The plaster is transparent on the transparent removable protective layer, the protective layer covers the patch with long and short sides; gel from transparent to opalescent, colorless, semi-solid, without mechanical inclusions.
capsaicin 179 mg per 280 cm 2 (8% by weight)
Auxiliary substances: BIO-PSA-4201 silicone adhesive is 1098 mg per 280 cm 2 (49% by weight), silicone adhesive BIO-PSA-4301 is 470 mg per 280 cm 2 (21% by weight), diethyleneglycol monoethyl ether (MEDG ) - 430 mg per 280 cm 2 (19.2% by weight), silicone oil 12500 cSt - 45 mg per 280 cm 2 (2% by weight), ethyl cellulose N50 18 mg per 280 cm 2 (0.8% by weight).
The composition of the coating film: polyethylene terephthalate with a siliconeized inner side.
Composition of the protective film: polyester film, coated with fluoropolymer.
The composition of the cleansing gel: macrogol 300 - 44.5 g per 50 g (89.1% by weight), carbomer - 0.5 g per 50 g (1.0% by weight), purified water - 4.9 g per 50 g (9.8% by weight), sodium pellets hydroxide (E524) 0.02 g per 50 g (0.03% by weight), disodium edetate 0.05 g per 50 g (0.1% by weight), butyl hydroxy anisole (E320) 0.01 g per 50 g (0.02% by weight).
1 plaster - sachet package (1) complete with cleansing gel (tuba 50 g) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
Mechanism of action
Capsaicin, or (E) -N - [(4-hydroxy-3-methoxyphenyl) methyl] -8-methylnon-6-ene-amide is a highly selective vanilloid receptor agonist with transient receptor potential type 1 (TRPV1). The initial effect of capsaicin is the activation of skin pain receptors expressing TRPV1, which leads to the development of burning and redness due to the release of vasoactive neuropeptides.
After exposure to capsaicin, the skin pain receptors become less sensitive to pain stimuli. Such effects of capsaicin are called "sensitivity reduction"; probably, they underlie the analgesic effect. It is assumed that the sensitivity of skin nerves that do not express TRPVI, including sensitivity to mechanical and vibration stimuli, remains unchanged. Capsaicin-induced change in cutaneous pain receptors is reversible; according to reports and observations of healthy volunteers, the restoration of normal function (reaction to irritant stimuli) occurs within a few weeks.
Clinical efficacy and safety
Based on the results of controlled clinical trials conducted in patients with HIV-associated neuropathy with pain syndrome (HIV-AH) and painful form of diabetic peripheral neuropathy, the effectiveness of a single 30-minute application of the Kutens plaster band on the foot area is shown. Based on the results of controlled clinical trials conducted in patients with postherpetic neuralgia (PGN), the efficacy of the Kutens plaster is shown with a single 60-minute application on the painful areas of the skin of other localization. Reduction of pain intensity was observed at week 1 in patients with PGN, at week 2 in patients with HIV-associated neuropathy with pain syndrome and at week 3 of patients with painful form of diabetic neuropathy. With all three diseases, the effect of the therapy persisted throughout the 12-week study period. With a painful form of diabetic neuropathy, constant and repeated efficacy was noted during the 52-week study period with repeated applications.
The safety profile of Kutense's patch in patients with diabetes was the same as in patients without diabetes.
The effectiveness of the Kutense plaster is confirmed both in monotherapy and in combination with other systemic drugs for the treatment of neuropathic pain.
Based on the results of controlled clinical trials conducted in patients with morbid HIV-associated neuropathy, the effectiveness of a single 30-minute application of the Kutens plaster band on the foot area is shown. Based on the results of controlled clinical trials conducted in patients with postherpetic neuralgia (PGN), the efficacy of the Kutens plaster is shown with a single 60-minute application on the painful areas of the skin of other localization. Reduction of pain intensity was noted already at 1 week; The effect of the therapy persisted throughout the 12-week study period. The effectiveness of the Kutens plaster is confirmed both in monotherapy and in combination with other systemic drugs for the treatment of neuropathic pain.
