Versatis 700 mg transdermal therapeutic system N5

INTRODUCTION

The first-line treatment for localized peripheral neuropathic pain currently includes a patch containing 5% lidocaine (Versatis, Grünenthal) [1].
Lidocaine penetrates the skin and, by blocking sodium channels in nerve endings, prevents the transmission of pain signals. As a result, the development of allodynia (the occurrence of a sensation of pain in response to non-painful irritation) and central sensitization, which is associated with chronic pain, is prevented. The lidocaine patch has been successfully used for a wide range of pain syndromes, such as peripheral polyneuropathies, including diabetic, compression-ischemic neuropathy (tunnel syndrome), post-surgical or post-traumatic pain in the area of ​​skin scars, back pain, etc. [2-9]. There is experience with the successful use of Versatis in diseases of the joints and spine, both inflammatory and degenerative, accompanied by pain (dorsopathy, osteochondrosis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, glenohumeral periarthritis) [10]. Since there is no systemic absorption of lidocaine, Versatis is highly safe. As a result, it can be used in patients with concomitant diseases, as well as in combination with other drugs.

Since the appearance of Versatis on the pharmaceutical market, many doctors have gained experience in its use, and this experience, along with successes, also includes failures. The time has come to celebrate “working on mistakes.” Some of the failures are explained by the fact that to achieve an effect, it is not enough to simply prescribe a drug - it is important to correctly determine the indications for its use, explain to the patient the features of its use and take into account psychological factors. Like other pain treatments, Versatisamo is neither effective nor useless on its own. It is effective when used correctly and according to indications, and when the doctor does not just write a prescription, but helps the patient gain control over pain, and is useless in all other cases. This article is devoted to the peculiarities of using the drug Versatis, knowledge of which will significantly increase the chances of success in treating pain.

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INDICATIONS FOR USE AND PREDICTORS OF EFFECTIVENESS

In accordance with research data and clinical experience, the following diseases and syndromes can be identified in which the use of Versatis is accompanied by a decrease in pain intensity [2-9]:

• postherpetic neuralgia;
• diabetic polyneuropathy;
• pain syndrome associated with vertebrogenic disorders;
• chronic back pain;
• muscular-tonic and myofascial pain syndrome;
• trigeminal neuralgia;
• cancer pain;
• osteoarthritis;
• tendonitis, sports injuries;
• tunnel syndromes.

To determine the indications for the use of a lidocaine patch, it is not enough to establish the nosological affiliation; one should focus primarily on the characteristics of pain [11]. The drug is effective for superficial localized pain, which is explained by the shallow diffusion depth of lidocaine and the inability to cover large areas of skin with patches. Versatis is especially indicated in the presence of allodynia, a painful condition manifested by a sensation of pain in response to even non-painful irritation, such as the touch of clothing. By blocking the ectopic spread of pain signals, lidocaine eliminates the phenomenon of allodynia more effectively than systemic drugs.

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Versatis

recommended as a first-line drug for the treatment of peripheral neuropathic pain. Peripheral neuropathic pain is a consequence of pathological excitation of neurons in the peripheral nervous system. Unlike nociceptive pain, it is not associated with a reaction to tissue damage (inflammation, swelling). Neuropathic pain is characterized by the following symptoms:

• allodynia;
• hyperesthesia;
• hyperalgesia;
• hyperpathia;
• dysesthesia (burning sensation, sensation of “electric current passing”, tingling, “crawling”, itching).

Identification of signs of neuropathic pain is an argument in favor of prescribing Versatis. However, in recent years, a number of open studies have shown that lidocaine plates can also be effective for certain types of local pain, which is traditionally classified as predominantly nociceptive (back pain, myositis, myofascial syndrome, arthritis). It has been shown that for local musculoskeletal pain, the clinical effectiveness of lidocaine sheets approximately corresponds to the effectiveness of selective cyclooxygenase-2 inhibitors [12]

Let us now consider those characteristics of pain for which lidocaine patches are less effective. Since Versatis acts primarily on nerve endings located in the superficial layers of the skin, in the case of pain localized deeply, the administration of Versatis will be less effective. If the patient has numbness, the administration of Versatis may lead to an increase in this sensation due to blocking of the sensory nerve endings. If you sweat profusely, lidocaine patches may not be effective because they do not stick to the skin. Experience shows that the use of Versatis is less effective for radiating pain, radicular pain, when the pain site is remote from the site of nerve damage, as well as for widespread pain. (Data on predictors of treatment effectiveness with lidocaine patch are summarized in the table.)

Probability of success of treatment with a 5% lidocaine patch for various pain syndromes According to a retrospective analysis of cases of pain treatment with Versatis, presented at an expert meeting in Vienna (December 2009) [11].

Special attention should be paid to the use of Versatis for lesions of the trigeminal nerve. Most experts agree that the drug is not suitable for the treatment of classic trigeminal neuralgia accompanied by paroxysmal pain. Versatis may be effective for persistent pain in the area of ​​trigeminal nerve innervation, for example due to postherpetic neuralgia, trauma or surgery in the facial area. The presence of the phenomenon of allodynia can serve as a predictor of effectiveness [11].

