Dexarom solution for injection 50 mg/2 ml ampoule 2 ml No. 10

Instructions Dexarom solution for injection 50 mg/2 ml ampoule 2 ml No. 10

Composition

active substance: 1 ml of solution for injection contains dexketoprofen trometamol 36.9 mg, equivalent to dexketoprofen 25 mg

(1 ampoule of 2 ml contains dexketoprofen trometamol 73.8 mg, which is equivalent to dexketoprofen 50 mg);

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 a propionic acid salt that has analgesic, anti-inflammatory and antipyretic effects and belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs). Its mechanism of action is based on a decrease in prostaglandin synthesis by inhibiting cyclooxygenase. In particular, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2a, PGD2 are formed, as well as prostacyclin PGI2 and thromboxanes TXA2 and TXB2. In addition, inhibition of prostaglandin synthesis may affect other inflammatory mediators, such as kinins, which may also indirectly affect the main action of the drug. The inhibitory effect of dexketoprofen trometamol on the isoenzymes of cyclogenesis COX-1 and COX-2 has been demonstrated in animals and humans. 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 trometamol 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 35-45%) than patients who received placebo.

Pharmacokinetics.

After intramuscular administration of dexketoprofen trometamol, 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. Pharmacokinetic studies of multiple use of the drug have shown that AUC and Cmax (mean maximum value) after the last intramuscular and intravenous administration do not differ from those after a single administration, which indicates the absence of cumulation of the drug. 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. 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 the drug is not transformed into the R-(−) optical isomer. After administration of single and multiple doses, the degree of exposure of healthy elderly volunteers (65 years and older) participating in the study was significantly higher (up to 55%) than that of young volunteers, but no statistically significant difference in the maximum concentration and time to its achievement was observed. The mean half-life increased (up to 48%), and the determined total clearance decreased.

Indication

Symptomatic treatment of acute pain of moderate to severe intensity in cases where oral administration of the drug is inappropriate, such as 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;

· active phase of peptic ulcer disease or bleeding, suspicion of them or history of recurrent peptic ulcer disease or bleeding (at least two confirmed facts of ulcer or bleeding);

· history of gastrointestinal bleeding or perforation related to previous NSAID therapy;

Crohn's disease or nonspecific ulcerative colitis;

· history of bronchial asthma;

· severe heart failure;

· moderate or severe renal impairment (creatinine clearance < 50 ml/min);

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

· hemorrhagic diathesis and other blood clotting disorders;

· III trimester of pregnancy and breastfeeding period;

· use for the purpose of neuraxial (intrathecal or epidural) administration (due to the ethanol content).

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 salicylates in high doses (≥ 3 g/day). The simultaneous use of several NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to their mutually reinforcing effects;

· 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 the control 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:

Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists. Dexketoprofen reduces the effectiveness of diuretics and other antihypertensive agents. In some patients with impaired renal function (for example, in cases of dehydration or in the elderly), the use of cyclooxygenase inhibitors simultaneously with ACE inhibitors or angiotensin II receptor antagonists may worsen renal function, which is usually reversible. When using dexketoprofen together with any diuretic, it is necessary to ensure that the patient is not dehydrated, and at the beginning of treatment it is necessary to monitor renal function;

· 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;

· sulfonylurea drugs: NSAIDs can enhance the hypoglycemic effect of these drugs by replacing them in their binding to blood 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: due to the theoretical possibility of a decrease in the effectiveness of mifepristone under the influence of prostaglandin synthetase inhibitors, NSAIDs should be prescribed only 8-12 days after mifepristone therapy;

· quinolone: results of animal studies have shown that the use of quinolone derivatives in high doses in combination with NSAIDs increases the risk of seizures.

Application features

Use with caution in patients with a history of allergic conditions. Avoid using Dexarom.

in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors. Adverse reactions can be reduced by using the lowest effective dose for the shortest time necessary to improve the condition.

Gastrointestinal bleeding, ulceration or perforation, in some cases fatal, has 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 occurs, the drug should be discontinued. The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose in patients with a history of ulcer, especially if complicated by bleeding or perforation, and in the elderly. Elderly patients have an increased incidence 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 disease (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation. Before starting the use of dexketoprofen trometamol in patients with 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, the condition of the gastrointestinal tract should be monitored for possible disorders, especially gastrointestinal bleeding, during the use of the drug.

For such patients and patients who use acetylsalicylic acid in low doses or other agents that increase the risk of adverse reactions from the digestive tract, the possibility of combination therapy with protective drugs, 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 notify their doctor of all unusual symptoms related to the digestive system, in particular gastrointestinal bleeding, especially in the initial stages of treatment.

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

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 has been 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 coumarins or heparins, should be closely monitored by a physician.

Patients with arterial hypertension and/or mild to moderate congestive heart failure should be closely monitored by a physician due to possible fluid retention and peripheral edema.

According to available clinical and epidemiological data, the use of some NSAIDs, especially at high doses and over long periods, is associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. There is insufficient evidence to exclude dexketoprofen trometamol from this list.

In uncontrolled hypertension, congestive heart failure, confirmed ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease, dexketoprofen trometamol should be used only after careful assessment of the patient's condition. The same applies to long-term treatment of patients with risk factors for cardiovascular disease, such as patients with arterial hypertension, hyperlipidemia, diabetes mellitus, and smokers.

