Pharmacological properties of the drug Dexalgin
An NSAID that has analgesic, anti-inflammatory and antipyretic effects due to a decrease in prostaglandin synthesis due to inhibition of the COX system. After oral administration, the effect of the drug begins after 30 minutes and lasts 3–6 hours. The maximum concentration of the drug in the blood serum when taken orally is achieved on average after 30 minutes (15–60 minutes). The distribution time and half-life of dexketoprofen are 0.35 and 1.65 hours, respectively. Metabolized primarily through binding to glucuronic acid followed by excretion by the kidneys. Does not accumulate in the body.
Journal "Emergency Medicine" 3(16) 2008
Since time immemorial, people have looked at pain as a harsh and inevitable companion, not always realizing that it is a faithful guardian, a vigilant sentinel of the body and at the same time a constant ally and a real assistant to the healer. The sensation of pain (its strength, severity, duration, reaction to it) is associated in the vast majority of cases with the individual characteristics of the patient. Pain, especially acute pain, on the one hand, indicates damage, on the other hand, it causes a whole cascade of biochemical reactions in the body that are close to stress damage. And these reactions, in turn, through a feedback mechanism, can aggravate pain [1, 2].
There are many classifications of pain syndromes. Most often, they are divided according to the mechanism of development, distinguishing four types of pain: somatogenic, neurogenic, vegetative and psychogenic [1].
Psychogenic pain includes pain associated with depression, hysterical reactions, neuroses, and phobias.
Autonomic pain occurs with pathological irritation of the structures of the autonomic nervous system, and is often associated with the involvement of the vascular system in the process in various pathologies of internal organs.
Neurogenic pain syndromes, or neuropathies, arise due to damage to the structures of the central and peripheral nervous system.
Somatogenic pain is associated with the impact of damaging factors on body tissues - compression, trauma, inflammation, ischemia, etc.
Undoubtedly, the patient's first reaction to pain is the desire to get rid of it as soon as possible.
There are a sufficient number of painkillers and, therefore, different classifications of analgesic drugs.
From our point of view, the most optimal is the existing classification of painkillers depending on the level of antinociceptive action, developed by the staff of the Department of Emergency and Emergency Care of KhMAPO (A.Yu. Pavlenko). In this classification, one of the main places is occupied by non-steroidal anti-inflammatory drugs (NSAIDs) [5].
Despite the high effectiveness of various types of pain relief, NSAIDs primarily affect pain transduction processes. The leading link in the mechanism of action of these drugs is the inhibition of the synthesis of prostaglandins (the main components of not only inflammatory reactions, but also pain syndromes of various etiologies), caused by a decrease in the activity of cyclooxygenase (COX), a key enzyme in the metabolism of arachidonic acid. Due to this, inflammatory components such as hyperemia, fever and pain are stopped, while the reactivity of lymphocytes and neutrophils is inhibited, which also explains the anti-inflammatory and analgesic effect of NSAIDs [3, 4].
Based on the degree of selectivity for the blockade of COX isoenzymes, NSAIDs can be divided into four groups:
- selective COX-1 inhibitors (for example, low doses of aspirin);
- non-selective inhibitors of COX-1 and COX-2 (such as diclofenac, ibuprofen, indomethacin, paracetamol, piroxicam, etc.);
- selective COX-2 inhibitors (for example, nimesulide, meloxicam);
- specific COX-2 inhibitors (such as celecoxib, rofecoxib, valdecoxib, etoricoxib, parecoxib (water-soluble salt of valdecoxib)).
In Fig. Figure 1 presents the role of two COX isoenzymes in the regulation of physiological and pathological processes in the human body. As we can see, both isoenzymes are involved in the regulation and modulation of pathological processes such as pain and inflammation. And COX-2, traditionally considered “pathological,” is responsible for a number of physiological processes, such as the regulation of reproductive function, kidney function, bone tissue remodeling, regulation of pancreatic function, etc. A number of studies have proven the participation of COX-1 in the development of inflammatory processes and pain [6–8].
Considering the fact that both COX isoenzymes take part in the pathophysiological mechanisms of the development of pain syndrome (acute pain syndrome), it seems most appropriate to use drugs with balanced inhibitory activity against COX-1 and COX-2.
Approaching the analgesic activity of opiates, NSAIDs do not have the side effects characteristic of the latter. In addition, NSAIDs eliminate not only nociceptive efferentation, but also endocrine manifestations of the pain stress response [3].
Injectable forms of NSAIDs are most suitable for pain relief at all stages of care, especially in urgent situations at the prehospital and hospital stages.
