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Systemic retinoid. Acitretin, the active ingredient of the drug – aromatic synthetic analog of retinoic acid. In preclinical studies of tolerance acitretin mutagenic or carcinogenic effects have been detected; there were no indications as to its direct hepatotoxicity. Acitretin what is trenbolone acetate exerted on the animals marked teratogenic effects. Clinical studies have confirmed that in psoriasis and disorders of keratinization acitretin normalizes processes of proliferation, differentiation and keratinisation of epidermal cells, and its side effects are generally well tolerated. The drug is purely symptomatic; its mechanism remains largely unknown.
Absorption Maximum plasma concentration acitretin observed 1-4 hours after administration. Best bioavailability acitretin is achieved while taking the drug with food. The bioavailability of a single dose is about 60%, but it is subject to considerable individual variations (36-95%).
Distribution Acitretin has a pronounced lipophilicity and easily penetrates tissue. Its protein binding is more than 99%. In animal studies, acitretin passed the placental barrier in quantities that can cause malformations in the fetus. The lipophilic properties of acitretin suggest that it is in significant quantities into breast milk.
Metabolism Acitretin is metabolized by isomerization of 13-cis isomer (cis acitretin), as well as by formation of glucuronide and side chain cleavage.
Excretion studies with patients receiving multiple drug aged 21 to 70 years have shown that the half-life (T1 / 2) acitretin is about 50 hours, and its major metabolite in plasma, cis acitretin, which is a teratogen – 60 hours. Considering the highest duration of half-life of acitretin (96 hours) and cis acitretin (123 hours) in these patients, as well as on the basis of their linear kinetics, it can be predicted that more than 99% of the drug will be printed from the body within 36 days after the termination of long-term treatment. Moreover, within 36 days after cessation of treatment and the concentration what is trenbolone acetate of cis-acitretin acitretin plasma decreased below the sensitivity limit of the method (<6 ng / ml). Acitretin is output solely in the form of metabolites in approximately equal amounts by the kidney and bile ducts.
Indications Severe forms of psoriasis, including erythrodermic psoriasis, localized or generalized pustular psoriasis. Severe dyskeratosis, such as congenital ichthyosis; red hair lichen; Darier’s disease; other severe disorders of keratinization that are resistant to conventional therapies.
Contraindications
- Hypersensitivity to the active substances or auxiliary drug hypersensitivity to other retinoids;
- severe hepatic and renal failure;
- severe chronic hyperlipidemia.
- concomitant use with tetracyclines, methotrexate, vitamin A and other retinoids. neotigazon has a strong teratogenic and should not be administered to pregnant women.The same applies to all women capable of child-bearing, if they do not use reliable contraception for four weeks before treatment, during treatment and for two years after its completion (see. Below).
Breastfeeding neotigazon should not be prescribed to nursing mothers.
Dosage and administration Because of individual differences in the absorption and rate of metabolism of acitretin dose should be adjusted individually. Capsules are better taken once a day with meals or with milk. The following are approximate recommendations.
Adults Initial daily dose of 25mg (i.e. 1 capsule 25 mg) or 30 mg per day (i.e., 3 capsules of 10 mg) for 2-4 weeks, may be sufficient to provide a therapeutic effect. The maintenance dose depends on the clinical efficacy and tolerability of the drug. Typically, the optimal therapeutic effect is achieved at a daily dose of 25-50 mg, received for another 6-8 weeks. In some cases it is necessary to increase the dosage to a maximum of 75 mg / day (i.e., 3 capsules of 25 mg). After sufficient regression of psoriatic lesions treated patients with psoriasis can be stopped. Relapses are treated as above. Whendyskeratosis usually require maintenance therapy, which can be carried out as smaller doses. They may be below 20 mg per day and should not exceed 50 mg per day.
Children Considering the possibility of severe side effects, the potential risk to the expected therapeutic effect should be carefully weighed against long-term treatment. Acitretin should be prescribed only after failure of other treatments. The daily dose depends on the body weight and about 0.5 mg / kg. In some cases, for a limited
Pregnancy neotigazon vysokoteratogenen. He not only is contraindicated in pregnant women and women who may become pregnant during treatment or within 2 years after the termination of his admission, but also to all the women, potentially able to bear children. The risk of having a baby with birth defects is particularly high if neotigazon taken before or during pregnancy, irrespective of the dose and duration of therapy. Action neotigazon the fetus is always fraught what is trenbolone with the risk of congenital malformations. Neotigazon contraindicated in any woman capable of child-bearing, if not satisfied with at least one of the following conditions:
1. The patient suffers from a serious violation of keratinization, resistant to standard treatments.
2. You can be sure that the patient receives and executes the instructions of the doctor.
3. The patient is able to accurately and continuously apply provided contraceptives.
4. It is absolutely essential that every woman capable of procreation, to apply effective contraceptives (preferably 2 methods of contraception at the same time) without interruption for 4 weeks before starting treatment, during treatment and for two years after completion of treatment neotigazon. The main method of contraception – is receiving a combined oral contraceptive or IUD, it is also recommended to use a condom or diaphragm (cap). Not recommended the use of low-dose progesterone monotherapies (minipilli) mean possible weakening of their contraceptive effect.
5. Treatment must not begin before the 2nd or 3rd of the next normal menstrual period.
6. At least one week prior to initiation of treatment negative screening for pregnancy should be obtained. During treatment, it is recommended to carry out further tests for pregnancy at least 1 time per month and at intervals of 1-3 months after discontinuation of the drug.
7. Before treatment neotigazon doctor should detail, orally and in writing, inform the women capable of child-bearing, the necessary precautions, the danger of very severe malformation of the fetus and the possible consequences of pregnancy during treatment neotigazon or within 2 years after its completion.
8. The same effective and uninterrupted contraceptive measures must be used each time you repeat the course of treatment, regardless of its duration, and observed for at least two years after completion of the course.
9. If, despite all precautions, during treatment neotigazon or within two years after the end of the pregnancy occurs, there is a high risk of severe fetal malformations (eg cerebral hernia).
10. A woman should avoid alcohol during treatment and for two months after discontinuation of the drug.
time may require a higher dose to 1 mg / kg per day (maximum 35 mg / day). The maintenance dose should be as small as possible, given the possible adverse effects during prolonged treatment.
Combination therapy . If neotigazon used in combination with other treatments, it is possible to reduce the dose depending on the individual patient’s response in the treatment of neotigazon can continue to use conventional external treatment; it does not affect the validity of neotigazon.
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