Tretinoin (When ATH D10AD01)

When ATH:
D10AD01

Characteristic.

A yellow or light orange crystalline powder with the characteristic floral scent, soluble in dimethyl sulfoxide, slightly soluble in polyethylene glycol, octanol and 100% ethanol, almost insoluble, mineral oil and glycerin.

Pharmacological action.
Antitumor, keratolytic, protivoseboreynoe, komedonoliticheskoe, Local anti-inflammatory.

Application.

Orally: induction of remission in acute promyelocytic leukemia, характеризующемся транслокацией t(15; 17) and / or the presence of a chimeric gene PML/RAR-альфа, in patients with previously untreated, incl. relapse after chemotherapy with anthracyclines, or refractory to standard chemotherapy.

For topical application,: acne drain, vulgar, incl. with the formation of comedones, papules, pustules, Favr disease — Rakusho (nodular cystic elastosis skin comedones), giperpigmentatsiya.

Contraindications.

Hypersensitivity, for local use — acute inflammatory (incl. eczematous) skin lesions (dermatitis, seborrhea, and others.), Rosacea, wounds, skin burns, photosensitivity, diseases of the rectum.

Restrictions apply.

The lack of reliable contraception in women of childbearing age, intracranial hypertension (especially in children), hypercholesterolemia, hypertriglyceridemia, leukocytosis (more than 5 10⁹/l), the liver and kidneys, pancreatitis, diabetes, hronicheskaya intoxication (incl. Alcoholic), older than 50 years, childhood (in the appointment of the Interior — to 1 year and up 12 years — the local use).

Pregnancy and breast-feeding.

Contraindicated in pregnancy. Assigning pregnant women retinoids leads to abortion and impaired formation of the fruit (violation of the formation and development of the central nervous system structures, eye, thymus, musculoskeletal system and others.). At the time of treatment should stop breastfeeding.

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): arrhythmia (23%), hypotension (14%), hypertension (11%), phlebitis (11%), heart failure (6%), in 3% cases of myocardial infarction, miokardit, perikardit, pulmonary hypertension, cardiomyopathy; coagulation failure (phlebitis, DIC, w / hemorrhage), peripheral edema, ascites, ʙazofilija, gipergistaminemiya, hypercalcemia.

From the nervous system and sensory organs: dizziness (20%), paraesthesia (17%), anxiety (20%), insomnia (14%), depression (14%), intracranial hemorrhage (9%), intracranial hypertension (9%, more children), excitation (9%), hallucinations (6%), headache, weakness, fatiguability, confusion, excitation, drowsiness, convulsions, dementia, hallucinations; 3% — agnozija, afazija, cephaledema, coma, dysarthria, encephalopathy, hemiplegia, giporefleksiя, tremor, spinal cord injury and other neurological reactions; impaired vision and hearing.

From the digestive tract: gastrointestinal bleeding (34%), abdominal pain (31%), diarrhea (23%), constipation (17%), dyspepsia (14%), hepatosplenomegaly (9%), hepatitis (3%), peptic ulcer (3%), non-specific disorders of the liver (3%), bullous stomatitis, anorexia, nausea and vomiting, weight change, jaundice, pancreatitis.

With the genitourinary system: impairment of renal function (11%), dizurija (9%), acute renal failure (3%), an enlarged prostate (3%), renal tubular necrosis (3%).

From the side of respiratory system: upper respiratory tract infection (63%), dyspnoea (60%), respiratory insufficiency (26%), pleurisy (20%), pneumonia (14%), crepitation (14%), expiratory dyspnea (14%), lower respiratory tract infections (9%), infiltration of the lung tissue (6%), pulmonary edema (3%), bronchial asthma (3%), laryngeal edema (3%), non-specific lung disease (3%), cough, rhinedema.

For the skin: alopecia, increased sweating, cellulitis, dryness of skin and mucous membranes, xerophthalmia, cheilitis, dermatitis, swelling of the face, rash, эritema, itch, intradermal hemorrhage; the local application is burning sensation, hyperemia, puffiness, bullation, peeling, temporary pockets of hyper- or hypopigmentation, photosensitivity; extremely rare — allergic contact, exfoliative, bullous dermatitis.