Possibility of combination therapy

It is always better to start treatment by prescribing one drug - monotherapy. However, in cases where monotherapy fails to achieve a clinical effect, the correct tactic would be the combined use of Versatis with other means of treating neuropathic pain. A study of the effectiveness of Versatis and pregabalin for the treatment of postherpetic neuralgia showed that patients who responded poorly to Versatis or pregabalin monotherapy experienced clinically significant improvement when combining the two drugs [13]. Increased effectiveness of therapy can also be achieved by combining Versatis with antidepressants (duloxetine, venlafaxine). The next step, if two drugs (Versatis + antidepressant or Versatis + anticonvulsant) are insufficiently effective, is the simultaneous use of three drugs for the treatment of neuropathic pain: Versatis + antidepressant + anticonvulsant. Since drugs from different groups have different mechanisms of action, their combined use increases the overall effectiveness of therapy [14].

APPLICATION FEATURES

In general, lidocaine patches are safe and easy to use. However, there are several features that the doctor should know about and which the patient must be told about.

If treatment with Versatis is ineffective, before replacing the drug with another, it is advisable to find out from the patient whether he is using the patches correctly.

Versatis 700 mg transdermal therapeutic system N5

Release form

The patch is in the form of a polymer adhesive (sticky) material from white to light yellow in color, with a slight characteristic odor, evenly distributed on one side of the non-woven material and covered with a plastic film.

Package

5 pieces.

pharmachologic effect

Versatis contains lidocaine, an acetamide derivative. The mechanism of action is related to the stabilization of neuronal membranes, which is believed to be the result of blockade of sodium channels. When applied topically to intact skin, a therapeutic effect occurs sufficient to relieve pain.

Pharmacokinetics

Suction:

With single or repeated use of the Versatis patch at the maximum recommended dose (simultaneous application of three patches for 12 hours), only 3 ± 2% of the lidocaine contained in the patch enters the systemic circulation. The concentration in blood plasma after using the maximum recommended dose of the drug in patients without clinical signs of postherpetic neuralgia was 84 - 125 ng/ml. In patients with postherpetic neuralgia - 52 ng/ml. Distribution: The volume of distribution does not depend on age and is reduced in patients with chronic heart failure, increases in liver failure. 70% of lidocaine, which penetrates into the systemic circulation after cutaneous application, binds to blood plasma proteins. Penetrates through the blood-brain and placental barriers by passive diffusion. Metabolism: Lidocaine is rapidly metabolized in the liver to form several metabolites. The main route of metabolism is N-dealkylation to form monoethylglycine xylidide (MEGC) and glycine xylidide (GK), metabolites that have less pharmacological activity than lidocaine and are present in lower concentrations. Metabolites are hydrolyzed to 2,6-xylidine, which is converted by conjugation to 4-hydroxy-2,6-xylidine. It has not been established whether 2,6-xylidine has pharmacological activity, however, when studied in biological models, 2,6-xylidine has a potential carcinogenic effect. Kinetic analysis revealed that with daily applications for up to one year, the maximum concentration of 2,6-xylidine averaged 9 ng/ml. Lidocaine and its metabolites (monoethylglycine xylidide, glycine xylidide and 2,6-xylidine) do not accumulate in the body; equilibrium concentration is achieved within the first four days of use.

When the number of simultaneously used patches increases from one to three, the concentration of lidocaine in plasma increases more slowly than the proportional ratio.

Removal:

Lidocaine and its metabolites are excreted in the urine (more than 85% in the form of metabolites, less than 10% unchanged). The main metabolite in urine is a 4-hydroxy-2,6-xylidine conjugate, accounting for approximately 70 - 80% of the dose excreted in the urine. The metabolite 2,6-xylidine is excreted in the urine in a concentration of less than 1% of the dose received. The half-life of lidocaine after skin application of the patch is 7.6 hours.

In case of cardiac, renal or liver failure, the elimination of lidocaine and its metabolites may be slowed down.

Indications

Neuropathic pain associated with a previous herpetic infection (Herpes zoster), postherpetic neuralgia.

Contraindications

— Increased sensitivity of allergic and non-allergic origin to the active and excipients of the drug;

- increased sensitivity of allergic and non-allergic origin to local anesthetics of the amide group (for example, bupivacaine, etidocaine, mepivacaine and prilocaine);

- inflammation or disruption of the integrity of the skin at the site of application of the patch (for example, herpes zoster rash, atopic dermatitis or wounds).

Carefully

Use with caution in severe cardiac, renal or liver failure (see "Special Instructions").

Use during pregnancy and breastfeeding

Versatis should not be used during pregnancy and lactation (breastfeeding).

special instructions

The Versatis patch should not be used on mucous membranes. Avoid contact of the patch with the eye area.

The Versatis patch contains propylene glycol, which can cause skin irritation, as well as methyl parahydroxybenzoate and propyl parahydroxybenzoate, which can cause allergic reactions (possibly delayed).

Caution should be exercised when using the Versatis patch in patients with severe cardiac, renal or hepatic impairment. After the first opening of the sachet, the drug must be used within 14 days; the opened sachet must be stored tightly closed. The drug should not be stored in the refrigerator or frozen.

Impact on the ability to drive vehicles and operate machinery

Since systemic absorption is minimal, there is no reason to assume that there is an effect on the ability to drive a car and the ability to operate machinery.

Compound

One patch contains:

Active substance: lidocaine 700 mg/patch;

Excipients: purified water 3367 mg, glycerol 2520 mg, sorbitol 2800 mg, polyacrylic acid solution 20% 1400 mg, sodium polyacrylate 400-600 mPa s 700 mg, sodium carmellose 90-168 mPa s 700 mg, propylene glycol 700 mg, urea 420 mg, kaolin 210 mg, tartaric acid 210 mg, gelatin 147 mg, polyvinyl alcohol (75,000) 58.8 mg, aluminum dihydroxyaminoacetate (aluminum glycinate) 32.2 mg, disodium edetate 14 mg, methyl parahydroxybenzoate 14 mg , propyl parahydroxybenzoate 7 mg, non-woven material 1750 mg, plastic film (polyethylene terephthalate, PET) 742 g. Patch size: length from 13.3 to 14.7 cm, width from 9.5 to 10.5 cm.