As with other NSAIDs, the drug may cause temporary and slight increases in some liver function tests, as well as significant increases in AST and ALT. If these values increase, treatment should be discontinued.

The drug should be prescribed with caution to patients with impaired liver and/or kidney function, as well as to patients with arterial hypertension and/or congestive heart failure, since they may experience deterioration of kidney function, fluid retention in the body and the appearance of peripheral edema against the background of the use of NSAIDs. Due to the increased risk of nephrotoxicity, the drug should be used with caution in treatment with diuretics, as well as in patients who may develop hypovolemia.

Particular caution should be exercised when treating patients with a history of heart disease, in particular with episodes of heart failure, since the use of the drug increases the risk of heart failure.

Most kidney, cardiovascular, and liver dysfunction occurs in elderly patients.

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

As with other NSAIDs, dexketoprofen trometamol may mask the symptoms of infectious diseases. There have been reports of exacerbation of soft tissue infections during the use of NSAIDs. Therefore, if symptoms of bacterial infection appear or worsen during use, patients are advised to seek medical advice immediately.

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. The drug should only be used during the first and second trimesters of pregnancy if clearly needed.

Each ampoule of Dexarom contains 200 mg of ethanol (alcohol), which is equivalent to 5 ml of beer or 2.08 ml of wine per dose. The drug is harmful to 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 dose, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

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

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. Epidemiological studies have shown that the use of drugs that inhibit prostaglandin synthesis in early pregnancy increases the risk of miscarriage, fetal heart defects and anterior abdominal wall nonunion. Thus, the absolute risk of developing cardiovascular anomalies increased from < 1% to approximately 1.5%. It is believed that the risk of such events increases with increasing dose and duration of therapy. Dexketoprofen trometamol should be prescribed in the first and second trimesters of pregnancy only if clearly needed. Women planning a pregnancy or women in the first and second trimesters of pregnancy should be given the lowest possible effective dose for the shortest possible duration of treatment.

During the third trimester, all prostaglandin synthesis inhibitors pose the following risks:

for the fetus:

· cardiopulmonary toxic syndrome (with obstruction of the ductus arteriosus and pulmonary hypertension);

· impaired renal function, which may progress to renal failure with the development of oligohydramnios;

for mother and child (at the end of pregnancy):

· 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.

There is no data on the penetration of dexketoprofen into breast milk.

Ability to influence reaction speed when driving vehicles or other mechanisms

When using dexketoprofen, dizziness and drowsiness are possible, which may affect the ability to drive and operate other mechanisms.

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. Adverse reactions can be reduced by using the lowest effective dose for the shortest possible time necessary to improve the condition. For moderate or severe postoperative pain, the drug can be used according to indications in the same recommended doses in combination with opioid analgesics.

Liver disease. For patients with mild or 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. The drug is contraindicated in severe liver disease (Child-Pugh score 10-15).

Renal dysfunction. For patients with mild renal impairment (creatinine clearance 50-80 ml/min), the maximum daily dose should be reduced to 50 mg. In patients with moderate or severe renal impairment (creatinine clearance < 50 ml/min), the drug is contraindicated.

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

Intravenous infusion.

For intravenous infusion, the contents of the 2 ml ampoule should be diluted in 30-100 ml of 0.9% sodium chloride solution, glucose solution or lactated Ringer's solution. The solution for infusion should be prepared under aseptic conditions, avoiding exposure to natural daylight. The prepared solution should be transparent. The infusion should be carried out within 10-30 minutes. Avoid exposure to natural daylight on the prepared solution.

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

Dexar 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 can be mixed in small volumes (e.g., syringes) with injectable solutions of heparin, lidocaine, morphine, and theophylline.

Dexar 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 can only be mixed with the medicines listed above.

For intramuscular or intravenous injection, the drug should be administered immediately after withdrawal from the ampoule. The solution for intravenous infusion should be used immediately after preparation. Further responsibility for the conditions and duration of storage lies with the healthcare professional. The prepared solution retains its properties for 24 hours at a temperature of 25 ºС, 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.

Dexarom is intended for single use, 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 use of the drug in children has not been studied, therefore, prescribing dexketoprofen to patients in this age group is not recommended.

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, based on clinical data, is considered to be minimally possible, 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, epigastric pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis and Crohn's disease may occur against the background of the drug. Gastritis is less common. Edema, arterial hypertension and heart failure, which may be caused by the use of NSAIDs, have also been noted. As with the use of 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 reactions (purpura, aplastic and hemolytic anemia, rarely - agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are possible.

According to clinical trial results and epidemiological data, the use of some NSAIDs, especially in high doses and for a long time, slightly increases the risk of developing pathology caused by arterial thrombosis, such as myocardial infarction and stroke.

Expiration date

4 years.

Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store in the original packaging out of the reach of children. No special storage conditions required.

Packaging

2 ml in a brown glass ampoule; 5 ampoules in a contour blister pack.

1 or 2 contour blister packs in a cardboard box.

Vacation category

According to the recipe.

Producer

K.T. ROMPHARM COMPANY SRL

(SC ROMPHARM COMPANY SRL)

Location of the manufacturer and its business address

Eroilor St. No. 1A, Otopeni, 075100, Ilfov County, Romania

(Eroilor str., No 1A, Otopeni city, 075100, county Ilfov, Romania)