Dexketoprofen, 5 pcs., 2 ml, 25 mg/ml, solution for intravenous and intramuscular administration
Dexketoprofen should be prescribed with caution to patients with a history of allergies.
Patients with symptoms of gastrointestinal disorders or a history of gastrointestinal diseases require constant monitoring. If gastrointestinal bleeding or ulcers occur, therapy with Dexketoprofen should be discontinued.
Caution should be exercised when prescribing Dexketoprofen to patients concomitantly taking medications that may increase the risk of ulceration or bleeding: corticosteroids, anticoagulants (for example, warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (including acetylsalicylic acid).
Dexketoprofen may cause a reversible inhibition of platelet aggregation and increase bleeding time.
Dexketoprofen should be prescribed with caution to patients with chronic heart failure of NYHA functional class I-II.
Like other NSAIDs, Dexketoprofen can lead to increased levels of creatinine and nitrogen in the blood plasma, have a negative effect on the urinary system, leading to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure.
As with the use of other NSAIDs, there may be a slight transient increase in the performance of some liver tests, a significant increase in the activity of AST and ALT in the blood serum. At the same time, monitoring of liver and kidney functions is necessary in elderly patients. In case of a significant increase in the corresponding indicators, Dexketoprofen should be discontinued.
Dexketoprofen should be prescribed with caution to patients with hematopoietic disorders, patients with systemic lupus erythematosus or other connective tissue diseases.
Like other NSAIDs, Dexketoprofen may mask the symptoms of infectious diseases. If signs of a bacterial infection are detected or if your health deteriorates during treatment with Dexketoprofen, the patient should immediately consult a doctor.
Caution should be exercised when prescribing the drug to patients with impaired liver, kidney, heart function or with conditions that may cause fluid retention in the body. In these patients, the use of NSAIDs can lead to worsening of the condition and fluid retention in the body. Caution should also be exercised when prescribing dexketoprofen to patients using diuretics or predisposed to hypovolemia, since they have an increased risk of developing nephrotoxicity.
Caution is necessary when prescribing the drug to elderly people, since they are more likely to have impaired renal, liver or cardiovascular function, as well as the occurrence of adverse reactions, such as gastrointestinal bleeding or intestinal perforation.
Dexketoprofen
Undesirable combinations
With other NSAIDs, including salicylates in high doses (more than 3 g/day)
The simultaneous use of several NSAIDs increases the risk of gastrointestinal bleeding and ulcers.
With oral anticoagulants, heparin in doses exceeding prophylactic doses, and ticlopidine
The risk of bleeding increases due to inhibition of platelet aggregation and damage to the mucous membrane of the digestive tract.
With lithium preparations
NSAIDs increase the concentration of lithium in the blood plasma (decreased renal excretion of lithium), which can reach toxic levels, so the concentration of lithium in the blood should be monitored when prescribing, changing the dose and discontinuing dexketoprofen.
With methotrexate in high doses (at least 15 mg/week)
The toxicity of methotrexate increases due to a decrease in its renal clearance when using NSAIDs.
With glucocorticosteroids
The risk of developing stomach ulcers and gastrointestinal bleeding increases.
Hydantoin derivatives and sulfonamides
The severity of their toxic manifestations may increase.
Combinations requiring caution
With diuretics, ACE inhibitors, antibacterial drugs from the group of aminoglycosides and angiotensin II receptor antagonists
Dexketoprofen weakens the effect of diuretics and other antihypertensive drugs. Treatment with NSAIDs is associated with a risk of acute renal failure in patients with dehydration (decreased glomerular filtration rate due to decreased prostaglandin synthesis). When using dexketoprofen and diuretics in combination, ensure that the patient is adequately hydrated and monitor renal function before prescribing.
With methotrexate in low (less than 15 mg/week) doses
The hematological toxicity of methotrexate increases due to a decrease in its renal clearance when using NSAIDs. Blood counts should be monitored weekly during the first weeks of combination treatment. In the presence of even minor impairment of renal function, as well as in the elderly, careful monitoring is necessary.
With pentoxifylline
The risk of bleeding increases. Active clinical monitoring and frequent monitoring of bleeding time or clotting time are necessary.
With zidovudine
A toxic effect of zidovudine on reticulocytes is possible, which after the first week of NSAID use can lead to the development of severe anemia. It is necessary to count all blood cells and reticulocytes 1-2 weeks after the start of combination therapy.