Directions for use and doses

The patch is intended for external use. The patch is glued to the skin in the area of ​​pain once a day for a period of up to 12 hours. No more than 3 patches can be used at a time. If necessary, the patch can be cut into pieces before removing the plastic protective film. The patch should be glued to intact, dry, non-inflamed skin (after complete healing of herpetic rashes) covering the area of ​​pain. Then the patch is removed and a break is taken for at least 12 hours. Do not reuse the removed patch.

The patch adheres to the skin immediately after removal from the sachet and removal of the plastic film from the adhesive layer. Hair must be cut with scissors (do not shave). The effectiveness of therapy should be re-evaluated 2-4 weeks from the start of treatment. If within this time frame the response to therapy is insufficient or the therapeutic effect is determined only by the protective properties of the patch, treatment should be discontinued. The effectiveness of therapy should be regularly assessed to determine the optimal number of simultaneously applied patches needed to cover the area of ​​pain or to increase the time periods between patch applications.

The use of the Versatis patch is not recommended for people under 18 years of age. There are no data on the safety and effectiveness of the Versatis patch in patients under 18 years of age.

After gluing the patch, you should avoid contact of your hands with your eyes and wash your hands immediately. The used patch contains the active substance. Dispose of Versatis patch immediately after use.

After removal from the skin, the patch should be folded in half with the sticky side inward, so that the surface containing the active substance is not visible. Used patches should not be accessible to children or pets.

Side effects

Allergic reactions:

allergic contact dermatitis (hyperemia at the site of application, skin rash, urticaria, itching), angioedema.

Other:

burning sensation at the application site.

Drug interactions

In the accumulated experience of using the drug, there were no clinically significant interactions with other drugs. Since the maximum plasma concentration of lidocaine is low, clinically significant pharmacokinetic interactions are unlikely to occur.

Although the absorption of lidocaine through the skin is generally low, caution should be exercised when using the lidocaine 5% patch in patients receiving class I antiarrhythmic drugs (eg, tocainide, mexiletine) or other local anesthetics, as there is a risk of additive systemic effects.

Overdose

An overdose of lidocaine when using the Versatis patch is unlikely. An overdose cannot be excluded if the drug is used incorrectly (for example, using more than 3 patches at the same time, applying a patch for more than 12 hours, or using a patch on areas of damaged skin); in such cases, the concentration of lidocaine in the blood plasma may increase. Symptoms of overdose may include: dizziness, vomiting, drowsiness, convulsions, mydriasis, bradycardia, arrhythmia and shock. In case of overdose, interaction of lidocaine with β-blockers, inhibitors of the CYP3A4 isoenzyme (for example, imidazole derivatives, macrolides) and antiarrhythmic drugs is possible.

If an overdose is suspected, the patch should be removed from the skin and measures taken to maintain the vital functions of the body. There is no antidote to lidocaine.

Storage conditions

Store at a temperature not exceeding 25 °C. Do not refrigerate or freeze. After opening, keep the sachet tightly closed. Keep out of the reach of children.

Best before date

3 years. Do not use after the expiration date stated on the packaging. The patches must be used within 14 days after opening the sachet.

NON-DRUG ASPECTS OF DRUG THERAPY

Versatis is most often prescribed to patients with chronic pain, a condition that requires a special approach to treatment. Research over the past 30 years indicates that chronic pain is not a purely physical phenomenon—psychological and sociocultural factors play a critical role in its formation and maintenance. According to the biopsychosocial model, chronic pain is the result of a dynamic interaction of biological, psychological, and sociocultural factors. In the acute phase of the disease, biological factors predominate, but over time, psychological and social factors come to the fore. Depression, anxiety, fear, irritability, and frustration lead to the maintenance and intensification of pain. In this regard, treatment of chronic pain aimed only at its physical component is ineffective in most cases [15].

For a patient with chronic pain, it is not enough to prescribe a drug. When conducting drug therapy, psychological factors should be taken into account and non-drug methods of pain control should be used. What the doctor says is no less important for the success of treatment than what drugs he prescribes. The patient may forget what dosage he was prescribed, but he is unlikely to forget how the doctor treated him and how he outlined the prospects for treatment.

Pain control

In various pain syndromes, a relationship has been demonstrated between the perceived ability to control pain and the pain itself. Jerome D. Frank associates the feeling of control (dominance, mastery) with the “raising of the material spirit” of the individual, generating positive feelings to replace negative ones - despair, isolation, hostility, failure, worthlessness, uselessness, helplessness, powerlessness [16]. “All successful types of therapeutic influence,” the scientist believes, “explicitly or implicitly change the image of the patient in his own eyes: a person drowned in his problems and symptoms becomes a person capable of managing them.” To understand how a physician's actions can help or hinder the achievement of this goal, consider 3 typical models of interaction with a patient: physician-parent, physician-salesperson, and physician-partner.

