Metvix® (Metvix®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMethylaminolevulinateMethylaminolevulinate
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  • Metvix®
    cream externally 
    Galderma S.A.     Switzerland
    • Dosage form: & nbspTOfor external use.
    Composition:

    In 1 g of cream contains:

    active substance: methylaminolevulinate hydrochloride - 200 mg (corresponding to 160 mg of methylaminolevulinate);

    Excipients: glyceryl monostearate 60 mg, cetostearyl alcohol 40 mg, macrogol stearate 30 mg, methyl parahydroxybenzoate (E 218) 2 mg, propyl parahydroxybenzoate (E 216) 1 mg, disodium edetate 10 mg, glycerol 60 mg, paraffin soft white - 70 mg, cholesterol 10 mg, isopropyl myristate 40 mg, peanut butter 30 mg, almond oil 20 mg, oleyl alcohol 10 mg, purified water 417 mg.

    Description:

    From cream to light yellow cream.

    Pharmacotherapeutic group:photosensitizing agent
    ATX: & nbsp

    L.01.X.D.03   Methylaminolevulinate

    Pharmacodynamics:

    After external application methylaminolevulinate in cells treated areas of the affected skin accumulate proactive porphyrins. Intracellular proactive porphyrins (including PpIX - protoporphyrin IX) are photoactive, fluorescent connections. After activation by light in the presence of oxygen, as a result of interaction with proactive porphyrins, oxygen goes into a singlet state, forming a "singlet" oxygen, which causes damage to the components of the cell, in particular mitochondria.

    With the use of Metvix® in combination with infrared radiation for LK (radial keratosis), BCC (basal cell carcinoma of the skin) and Bowen's disease, light activation of accumulated proactive porphyrins leads to a photochemical reaction and subsequent phototoxicity to light-irradiated target cells.

    With the use of Metvix® in combination with daylight with radial keratosis, there is a continuous formation PpIX, which are activated in target cells within 2 hours after exposure to daylight, causing a permanent micro-phototoxic effect.
    Pharmacokinetics:

    In studies in vitro the absorption of radioactive methylamine levulinate through the skin. 24 hours after treatment, the average total absorption through the human skin was 0.26% of the applied dose. In the skin, a depot of methylamine levulinate was formed, containing 4.9% dose.

    In the course of the studies, it was noted that, after treatment of patients' skin with Métvix® cream, proactive porphyrins accumulated more in the affected areas than in healthy skin areas.After the application of the cream for 3 hours and subsequent illumination with incoherent light with a wavelength of 570-670 nm at a total dose of light of 75 J / cm2 complete photobleaching took place and the content of proactive porphyrins returned to the original value, prior to treatment with Metvix®.

    Indications:

    - Thin layered or unpigmented and non-hyperkeratized radial keratosis of the face and scalp in cases where other methods are considered less appropriate.

    - Surface and / or nodal basal cell carcinoma of the skin, which can not be treated by other methods due to possible complications caused by treatment, and also because of unsatisfactory cosmetic effect, for example, in the localization of lesions on the face and ears, on sun-damaged skin , as well as with extensive or recurrent lesions.

    - IntraEpidermal squamous cell carcinoma (squamous cell carcinoma in situ, Bowen's disease), when surgical treatment is considered less expedient.

    Contraindications:

    - Hypersensitivity to the components of the drug;

    scleroderm-like basal cell carcinoma of the skin;

    - porphyria;

    - Allergic reactions to peanut butter.

    Experience with children:

    It is not recommended, as the experience of treating children under the age of 18 is not available.

    Carefully:Avoid direct exposure to Metvix® cream in the eyes.
    Pregnancy and lactation:

    Pregnancy

    Studies in animals have not revealed a direct or indirect adverse toxic effect on reproductive function.

    Clinical data on the use of methylaminolevulinate during pregnancy are limited or absent, so it is not recommended to use Metvix® during pregnancy.

    Lactation

    It is not known whether methylaminolevulinate or its metabolites in breast milk after the application of the cream Metvix®.

    Risk for newborns and infants who are breastfed can not be ruled out.

    In the absence of clinical experience, breastfeeding should be canceled for 48 hours after the application of the cream.

    Dosing and Administration:

    For external use only.

    Adults (including the elderly):

    Application in combination with infrared radiation for LC, RBB and Bowen's disease

    To treat radiation keratoses (LC), one session of photodynamic therapy should be performed.

    For the treatment of basal cell carcinoma of the skin (BCC) and Bowen's disease, two sessions should be conducted with a 1-week interval between them. Three months after the session, you should evaluate the results of treatment and, if necessary, hold a second session.

