.

Liver disease. For patients with mild to moderate liver disease (Child-Pugh score 5-9), the maximum daily dose should be reduced to 50 mg and liver function should be closely monitored. In severe liver disease (Child-Pugh score 10-15), dexketoprofen is contraindicated.

Renal dysfunction. For patients with mild renal impairment (creatinine clearance 60–89 ml/min), the maximum daily dose should be reduced to 50 mg. In patients with moderate or severe renal impairment (creatinine clearance 59 ml/min), dexketoprofen is contraindicated.

Children and adolescents: The drug should not be prescribed to children and adolescents due to the lack of data on the efficacy and safety of its use in pediatric patients.

Method of application

Intramuscular administration. The solution for injection should be injected slowly deep into the muscle.

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 lactated Ringer's 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 carried out within 10–30 minutes. Avoid exposure to natural daylight on the prepared solution.

The drug Deceta, diluted in 100 ml of 0.9% sodium chloride solution or glucose solution, can be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

The drug Deketa should not be mixed in an infusion solution with promethazine and pentazocine.

Intravenous injection (bolus administration).

If necessary, the contents of one ampoule (2 ml of solution for injection) are administered intravenously over at least 15 seconds.

The drug Deketa should not be mixed in small volumes (e.g. in a syringe) with solutions of dopamine, promethazine, pentazocine, pethidine, and hydrocortisone, because a white precipitate forms.

The drug Deketa can only be mixed with the drugs listed above.

For intramuscular or intravenous injection, Deketa should be administered immediately after withdrawal from the ampoule. The intravenous infusion solution should be used immediately after preparation. The healthcare professional is responsible for the storage conditions and duration. The prepared solution retains its properties for 24 hours at 25°C, provided that it is protected from daylight.

When storing diluted drug solutions in polyethylene bags or in products made of ethyl vinyl acetate, cellulose propionate, low-density polyethylene, and polyvinyl chloride designed for administration, no changes in the content of the active substance due to sorption were observed.

The reconstituted Deketa solution is intended for single use only, therefore any remaining solution should be discarded. Before administering the drug, ensure that the solution is clear and colorless. Do not use a solution containing solid particles.

Children.

The drug should not be prescribed to children and adolescents due to the lack of data on the efficacy and safety of its use in pediatric patients.

Overdose

Symptoms of overdose are unknown. Similar drugs cause disorders of the digestive tract (vomiting, anorexia, abdominal pain) and the nervous system (drowsiness, dizziness, disorientation, headache). In case of accidental overdose, symptomatic treatment should be immediately initiated according to the patient's condition. Dexketoprofen trometamol is removed from the body by dialysis.

Adverse reactions

The table below lists adverse reactions whose relationship to dexketoprofen trometamol is considered minimally possible based on clinical data, as well as adverse reactions reported during the post-marketing period.

Possible development of peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients. According to available data, nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic phenomena, abdominal pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis and Crohn's disease may occur with the use of dexketoprofen. Gastritis is less common. Edema, arterial hypertension and heart failure have also been noted.