Versatis 700 mg 5 pcs. transdermal therapeutic system

Compound

One patch, 13.3-14.7 cm long, 9.5-10.5 cm wide, contains 700 mg of active lidocaine and the following inactive auxiliary compounds: 3367 mg of purified water, 2520 mg of glycerol ; 2800 mg sorbitol , 1400 mg polyacrylic acid solution 20%, 700 mg sodium polyacrylate, 700 mg sodium carmellose, 700 mg propylene glycol, 420 mg urea, 210 mg kaolin, 210 mg tartaric acid, 147 mg gelatin, 58.8 mg polyvinyl alcohol (75000), 32.2 mg aluminum dihydroxyaminoacetate (aluminum glycinate), 14 mg disodium edetate, 14 mg methyl parahydroxybenzoate, 7 mg propyl parahydroxybenzoate, 1750 mg nonwoven fabric and 742 mg plastic film (polyethylene terephthalate, PET).

Pharmacodynamics and pharmacokinetics

Versatis contains a local anesthetic - lidocaine , which is an acetamide with membrane-stabilizing activity and the ability to block sodium channels in excitable neuronal membranes. When used topically on undamaged skin, the expected therapeutic effect occurs - pain , without systemic influence.

Pharmacokinetic data

Approximately 3±2% of lidocaine from the total amount contained in the patch is adsorbed. Achieving a maximum blood concentration of 0.13 mcg/ml is possible by applying 3 patches over 12 hours. Binding to plasma proteins occurs by 50-80%.

Distribution is rapid (the half-life of the distribution phase lasts 6-9 minutes) begins with penetration into well-supplied tissues, then into adipose and muscle tissue.

Lidocaine is able to penetrate the blood-brain and placental barriers and is excreted in breast milk (approximately 40% of the concentration in a woman’s blood plasma). Metabolism occurs in the liver by 90-95%, taking into account the action of microsomal enzymes until the formation of pharmacologically active metabolites . Excretion through the kidneys and bile , with up to 10% eliminated unchanged.

Features of pharmacokinetics in special groups of patients

• In persons with liver disease, the metabolic rate is reduced to 10-50% of the normal value.
• With chronic renal failure , accumulation of metabolites is possible, while acidification of urine causes an increase in the excretion of lidocaine .

Versatis 700 mg 5 pcs. transdermal therapeutic system

pharmachologic effect

Local anesthetic.

Composition and release form Versatis 700 mg 5 pcs. transdermal therapeutic system

Plaster - 1 pc.:

• Active substance: lidocaine 0.700 g/patch;
• Excipients: purified water 3.367 g, glycerol 2.520 g, sorbitol 2.800 g, polyacrylic acid solution 20% 1.400 g, sodium polyacrylate 400-600 mPa s 0.700 g, sodium carmellose 90-168 mPa s 0.700 g, propylene glycol 0.700 g , urea 0.420 g, kaolin 0.210 g, tartaric acid (tartaric) 0.210 g, gelatin 0.147 g, polyvinyl alcohol (75,000) 0.0588 g, aluminum dihydroxyaminoacetate (aluminum glycinate) 0.0322 g, disodium edetate 0.014 g, methyl parahydroxybenzoate 0.01 4 g , propyl parahydroxybenzoate 0.007 g, non-woven material 1.750 g, plastic film (polyethylene terephthalate, PET) 0.742 g.

Patch size: length from 13.3 to 14.7 cm, width from 9.5 to 10.5 cm.

5 patches in a sachet. 1, 2 or 6 sachets in a cardboard box along with instructions for use.

Description of the dosage form

White to light yellow polymer adhesive (sticky) material with a slight characteristic odor, evenly distributed on one side of the non-woven material and covered with plastic film. The non-woven material is engraved with the words “Lidocaine 5%”.

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. Discard the 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.

Pharmacodynamics

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 symptoms 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 and 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 with the formation of monoethylglycine xylidide (MEGC) and glycine xylidide (GK), metabolites 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 for use Versatis 700 mg 5 pcs. transdermal therapeutic system

Neuropathic pain associated with a previous herpes zoster infection, 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).

Use with caution in severe cardiac, renal or liver failure.