Capsaicin, contained in the preparation of Kutensa, is intended for delivery to the skin. The data obtained in vitro (when studying the dissolution of the active substance and its penetration into the skin) showed that the release rate of capsaicin from the preparation of Kutensa throughout the period of application is linear.According to the in vitro data, about 1% capsaicin is exposed to the application of transepidermal and transdermal absorption for an hour. The amount of capsaicin released from the patch in one hour is proportional to the surface area of вЂ‹вЂ‹the application and this amount to approximately the maximum possible dose at an application area of вЂ‹вЂ‹1000 cm 2 is approximately 7 mg. Assuming that a plaster area of вЂ‹вЂ‹1000 cm 2 carries approximately 1% capsaicin to a patient weighing 60 kg, the maximum possible exposure of capsaicin is approximately 0.12 mg / kg once every 3 months.
According to the Scientific Committee of the European Union on Foodstuffs, the average consumption of capsaicin inside Europe is 1.5 mg / day (0.025 mg / kg / day for a person weighing 60 kg), and the maximum intake with food is 25-200 mg / day (up to 3.3 mg / kg / day for a person weighing 60 kg).
According to pharmacokinetics in humans, after a 60-minute application of the patch Kutensa, transient, insignificant (<5 ng / ml) systemic exposure of capsaicin was observed in approximately one-third of patients with PGN, in 3% of patients with painful form of diabetic neuropathy. In patients with HIV-associated neuropathy, systemic exposure was not observed. Data on systemic exposure after a 30-minute application is not available. In general, the percentage of patients with PGN who had a systemic exposure of capsaicin increased with the area of вЂ‹вЂ‹the treated surface and the duration of therapy. C max capsaicin, detected in patients after a 60-minute application, was 4.6 ng / ml and was fixed immediately after removal of the Kutens plaster. The largest quantifiable concentrations were detected at the time of removal of the Kutens plaster with a clear tendency to disappear from 3 to 6 hours after removal of Kutens. None of the patients had capsaicin metabolites.
Results of the population pharmacokinetic analysis of patients treated for 60 and 90 minutes demonstrated that the concentration of capsaicin in the blood plasma reaches a maximum value approximately 20 minutes after removal of the Kutens plaster and then rapidly decreases. The average T 1/2 is approximately 130 minutes.
- treatment of peripheral neuropathic pain in adult patients as a monotherapy or in combination with other medications for the treatment of pain.
For external use only.
Plaster Kutensa should be imposed on the most painful skin areas (at the same time it is allowed to use no more than 4 patches). The attending physician should identify the painful areas of the skin and note them. Kutens plaster should be applied to intact, non-irritated dry skin for 30 minutes in the area of вЂ‹вЂ‹the feet (for example, in HIV-associated neuropathy, painful form of diabetic peripheral neuropathy) and for 60 minutes to other areas (eg, postherpetic neuralgia). Treatment with Kutens plaster is allowed to be repeated every 90 days, if this is necessary while maintaining or relapsing the pain syndrome.
A Kutens plaster should be applied by a doctor or a medical professional under the supervision of a doctor.
It is recommended to use a mask and goggles, especially when sticking and removing the patch.
Each time, when contacting the Kutens plaster and cleaning the plaster patch areas, nitrile gloves should be worn. Latex gloves are not suitable for this. they do not provide the necessary protection.
Avoid direct contact of unprotected skin with a Kutens plaster, with used gauze or cleansing gel.
Precautions should be taken to avoid inadvertent contact with the patch or materials in contact with the skin. Failure to take precaution can lead to reversible reddening of the skin and a burning sensation (mucous membranes are especially sensitive), eye pain, irritation of the mucous membranes of the eyes, oral cavity and pharynx, coughing.
Plasters should not be applied to areas located near the eyes or mucous membranes.
If necessary, cut the hairline (not to shave) on the affected areas in order to facilitate a close contact of the skin with the plaster. The surface to be treated should be washed gently with soap and water. After hair removal and rinsing, the skin should be thoroughly dried.