Doctor - parent

always knows what the patient needs. He tells the patient what to do, and he obeys meekly. “If you stick Versatis, this is the best option for you,” says the doctor-parent, and that’s where the appointment ends. The psychological “benefit” of a patient seeking help from a doctor-parent is freedom from responsibility. Based on the task of establishing control over pain, this benefit is apparent - getting rid of responsibility brings only temporary relief, without making the patient the master of the situation. Often he returns to the doctor after a few days, disappointed in the drug. “This Versatis of yours is not helping,” he declares and thinks to himself: “and the doctors don’t know how to do anything, no matter how many I went to, not one of them baked me.” And the more irritated the patient is, the stronger the pain becomes.

Doctor - seller

avoids making decisions, leaving the patient to choose what to do. “There is a drug called Versatis, you can read about it on the Internet and, if you want, try it,” says the sales doctor. The ineffectiveness of this interaction model is due to the fact that, just as there are no omnipotent doctors, there are no omnipotent patients. If the patient could cope with the pain himself, he would not come to the doctor. He needs not only information from the doctor, but also support that he cannot get from the seller.

Doctor - partner

bears responsibility for the treatment process, but does not relieve the patient of the responsibility for his own health that every adult bears. “Let's try the drug Versatis. The burning and tingling you described indicates neuropathic pain—pain that occurs when a nerve is damaged. It is not surprising that diclofenac and ibuprofen did not help you - they do not work well for neuropathic pain. And Versatis helps with neuropathic pain. So I think that despite previous failures with medications, this drug will help you." Of course, it is not the doctor’s words themselves that are important, but what is hidden behind them - sincere (sympathy, support and at the same time respect for the patient’s free will. “Versatis is not a pill, but a patch soaked in lidocaine. You will stick patch on the skin, and the medicine will be absorbed from it. Lidocaine blocks the nerve endings through which the signal for pain is transmitted." The partner doctor explains the essence of the new treatment method: understanding contributes to a feeling of control over pain. Then the doctor answers the patient's questions, discusses with him alternative methods of treatment, talks about future prospects.The final decision whether to take the drug or not belongs to the patient.

Setting realistic expectations

Many patients, when starting to use any medicine, including Versatis, expect instant and complete relief from pain. As a result, they are almost always left disappointed. With a pessimistic attitude, which is typical for patients with chronic pain, disappointment in the effectiveness of the drug often leads to disappointment in the doctor, medicines and medicine in general and to a loss of faith in the possibility of getting rid of pain. For this reason, when prescribing Versatis, it is very important to create realistic expectations in the patient.

First of all, it is necessary to explain that the analgesic effect usually occurs within 30 minutes, increases over 4 hours and is then maintained throughout the day. However, there is wide interindividual variability in the timing of response to treatment. In some patients, a noticeable effect occurs already in the first days of using the drug, in others - after a week, and in others - only after 2-4 weeks. In this regard, we can talk about the ineffectiveness of Versatis only after 2-4 weeks of its use.

According to statistics, the use of Versatis leads to a significant reduction in pain intensity in 76% of patients who are prescribed the drug [11]. However, in the vast majority of cases, complete relief from chronic pain is not possible using only one treatment method; a comprehensive multidisciplinary approach is required. The patient should be oriented towards the fact that Versatis will become one of the elements of pain control, and not a panacea that allows one to completely cope with the disease. A feature of the lidocaine patch is the absence of systemic absorption, which eliminates the risk of unwanted drug interactions with other drugs. As a result, Versatis is successfully used in combination with drugs of various groups, which makes it possible to reduce their dosage and, accordingly, increase the safety of treatment.

The effectiveness of the drug should not be underestimated when talking with the patient. Both overly high and low expectations can lead to treatment failure. The doctor’s task is to find the “golden mean”.

Alarm warning

Many patients, when receiving a prescription for a new drug from a doctor, are worried about its safety. This is especially true for chronic patients receiving a large number of medications - they are rightly afraid of polypharmacy. Patients do not always ask the doctor questions that concern them, therefore, given that anxiety is one of the factors leading to the maintenance of chronic pain, unspoken doubts should be dispelled in advance. It is advisable to clarify the following points.

When using Versatis, lidocaine is not absorbed into the blood. The drug acts locally, only at the level of nerve endings located in the skin. This prevents the development of adverse reactions and negative effects on the body as a whole.

Since Versatis does not enter the bloodstream, it does not interact in any way with other drugs. Its use can be combined with the use of any medications, painkillers and more.

Versatis does not cause drowsiness, does not reduce the ability to work, does not affect driving, and does not interact with alcohol.

Versatis is odorless and does not stain clothes.