With oral hypoglycemic drugs
Due to the possible increase in hypoglycemic effect due to the ability of NSAIDs to displace them from sites of binding to plasma proteins.
With heparins (low molecular weight)
Increased risk of bleeding.
Combinations to consider
With beta blockers
Their antihypertensive effect may be reduced due to the inhibition of prostaglandin synthesis by NSAIDs.
With cyclosporine and tacrolimus
Their nephrotoxicity may be enhanced due to the effect of NSAIDs on renal prostaglandins. When carrying out combination therapy, it is necessary to monitor renal function.
With thrombolytic drugs
The risk of bleeding increases.
With probenecid
An increase in the concentration of dexketoprofen in the blood plasma is possible, which may be due to an inhibitory effect on tubular secretion and/or conjugation with glucuronic acid and requires dose adjustment of dexketoprofen.
With cardiac glycosides
NSAIDs may lead to an increase in their plasma concentrations.
With mifepristone
Due to the theoretical risk of changes in the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should be prescribed 8-12 days after taking mifepristone.
With quinolone antibiotics
There is a high risk of developing seizures when using NSAIDs in combination with high doses of quinolones.
Pharmaceutical interactions
Dexketoprofen should not be mixed in the same syringe with a solution of dopamine, promethazine, pentazocine, pethidine or hydroxyzine (a precipitate will form).
Dexketoprofen can be mixed in one syringe with a solution of heparin, lidocaine, morphine and theophylline.
A diluted solution of the drug for intravenous drip administration should not be mixed with promethazine or pentazocine.
The diluted solution of the drug is compatible with the following injection solutions: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.
DEXONAL® (Dexonal)
When using the drug DEXONAL® in patients with a history of allergic reactions, caution must be exercised.
The use of DEXONAL® in combination with other NSAIDs, including selective COX-2 inhibitors, should be avoided.
Undesirable side effects can be minimized by using the drug at the lowest effective dose for the minimum duration of use necessary to relieve symptoms.
Safety of use in relation to the gastrointestinal tract
There are reports of gastrointestinal bleeding, ulcers or perforations (in some cases fatal) during the use of any NSAIDs at different stages of treatment, both with and without the appearance of warning symptoms, and regardless of the presence of serious gastrointestinal history of intestinal complications. If gastrointestinal bleeding develops while using DEXONAL®, its use should be discontinued. The risk of developing gastrointestinal bleeding, peptic ulcer or peptic ulcer perforation increases with increasing dose of NSAIDs, in patients with a history of ulcers, especially those complicated by bleeding or perforation, and in elderly patients.
Elderly patients:
In elderly patients, the incidence of side effects associated with the use of NSAIDs, especially gastrointestinal bleeding and perforation of ulcers, which can be life-threatening, increases. Treatment of these patients should be started with the lowest possible dose.
If the patient has a history of esophagitis, gastritis and/or peptic ulcer, before starting treatment with dexketoprofen (as in the case of other NSAIDs), you should ensure that these diseases are in remission. Patients with gastrointestinal symptoms or chronic gastrointestinal diseases should be monitored for digestive disorders, especially gastrointestinal bleeding.
NSAIDs should be prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), since there is a risk of exacerbation of these diseases.
For these patients, as well as patients who require concomitant use of low-dose ASA or other drugs that increase the risk of gastrointestinal disorders, combination therapy with protective drugs, such as misoprostol or proton pump inhibitors, should be considered.
Patients with a history of gastrointestinal side effects, especially older patients, should report any unusual gastrointestinal symptoms (especially symptoms that may indicate gastrointestinal bleeding) to the physician, especially during the initial stages of treatment.
Caution should be exercised when prescribing the drug to patients concomitantly taking medications that may increase the risk of ulceration or bleeding: oral corticosteroids, anticoagulants (for example, warfarin), selective serotonin reuptake inhibitors or antiplatelet agents, such as ASA.