Before applying Kutens plaster, the surface of the skin should be pretreated with a local anesthetic in order to reduce the associated discomfort. Local anesthetic should be treated the entire surface, which is applied to the patch Kutensa, as well as surrounding areas 1-2 cm wide. Local anesthetic should be used in accordance with the instructions for its use. In clinical trials, patients' skin was pre-treated with 4% lidocaine for external use, or a combination of lidocaine (2.5%) and prilocaine (2.5%) for external use or given tramadol in patients with a dose of 50 mg. An anesthetic cream should be removed before applying Kutens plaster, the skin in the place of application should be thoroughly washed and dried.
The medicinal preparation of Kutensa is a plaster intended for single use, from which it is possible to cut out a site suitable for the shape and size of the affected area of вЂ‹вЂ‹the skin. Plaster Kutensa should be cut before removing the protective film. Protective film can not be removed until the moment of application. A diagonal cut on the protective film makes it easier to remove. It is necessary to separate the area of вЂ‹вЂ‹the protective film, bend it and apply an adhesive (adhesive) surface of the patch to the treated area of вЂ‹вЂ‹the skin. The plaster must be fixed immediately. With one hand, the protective film should be slowly and carefully separated from the lower surface while simultaneously smoothing the patch with the other hand on the surface of the skin to ensure contact of the plaster with the skin, preventing the formation of air bubbles and moisture.
When applying Kutens plasters on foot, they can be wrapped around the back, side and plantar surfaces of the foot to completely cover the area being treated. In order to ensure the contact of the patch Kutenza with the affected surface, it is allowed to use elastic socks or gauze bandage.
Remove the patch Kutensa should be cautious and slow, turning it inward in order to minimize the risk of aerosol formation from capsaicin. After removing the Kutens plaster, the surface of the skin should be treated with a lot of cleansing gel and leave it for at least 1 minute. The cleansing gel should be wiped off with a dry gauze cloth to remove the remains of capsaicin from the skin. After the cleansing gel is removed, the surface of the skin should be gently washed with water and soap.
If acute pain occurs during and after the procedure, local cooling (eg cold compress) or analgesics for oral administration (eg short-acting opioid analgesics) should be used.
Correction of the dose in patients with impaired renal or hepatic function is not required.
The safety and effectiveness of the use of Kutens plaster in children from birth to 18 years is not established. No data available.
Instructions for disposal and handling
When handling the Kutens plaster and cleaning the areas of application, medical workers should wear nitrile gloves.
It is possible to use a mask and goggles.
Used and unused patches, as well as other materials that come into contact with the treated areas of the skin, must be disposed of immediately after use, tightly packed in a plastic bag for medical waste and mixed in a suitable container for medical waste.
1089 of 1826 patients (59.6%) who received Kutens plaster therapy in randomized controlled trials reported on the development of adverse reactions that the investigator considered to be medically induced. The most frequently reported adverse reactions such as transient burning at the site of application, pain, redness and itching. Unwanted reactions were transient, in most cases mild or moderate severity, and stopped on their own. In all controlled trials, the proportion of patients who discontinued therapy due to adverse events was 2% in the group receiving Kutens, and 0.9% in the control group.
Table 1 lists all unwanted reactions that developed at a frequency greater than that in the control group and in more than one patient in controlled clinical trials among patients with postherpetic neuralgia and with HIV-associated neuropathy with pain, as well as with diabetic pain peripheral neuropathy. Reactions are presented in accordance with the distribution of organ systems and frequency of occurrence. The frequency of occurrence of unwanted reactions is classified as follows: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), unknown (frequency can not be is established according to available data). Within each frequency category, adverse reactions are presented in order of decreasing severity.