    Before treatment each lesion on the skin should be treated: remove all scales and crusts and give the surface of the skin roughness. With nodular lesions of the RBB, a layer of intact epidermis is removed. The outer layer of the tumor is gently excised without leaving its boundaries. Then follows a coat Metviks® cream (about 1 mm thick) on the affected area and the surrounding healthy skin of 5-10 mm with a spatula and cover the treated area occlusive bandage for 3 hr.

    After 3 chasa remove bandage treated area cleaned 0.9% sodium chloride solution and immediately irradiated with red light of its sodium with continuous spectrum 570-670 nm to the total dose of light emission, the obtained surface of the affected area was 75 J / cm2. It is possible to use red light with a narrower spectrum (and a total irradiation dose of 37 J / cm2), providing the same activation of accumulated proactive porphyrins.The intensity of light exposure to the surface of the affected area should not exceed 200 mW / cm2. It is allowed to use lamps only with the "CE" marking, equipped with necessary filters and / or reflecting mirrors to minimize the effects of heat, blue light and UV radiation. It is important to ensure an appropriate dose of radiation, which is determined by a number of factors, including the size of the light field, the distance between the lamp and the skin surface and duration of exposure. These factors depend on the type of lamp, so it should be used in accordance with the enclosed operating instructions. The radiation dose can also be monitored by the presence of an appropriate detector.

    The patient and the operator must comply with safety regulations according to instructions attached to the light source. For the duration of the irradiation session, the operator and patient should wear special glasses that provide protection in accordance with the spectrum of the lamp radiation.

    Protecting healthy skin around affected areas is not mandatory during irradiation. During one treatment session, several lesions can be treated.

    The response to treatment should be evaluated 3 months after treatment. In the treatment of BCC and Bowen's disease, it is recommended to confirm the response to treatment with biopsy and subsequent histological examination. If necessary, affected areas with incomplete response to treatment can be re-treated. In the future, long-term clinical monitoring of the course of BCC and Bowen's disease is recommended, with histological analysis, if necessary.

    Application in combination with daylight with LC

    The treatment of affected areas with Metvix® in the treatment of LC may be performed under daylight conditions if the temperature conditions allow it to be outdoors for two hours after applying Metvix® cream. Carrying out this procedure in rainy weather is not recommended.

    Before preparing the affected areas for treatment on all exposed skin areas, including areas of lesions, it is necessary to apply sunscreen with a protective factor SPF30 or higher, does not contain physical filters (such as: titanium dioxide, zinc oxide, iron oxide), because these substances suppress absorption of the visible part of the spectrum, which can affect the effectiveness of treatment.When treating affected areas with the use of daylight, sunscreens can only be used with chemical filters.

    After the sunscreen has dried, scales and crusts must be removed and roughness of the skin surface should be applied before applying a thin layer of Matvix® cream to the areas to be treated. The use of an occlusive dressing is not required. Not later than 30 minutes after the application of the Matvix® cream, it is necessary to go outside to avoid excessive accumulation of protoporphyrin IX and, consequently, pain intensification when exposed to light. To reduce the degree of possible pain and maximize the effectiveness of treatment, the patient should be out in the daylight and do not enter the room for two hours after applying Metvix®. In sunny weather, it is permissible to stay in the shade if the patient feels unwell under direct sunlight. Two hours after application, the preparation should be washed off with water.

    Application in children:

    The safety and efficacy of Metvix® in children under the age of 18 years has not been studied.

    Side effects:

    In the treatment with Metvix® in combination with infrared radiation in LC, BCC and Bowen's disease, adverse reactions attributed to the toxic effects of photodynamic therapy (phototoxicity) or associated with the preparation of the affected surface for treatment are observed in approximately 60% of patients on the treated skin surface.

    The most common pain and burning sensation of the skin, which usually begin during irradiation with light or soon after it, and last for several hours, disappearing towards the end of the day. The intensity of local phototoxicity reactions is usually weak or moderate and rarely requires an early cessation of light therapy. The most frequent symptoms of phototoxicity are erythema and scab formation, which in most cases are mild or moderate and can persist for 1-2 weeks, sometimes longer.

    When repeated treatment with Matvix® cream, the frequency and severity of local phototoxic reactions decreases.

    The table below lists the adverse reactions observed in a clinical trial involving 932 patients,who received a standard treatment regimen using infrared radiation, as well as unwanted reactions described in the post-registration period.

    Undesirable reactions were classified according to organ systems and frequency of occurrence: very often (> 1/10), often (> 1/100 - <1/10), infrequently (> 1/1000 - <1/100), rarely (> 1 / 10 000 - <1/1000), very rarely (<1/10 000), the frequency is unknown (can not be estimated based on available data).