G.R. Abuzarova, B.M. Prokhorov, A.S. Sokolenov

MNIOI named after. P.A. Herzen, Moscow

In the world, more than 24.6 million people are diagnosed with cancer, with about 11 million new cases of malignant neoplasms recorded annually. Based on the results of the latest and most comprehensive study to date, experts from the World Health Organization (WHO) stated that by 2021, the cancer incidence rate could increase to 15 million new cases per year, and mortality to 10.3 million. In Russia, according to the latest data 2006, about 2.5 million patients are registered with the oncology service; Every year, about 0.5 million patients are newly diagnosed, and about 300 thousand die, with an annual increase in incidence of 1.3% [7]. It is believed that from 30 to 60% of cancer patients at the first visit to the doctor complain of pain of varying intensity and localization. Their cause can be the direct tumor process (mass formation, tumor ulcer, etc.) or its complications (lymphostasis, pathological fracture, etc.). Successful antitumor therapy in most cases leads to regression of pain, but sometimes in 12-20% of cases pain accompanies antitumor treatment and even intensifies for some time. Thus, the problem of pain therapy both during antitumor treatment and its complications, as well as at the stage of generalization of malignant neoplasms, is quite relevant. From the above figures it is clear that it concerns millions of patients. In order to optimize and simplify complex pain pharmacotherapy regimens for practicing physicians, in 1986 WHO published the “Cancer Pain Relief” manual, which presents cancer pain therapy in the form of a three-step “pain ladder” [6]. Now this technique has become a classic and is successfully used all over the world. Much has changed between the first (1986) and second edition (1996) of this internationally recognized algorithm for the pharmacotherapy of cancer pain. New directions in pain therapy have emerged, new analgesic drugs in convenient non-invasive forms that can improve the quality of life of cancer patients and, accordingly, their loved ones. One of these new analgesic drugs that have emerged recently is the transdermal lidocaine therapeutic system. The drug first appeared in 1999 in the United States under the name Lidoderm. Russia became the second country where it began to be used in 2006 under the name Versatis. Lidocaine has been known for a long time as a peripheral anesthetic and antiarrhythmic agent. The mechanism of action is based on the ability of the drug to block sodium channels on the surface of neurons (and membranes of cardiomyocytes), which leads to a change in their bioelectrical activity and stabilization, reduces the ability of nerve cells to generate spontaneous nerve impulses, reduces the duration of the action potential and the effective refractory period in Purkinje fibers, suppresses their automaticity. Lidocaine, as an anesthetic, is widely used in terminal (superficial), infiltration, conduction, spinal (epidural) anesthesia, for blockade of peripheral nerves and nerve ganglia in surgery, neurology, ophthalmology, dentistry and other areas of medicine. In oncology clinics, local anesthetics have been used for a long time and often (blockades of nerves, plexuses, with superficial anesthesia), mainly for the treatment of acute conditions. As a rule, injection methods of administering drugs are used. For the treatment of chronic pain, these methods are quite traumatic and it is inappropriate to use them for a long time. Lidocaine, along with anesthesin, is used for acute pain reactions accompanying mucositis, ulcerations and defects of the mucous membranes during radiation or chemotherapy. There are works where lidocaine was successfully used intravenously to treat pain caused by postherpetic neuralgia. Lidocaine is administered dropwise over 40-60 minutes at a dose of 5 mg/kg in 100-200 ml of isotonic solution. The duration of the course is from one to three weeks. Such therapy is quite risky due to the systemic effect of lidocaine on the cardiovascular system; its implementation is possible only in a hospital setting in “safe” patients who do not have concomitant cardiac pathology, without a deficiency of water balance, with preserved liver function. Thus, it is difficult to imagine the possibility of widespread use of this method in elderly patients and, especially, in cancer patients. The use of lidocaine in the form of a cream or spraying the drug onto the mucous membranes in the form of an aerosol gives a quick but short-term effect [5, 9, 10]. However, there remains a need to use lidocaine for terminal (superficial) analgesia over a long period of time, but without its systemic effects on the cardiovascular system. It is these two necessary and partly mutually exclusive qualities that the Versatis transdermal system combines. An interesting fact is that the author of the idea of ​​​​transdermal use of lidocaine is the pharmacist H. Hind, who tried to relieve the pain of his wife, who had been suffering from postherpetic neuralgia for a long time. She did not tolerate intravenous lidocaine infusions well, and systemic tablets did not help her. As a result, H. Hind proposed applying a special cloth soaked in lidocaine to the skin. Thus, when applied, the effect of lidocaine was prolonged for several days. The same principle underlies the action of the lidocaine patch - TTC Versatis. [2]. TTS is available in the form of plates measuring 10 and 14 cm, which contain 700 mg of