Table 1. Frequency of treatment-induced adverse reactions
Organ system and frequency Undesirable reaction
Infections and invasions
From the nervous system
Often Burning sensation
Infrequent taste distortion, hypoesthesia
From the side of the organ of vision
Irritation of eyes
From the side of the cardiovascular system
Infrequent AV blockade of I degree, tachycardia, palpitation, arterial hypertension
From the respiratory system
Infrequent Cough, throat irritation
From the digestive system
From the skin and subcutaneous tissues
From the musculoskeletal system
Often Pain in the extremities
Infrequently Muscle Cramps
General violations and violations in the place of application
Very often Pain and redness in the place of application
Often itching, papules, blisters, swelling, swelling, dryness at the place of application
Infrequent urticaria, paresthesia, dermatitis, hyperesthesia, inflammation, reaction, irritation, (hemorrhagic elements) at the site of application, peripheral edema
Abnormalities detected during diagnostic studies
Infrequently Increased blood pressure
Injuries, poisoning and reactions associated with procedures
Unknown Burns of the 2nd degree, accidental exposure to the components of the plaster (including eye pain, irritation of the mucous membranes of the eyes, mouth and pharynx, cough)
When performing studies in healthy volunteers, transient minimal changes in thermal sensitivity (from 1 В° to 2 В° C) and tingling sensations at the site of the application of the Kutens plaster patch were noted.
- hypersensitivity to the active substance or to any of the excipients.
PREGNANCY AND LACTATION
Information on the use of capsaicin in pregnant women is limited or absent.
The results of studies conducted on animals did not reveal teratogenic effects.
Based on data from pharmacokinetics studies in humans showing a transient, insignificant systemic absorption of capsaicin, the likelihood of an increased risk of developmental abnormalities due to the use of Kutens plaster is very low. Nevertheless, care must be taken when prescribing the drug to pregnant women.
It is not known whether capsaicin and / or its metabolites penetrate human breast milk. The available pharmacodynamic / toxicological data obtained in vivo have shown that capsaicin / its metabolites penetrate the milk of lactating animals. Risk for newborns / children can not be ruled out. When applying Kutens plaster, breastfeeding should be discontinued.
Data on the impact on human reproductive function are absent. Toxicological studies of reproductive function in rats showed a decrease in the number and percentage of motile sperm, and the number of pregnancies.
APPLICATION FOR FUNCTIONS OF THE LIVER
Dose adjustment in patients with impaired renal function is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Dose adjustment in patients with hepatic impairment is not required.
APPLICATION FOR CHILDREN
The safety and efficacy of the patch Kutenza in children from birth to 18 years of age has not been established. No data available.
When dealing with plaster Kutenza and washing the treated zones of health professionals should wear nitrile gloves. It is recommended to perform manipulation with a plaster Kutenza in a well-ventilated area.
Kutenza the patch should be applied on a dry intact skin; It is not allowed to use the drug to the skin of the face, scalp and (or) close to the mucous membranes. In patients with painful diabetic peripheral neuropathy, a form prior to application of the patch Kutenza and at follow-up visits should be carefully inspect your feet for skin lesions due to neuropathy and vascular insufficiency.
There is evidence of reducing the sensitivity of the patch after Kutenza. Generally, these changes are minor and transient nature (including heat sensation during stimulation and stab), but it is known one in the case of persistent clinical study hypesthesia pain form of diabetic neuropathy. It is possible that this is a consequence of the drug. Precautions should be taken in patients with a decrease in sensitivity in the feet and with an increased risk of such changes. All patients with a decrease in sensitivity to history should be carefully inspected for loss of sensitivity before each use plaster Kutenza. If detected or exacerbated by the loss of sensitivity, it is necessary to raise the question about the further use of the drug Kutenza.
The reactions at the application site, such as a transient burning sensation at the site of application, pain, redness and itching are common or very common. Moreover, cases were reported burns, including II degree burns, in patients treated with capsaicin patches. Patients complaining of severe pain, the patch should be removed and the skin to check for the presence of chemical burns.