Recently, a new injectable and tablet analgesic has appeared in clinical practice - dexketoprofen trometamol (Dexalgin).
Dexalgin is an optically pure dextrorotatory isomer of ketoprofen, due to which it has a better gastrointestinal tolerance profile and a lower metabolic load on the body due to the possibility of using lower therapeutic doses. In addition, it is important that dexketoprofen (Dexalgin) is metabolized in the body without the participation of liver cytochromes, which significantly reduces the risk of drug-drug interactions.
In terms of its effect on COX isoenzymes, Dexalgin is a balanced inhibitor of COX-1 and COX-2, blocking their activity to the same extent.
The mechanism of the analgesic action of Dexalgin is:
- blocking the production of pain mediators in the periphery due to inhibition of COX activity;
- blockade of pain transmission along peripheral nerves and pathways of the central nervous system due to depolarization of neuron membranes;
- blockade of the production of pain mediators in the central nervous system, including the cortex and deep parts of the brain, due to inhibition of COX activity in these parts.
The effect of Dexalgin on the production of pain mediators at the level of the central nervous system is due to its ability to penetrate the blood-brain barrier due to its high lipophilicity.
On the basis of the traumatology department of ZMAPO, in 21 patients admitted to the trauma department with injuries of the musculoskeletal system (of which 8 had injuries to the upper limb and 13 had fractures of the lower limbs at various levels), the drug Dexalgin was used as postoperative pain relief. a dose of 50 mg intravenously immediately after the patient recovers from anesthesia 1 time per day instead of administering narcotic drugs. Over the next 24 hours, Dexalgin was administered 2 times a day instead of opiates. The age of the patients ranged from 22 to 64 years.
The victims were distributed by gender as follows: women – 9, men – 12.
A group of 21 patients, comparable in severity of injury, age and gender, who received opiates as postoperative pain relief, was selected as a control.
The following indicators were assessed in patients of both groups: speed of pain relief, reduction in its intensity, effect of the drug on the general well-being of the patient, side effects. The assessment was carried out 1 and 6 hours after the administration of Dexalgin.
Analysis of the results revealed the following: in the group of patients receiving opiates, almost all patients, regardless of age, gender and severity of injury, noted increased lethargy, drowsiness, and persistent weakness. All these manifestations had a clear temporal connection with the administration of opiates. Three patients experienced urinary retention on the second day of administration of narcotic analgesics.
In the main group of patients, during the use of Dexalgin, the above subjective sensations were not identified, nor was the effect of the drug on urinary function noted.
The analgesic effect of opiates (17 patients were administered omnopon at a dose of 4 mg and four patients were administered morphine at a dose of 4 mg) occurred 9–10 minutes later than in the main group of patients. We attribute this to different routes of administration: opiates were administered subcutaneously or intramuscularly, Dexalgin was administered intravenously. At the same time, it should be noted that the duration of action of opiates is much shorter; in some cases, 3 and sometimes 4 injections of the drug were required, especially in the first day after surgery.
In the group of patients receiving Dexalgin, in 81% of cases (17 patients), a double dose (every 12 hours) in the first two postoperative days was sufficient, thus replacing the administration of opiates. The remaining 4 (19%) patients received the drug once. Only 2 patients in the Dexalgin group required additional prescription of narcotic analgesics to achieve adequate pain relief. Starting from the third day after surgery, without the use of narcotic drugs, Dexalgin (50 mg) was administered intramuscularly once a day. In 76% of patients in the control group and in 86% of patients in the main group, significant pain relief occurred by the end of the first hour after administration. The duration of the analgesic effect, that is, the state when pain practically did not bother the patient, averaged 4.5 ± 1.8 hours in the control group and 6.5 ± 1.2 hours in the main group.
These indicators confirm the data on the prolonged analgesic effect of Dexalgin, which is associated with a blocking effect on prostaglandins and, as a consequence, a decrease in the inflammatory response.
The remaining 5 (23.8%) patients in the control group and 3 (14%) in the main group noted slight relief after the administration of these drugs, which, in our opinion, is associated with the severity of the injuries. In these cases, patients in the main group were given an additional dose of Dexalgin 50 mg, and patients in the control group were given opiates. This made it possible, in both the first and second cases, to transfer the feeling of pain in patients from the category “strong” to the category “moderate”, and most often - “insignificant”.
Against the background of analgesia, patients in the control and main groups were administered sedatives in order to prevent the development of stress injuries, in most cases sibazon at a dose of 10 mg, which increased the effectiveness of analgesic therapy.