Application of Versatis 700 mg 5 pcs. transdermal therapeutic system during pregnancy and lactation

Lidocaine crosses the placenta. There are no data on the use of lidocaine in pregnant women; therefore, the drug is used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus. Lidocaine is excreted in breast milk. Since lidocaine is metabolized relatively quickly and predominantly in the liver, it can be expected that very small amounts of lidocaine may be excreted in breast milk. There is no data on the use of the Versatis patch in nursing mothers, therefore, during breastfeeding, the drug is used only if the expected benefit to the mother outweighs the potential risk to the child.

special instructions

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

The patch contains propylene glycol, which may cause skin irritation, and methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may 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.

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.

Side effects Versatis 700 mg 5 pcs. transdermal therapeutic system

Adverse reactions were observed in approximately 16% of patients using Versatis. Since the drug is used externally, in most cases, adverse reactions are local in nature and occur in the area where the patch is applied. The most common adverse reactions are the following local reactions in the area of ​​application of the patch: erythema, rash (up to vesicular), skin itching, burning sensation, dermatitis at the site of application.

The table below shows the adverse reactions identified during the clinical use of the drug for postherpetic neuralgia. They are listed by organ system and frequency of occurrence. The frequency of occurrence is defined as follows: “very often” (≥ 1/10), “often” (≥ 1/100 -

The following adverse reactions were observed during post-marketing use of the drug:

All adverse reactions were of mild or moderate intensity. In less than 5% of cases, the development of adverse reactions was the reason for stopping the use of the drug.

If the drug is used correctly, the development of systemic adverse reactions is unlikely, since when treated with a patch containing 5% lidocaine, the entry of the active substance into the systemic circulation is insignificant. Systemic adverse reactions associated with the use of lidocaine are identical to those characteristic of local anesthetics of the amide group (see section "Overdose").

If any of the side effects indicated in the instructions occur, or any other side effects not listed in the instructions are noticed, tell your doctor.

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.

Contraindications

Versatis lidocaine patch is contraindicated:

• in case of violations of the integrity of the skin of the application site;
• with established hypersensitivity to lidocaine and other components of the patch;
• pregnant and breastfeeding mothers.

Should be used with caution

• in case of infectious or traumatic skin lesions at the intended site of application;
• in acute phases of diseases or in weakened patients;
• during therapy with class I antiarrhythmic drugs and other local anesthetics ;
• in pediatrics;
• in elderly people

VERSATIS Lidocaine patch 5 patches #

Pharmacokinetics

With a single or multiple use of the Versatis medical patch at the maximum recommended dose (simultaneous application of three patches for 12 hours), only 3 ± 2% of the total applied dose of lidocaine 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.

The volume of distribution does not depend on age, decreases in patients with chronic heart failure and increases in liver failure. 70% of lidocaine, which penetrates into the systemic circulation after application to the skin, binds to blood plasma proteins. Lidocaine penetrates the placental and blood-brain barriers by passive diffusion.

Lidocaine is rapidly metabolized in the liver to form several metabolites. The main metabolic pathway is N-dealkylation to form monoethylglycine xylidide (MEGC) and glycyl xylidide (GC). Metabolites have less pharmacological activity than lidocaine and are present in lower concentrations. They are hydrolyzed to 2,6-xylidine, which is converted to conjugated 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 (MEGC, HA and 2,6-xylidine) do not accumulate in the body, and equilibrium concentrations are 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. There are no data on the metabolism of lidocaine in the skin.

Lidocaine and its metabolites are excreted by the kidneys. More than 85% of the dose is found in the urine in the form of metabolites or active substance. Less than 10% of the lidocaine dose is excreted unchanged. The main metabolite in urine is 4-hydroxy-2,6-xylidine, accounting for about 70–80% of the dose excreted in the urine. 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 delayed.

Pharmacodynamics

The mechanism of the analgesic effect of topical application of lidocaine in the form of a patch is associated with the stabilization of neuronal membranes, which, despite the decrease in regulation of sodium channels, leads to a decrease in pain.

Side effects

On the part of the immune system, the development of allergic contact dermatitis , manifested in the form of hyperemia at the site of application, skin rash , urticaria , itching , and there have also been cases of burning of the area of ​​the skin exposed to the drug. Cases of angioedema .

Versatis, instructions for use (Method and dosage)

Dosage

The patch is glued to intact, non-inflamed dry skin in the area where pain - once a day for a maximum of 12 hours. It is possible to use no more than 3 patches at a time. If the plastic protective film has not been removed, the patch can be cut into the required number of pieces. The duration of treatment is up to 2–4 weeks; if the therapeutic effect is insufficient or is provided only by its protective properties, then treatment is stopped.