    System of organs (MedDRA)

    Frequency of occurrence

    Undesirable reactions

    Disturbances from the nervous system

    often

    Paresthesia, headache

    Disturbances on the part of the organ of sight

    infrequently

    Swelling of the eyes, pain in the eyes

    frequency unknown

    Edema of eyelids

    Vascular disorders

    infrequently

    Bleeding of the wound surface

    frequency unknown

    Hypertension

    Disorders from the digestive system

    infrequently

    Nausea

    Disturbances from the skin and subcutaneous tissues

    Often

    Pain, burning sensation of the skin, formation of a scab, erythema

    often

    Skin infection, ulceration, swelling of the skin, swelling of the skin, blistering, bleeding of the skin, itching, scaling of the skin, sensation of heat in the skin

    infrequently

    Urticaria, rash, skin irritation, photosensitivity reaction, hypopigmentation of the skin, hyperpigmentation of the skin, sweating, discomfort

    frequency unknown

    Angioedema, edema of the face (swelling of the face), pustular eruptions (pustules in the field of application), eczema in the field of application, allergic contact dermatitis

    Common disorders a and violations at the site of administration

    often

    Allocations in the application area, sensation of heat

    infrequently

    Feeling tired

    The study, conducted with the participation of patients with reduced immunity after organ transplantation, revealed no data indicating the effect on the safety of the drug in this category of patients. Adverse events were consistent with those described in studies involving immunocompetent patients.

    In two Phase III studies of the Metvix® preparation in combination with daylight, no new local adverse reactions were reported as compared with the already known local adverse reactions that occur with the use of infrared radiation. Metvix® combined with daylight almost did not cause pain in patients compared to its use in combination with infrared radiation.

    In two Phase III trials involving 231 patients, local adverse events were less common with Metvix® in combination with daylight,than with the use of Metvix® in combination with infrared radiation (45.0% and 60.1% of patients, respectively).

    Overdose:

    In the case of longer exposure to the cream or the use of light of a much higher intensity, pain, erythema and burning sensation may be intensified.

    Interaction:

    Drug interactions are unknown.

    There is a possibility that simultaneous use of other means with a photosensitizing effect may enhance photosensitization when treated with Matvix® cream.

    Special instructions:

    Methvix®, in combination with infrared radiation, should be applied only in the presence of a doctor, nurse or other medical professional with experience photodynamic therapy with Metvix®.

    The use of the Matvix® cream in combination with daylight does not require special training.

    Do not use a cream to treat dense (hyperkeratinized) ray keratosis.

    There is no experience of treatment with Metvix® cream of pigmented lesions, lesions with a high degree of infiltration or located in the genital area, as well as Bowen's disease with a lesion lesion size of more than 40 mm.

    As in the treatment of Bowen's disease using cryotherapy and fluorouracil, the response rate for large foci (> 20 mm in diameter) is lower than in the treatment of small foci.

    There is no experience in treating Bowen's disease in patients who undergone transplantation and receiving immunosuppressive therapy, as well as in patients after exposure to arsenic.

    After contact with skin methylaminolevulinate may cause sensitization leading to angioedema, eczema or allergic contact dermatitis in the area of ​​application of the cream.

    Excipients such as: cetostearyl alcohol and peanut butter, in rare cases can cause local skin reactions (eg, contact dermatitis); methyl and propyl parahydroxybenzoates (E218, E216) can cause allergic reactions (possibly, delayed type).

    It is necessary to cancel any form of therapy with UV light before starting treatment.

    Avoid sun exposure to treated affected areas and surrounding skin areas within two days after application of the cream.

    Avoid exposure to Metvix® in the eyes.

    In patients with hypertension in a history of pain during exposure can cause high blood pressure.therefore it is recommended to measure arterial pressure in patients experiencing severe pain. With the development of severe hypertension should be interrupted by radiation and, if necessary, take appropriate measures to normalize blood pressure.

    Form release / dosage:

    Cream for external use, 16%.

    Packaging:

    By 2.0 grams in an aluminum tube, covered with white enamel on the outside, inside - an epoxy resin grade for food. The end of the tube is covered with an aluminum membrane and a screw cap with a punch.

    1 tube with instructions for use in cardboard pack.
    Storage conditions:

    At a temperature of 2 to 8 ° C.

    Keep out of the reach of children.
    Shelf life:

    15 months. Do not use after expiry date.

    Shelf life after the opening of the package - 1 week.

    Terms of leave from pharmacies:For hospitals
    Registration number:LP-000468
    Date of registration:01.03.2011 / 02.03.2016
    Expiration Date:Unlimited
    The owner of the registration certificate: Galderma S.A. Galderma S.A. Switzerland
    Manufacturer: & nbsp
    Representation: & nbspGALDERMA, LLCGALDERMA, LLCRussia
    Information update date: & nbsp11.08.2016
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