lidocaine. The plates are applied to dry, intact skin, and the absorption of lidocaine is about 3% of the total amount of lidocaine in the plate, and the degree of absorption does not depend on the functionality of the patient. Lidocaine, gradually released from the plate, creates a clinically significant concentration only in the superficial layers of the skin, where the receptors that perceive pain and temperature changes are located [1, 5]. It is believed that lidocaine, during transdermal diffusion into tissue, selectively acts only on those areas of nerve fibers and pain receptors that have an increased density of activated sodium channels on their surface. In this case, lidocaine interacts with pathologically active substances that are involved in the formation of neuropathic pain. By coming into contact with sodium channels, lidocaine blocks the excess flow of sodium ions into the nerve fiber and, thereby, reduces its bioelectrical activity, which is accompanied by a decrease in the generation of pain impulses from the periphery, a decrease in the speed of impulses along nociceptive A-delta and C-fibers, and a decrease in the number of ectopic impulses and pathological pain flow in general [4, 5, 11]. Since the concentration of lidocaine in tissues is low enough, at which conduction along thicker A-beta tactile fibers remains virtually unchanged, the analgesic effect of TTC Versatis is not accompanied by loss of skin sensitivity and unpleasant sensations of numbness, which contributes to a better quality of life for patients. TTS with lidocaine, as a rule, is recommended to be applied throughout the day for 12 hours, which is important for maintaining normal skin condition during long-term use. The analgesic effect often begins within 30 minutes after the plate is attached, increases over 4 hours and then is maintained as long as the plate is attached to the skin. Lidocaine practically does not penetrate into the deeper layers of the skin, where blood vessels pass under the basement membrane layer, so the entry of lidocaine into the systemic circulation is minimized. In support of this, the literature [13] describes a unique clinical case in which an oncology patient diagnosed with chondroblastic osteosarcoma of the gluteal region, accompanied by severe pain syndrome with a neuropathic component and pain with an intensity of 6-8 points (on a 10-point scale), received morphine 180 mg/day. day, amitriptyline – 50 mg/day, gabapentin – 2700 mg/day. Pharmacotherapy reduced the severity of pain to 4-6 points, but with the addition of two TTS lidocaine plates, the pain decreased to tolerable and was assessed by the patient at 2-4 points. After 5 months, as the tumor progressed, the pain intensified, despite the systemic therapy the patient was receiving. The area of ​​allodynia (burning unbearable pain when lightly touching the skin) also increased significantly, and therefore the amount of TTC lidocaine for the patient was increased from 2 to 4 patches, and the duration of application was increased to 16 hours. After another month, allodynia covered almost the entire surface of the leg and buttock, and the patient independently increased the amount of TTS lidocaine to 10 plates, and the duration of application to 24 hours. Thus, he more than tripled the maximum allowed number of patches and doubled the exposure time of the plates. Despite this, the level of lidocaine in the patient’s blood plasma was 0.47 mcg/ml, which is 3-10 times lower than the concentration causing a therapeutic effect (the systemic effect of the drug develops at a concentration in the blood plasma of 1.5-5 mcg/ml ). The concentration of lidocaine in the blood plasma with the usual use of TTS (no more than 3 plates for 12 hours a day) is 20 times lower than the therapeutic concentration of the drug and 60 times lower than the toxic one. This indicates the high safety of the use of lidocaine in the form of TTC and the absence of systemic action. It should be noted that with long-term use of TTS with lidocaine, the concentration of the active substance in the plasma remains stable - there is no effect of its accumulation. Thus, due to the peculiarities of pharmacokinetics, transdermal lidocaine is in demand not only in the neurological clinic, but also in the treatment of pain in the most severe patient population - in oncology. As mentioned above, in oncology practice, pain is the most common complaint presented by patients. For many of them, the cause of pain is dysfunction of the nervous system, which is caused by a tumor disease or antitumor therapy. These can be neuropathic and mixed (nociceptive and neuropathic) pain syndromes. On average, 15-35% of patients have neuropathic pain. The progression of a malignant neoplasm is usually accompanied by increased pain, and therefore, among patients with generalized forms of tumors, the number of patients with neuropathic pain increases from 15 to 75% [1, 3]. As a rule, these are tumor damage to peripheral nerves and the central nervous system, complications of the tumor process, complications of antitumor treatment (surgery, chemotherapy or radiation therapy), systemic metabolic disorders. Malignant neoplasms and their complications (most often compression or damage to peripheral nerves) are the direct cause of this type of pain in 72% of cases, and in 12% of patients the cause of pain is antitumor therapy. The main criteria for the manifestation of the neuropathic component in the general sensory complex of the pain syndrome are:

