Description overdue on 05/08/2014

• Composition
• Product form
• Pharmacological action
• Pharmacodynamics and pharmacokinetics
• Indications
• Contraindications
• Side effects
• Tretinoin Cream: instructions for use, method and dosing regimen
• Overdose
• Cooperation
• Cautions
• Terms of sale
• Storage conditions
• Shelf life
• Reviews
• Price, where to buy

Composition

Tretinoin (transretinovaya acid) is the active substance is a crystalline powder with a pronounced floral aroma. The substance is highly soluble in dimethyl sulfoxide , Hardly soluble in polyethylene glycol . octanol   and 100% ethanol ( ethanol ), Almost insoluble in water (solubility parameter at a temperature of 25 ° C, at 0, 126 mg / l), mineral oils, and glycerol . The color of the powder can vary from yellow to light orange.

Product form

Tretinoin is available as:

• lotions with active substance concentration 0, 05%;
• gel at a concentration of active substance 0% 025, 0, 05% or 0 to 1%;
• cream with a concentration of active substance 0, 05% or 0 to 1%);
• solution for external application to the concentration of the active substance 0, 1%;
• Capsules for oral preparation (content of active substance in each capsule is 10 mg).

Pharmacological action

Tretinoin substance belongs to groups "protipoopuholevye Other drugs," "dermotropic means" and the group "Vitamins such as vitamins and drugs."

Acting on the body, it provokes:

• antitumor ;
• keratolytic ;
• antiseborrheic ;
• komedonolitichesky ;
• immunostimulatory ;
• stimulating tissue regeneration ;
• a local anti-inflammatory effect .

Tretinoin is also used as a treatment for acne vulgaris   and how provitamin A .

Pharmacodynamics and pharmacokinetics

Tretinoin belongs to the category system retinoids Which are inducers of cell differentiation. Its structure is similar to Vitamin A   and is a product of metabolization retinol .

The substance facilitates the induction of cellular differentiation, while inhibiting the proliferation promyelocytic   (precursors granulocytes ), Which is caused by a change in the binding transretinovoy acid   receptor cell nuclei retinoic acid   (including the myeloid leukemia ).

Under the influence of tretinoin activates the initial maturation of leukemic clone derived from the primitive promyelocytic As well as processes for their substitution bone marrow   and peripheral blood transformed normal polyclonal hematopoietic cells .

Against this background, the patient develops a remission of the disease, which is an average of two to four months.

When applied topically Tretinoin is able to penetrate cell membranes Thus forming cytoplasmic complex Entering the cell nucleus. Formed in this hormone-receptor complex is capable of binding to DNA   and impede the process of transcription, thereby violating protein biosynthesis   (on these processes is based gipopigmentnoe action tretinoin).

The substance has a stimulating effect on the cell mitosis   epidermal layer of the skin, helps to increase the amount of mucopolysaccharides   protein elastin and formed elastic fibers that are in the papillary layer of the skin.

Furthermore, Tretinoin:

• inhibits the formation of   Melanin ;
• stimulates growth and differentiation of cells epithelial ;
• inhibits cell adhesion, which form acne ;
• when applied to open acne   evens epidermis , Without leaving evidence of inflammation;
• when applied to closed acne   contributes to their transformation into open or papular nodules   and further healing without the formation of scars   after removing them from the keratin plug;
• prevents the formation of new acne .

Keratolytic action of tretinoin is to eliminate the phenomena keratoses . Its mechanism is due to the suppression keratinocyte proliferation   and improved the processes of their exfoliation.

Antiseborrhoeic effect is due to inhibition of proliferation of epidermal cells , Inhibition of proliferation epithelial tissue   excretory ducts sebaceous glands , Decrease sebum production and normalization of its evacuation, decrease the severity of the inflammatory reaction around sebaceous glands And stimulation processes skin regeneration .

Komedonoliticheskoe and local anti-inflammatory effects are expressed in the form of absorption of excessive amounts of sebaceous secretion, inhibition processes of its development sebaceous glands , Narrowing the pores and remove signs inflammation .

Notable therapeutic effect of the use of tretinoin is noted after approximately six weeks after the start of use of the drug (usually 6 or 7 weeks). The maximum effect is observed after 8-12 weeks of its application.

Transretinovaya acid   represents   endogenous metabolite of vitamin A Which is normally always present in the plasma   human. After oral administration of the substance is well absorbed in the stomach and intestine, the maximum concentration in plasma   It observed after three hours.

Suction- tretinoin can vary, both in different groups of patients and each individual patient. The substance capable of binding to a large extent with proteins   at plasma   (mainly albumin ). Indicator binding is within 95%.

Long half-life averages 0 7:00. After a single use of tretinoin in a dose of 40 mg, the maximum concentration in plasma   It returns to baseline after about 7-12 hours.

The drug does not accumulate in the body and fixed in its various tissues even after repeated administration.