Kidney safety
In patients with impaired renal function, the drug should be prescribed with caution, since the use of NSAIDs may cause deterioration in renal function, fluid retention in the body, and the development of edema. Caution should be exercised when using the drug in patients concomitantly taking diuretics and patients who may develop hypovolemia due to an increased risk of nephrotoxicity. During treatment, it is necessary to ensure adequate fluid intake to prevent dehydration and increased toxic effects on the kidneys. Like other NSAIDs, DEXONAL® may lead to increased concentrations of urea nitrogen and creatinine in the blood plasma. Like other prostaglandin synthesis inhibitors, DEXONAL® 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.
Elderly patients are especially susceptible to impaired renal function.
Safety of use in relation to the liver
In patients with impaired liver function, the drug should be prescribed with caution. As with the use of other NSAIDs, the drug can cause a short-term and slight increase in some “liver parameters”, as well as a pronounced increase in the activity of AST and ALT in the blood plasma. If these indicators increase, treatment with the drug should be stopped.
Elderly patients are especially susceptible to liver dysfunction.
Safety of use in relation to the cardiovascular system and cerebral circulation
In patients with a history of arterial hypertension and/or heart failure of mild to moderate severity, appropriate monitoring and recommendations are required. Particular caution should be observed when treating patients with a history of heart disease, in particular with previous episodes of heart failure, since NSAID therapy increases the risk of developing heart failure; Cases of fluid retention and edema associated with the use of NSAIDs have been described.
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 arterial thrombosis (for example, myocardial infarction or stroke).
There is insufficient data to exclude the risk of such events when using dexketoprofen.
In patients with uncontrolled arterial hypertension, congestive heart failure, confirmed coronary heart disease, peripheral arterial and/or cerebrovascular disease, the drug should be used after a careful assessment of the benefit-risk ratio.
Before starting long-term treatment in patients with risk factors for cardiovascular disease (for example, high blood pressure, hyperlipidemia, diabetes mellitus, smoking), a careful assessment of the benefit-risk ratio is also necessary.
Non-selective NSAIDs can reduce platelet aggregation and increase bleeding time by suppressing prostaglandin synthesis. The simultaneous use of dexketoprofen and low molecular weight heparin in prophylactic doses in the postoperative period was studied in controlled clinical studies; no effect on coagulation parameters was found. However, patients receiving drugs that affect hemostasis, such as warfarin, other coumarin derivatives or heparins concomitantly with dexketoprofen, should be closely monitored by a physician. Elderly patients are particularly susceptible to cardiovascular dysfunction.
Skin reactions
Very rarely, serious skin reactions have been reported with the use of NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which were fatal. The risk of developing such reactions in patients appears to be highest at the beginning of treatment, since most of the described phenomena were observed in the first month of therapy. At the first appearance of a skin rash, damage to the mucous membranes or any other signs of hypersensitivity, the use of DEXONAL® should be discontinued.
Particular caution is required when prescribing the drug to patients with congenital disorders of porphyrin metabolism (for example, acute intermittent porphyria), dehydration, and immediately after extensive surgery.
In very rare cases, severe acute hypersensitivity reactions (eg anaphylactic shock) have been observed. At the first sign of a severe hypersensitivity reaction, discontinue use of DEXONAL®. Patients suffering from asthma in combination with chronic rhinitis, chronic sinusitis and/or nasal polyps are at higher risk of allergy to ASA and/or NSAIDs than the general population. The use of the drug may cause an asthma attack or bronchospasm, especially in patients with allergic reactions to ASA or NSAIDs (see section “Contraindications”).
In special cases, it is possible to develop severe infectious complications of the skin and soft tissues against the background of chickenpox. It is currently impossible to completely exclude the possibility of a relationship between the use of NSAIDs and the development of such infectious complications. Therefore, in case of chickenpox, the use of DEXONAL® should be avoided.
The drug DEXONAL® should be used with caution in case of hematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disease.
Like other NSAIDs, dexketoprofen can mask the symptoms of infectious diseases. Isolated cases of activation of infectious processes localized in soft tissues due to the use of NSAIDs have been described. Therefore, if symptoms of a bacterial infection develop or worsen during treatment, patients are advised to consult a doctor immediately.
One ampoule of the drug DEXONAL® contains 12.35 vol. % ethanol (corresponding to 200 mg ethanol [alcohol] per ampoule), which corresponds to 5 ml beer or 2.08 ml wine and may have a detrimental effect on patients suffering from alcoholism. This must be taken into account when prescribing to patients at high risk, for example with liver disease or epilepsy.