1. Quite a clear clinical picture: • complaints of shooting, sharp, piercing (lancing) pain; • pain as from an electric shock; • the presence of unusual sensory sensations (crawling sensations, insects, the feeling of broken glass, etc.); • the presence of local symptoms of weakening or increasing sensitivity (tactile, temperature, pain); • burning pain in response to light touch or change in temperature (tactile or temperature allodynia).

2. Localization of these sensory disorders in the area of ​​the damaged nerve. 3. Ineffectiveness of NSAIDs or insufficient effectiveness of opioid analgesics.

Neuropathic pain, which lasts a long time, debilitates, weakens patients already suffering from the tumor process, deprives them of sleep and appetite, and sharply reduces their quality of life. For the treatment of neuropathic pain in oncological practice, systemic pharmacotherapy is used, including tricyclic antidepressants, modern anticonvulsants (gabapentin, pregabalin), opioids (oxycodone, tramadol, buprenorphine, fentanyl, etc.), as well as local anesthetics, which include TTC lidocaine versatis [12 ]. Taking into account the proven effectiveness of TTC lidocaine plates in a number of clinical studies in the treatment of neuropathic pain syndromes, as well as taking into account the data on their safety presented in a number of publications and recommendations for the treatment of neuropathic pain, in our practice we used TTC Versatis precisely in those patients who complained of superficial sensory disorders associated with increased pain or perverted skin sensitivity. Such disorders often occur in the postoperative period after radical oncological operations, accompanied by extensive lymph node dissection and intersection of individual branches of peripheral nerves. Often the tumor itself and conglomerates of lymph nodes affected by its metastases are intimately adjacent to the neurovascular bundles, growing into muscle masses, bones or nerve plexuses. Removal of these tumors is accompanied by extensive tissue trauma, including nerve fibers. After these operations, it is possible to develop a variety of neurological pathologies - both increased symptoms and symptoms of loss in the sensory and motor areas. Postmastectomy and postthoracotomy syndromes should be considered one of the neurological complications of surgical treatment. The incidence of postmastectomy pain syndrome varies, according to different authors, from 4 to 30% and, as a rule, depends on the stage of the oncological process and the degree of trauma of the surgical intervention [3, 8]. During a radical mastectomy, it is possible to transect the intercostal brachial nerve, as well as many small cutaneous branches of the intercostal nerves, which subsequently causes pain and loss of sensation in the corresponding area. The radicalism of surgical intervention involves the removal of the mammary gland with tissue and regional subclavian and axillary lymph nodes, some of which are located along the neurovascular bundle. And although the branches of the brachial plexus lie quite deep in the axillary fossa, in some cases, with widespread tumor processes, the surgeon is forced to remove tumor tissue, injuring them. In these cases, a postoperative complication may be plexitis with neuropathic pain syndrome and impaired motor function of the hand. The clinical picture of sensory disturbances in this case is quite varied: shooting pain (like an electric shock) from the cervical spine to the elbow or hand; local burning on any area of ​​the skin; pathological itching; the feeling of goosebumps or insects crawling on the skin, tingling by many needles or pressure from glass shards. Patients have a hard time with these phenomena, which can go away on their own 1-3 months after surgery, but in some cases they develop into a chronic disease that requires observation and treatment by a neurologist. Versatis was used in 23 patients (12 men and 11 women) aged from 22 to 77 years, body weight from 50 to 91 (70.2 ± 12.3) kg with various localizations of malignant neoplasms, among which patients with generalized forms of the disease predominated (16 patients) and metastases to the bones of the spine and ribs, accompanied by compression of peripheral nerves and complaints of local pain in the corresponding area and high-intensity shooting pains radiating along the affected nerve. In the remaining patients, the neuropathic component was caused by postmastectomy pain syndrome (5 patients) and post-thoracotomy pain (2 patients) at various times after surgery (from 3 days to 2 months). Most patients complained of burning pain, locally in the area below the armpit and along the inner surface of the shoulder. Three patients described local pain in the interscapular region, on the side of the surgical intervention and below the angle of the scapula. True dynamic allodynia (the occurrence of burning pain to a light tactile touch) was detected in 6 patients. Shooting pain (as from an electric shock) was noted by all 7 patients; pathological itching was detected in 2 patients. Previous therapy in all patients was quite heterogeneous: NSAIDs (diclofenac, ketorol, nimesil) in average therapeutic doses - in 6 patients; NSAIDs in combination with an anticonvulsant (Neurontin) – 2 patients; pentalgin at a dose of 4 tablets/day – 2 patients. The opioid analgesic tramadol in a dose of 100 to 300 mg/day (or its combination with paracetamol - Zaldiar) was taken by 9 patients, of which 3 patients combined Tramal with NSAIDs, and Tramal with an anticonvulsant (Neurontin) - 2, with a TCA (amitriptyline) – 2 patients. Only 4 patients received strong opioids: morphine (MCT 60 mg/day) – 1 patient, TTS buprenorphine Transtek at a dose of 35 mcg/h – 1 patient, TTS buprenorphine Transtek at a dose of 52.5 mcg/h – 2 patients. In some patients (10) with moderate and mild pain, therapy was adequate only during the day, and pain attacks were observed at night. In others, with severe pain syndrome, against the background of systemic therapy, it decreased only to a moderate level. The majority (16) of patients reported sleep disturbance due to pain. Side effects of previous systemic therapy for CHD were moderate and were recorded in 9 patients (drowsiness - in 5 patients, epigastric pain - 2 patients (while taking ketorol), constipation - in 6 patients). The effectiveness of pain relief was assessed using a 4-point verbal rating scale (VRS): 0 points – no pain, mild pain – 1 point, moderate pain – 2 points, severe pain – 3 points, unbearable pain (the patient writhes and groans in pain) – 4 points. The average pain relief score on this scale was 1.65 ± 0.8 (from 3 to 0.5 points), which was generally regarded as an insufficient effect of analgesic therapy. All patients required a further increase in the dose of systemic analgesics, instead of which Versatis was used. Without canceling previous treatment, patients were additionally prescribed an application of Versatis 1-3 plates (depending on the extent of the area of ​​sensory disorders), while about half of the patients (14) preferred to use it at night. The duration of observation ranged from 7 to 22 days, although later some patients used it for more than 1 month. After the initial stage and the prescription of the drug, a re-examination was carried out on days 3, 7 and 14, when the level of pain intensity (on a 4-point PVR scale), the quality of night sleep, and the presence of side effects of analgesic therapy were recorded. On the 3rd day after adding TTS lidocaine Versatis to insufficiently effective systemic therapy with non-opioid and opioid analgesics, significant positive dynamics were revealed in the form of a decrease in the level of pain according to the WRS in the whole group from 1.65 ± 0.8 (before the start of application of the patches) to 0. 70 ± 0.5, improved sleep quality in 9 patients out of 16. At the same time, the best effect was observed in patients with local sensory disorders, and in patients with shooting pains, the reduction in pain level was unreliable, and in 2 cases the effect was short-lived (about 2 days ), which can be mistaken for a placebo effect. For these patients, therapy was subsequently enhanced with anticonvulsants (gabapentin, pregabalin) and antidepressants (amitriptyline). The addition of TTC Versatis to the treatment regimen by day 7 made it possible to reduce the daily dose of NSAIDs by almost 1.5 times and reduce the dose of tramadol by 2.1 times. As a result of corrective therapy, by day 7, the average pain relief score in patients was 0.57 ± 0.4; night sleep returned to normal in 16 patients. Accordingly, with a decrease in the drug load, the number of side effects caused by the use of analgesics also decreased slightly: daytime sleepiness while taking opioids (tramadol) was noted by 2 patients (before the application of Versatis - 5). By day 14, two patients stopped taking NSAIDs and kept only the patch for pain relief. It should be noted that no one experienced any symptoms of allergy or contact dermatitis at the site of application of the patch; it was quite easily and painlessly removed from the surface of the skin. But in some cases, patients had to additionally fix the patch to the skin with a mesh bandage or other means. The most illustrative were two clinical examples of the successful combination of TTC Versatis with systemic therapy.