If the patch Kutenza in contact with the skin, which is expected not to care for the skin, apply cleansing gel for 1 minute, then wipe the skin dry gauze to remove any remaining capsaicin from the surface. After cleansing gel is removed, the skin surface must be carefully cleaned with water and soap. When the burning sensation in the eyes, skin or respiratory tract, you must immediately cease contact with the adhesive. The eyes and mucous membrane must be washed with water. With the development of dyspnea should provide the necessary medical care.
In connection with treatment caused an increase in pain intensity during or shortly after application of the patch Kutenza transient increase in blood pressure may be observed in patients (mean <8 mm Hg. V.). During the medical procedure necessary to control blood pressure. In patients with unstable or poorly controlled hypertension or with recent illnesses of the cardiovascular system before starting therapy patch Kutenza should consider the risk of adverse reactions on the part of the cardiovascular system due to the potential stress associated with the procedure. Particular attention should be given to patients with diabetes with complications in the form of coronary heart disease, hypertension and cardiovascular autonomic neuropathy.
Patients who during and after application of the patch increased pain intensity should designate symptomatic treatment, for example, local cooling or analgesics for oral administration (e.g., short-acting opioids). Patients taking opioids in high doses, may not respond to opioid analgesics for oral administration, is used to eliminate acute pain at the time of or after a medical procedure. Before starting therapy should be carefully collected history; for patients with suspected high opioid tolerance is necessary to use an alternative strategy for reducing the intensity of pain.
Cleansing gel patch Kutenza contains butylhydroxyanisole which may cause local skin reactions (e.g., contact dermatitis) or irritation to the eye or mucous membranes.
These pre-clinical safety studies
preclinical data on the basis of standard pharmacological safety studies, toxicity after a single dose and toxicity after repeated administration showed no particular risk for humans.
Genotoxicity studies performed with capsaicin show a weak mutagenic response in the mouse lymphoma study and negative responses in the Ames test, in the study of mouse micronucleus and chromosomal aberrations in human peripheral blood lymphocytes.
Carcinogenicity study conducted in transgenic mice indicates that capsaicin is not carcinogenic.
Toxicological studies of reproductive function, conducted on rats, showed a statistically significant reduction in the number and percentage of motile sperm in rats receiving the drug for 3 hours / day for 28 days before mating, during mating, and after him until the conclusion of the experiment the rats. In spite of the statistics or the dose dependency, the rate of reproduction and the number of pregnancies per number of rats in the pairing was reduced in all groups treated with capsaicin.
Teratology studies were conducted in rabbits; the study did not reveal any potential embriofetotoksichnosti. Observed delay in ossification of bones (reduction metatarsals ossification) in rats during teratological studies when taken in doses exceeding the therapeutic dose for man; the importance of this observation has not been established for humans. Peri- and postnatal toxicity studies conducted in rats have not revealed the potential reproductive toxicity. In lactating female rats exposed Kutenza drug for 3 hours, it was detected in the milk of capsaicin.
Moderate degree of sensitization was seen in a cutaneous sensitization study in guinea pigs.
Impact on the ability to drive vehicles and manage mechanisms
Kutenza patch has no or insignificant influence on the ability to drive and operate the various mechanisms.
Cases of overdose were reported. Plaster Kutenza should impose a doctor or other health care professional under the supervision of a physician. In this connection, the risk of overdose is small.
Symptoms may experience severe reactions at the site of application, such as pain, redness, itching.
Treatment: suspected overdose plaster must be removed carefully, apply cleansing gel for 1 minute and wipe with a dry gauze, after which the area of skin must be carefully cleaned with water and soap. If clinically indicated should be carried out symptomatic treatment. Capsaicin antidote does not exist.
Studies of interaction with other drugs has been conducted, since the application of the patch Kutenza noted only minor transient systemic absorption of capsaicin.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Plaster Kutenza be stored on a flat surface in the original sachet and carton at a temperature not higher than 25 В° C. Cleansing gel should be stored at a temperature not higher than 25 В° C. The drug should be stored out of the reach of children. Shelf life - 4 years.
The information is provided for your information, do not self-medicate, it is dangerous for your health.