The drug contains less than 1 mmol of sodium (23 mg) per ampoule, i.e. it contains practically no sodium.
Pediatric population
Safety of use in children has not been established.
Dexketoprofen-SZ tablet p/pl/o 25 mg N10 (Northern Star)
The following interactions are common to all NSAIDs. Undesirable combinations. With other NSAIDs, including salicylates in high doses (more than 3 g/day): simultaneous use of several NSAIDs due to a synergistic effect increases the risk of gastrointestinal bleeding and ulcers. With anticoagulants: dexketoprofen, like other NSAIDs, can enhance the effect of anticoagulants such as warfarin due to a high degree of binding to plasma proteins, inhibition of platelet aggregation and damage to the gastrointestinal mucosa. If simultaneous use is necessary, careful monitoring of the patient's condition and regular monitoring of laboratory parameters is necessary. With heparin: with simultaneous use, the risk of bleeding increases (due to inhibition of platelet aggregation and damaging effects on the mucous membrane of the gastrointestinal tract). If simultaneous use is necessary, careful monitoring of the patient's condition and regular monitoring of laboratory parameters is necessary. With glucocorticosteroids: with simultaneous use, the risk of ulcerative lesions of the gastrointestinal tract and bleeding increases. With lithium preparations: NSAIDs increase the concentration of lithium in the blood plasma up to toxic levels, and therefore this indicator must be monitored when used simultaneously with dexketoprofen, changing the dosage, and also after discontinuation of NSAIDs. With methotrexate in high doses (15 mg/week or more): the hematological toxicity of methotrexate may increase due to a decrease in its renal clearance when used simultaneously with NSAIDs. With hydantoins and sulfonamides: their toxic effect may be enhanced. Combinations requiring caution. With diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, angiotensin-II receptor antagonists: simultaneous use with NSAIDs is associated with the risk of developing acute renal failure in dehydrated patients (decreased glomerular filtration rate due to decreased synthesis of prostaglandins). When used concomitantly, NSAIDs may reduce the antihypertensive effect of some drugs. When using dexketoprofen and diuretics simultaneously, it is necessary to ensure that the patient has no signs of dehydration, and also monitor renal function at the beginning of simultaneous use. With methotrexate in low doses (less than 15 mg/week): an increase in the hematological toxicity of methotrexate is possible due to a decrease in its renal clearance during simultaneous use with NSAIDs. A blood cell count is necessary when coadministration is initiated. In the presence of even mild renal dysfunction, as well as in elderly people, careful medical supervision is necessary. With pentoxifylline: there may be an increased risk of bleeding. Close clinical monitoring and regular checking of bleeding time (blood clotting time) is necessary. With zidovudine: there is a risk of increased toxicity to red blood cells due to effects on reticulocytes, with the development of severe anemia one week after starting NSAID use. It is necessary to conduct a general blood test with counting the number of reticulocytes 1-2 weeks after starting NSAID therapy. With oral hypoglycemic agents: NSAIDs may enhance the hypoglycemic effect of sulfonylureas due to the displacement of sulfonylurea from sites of binding to plasma proteins. Combinations to take into account. With beta-blockers: When used concomitantly with NSAIDs, the antihypertensive effect of beta-blockers may be reduced due to inhibition of prostaglandin synthesis. With cyclosporine and tacrolimus: NSAIDs may increase nephrotoxicity, which is mediated by the action of renal prostaglandins. During simultaneous use, it is necessary to monitor renal function. With thrombolytics: the risk of bleeding increases. The risk of bleeding from the gastrointestinal tract increases when used simultaneously with serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) and anticoagulants. With probenecid: an increase in the concentration of NSAIDs in the blood plasma is possible, which may be due to the inhibitory effect of probenecid on renal tubular secretion and/or conjugation with glucuronic acid; NSAID dose adjustment may be required. With cardiac glycosides: simultaneous use with NSAIDs may lead to an increase in the concentration of cardiac glycosides in the blood plasma. With mifepristone: due to the theoretical risk of changes in the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be used earlier than 8-12 days after discontinuation of mifepristone. With quinolones: data obtained from experimental studies in animals indicate a high risk of developing seizures when NSAIDs are used concomitantly with quinolones in high doses. If it is necessary to use Dexketoprofen-SZ simultaneously with the above-mentioned drugs, you should consult your doctor.