Transretinovaya acid   characterized by the ability to induce its own metabolism , Resulting in reduction of AUC and plasma concentrations decline in average a third week after continuous administration of the drug. The increase in dose is not conducive to an adequate increase in plasma concentrations.

About 60% of tretinoin metabolites Which are formed during the oxidation and glyukuronirovaniya are eliminated by the kidneys within 3 days (72 hours). Partially metabolites   derived from intestinal contents within 3 to 6 days.

Repeated reception provokes reduction in the concentration, which is due to induction of the enzyme cytochrome c oxidase (cytochrome P450). As a result of this increased clearance, and reduced bioavailability indicator substance after oral administration.

If the drug is used for epicutaneous application, tretinoin absorption rate range from 1, 41-31%. Primarily it is influenced by parameters such as:

• General condition of the skin of the patient;
• the surface area to be treated;
• the duration of the drug.

After cutaneous application of 4, 45% of the absorbed dose is eliminated by the kidneys tretinoin in the urine, and about 1, 6% - together with bile.

Indications

Oral administration of tretinoin administered to patients diagnosed with variant acute myeloid leukemia Characterized by abnormal accumulation of one of the varieties of myeloid cells - promyelocytic .

Moreover, use of the drug triggers the induction of remission of the disease as the patients who previously were treated as well as in patients who have suffered a relapse / recurrence of APL (acute form promyelocytic leukemia ) Or refractory to standard Chemotherapy Conducted using rubomycin . cytarabine   or analogs thereof.

After the onset of complete remission of the disease patients showed a consolidating chemotherapy   at full doses.

Instructions drug warns that patients who are receiving maintenance therapy with tretinoin, there may be a loss of response to treatment.

As an external agent Tretinoin is used to treat:

• drain acne   (ie acne, which are the result of the merger of several induratum acne , Interconnected by a deep strokes);
• acne vulgaris Which are accompanied by the formation of papules   (nodules) comedones   (traffic jams formed at the mouth of sebum hair follicles) or pustules   (filled with purulent contents elements rash);
• Favre disease-Rakusha (colloidal degeneration of the skin, which is a dermatosis uncertain nature of origin);
• skin hyperpigmentation .

Contraindications

Contraindication to tretinoin capsules are:

• Individual hypersensitivity to tretinoin;
• Pregnancy (drug has on the fetus teratogenic, causing a serious breach of embryonic development);
• breastfeeding (if you can not avoid prescribing, feeding should be discontinued).

Outdoor use is prohibited:

• during pregnancy;
• people who have acute inflammation of the skin;
• at eczema ;
• in the presence of wounds and burns;
• at cutaneous epithelioma   (including those cases in which the disease was observed in family history).

Side effects

When taken orally, the drug about a quarter of patients noted the development of so-called " retinoic acid syndrome "That without proper treatment can be fatal.

The main features of " retinoic acid syndrome "Are breathlessness . fever . acute respiratory distress syndrome , Education infiltrates   in the lung, hyperskeocytosis   (increased white blood cell count, wherein the indicator concentration in the blood exceeds 40-50 thousand per 1 cc. mm)   hypotension , An abnormal accumulation of fluid in the pleural cavity ( pleural effusion ), Liver and kidney and multiple organ failure .

Other possible adverse reactions include:

• Skin reactions, which are expressed in the form of symptoms xeroderma   (excessive dryness and flaking of the skin), increased dryness in the mouth, cheilosis   (inflammation of the skin and red border of the lips), rash, itching, intradermal hemorrhage, increased sweating, hair loss ( alopecia ), The appearance of cellulite, increasing the body's sensitivity to the action of ultraviolet rays ( photosensitization ), Blisters or crusts on the skin, the emergence of pockets of temporary hyper- or hypopigmentation .
• Violations of the digestive system, including the nausea . vomiting , Epigastric pain, frustration of a chair   (available as constipation and diarrhea), development   bullous stomatitis , Increased activity of intracellular liver enzymes ALT and AST ( alanine   and aspartatovoy amino-transferase ).
• Violations of the CNS Which are expressed in the form depression , Impairment of consciousness, hearing and visual appearance dizziness , Increase the level of anxiety, improve performance intracranial pressure .
• Metabolic disorders, expressed in the form of increased plasma concentrations of Cholesterol   and triglycerides As well as changes in body weight.
• Violations of the respiratory system, which can be expressed in the form Cough . infections of the upper and lower respiratory tract . shortness of breath . dyspnea . flow off of the nasal mucosa   and larynx , Appearance pleural effusion   and wheezing, development pharyngitis   and appearance stridor .
• Violations of the musculoskeletal system, expressed in the form muscle aches   and bone pain .
• Violations by the function of the heart and circulatory system, which are expressed in the form arrhythmias .
• Increasing bleeding .
• Increasing weakness and drowsiness.
• The development of secondary   Infections .
• Appearance of pain in the chest and back.

Depending on the severity of side effects to the patient may be recommended a complete rejection of drug treatment or his temporary cancellation.

