Acitretin - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Dermatotropona funds

Included in the formulation

Neotigazon®

capsules inwards

Actavis PTS ehf Group Iceland

АТХ:

D.05.B.B Retinoids for the treatment of psoriasis

Pharmacodynamics:

The pharmacological action is antipsoriatic.

Acitretin is a synthetic aromatic analogue of retinoic acid.

In preclinical studies on the tolerability of acitretin, there was no mutagenic or carcinogenic effect; there was also no indication of its direct hepatotoxicity. Acitretin had a pronounced teratogenic effect on animals.

Clinical studies have confirmed that with psoriasis and disorders of keratinization acitretin normalizes the processes of proliferation, differentiation and keratinization of epidermal cells, and its side effects are generally quite tolerable. The effect of the drug is purely symptomatic; its mechanism remains largely unknown.

Pharmacokinetics:

Well absorbed from the gastrointestinal tract, maximum concentration of substance in blood plasma (serum) is achieved in 1-4 hours. Bioavailability - about 60% (increases with admission during or after meals). Well passes into the fabric; binding to plasma proteins - 99%. Penetrates through the placental barrier and into breast milk. Metabolized by isomerization and the formation of glucuronides. PElimination half-life Acitretinum - 50 hours, and its basic metabolite - 60 hours. Within 36 days after discontinuation of treatment, 99% of the drug is excreted in the form of metabolites with urine and bile in equal amounts. In some cases, the body produces etretinate, half-life which - about 4 months, that is, in a similar situation the drug is excreted completely within 2 years after the end of treatment.

The therapy continues until the disappearance of psoriatic lesions. In violation of keratinization, supportive, minimally effective doses (up to 50 mg daily) are prescribed for a long time.

Indications:

Heavy forms of psoriasis, including psoriatic erythroderma, localized or generalized pustular psoriasis.

Severe dyskeratosis, such as congenital ichthyosis; red hair follicle; Darya's disease (follicular dyskeratosis); other severe disorders of keratinization, resistant to traditional therapies.

ICD-10

XII.L20-L30.L30.8 Other specified dermatitis

XII.L40-L45.L40.1 Generalized pustular psoriasis

XII.L40-L45.L40 Psoriasis

XII.L40-L45.L40.3 Pustulosis of the palmar and plantar

XII.L40-L45.L43 Lichen red flat

XII.L40-L45.L44.9 Papulosquamous changes, unspecified

XVII.Q80-Q89.Q80 Congenital ichthyosis

Contraindications:

Hypersensitivity to acitretinum, allergy to parabens, hyperlipidemia (including in the anamnesis), pancreatitis, hypervitaminosis A; simultaneous application with tetracyclines, vitamin A, other retinoids, methotrexate; hepatic and / or renal failure, pregnancy, breast-feeding.

Carefully:

Diabetes mellitus, pancreatitis in the anamnesis.

Pregnancy and lactation:

Action category for the fetus by FDA - X.

Effects on the fetus: malformations of the heart, lungs, anophthalmia, microcephaly, multiple malformations of bones and connective tissue. Do not apply!

Acitretin is excreted in breast milk. The drug should not be given to nursing mothers.

Women of childbearing age should use reliable methods of contraception without interruption for 4 weeks before the initiation of therapy, during the course of treatment and at least 2 years after its termination.

The drug is contraindicated for any woman capable of childbearing, unless each of the following conditions is met:

The patient suffers from a severe disruption of keratinization, resistant to standard types of treatment.

You can be sure that the patient understands and complies with the doctor's instructions.

The patient is able to accurately and continuously apply the prescribed contraceptives.

It is absolutely necessary that every woman capable of childbearing use effective contraceptives without interruption for 4 weeks before the start of treatment, during treatment and for two years after the completion of treatment.

Treatment should not begin before the 2nd or 3rd day of the next normal menstrual cycle.

Two weeks before the start of treatment, a negative result of a pregnancy test should be obtained. During treatment it is recommended to conduct additional tests for pregnancy at least once a month.

Before the beginning of the treatment, the doctor should inform in detail, verbally and in writing, the women capable of giving birth, the necessary precautions, the danger of very serious malformations of the fetus and the possible consequences of pregnancy during treatment or within 2 years after its termination.

The same effective and continuous contraceptive measures should be applied every time a course of treatment is repeated, regardless of its duration, and be followed for two years after the end of the course.