Currently, acute lumbar pain (LP) remains a pressing problem due to its widespread prevalence, which in developed countries reaches the size of a non-infectious epidemic. PA is the fifth most common reason for visiting a doctor, and one of the most common (56.7%) forms of chronic pain syndromes [1]. The probability of experiencing an episode of BE during your lifetime is 60-90%, the number of cases of BE per year is 15-45 per 100 people; about 40% of patients seek medical help for BE [2]. About 80% of Europeans experience LBP during their lifetime; the prevalence of its severe forms is 14% [3]. About 1/3 of patients suffering from BE complain of limited mobility due to persistent or recurrent episodes of pain. The high level of disability among people of working age due to lesions of the musculoskeletal system makes the problem of treating BE relevant [4].
BE, or dorsopathy, in ICD-10 is divided into deforming dorsopathies, spondylopathies, other dorsopathies (degeneration of intervertebral discs, sympathalgic syndrome) and dorsalgia. Dorsopathies can occur acutely (up to 3 weeks), subacutely (3-12 weeks) and chronically (more than 12 weeks). All back pain syndromes can be classified into the following categories [5]: 1) by reason of occurrence (vertebrogenic and non-vertebrogenic); 2) according to the mechanism of development (reflex, compression, against the background of instability of the spinal motion segment, vascular, inflammatory); 3) by localization (local, reflected and irradiating); 4) by duration (acute and chronic). Depending on the cause, vertebrogenic (caused by changes in the spine) and non-vertebrogenic pain syndromes are distinguished [6]. Dorsopathies are characterized by a chronic course and periodic exacerbations, in which the leading factor is pain. Doropathy affects more than 45% of the population in developed countries. Although an episode of back pain is often short-lived, approximately 25% of patients subsequently develop chronic pain, which can cause long-term disability [5].
The leading mechanism for the formation of pain syndrome in musculoskeletal disorders is the effect of algogens - arachidonic acid metabolite substances on nociceptors with the formation of nociceptive pain. In these cases, it is most advisable to use non-steroidal anti-inflammatory drugs (NSAIDs), which are considered the “gold standard” in relieving BE [2]. NSAIDs, with a history of more than 50 years, are the most popular drugs in the modern world. With the general trend towards an aging population, the number of patients requiring the use of NSAIDs is also growing. Treatment is primarily aimed at reducing and stopping pain. It is recommended to limit physical activity, use NSAIDs in combination with muscle relaxants, and for chronic pain, rehabilitation programs, gradually expanding dosed physical and rational physical activity, sleeping on a hard bed using an orthopedic mattress, and teaching the patient an individually selected movement regimen [6].
The widespread introduction into clinical practice of a new class of NSAIDs - selective (nimesulide, etc.) and specific inhibitors of cyclooxygenase COX-2 (coxibs) has significantly reduced the number of side effects of NSAIDs. The mechanism of action of NSAIDs is the inhibition of COX, a key enzyme that regulates the biotransformation of arachidonic acid into prostaglandins, prostacyclin and thromboxane. Most NSAIDs are organic acids that bind to blood proteins, accumulate at the site of inflammation and have the ability to suppress COX activity. COX is a multienzyme complex that includes a number of components (dioxygenase, isomerase, reductase), which, in the presence of molecular oxygen, catalyzes the main reactions in the transformation of arachidonic acid with the formation of cyclic endoperoxides. NSAIDs are classified according to the degree of selectivity for the COX-1 and COX-2 isoforms (Table 1).
Table 1. Distribution of NSAIDs by degree of selectivity [7]
When treating patients with BE, selectivity is not always critical, since, firstly, to relieve acute pain syndrome, drugs are prescribed for a short time, and secondly, the use of the multimodal analgesia method can significantly reduce the dosage of each of the drugs used and reduce the risk development of adverse reactions. In addition, high selectivity for COX-2 reduces the antinociceptive potential of the drug, i.e., it is enough to choose a non-selective COX inhibitor with minimal parameters of gastrointestinal toxicity.