Restrictions on the assignment are:

• Children under one year when administered orally;
• Children under twelve years in the appointment of tretinoin as an external means;
• the absence of reliable contraception for women who are of childbearing age;
• renal dysfunction;
• abnormal liver function;
• increased intracranial pressure ;
• age greater than fifty years;
• leukocytosis ;
• chronic intoxication   (particularly alcohol);
• gipertriglitseridermiya ;
• hypercholesterolemia ;
• pancreatitis ;
• diabetes .

Tretinoin Cream: instructions for use, method and dosing regimen

The drug is given only a doctor who has experience with hematological   and cancer   diseases.

The recommended daily dose for oral administration - 45 mg of tretinoin for each square meter of skin surface of the body for ninety days (or within thirty days after the complete remission of the disease, treatment supplement   Chemotherapy   using drugs, cytostatics ). The dose is not dependent on the age of the patient and is the same both for adults, and for elderly people and children.

The maximum permissible dose is considered a daily dose equal to 195 mg of tretinoin for each square meter of skin surface of the body. Maximum allowable children's daily dose - 60 mg of tretinoin for each square meter of skin surface of the body.

If a patient is diagnosed renal   and / or hepatic failure , It is recommended to reduce the daily dose to 25 mg of tretinoin for each square meter of body surface of the skin.

For patients with large tumors of the daily dose is a third of the maximum permissible for children - below the maximum recommended by the attending physician appointment.

After two to four months after treatment Tretinoin is possible relapse .

When taken orally, the drug to reduce the likelihood of " retinoic acid syndrome "With increasing concentrations leukocytes   or the appearance of any sign of this state to a patient administered the complete chemotherapy , Involves the introduction of cytostatics in adequate doses.

As a topical agent lotion, gel or cream Tretinoin is applied to the affected skin is very thin layer once per day and left on them for six hours. After this time, the drug must be washed under running water.

A small amount of cream extruded finger on the pad and spread evenly on the face, starting from the forehead, chin and neck. Then move to the other affected areas.

The cream is rubbed lightly. He just has to become invisible, or at least unobtrusive. If there is peeling cream after drying, or it is too noticeable on the skin, it is an indication that the dose is exceeded.

It is important to remember that an excessive amount of the cream is not a guarantee better or faster results.

Light-skinned people, and people with increased dryness of the skin, in the early stages of treatment is recommended to apply Tretinoin no more than half an hour. Then allowed to gradually increase skin contact time with the drug.

In the course of treatment is also allowed to remove gradually matured and fully soften blackheads and pustules.

According to the instructions duration of treatment may vary from one to two weeks to three months. For the prevention of acne Tretinoin is applied after a warm bath for one to three times during the day over a long period of time.

Overdose

The consequences of exceeding the recommended dose of tretinoin are the symptoms described above " retinoic acid syndrome ".

If they occur in therapy involves a course of treatment dexamethasone . The drug should be administered for three days, 10 mg every twelve hours).

Cooperation

Tretinoin metabolization in the liver by enzymes of the cytochrome c oxidase. For this reason, the combined use of drugs with a drug affecting this enzyme system may provoke a change in the pharmacokinetic parameters of tretinoin.

Against the backdrop of the simultaneous use of tretinoin and contraceptives , Which are based on progesterone , The effectiveness of the latter is significantly reduced.

Simultaneous use with tretinoin tetracyclines   patients may experience an increase intracranial pressure .

Simultaneous use with drugs vitamin A   provokes symptoms gipervitaminoza .

Cautions

Using creams, gels and lotions for topical application, to avoid contact with the eyes, mouth, nose corners, open wounds, and mucous membranes. If this happens, you should immediately rinse thoroughly with water Tretinoin.

During the course of treatment is recommended to avoid exposure to the sun. Those patients who had a tan, treatment should be started after tanning ease somewhat.

Over damaged skin should apply sunscreen or cover them with clothing. While using Tretinoin preparations for external use is not recommended to be in the wind or the cold.

In the early days of using Tretinoin may increase acne , Due to the influence of the drug on localized in the deeper layers of the skin acne Which remained visible until the beginning of treatment.

When taken orally, the drug in women of childbearing age (even if they are diagnosed with infertility) it is recommended to use reliable contraceptives . They begin to receive at least one month prior to initiation of therapy, continue throughout the course of treatment and then once a month after discontinuation of the drug.

Treatment starts, usually on the second or third day of normal menstrual cycle . Two weeks prior to initiation of therapy should be made laboratory confirmation that the woman is not pregnant. In the following tests to determine pregnancy it is recommended to take a month.

If pregnancy occurs during the course of treatment Tretinoin because of high teratogenic very high risk of having a baby with malformations and other developmental disabilities.

There is insufficient information regarding the efficacy and safety of children Tretinoin. There are, however, information about the quickening   ). .

headaches   and dizziness .

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Terms of sale

Storage conditions

Shelf life

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