Subsequently, the duration of use of Dexalgin or opiates depended on the patient’s subjective sensation of pain, the severity of the condition, and the development of complications.
On average, the duration of use of Dexalgin was 4.6 ± 2.0 days, of opiates - 4.8 ± 1.6 days. The patient's overall assessment of the effectiveness of Dexalgin was also studied. 17 (81%) patients rated it as good, 2 (9.5%) as excellent, 1 (4.8%) as satisfactory, and in 1 (4.8%) case the drug was rated as ineffective. In the last 2 cases, opiates were administered to patients to achieve adequate pain relief.
We did not find any side effects when taking Dexalgin in patients of the main group.
An important advantage of Dexalgin over narcotic analgesics is its effect on damage such as reducing inflammation, antipyretic effect, and preventing peripheral sensitization. These positive properties of the drug, plus a pronounced analgesic effect, make it possible to expand the scope of its use and use it as an analgesic not only for injuries, but also for various somatic diseases, for which NSAIDs have already proven themselves well.
The results of studies of the analgesic effect of Dexalgin in patients in the trauma department allowed us to draw the following conclusions:
— a single (if necessary, double) administration of dexketoprofen trometamol at a dose of 50 mg intravenously or intramuscularly provided stable, effective and long-lasting pain relief;
— the effectiveness of dexketoprofen trometamol at a dose of 50 mg was similar to 4 mg of morphine in terms of the speed of onset of effect, but the duration of pain relief was significantly longer;
— the use of dexketoprofen trometamol in a dose of 50 mg 1 or 2 times a day significantly reduces the need for narcotic analgesics and does not cause lethargy, drowsiness, or respiratory dysfunction, which is typical of narcotic analgesics;
— during the study, no side effects or complications were identified when taking dexketoprofen trometamol.
Use of the drug Dexalgin
Depending on the intensity of the pain, a single dose of the drug is 12.5–25 mg every 8 hours. It is not recommended to take 75 mg (3 tablets) per day. Dexalgin is taken as needed and is not intended for long-term treatment. It is advisable to start therapy in elderly patients, with mild renal impairment, as well as with mild or moderate liver dysfunction with low doses (daily dose is 50 mg - 2 tablets). If well tolerated, the dose can be increased to the usual one.
Dexalgin®
Undesirable side effects can be minimized by using the drug in the lowest effective dose with the minimum duration of use necessary to relieve pain.
Gastrointestinal disorders
Erosive and ulcerative lesions of the gastrointestinal tract, gastrointestinal bleeding or perforation (in some cases, fatal) were observed with the use of any NSAIDs at different stages of treatment and regardless of the presence of characteristic symptoms or a history of serious gastrointestinal pathology. If gastrointestinal bleeding or ulcerative lesions occur, use of Dexalgin® should be discontinued.
The risk of serious gastrointestinal complications increases with increasing doses of NSAIDs in elderly patients. Elderly patients have a higher incidence of side effects, especially gastrointestinal bleeding and perforation, which can be fatal. In this category of patients, the maximum daily dose is 50 mg (see section “Dosage and Administration”).
As with any NSAID, it is necessary to ascertain the patient's history of esophagitis, gastritis and/or peptic ulcers before prescribing treatment with dexketoprofen. Patients with gastrointestinal symptoms or a history of gastrointestinal disease should be monitored for the occurrence of digestive disorders, especially gastrointestinal bleeding.
The simultaneous administration of gastroprotectors (misoprostol or proton pump blockers) is recommended for such patients, as well as patients who require the simultaneous use of low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (see section “Interaction with other drugs”).
Patients with a history of gastrointestinal drug toxicity, especially elderly patients, should report any gastrointestinal symptoms (especially bleeding), especially during initiation of therapy.
Patients concomitantly taking corticosteroids, antiplatelet agents (for example, aspirin) or anticoagulants (for example, warfarin), selective serotonin reuptake inhibitors should be under close medical supervision, as they have an increased risk of gastrointestinal bleeding.
Kidney disorders
Caution should be exercised in patients with impaired renal function. The use of NSAIDs may lead to deterioration of renal function, fluid retention and edema.
Caution should be exercised when using Dexalgin® in patients concomitantly taking diuretics and patients who may develop hypovolemia, due to the increased risk of nephrotoxicity.
Like other NSAIDs, Dexalgin® can lead to increased concentrations of creatinine and nitrogen in the blood plasma.
Like other prostaglandin synthesis inhibitors, Dexalgin® may have side effects on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure.