Patient K., 55 years old. Without significant concomitant pathology. Condition after radical mastectomy (day 29) for stage IIB left breast cancer. The patient complains of severe pain in the left arm, localized along the inner surface, from the axillary fossa to the hand, of a shooting nature, as well as pain below the surgical scar, of a local nature (25 × 20 cm), burning, arising even from a light touch of clothing. When moving, both types of pain increase sharply. The patient takes Pentalgin on her own, 4-6 tablets per day, and diclofenac up to 150-300 mg/day (im injections and suppositories), but there is practically no effect of pain relief. Due to pain, the patient cannot raise her arm in an extended position, which is a necessary condition for postoperative radiation therapy. This situation led the patient to complete despair, since the timing of the start of effective RT was already at its limit. The patient is in a state of depression, constantly cries, night sleep and appetite are disturbed. The patient was diagnosed with postmastectomy pain syndrome, complicated by local allodynia and partial paresis of the left arm. At the appointment, after examination and establishment of the initial status of the pain syndrome, two Versatis patches were applied to the area of ​​burning pain (allodynia) below the surgical scar. After 1 hour, the patient noted the beginning of the effect - a decrease in pain. By the 3rd day, the patient increased the number of patches to 3, which she used during the day, thanks to which, gradually, by the 10th day, she was able to perform the entire complex of restorative gymnastics and increased the range of motion in the shoulder joint to the level necessary for administering a dose of radiation therapy to area of ​​the axillary fossa. Against this background, sleep normalized, symptoms of depression and psycho-emotional instability disappeared. It should be noted that the patient refused to take pentalgin for 7 days, but continued to take diclofenac, reducing its daily dose by three times (100 mg). The patient used Versatis daily for 14 days, then only occasionally. In this case, the use of Versatis allowed the patient to undergo the second stage of antitumor therapy on time, without resorting to potent opioid drugs.

Another clinical example concerns the use of TTC Versatis as a component in the complex of antineuropathic therapy for postoperative pain syndrome.

Patient G., 51 years old, underwent surgery to remove a bronchogenic cyst of the superior posterior mediastinum. Before the operation, the patient was diagnosed with the following concomitant pathology: coronary artery disease, angina pectoris class II, arterial hypertension grade 2, stage 2, high risk, diabetes mellitus type II, moderate severity in the compensation phase. Against the background of multicomponent anesthesia, the surgical stage passed without any special features. In the immediate postoperative period, the patient experienced severe pain, to relieve which on the first day after surgery it was necessary to administer buprenorphine 0.3 mg every 4-6 hours (daily dose 1.2 mg/day), tramadol 300 mg/day, Relanium 20 mg/day, ketonal 200 mg/day IM, which is almost twice the usual requirement for analgesics. From the second day, the dose of the narcotic analgesic buprenorphine was reduced; the doses of tramadol, relanium and ketonal remained the same for the next three days. In this case, the patient complained of severe pain (up to 3 points) in the area of ​​the surgical wound, a burning sensation, itching (“like pepper”), extending significantly below the level of the surgical incision. The pain limited the patient's movements and made it impossible to clear his throat. Upon examination, a zone of hyperalgesia around the surgical wound (increased pain response to mild irritation) and a local zone of allodynia (burning pain to touch) below the level of the surgical wound were revealed. Since the patient received buprenorphine intramuscularly at a dose of 0.6-0.9 mg/day for 3 days, and its effect lasted no more than 2-3 hours, it was decided to replace it with the non-invasive form of TTS Transtek at a dose of 52.5 mcg/h, which in the next 3 days, it ensured a constant supply of buprenorphine into the systemic circulation at a dose of 1.2 mg/day, without subsidization with tramadol. Additionally, 2 lidocaine patches were applied to the area of ​​allodynia. The use of systemic therapy in combination with the Versatis patch significantly expanded the patient’s motor activity; he could freely perform breathing exercises and cough up sputum. The maximum effect of Versatis began after 2 hours and lasted throughout the day. Subsequently, after discontinuation of TTS Transtek, to enhance the systemic effect of analgesia, the anticonvulsant Neurontin, 600 mg/day, was prescribed from the 5th day, and Zaldiar (2 tablets 3 times a day) was prescribed to relieve the nociceptive component (surgical wound). The patient was discharged on the 11th day after surgery in satisfactory condition with recommendations for gradual withdrawal of all painkillers.

Thus, the post-thoracotomy pain syndrome that arose in the early postoperative period was successfully relieved with the help of non-invasive complex therapy, including modern opioid analgesics (TTS Transtek) and special antineuropathic drugs - TTC Versatis, anticonvulsant Neurontin. In this case, Versatis made it possible to reduce the opioid dose and increase the patient’s motor activity both due to the analgesic effect and by reducing opioid-induced sedation.

Conclusion Treatment of pain in cancer patients is a difficult task, but quite feasible in the vast majority of cases. It requires the clinician to take a thoughtful approach to this problem, to study all possible causes and sources of cancer pain, especially since an cancer patient can have many of them, and they differ in etiology and pathogenesis. In each specific case, delving into the medical history, studying the data of clinical and laboratory research methods, identifying the degree of disorder of the patient’s organs and systems, it is necessary to find those optimal painkillers that will have their effect with minimal side effects and will be eliminated through systems unaffected by the pathological process. Therefore, it is so important to have in the arsenal of painkillers for the treatment of cancer pain such safe and effective forms of analgesics as TTC lidocaine Versatis and to be able to use them. The clinician is required to have knowledge of the clinical pharmacology of analgesics and the pathophysiology of pain in order to competently, without discrediting the drugs, use them exactly as intended: in the right place, at the right time, in the right combination.

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