Based on the characteristics of pharmacokinetics and analgesic activity, NSAIDs can be divided into 4 large groups: 1) with relatively low analgesic activity and a short half-life; 2) with high analgesic activity and short half-life; 3) with moderate analgesic activity and an average half-life; 4) with high analgesic activity and a long half-life [1]. The classic representative of group 1 is ibuprofen; this group also includes salicylates (aspirin) and mefenamic acid. Group 2 drugs are classic drugs for the relief of rheumatic (arthritic) pain; the most widely used are diclofenac, indomethacin, lornoxicam and ketoprofen. Group 3 drugs include naproxen. Group 4 included oxicams: meloxicam, piroxicam and tenoxicam.
For the treatment of acute musculoskeletal pain syndromes, special attention should be paid to drugs of group 2 [2]. A relatively new drug is dexketoprofen (a propionic acid derivative) - a water-soluble salt of the dextrorotatory enantiomer of ketoprofen. Many drugs are combinations of so-called enantiomers, differing in their three-dimensional spatial configuration, the direction of rotation of the plane of polarization of light and, most importantly, their pharmacological properties. Ketoprofen is also a racemic mixture containing equal amounts of two enantiomers: levorotatory R-ketoprofen and dextrorotatory S-ketoprofen. Only one has an antinociceptive effect, while the other has a weak analgesic effect, but significantly increases the incidence of side effects. It has been established that only the S (+) isomer (dextrorotatory) inhibits COX [8]. These two enantiomers have different characteristics, for example, S-ketoprofen is 3000 times more active in inhibiting prostaglandin synthesis than R-ketoprofen. Dexketoprofen, unlike ketoprofen, contains 99.9% of the active S-enantiomer.
The combination of dexketoprofen with trometamol salt and the high degree of purification of the active substance from R (-)-ketoprofen provide improved physicochemical properties of the drug. The results of pharmacokinetic studies indicate that dexketoprofen trometamol is quickly and completely absorbed after oral administration, and the maximum concentration in the blood plasma is achieved faster than that of ketoprofen and is 15-45 minutes. Up to 70-80% of the drug is excreted in the urine during the first 12 hours, mainly as an acyl glucurone conjugate. The absence of the R (-)-isomer in the urine after taking dexketoprofen indicates the absence of bioinversion of the S (+)-isomer in humans. The powerful inhibitory activity of the drug dexketoprofen trometamol against COX determines its analgesic effect on the peripheral and central nervous system, while the high anti-inflammatory activity of the drug is combined with good tolerability.
It is believed that patients with no risk of gastrointestinal (GI) tract damage and low cardiovascular risk can be prescribed any NSAIDs (Table 2).
Table 2. Selection of NSAIDs depending on the degree of risk of complications
J. Beltrán et al. [9] compared the analgesic efficacy and tolerability of dexketoprofen trometamol with racemic ketoprofen in the short-term treatment of knee osteoarthritis. The multicenter, randomized, double-blind study included 183 patients aged 30 to 75 years with a pain duration of at least 3 months. Initial pain intensity and level of functional ability were comparable in the two groups. After 3 weeks of treatment, a statistically significant difference appeared between the groups in favor of dexketoprofen. It turned out that intravenous administration of dexketoprofen causes less pain than injections of racemic ketoprofen [10].
An analysis of the effectiveness of dexketoprofen is presented in a number of studies conducted by domestic authors over the past decade. Thus, the analgesic effectiveness of dexketoprofen was studied in the treatment of 30 patients with acute LBP [2]. The duration of the disease was no more than 3 weeks, the pain intensity on the visual analogue scale (VAS) was no less than 5 points; in the main group ( n
=20) dexketoprofen was prescribed 75 mg per day for 5 days;
in the comparison group ( n
=10) - diclofenac sodium 100 mg per day for 5 days. Pain intensity was assessed using a VAS every 15 minutes during the first 1.5 hours, as well as 3, 4, 5 and 6 hours after taking the first dose of the drug, the presence of restrictions in daily activity due to back pain (according to subjective assessment patient) on the 2nd, 3rd, 4th and 5th days of taking the drugs. A significant decrease in pain intensity was noted 30 minutes after taking the first dose of the drug in the main group, in the comparison group - by the 45th minute. By the end of treatment in the main group, complete regression of pain syndrome was observed in 30%, significant - in 45%. Patients of the main group noted regression of pain 33.80±21.63 minutes after taking the drug. A significant decrease in the limitation of daily activity while taking dexketoprofen was noted by the 3rd day of treatment. Based on the results of the study, it was concluded that dexketoprofen is an effective drug for the treatment of patients with acute LBP when prescribed a short 5-day course of monotherapy; dexketoprofen is superior to diclofenac sodium in the rate of onset of analgesic effect [2].