Other: gipotermiя, elevated triglycerides, cholesterol, transaminases, general pain (myalgia, bone pain), Acidosis, "Retinoic acid syndrome" (fever, dryness of mucous membranes, nausea, vomiting, rash, mucositis, acute respiratory distress syndrome, breathlessness, feeling short of breath, pneumonia, laryngeal edema, pulmonary edema, bronchial asthma, infiltration of the lung tissue, hyperskeocytosis, gipotenziya, pleurisy, renal, hepatic or multiple organ failure (possible death), the development of infections (septicemia), lethargy.

Cooperation.

Incompatible with tetracyclines (increased risk of intracranial hypertension), oral contraceptives, containing progesterone (reduces the effect of contraception), Vitamin A (the risk of hypervitaminosis A), as well as photosensitizing agents (sulьfonamidami, thiazide duiretikami, phenothiazines et al.), cosmetic and hygiene products, causing desquamation, dryness and irritation of the skin. Tretinoin increases systemic action at the local use of minoxidil. When applied topically, systemic use of retinoid-containing substances, as well as prolonged exposure to the sun, hot climate, UV radiation increases the risk of adverse reactions. Ketoconazole and other drugs, affecting the hepatic cytochrome, increase in the plasma concentration of tretinoin. The therapeutic effect is enhanced when local appointment when combined with benzoyl peroxide and antibiotics (should not be administered simultaneously).

Overdose.

Symptoms: "Retinoic acid syndrome".

Treatment: a course of treatment with dexamethasone (10 mg every 12 h for 3 days).

Dosing and Administration.

Inside: 45 mg / m² /sut 2 reception within 90 days or for 30 days after achieving complete remission, followed by consolidation chemotherapy cytostatics. Maximum permissible dose for adults is 195 mg / m² /d, for children - 60 mg / m² /d. When kidney and/or liver failure the dose to 25 mg / m² /d, in patients with solid tumors is to 1/3 Larger, in children is below the maximum recommended.

Locally: on washed and dried surface of the affected area of ​​skin is applied uniformly thin layer (gel and cream is applied with your finger, lotion and solution — with a cotton swab) 1-2 times a day 6 no, then washed with water. The course of treatment is 4-6 weeks (to 14 Sun). As a preventive measure is 1-3 times a week for a long time (after treatment with lukewarm water). For people with fair skin and dry the exposure at the beginning of treatment is 30 m, then gradually increase the duration of exposure.

Precautions.

When administered treatment is carried out in a hospital under the close supervision of an oncologist or hematologist. Before the treatment of leukemia is necessary to conduct cytogenetic studies to detect chromosome changes (in the absence of the translocation chromosome t(15; 17) and / or the transkriptata PML/RAR-альфа It shows the assignment of other drugs). During treatment requires monitoring of blood cholesterol, triglycerides, the number of leukocytes, liver function. It should provide for adequate measures and tools for the diagnosis and treatment of possible complications. After cessation of treatment within 2-4 weeks relapse of acute leukemia. Women (even with unaccounted guidance on infertility) you must apply the appropriate measures of contraception one month before, during and for one month after completing the course. Application start at 2-3 day normal menstrual cycle. The absence of pregnancy should be confirmed by laboratory methods for 2 weeks before the start of treatment, Similar studies carried out at least 1 once a month. It should refrain from the use in pediatric practice, because the safety and efficacy of their use in children is not identified. With a significant increase in the number of leukocytes in the blood to prevent "retinoic acid syndrome" treatment should be combined with chemotherapy course polnodozovym (it is assigned to 5 day of treatment - with a total number of leukocytes 6 10⁹/l, on 10 day - with a total number of leukocytes 10 10⁹/l, on 15 day - with a total number of leukocytes 15 10⁹/l and more, immediately - if treatment is started against the background of an increased number of leukocytes of more than 10 10⁹/l).

For external use during treatment should protect the treated skin from exposure to sunlight and artificial UV radiation, of the wind, cold; patients, having a tan, Treatment should be initiated after the weakening Sun. After contact with the mucous membranes wash with water.

Cooperation