Features of applying the patch

The patch is applied externally and should be glued to the skin immediately after it has been removed from the sachet and the plastic film has been removed from the adhesive layer. It is recommended to cut the hair with scissors, but do not shave it off!

Attention! After gluing the patch, you should immediately wash your hands. Avoid contact of hands with eyes!

Disposal

Do not reapply a used patch. Since it contains an active substance that must be discarded immediately after removal, fold the patch in half with the sticky side facing in and make sure it is out of the reach of children and pets.

Directions for use and doses

Externally. 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 the same time. If necessary, the patch can be cut into pieces before removing the plastic protective film. The patch should be applied to intact, dry, non-inflamed skin (after complete healing of the herpetic rash), covering the area of ​​pain. Then the patch is removed and a break of at least 12 hours is taken. The removed patch should not be reused.

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 after 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. The patch should be discarded immediately after discontinuation of 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.

Overdose

Taking in excess of doses of the drug Versatis is unlikely, but not completely excluded, because if used incorrectly, it is possible to achieve higher plasma concentrations that differ from the established norms for a therapeutic effect. of lidocaine as a local anesthetic may occur It is accompanied by the following symptoms:

• anaphylaxis;
• convulsions;
• tremor;
• depression;
• euphoria;
• stimulation of the central nervous system;
• headache;
• dizziness;
• feeling of fear;
• anxiety;
• visual impairment;
• tinnitus;
• bradycardia;
• hypertension;
• feeling of heat or cold;
• respiratory depression.

Actions taken in case of overdose

antidote for lidocaine . If suspicious symptoms are detected, the patch should be immediately removed, discarded and consult a doctor.

Analogs

Level 4 ATX code matches:
Markain

Scandonest

Emla

Naropin

Lidocaine

Ubistezin

Ultracaine D-S Forte

Ultracaine D-S

Ultracaine

Artikain

It is possible to use Lidocaine in other forms:

• 10% spray, a package of Lidocaine 38 g will cost 360-400 rubles;
• 10% solution for injection, 10 ampoules of 2 ml - approximate cost 29-40 rubles.

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.

Literature 1. Danilov A.B., Davydov O.S. Neuropathic pain. M.: Borges. 2007; 192. 2. Zyryanov S.K., Belousov Yu.B. Transdermal therapeutic system with lidocaine - a new approach to the treatment of peripheral neuropathic pain // Consilium-medicum. 2006; 8: 61-64. 3. Kanner R.M. Secrets of pain treatment. M.: - BINOM. 2006; 400 s. 4. Kukushkin M.L., Khitrov N.K. General pathology of pain. M.: Medicine. 2004; 144. 5. Levin O.S. The use of a transdermal therapeutic system with lidocaine in the treatment of pain syndromes. Consilium-medicum. 2007; 9:2:51-59. 6. Pain relief for cancer. Second edition. WHO. Geneva, 1996; 71. 7. The state of oncological care to the population of Russia in 2006 / Ed. Chissova V.I., Starinsky V.V., Petrova G.V. M.: 2007; 180. 8. Ashok KR. Saxena Pain Practice. Management Strategies for Pain in Breast Carcimoma Patients: Current Opinions and Future Perspectives., Vol 7, Issue 2, 2007; 163-177. 9. Collins PD EMLA cream and herpetic neuralgia // Med J Aust, 1991; 155: 206-207. 10. Meier T. et al. Efficacy of lydocaine patch 5% in treatment of focal peripheral neuropathic pain syndromes // Pain. 2003; 106: 151-158. 11. Davies PS, Galer BS Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia // Drugs. 2004; 64:937-947. 12. Fennerup NB, Otto M., McQuay NJ Algorithm of neuropathic pain treatment // Pain. 2005; 118: 289-305. 13. Wilhelm IR, Griebinger N. et al. // J Pain Symptom manage. 2005.

Versatis price, where to buy

You can buy Versatis (5 patches in a package) for 480-560 rubles.

• Online pharmacies in RussiaRussia

ZdravCity

• Versatis patch 700 mg 5 pcs. Teikoku Seiyaku Co.
  Ltd. RUR 717 order
• Versatis ttc 30 systems (5 transdermal systems in a pack of 6 sachets)Grunenthal GmbH

  RUB 3,327 order