A study was conducted of the effect of dexketoprofen on the mechanisms of dysregulation in complex therapy in patients ( n
=39) with PB [11].
The patients were divided into two groups: with vertebrogenic ( n
= 23) and non-vertebrogenic pain syndrome (
n
= 16). Dexketoprofen was prescribed at a dose of 75 mg per day (25 mg 3 times a day) for 5 days. The dynamics of the condition were assessed using: VAS, pain rank index according to the McGill questionnaire, the Oswester Disability Questionnaire (ODI) for BE, electromyographic (EMG) and MRI examinations assessing changes in the lumbar spine. The background values of the rank index were 18.4±9.7 and 21.2±11.7 points, respectively. On the 5th day, a significant decrease in this indicator to 14.6±9.2 was revealed in the 2nd group of patients. The dynamics of UNV indicate a predominant decrease in the latter in patients with non-vertebral back pain; EMG indices showed a tendency to decrease the spontaneous activity of muscle fibers and normalize the latency of the H-reflex when studying the tibial nerves in patients with vertebrogenic dorsalgia. The authors concluded that dexketoprofen is highly effective in patients with acute dorsalgia [11].
A study of the analgesic effectiveness and tolerability of complex therapy with dexketoprofen and nimesulide in patients with acute vertebrogenic pain syndromes was carried out by E.Yu. Solovyova et al. [12]. The study included 60 patients with a disease duration of no more than 7 days. The patients were divided into two groups taking into account the prescribed treatment regimen: in group 1 - dexketoprofen (75 mg per day) for 5 days followed by discontinuation of the drug, in group 2 - dexketoprofen (75 mg per day) for 5 days , from the 6th to the 19th day, nisemulide (200 mg per day) was prescribed. The dynamics of the condition were assessed using a VAS in several categories (spontaneous pain, pain with movement, degree of limitation of function initially and during therapy), laboratory blood parameters (creatinine, AST, ALT) and subjective tolerability of drugs were also assessed. In both groups, a positive effect from the treatment was noted in the form of a decrease in the severity of spontaneous pain, pain during movement and limitation of motor function. A significant decrease in pain intensity was noted during the first 90 minutes after taking dexketoprofen. No increase in transaminase levels was recorded. The study obtained data on the pronounced analgesic and anti-inflammatory effects of dexketoprofen (75 mg per day) for 5 days, drug tolerability in 75% was assessed as “very good”, a significant improvement in condition was noted in 59%. Thus, the effectiveness of dexketoprofen as monotherapy in the treatment of acute vertebrogenic pain syndromes was confirmed [12].
Dexketoprofen has been successfully used in orthopedics for a long time. Its parenteral administration is an effective way to relieve pain after arthroscopic operations [13]. One of the widest areas of application of dexketoprofen in medicine is surgery. Adequate management of postoperative pain is one of the most important factors in patient therapy and prevention of disease complications, the main condition for the implementation of a postoperative rehabilitation program [14]. In the postoperative period, despite the use of a wide range of drug and non-drug analgesia, pain syndrome is observed in 1/3-3 of patients. The effectiveness of pain relief when opioids are prescribed as monotherapy does not exceed 25-30%, since their effective analgesic dose is often close to the dose at which respiratory depression, sedation, gastrointestinal tract paresis, and dysfunction of the urinary and biliary tract develop. It is estimated that only 1 in 25 hospitalized trauma patients are satisfied with prehospital pain management. A study of 3000 patients with various injuries found that 62% of them were not satisfied with pain relief at the prehospital stage, which resulted in chronic pain syndrome [15]. E.A. Pobel [7] conducted a comparative study of the injectable form of dexketoprofen and opioids as postoperative pain relief. The study included 42 patients from the trauma department: the main group consisted of 21 patients receiving opioids, the comparison group included 21 patients receiving dexketoprofen trometamol (IV or IM injections). In 81% of patients receiving dexketoprofen, a 2-fold administration of the drug per day (every 12 hours) in the first postoperative 48 hours was sufficient, thus replacing the administration of opioids; in the remaining 19% of patients, the drug was administered once a day. Starting from the 3rd day after surgery, patients in both groups were administered 50 mg of dexketoprofen intramuscularly once a day. In 76% of patients in the comparison group and in 86% of the main group, a decrease in the severity of pain was recorded by the end of the 1st hour after administration of the drug. The duration of the analgesic effect in the comparison group was 4.5±1.8 hours, in the main group - 6.5±1.2 hours; duration of prescription of dexketoprofen - 4.6±2.0 days, opioids - 4.8±1.6 days. Good and excellent tolerability of dexketoprofen was noted in 90.5% of patients. The study concluded that a single administration of dexketoprofen (50 mg IV or IM) provided long-term pain relief; in terms of the speed of onset of the effect, the effect of dexketoprofen (50 mg IM) is similar to 4 mg of morphine subcutaneously, however, the duration of pain relief was significantly longer; IM administration of dexketoprofen (50 mg 1 or 2 times a day) reduces the need for narcotic analgesics; No undesirable effects were detected while taking dexketoprofen trometamol [7].