If, despite all the precautions, during treatment or within 2 years after the end of pregnancy, there is a large risk of severe fetal malformations (for example, a hernia of the brain).

Dosing and Administration:

Inside, once a day, with food or with milk. Adults - start with 25-30 mg per day for 2-4 weeks, then - for 25-50 mg for 6-8 weeks, it is possible to increase the maximum daily dose to 75 mg. Children - the initial dose of 500 mcg / 1 kg per day, possibly a short-term increase to 1 mg / kg per day (but not more than 35 mg per day); The maintenance dose is as low as possible.

Duration of admission is 6-8 weeks.

Side effects:

Adverse reactions are noted in the majority of patients taking the drug. However, they usually disappear after a dose reduction or drug withdrawal. Sometimes at the beginning of treatment there is an exacerbation of the symptoms of the disease.

Dermatological reactions: dryness of mucous membranes, cheilitis, cracks in the corners of the mouth, thinning and peeling of the skin throughout the body, alopecia, brittle nails, paronychia, photosensitivity.

From the side of the central nervous system: headaches, violation of twilight vision, conjunctivitis.

From the musculoskeletal system: pain in the bones and muscles, hyperostosis and calcification of tissues. A case of vertebral hyperostosis and calcinosis of vertebral ligaments with subsequent compression of the spinal cord is described.

On the part of laboratory indicators: a transient increase in the activity of transaminases and alkaline phosphatase, hypercalcemia, an increase in the concentration of triglycerides and cholesterol in the blood plasma.

Overdose:

Symptoms: headache, dizziness.

Treatment: symptomatic with the mandatory cancellation of the drug.

Interaction:

Incompatible with tetracyclines, methotrexate, vitamin A and other retinoids. Displaces phenytoin from the connection with proteins.

Ethanol-containing preparations and beverages promote the formation of etretinate.

Since both acitretin, and tetracyclines can cause an increase in intracranial pressure, their simultaneous use is contraindicated.

Acitretin can reduce the contraceptive effect of mini-pili with progesterone, so during treatment with acitretin should not use them for contraception.

The combined use of glibenclamide with acitretin may lead to a decrease in the hypoglycemic effect of glibenclamide (shown in healthy male volunteers).It is recommended that careful monitoring of patients with diabetes mellitus taking and glibenclamide, and acitretin.

The simultaneous use of isotretinoin with acitretin increases the risk of hypervitaminosis A.

Cyclosporine is an inhibition of the metabolism of cyclosporins and its metabolites (by 33-45%).

Special instructions:

Before and during the application, and also within 3 months after the abolition of acitretin, liver function should be monitored. During the period of treatment, the following parameters should be monitored: cholesterol, triglycerides in fasting serum (especially in cases of lipid metabolism disorders, diabetes, obesity, chronic alcoholism, and long-term therapy); the level of glycemia in patients with diabetes mellitus; in children - indicators of growth and development of bones.

The use of acitretin in children is justified in cases of ineffectiveness of alternative therapies. Until now, all the consequences of therapy with acitretin have not been established.

In patients receiving acitretin, etre- tinate is sometimes detected in the blood plasma.

The drug may be prescribed only by physicians who have experience in the use of systemic retinoids and who understand the risk of teratogenic effects of acitretin.

Women of childbearing age during the treatment of the drug should not consume alcohol, because there are clinical data that when concomitantly taking acitretin and alcohol in the body, etretinate can be formed. The mechanism of this metabolic transformation is not established, so it is unclear whether other substances can participate in it. The intake of ethanol should be avoided for 2 months after discontinuation of therapy with acitretin.

Women of childbearing age can not receive blood from patients receiving acitretin. Consequently, during the treatment and within a year after its completion, blood donation is prohibited.

In patients with diabetes mellitus retinoids can improve or worsen glucose tolerance, so in the early stages of treatment, the concentration of glucose in the blood should be checked more often than usual.

Adults receiving long-term therapy with the drug should regularly conduct appropriate examinations, taking into account the possibility of anomalies of ossification. In case of occurrence of such violations, it is necessary to discuss with the patient the question of continuing treatment, carefully correlating the possible risk and benefit of using the drug.

Due to the possibility of disturbing the night vision of patients, caution should be warned when driving a car or working with cars and machinery at night. Care must be taken to monitor for visual impairment.

At present, not all the effects of acitretin, which can occur during life, are known.

Instructions

Acitretin (Acitretinum)