When using the drug Dexalgin®, it is necessary to consume a sufficient amount of fluid to prevent the development of dehydration and possible toxic effects on the kidneys. Renal dysfunction is more likely in elderly patients (see section "Dosage and Administration").
Liver disorders
Caution must be exercised when using Dexalgin® in patients with impaired liver function. As with the use of other NSAIDs, during therapy with Dexalgin®, a slight transient increase in laboratory parameters characterizing liver function and a significant increase in the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) may be observed. In case of a significant increase in the corresponding indicators, the use of the drug Dexalgin should be discontinued. Elderly patients are more likely to develop liver problems.
Cardiovascular and cerebrovascular complications
Before starting to use Dexalgin® in patients with arterial hypertension and/or mild to moderate heart failure, caution should be exercised and consult a doctor, since in this category of patients the use of NSAIDs can lead to fluid retention, edema and increased blood pressure .
Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a slight increase in the risk of acute myocardial infarction or stroke. There is insufficient data to exclude the risk of these events when using dexketoprofen.
In patients with uncontrolled arterial hypertension, coronary heart disease (CHD), congestive heart failure, peripheral arterial disease and/or cerebrovascular disease, Dexalgin® should be used with caution.
A similar approach is applicable to patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking).
All non-selective NSAIDs can inhibit platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of Dexalgin® in patients simultaneously taking drugs that affect the hemostatic system, such as warfarin, coumarin derivatives and heparins, is not recommended.
If the doctor decides on long-term use of dexketoprofen, monitoring of peripheral blood parameters and the functional state of the liver and kidneys is necessary.
Elderly patients
Elderly patients are especially susceptible to adverse reactions when using NSAIDs, including the risk of life-threatening gastrointestinal bleeding and perforation, and decreased renal, liver, and cardiac function. When using the drug Dexalgin® in this category of patients, proper clinical monitoring is necessary.
Elderly patients should take Dexalgin® starting with a lower dose (maximum daily dose is 50 mg). If well tolerated, doses recommended for the general population may be used.
There is evidence of rare cases of severe skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis), including death, with the use of NSAIDs.
It is assumed that the greatest risk of developing toxic skin reactions exists during the initial period of therapy, since in most cases the development of skin reactions was noted during the first month of treatment. At the first manifestations of a skin rash, damage to the mucous membranes or other signs of an allergic reaction, the use of the drug Dexalgin® should be stopped immediately.
In very rare cases, severe hypersensitivity reactions (eg anaphylactic shock) have been observed. If the first signs of a hypersensitivity reaction appear, use of the drug Dexalgin should be stopped and consult a doctor. Depending on the severity of symptoms, the patient should receive specialized medical care.
Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. If signs of infection or deterioration in health are detected while using the drug Dexalgin®, the patient should immediately consult a doctor.
In very rare cases, severe soft tissue skin infections may occur during a chickenpox infection. The use of Dexalgin® for chickenpox should be avoided.
The drug Dexalgin® contains sucrose, therefore patients with hereditary fructose intolerance, sucrase-isomaltase deficiency and glucose-galactose malabsorption syndrome should not take the drug Dexalgin®.
The use of Dexalgin® may adversely affect female fertility and is not recommended for women planning pregnancy. In women who have problems conceiving or are undergoing examination for infertility, it is necessary to consider the possibility of discontinuing the drug Dexalgin®.
Side effects of the drug Dexalgin
Often (1–10% of cases) nausea and/or vomiting, abdominal pain, dyspepsia, diarrhea occur; in 0.1–1% of cases - weakness, increased fatigue, sleep disturbances, anxiety, fear, headache, dizziness, hot flashes, skin rash, palpitations, dry mouth, gastritis, constipation, bloating, in 0.01–0 .1% - paresthesia, increased blood pressure, peripheral edema, bradypnea, peptic ulcer, ulcer perforation, bleeding, anorexia, increased activity of liver enzymes, urticaria, increased sweating, polyuria, back pain, loss of consciousness, in women - menstrual irregularities, in men - dysfunction of the prostate gland. In isolated cases (≤0.01%), neutropenia, thrombocytopenia, visual impairment, tinnitus, tachycardia, hypotension, bronchospasm, shortness of breath, damage to the pancreas, liver, severe reactions from the skin and mucous membranes (Stevens-Johnson syndrome, Lyell's syndrome), vascular edema, photosensitivity skin reactions, skin itching, kidney damage (nephritis or nephrotic syndrome), anaphylactic reactions, angioedema of the face.