The applications of dexketoprofen trometamol cover such areas of medicine as gynecology and dentistry. All studies have shown the high effectiveness of dexketoprofen trometamol, similar to other analgesic drugs. A prospective, randomized, placebo-controlled study of the analgesic efficacy of the tablet form of dexketoprofen trometamol (25 mg) was conducted in 26 women after medical abortion [16]. Comparative evaluation of effectiveness was carried out with intravenous injections of acetaminophen 1000 mg ( n
=23), applying lidocaine in the form of a spray to the mucous membrane of the cervical canal (
n
=23), pethidine 100 mg (
n
=25) and diclofenac sodium (
n
=25). The study showed similar therapeutic efficacy of the studied analgesics when used in the intra- and postoperative periods. In a study by C. Eroglu et al. [19] assessed the comparative effectiveness of low-dose injections of methylprednisolone (40 mg), acetaminophen (300 mg) and dexketoprofen trometamol (12.5 mg) for edema that developed after removal of impacted third molars. The drugs were prescribed 1 hour before the procedure. In the postoperative period, drugs were prescribed in doses that were used before the start of the procedure for 2 days. There was no statistically significant difference in the effectiveness of the drugs.
The research results confirm the high effectiveness of joint administration for the relief of acute pain (moderate, severe intensity) of dexketoprofen trometamol (25 mg) and tramadol hydrochloride (37.5-75 mg) after abdominal hysterostomy ( n
=606) [20, 21] and dexketoprofen trometamol (25 mg) and tramadol hydrochloride (100 mg) after hip arthroplasty (
n
=641) [20].
In 2015, the drug Flamadex (Sotex, Russia) was registered, containing 50 mg of dexketoprofen trometamol in injection form [9], and 25 mg of dexketoprofen trometamol in tablet form [10]. The treatment regimen for acute pain syndrome with dexketoprofen includes sequential administration of injectable and tablet forms.
Studies have shown the high effectiveness of tablet and injection forms of dexketoprofen trometamol. A pronounced and rapid analgesic effect, a favorable safety profile and good tolerability of dexketoprofen have been confirmed, which allows it to be recommended in adult patients for the relief of acute pain and the treatment of chronic pain syndromes during exacerbations, as well as in the complex treatment of degenerative-dystrophic diseases of the spine.
Recommended dose for the injection form of Flamadex: 50 mg every 8-12 hours; if necessary, the drug can be re-administered at 6-hour intervals. The daily dose should not exceed 150 mg. Flamadex is indicated for short-term use; treatment should be limited to the period of acute symptoms (no more than 2 days). Dose adjustment for elderly patients is usually not required, however, due to physiological decline in renal function, it is recommended to reduce the dose of the drug: a total daily dose of 50 mg for mild renal impairment in elderly patients.
Depending on the intensity of the pain syndrome, the recommended dose for the tablet form of Flamadex is 12.5 mg (½ tablet) every 4-6 hours or 25 mg (1 tablet) every 8 hours, the drug is taken orally with meals; the maximum daily dose is 75 mg. For patients with impaired liver and/or kidney function and the elderly, Flamadex therapy should be started with lower doses; the maximum daily dose is 50 mg per day. The course of treatment with the tablet form of Flamadex should not exceed 3-5 days.