Dexalgin film-coated tablets 25 mg 10 pcs
Undesirable side effects can be minimized by using the drug in the lowest effective dose with the minimum duration of use necessary to relieve pain.
The risk of complications from the gastrointestinal tract increases in patients with a history of ulcerative lesions of the gastrointestinal tract, in elderly patients, with an increase in the dose of NSAIDs; therefore, the use of Dexalgin® 25 in this category of patients should begin with the lowest recommended dose.
For patients in the above categories, as well as patients who require simultaneous use of low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, additional simultaneous use of gastroprotectors (misoprostol or proton pump blockers) is recommended.
In patients simultaneously taking antiplatelet agents or anticoagulants, glucocorticosteroids, the risk of gastrointestinal bleeding also increases.
Patients with gastrointestinal disorders or a history of gastrointestinal diseases should be under close medical supervision. If gastrointestinal bleeding or ulcerative lesions occur, use of Dexalgin® 25 should be discontinued.
The drug Dexalgin ®25 should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), since exacerbation of these diseases is possible.
All NSAIDs can inhibit platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of Dexalgin® 25 in patients simultaneously taking drugs that affect the hemostatic system, such as warfarin, coumarin derivatives and heparins, is not recommended.
Like other NSAIDs, Dexalgin® 25 can lead to increased concentrations of creatinine and nitrogen in the blood plasma. Like other prostaglandin synthesis inhibitors, Dexalgin® 25 may have side effects on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Caution should be exercised when using the drug in patients concomitantly using diuretics and patients who may develop hypovolemia, due to the increased risk of nephrotoxicity.
As with the use of other NSAIDs, during therapy with Dexalgin® 25, a slight transient increase in the activity of liver enzymes may be observed. In elderly patients, monitoring of liver and kidney function is necessary. In case of a significant increase in the corresponding indicators, the use of the drug Dexalgin® 25 should be discontinued.
Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. If signs of infection or deterioration in health are detected while using the drug Dexalgin® 25, the patient should immediately consult a doctor.
The drug can cause fluid retention in the body, therefore, in patients with arterial hypertension, renal and/or heart failure, Dexalgin® 25 should be used with extreme caution. If the condition worsens, the use of Dexalgin® 25 should be discontinued.
In patients with uncontrolled arterial hypertension, coronary artery disease, congestive heart failure, peripheral arterial disease and/or cerebrovascular disease, the drug should be used with caution. A similar approach is applicable to patients with risk factors for developing cardiovascular diseases (arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).
Caution must be exercised when prescribing Dexalgin® to patients with a history of cardiovascular disease, especially patients with heart failure, due to the possible risk of progression.
Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a small risk of acute myocardial infarction or stroke. There is insufficient data to exclude the risk of these events when using dexketoprofen.
Elderly patients are especially susceptible to adverse reactions when using NSAIDs, including the risk of life-threatening gastrointestinal bleeding and perforation, and decreased renal, liver, and cardiac function. When using the drug Dexalgin® 25 in this category of patients, proper clinical monitoring is necessary.
There is evidence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) with the use of NSAIDs. At the first manifestations of a skin rash, damage to the mucous membranes or other signs of an allergic reaction, you should immediately stop taking Dexalgin® 25 and consult a doctor.
Impact on the ability to drive vehicles and other mechanisms
Due to the possible occurrence of dizziness and drowsiness during the period of use of the drug Dexalgin® 25, the ability to concentrate and the speed of psychomotor reactions in patients may decrease, especially in the first hour after administration. Therefore, while using the drug Dexalgin® 25, care should be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Drug interactions Dexalgin
Combined use with other NSAIDs, oral anticoagulants, pentoxifylline is not recommended due to the increased risk of bleeding; with lithium preparations - due to a possible increase in the concentration of the latter in the blood and the development of its toxic manifestations; with methotrexate in high doses (15 mg/week) - due to an increase in its toxic effect on the blood. When used in combination, dexketoprofen may increase the toxicity of hydantoin and sulfonamides. Caution is required when used in combination with diuretics and ACE inhibitors - a weakening of the antihypertensive effect and/or development of acute renal failure is possible; with methotrexate in low doses (≤15 mg/week) - its hematotoxicity may increase; with zidovudine - possible inhibition of erythropoiesis; with sulfonylurea drugs - their hypoglycemic effect may be increased. It is necessary to take into account the possibility of weakening the antihypertensive effect of beta-adrenergic blockers; increased toxicity of cyclosporine and tacrolim, increased risk of bleeding when using thrombolytic drugs. Probenocid may increase the concentration of dexketoprofen in the blood.