Synthetic steroid, a 17α-acetyl testosterone derivative. It has pronounced affinity for androgen receptors, weaker to progestogen and smallest for estrogen receptors. It inhibits the synthesis and release of luteinizing and follicle stimulating hormone from the pituitary gland and the synthesis of ovarian hormones. It binds to receptors for sex hormones in the target organs. The suppressive action on the hypothalamic-pituitary-gonads axis is reversible, the cyclic function of this system usually returns after 60-90 days after the end of treatment. It is well absorbed from the gastrointestinal tract, reaching a maximum concentration of 2 hours in the blood. It is metabolised in the liver, excreted in the urine, partly in the unaltered state. T0,5 it is about 4.5 hours.
Contraindications:
Hypersensitivity to danazol or other components of the drug. Pregnancy. Breast-feeding. Severe liver, kidney or heart problems. Porphyria. Active thrombosis or thromboembolic events or the occurrence of these diseases in the past. Androgen-dependent cancer. Bleeding from the genital tract of unknown cause.
Precautions:
Treatment should be discontinued if virilization symptoms and significant side effects occur, especially if there is evidence of swelling of the optic nerve head, headache, visual disturbances or other symptoms of elevated intracranial pressure, jaundice, liver dysfunction, thrombosis or thromboembolic events. Caution should be exercised when the treatment cycle is repeated (no safety data). The use of danazol may increase the initial risk of ovarian cancer in patients treated for endometriosis. Exercise caution in patients with liver disease, kidney disease, high blood pressure or other cardiovascular disease, and in any other condition that may deteriorate in fluid retention and in patients with diabetes, polycythaemia, epilepsy, lipid disorders and patients who previous treatment with sex hormones has been found to have a clear or fixed androgenic effect and in patients suffering from migraine. Caution is advised when using the drug in people with diagnosed or suspected cancer; before and during treatment, androgen-dependent cancer should be excluded (contraindications). Hepatic function should be monitored during treatment, as well as periodic blood function tests. During long-term treatment with patients using contraception, it is recommended that hormonal contraceptives should not be used during treatment.
Pregnancy and lactation:
The drug is contraindicated during pregnancy and breastfeeding (danazol increases the risk of virilization of the fetus and infant). In the event that the patient becomes pregnant during treatment, danazol should be immediately discontinued.
Side effects:
The following were observed: weight gain, increased appetite, acne and seborrhea, hirsutism, hair loss, voice alteration in the form of hoarseness, sore throat or variability or lowering of voice tone, clitoral hypertrophy (rarely), fluid retention (rare); disorders of the menstrual cycle (spotting), disturbances in the regularity of the cycle and menstrual arrest, reduction of estrogen concentration - symptoms: hot flushes, vaginal dryness, libido disorders, irritation and reduction of breast size, increased inhibition of spermatogenesis; insulin resistance, symptomatic hyperglycemia in non-diabetic subjects, increased plasma glucagon, increased plasma insulin levels, impaired Glucose tolerance, metabolic disorders and increased LDL cholesterol, decreased HDL cholesterol, decreased AI and AII cholesterol, induction of acid synthesis aminolevulinic acid; dizziness, headache, mild increase in intracranial pressure, epilepsy, carpal tunnel syndrome (isolated cases), migraine; rash (maculopapular, ecchymosis, purpura, urticaria), face edema, fever, sun exposure rash, red papules with inflammatory reaction,changes in skin pigmentation, exfoliative dermatitis and erythema multiforme; back pain, muscle cramps, increased creatine kinase activity, muscle tremors, fasciculation, limb pain, joint pain and swelling; hypertension, palpitations, tachycardia, myocardial infarction; thrombotic disorders, sinus and cerebral sinus thrombosis, arterial thrombosis; visual impairment, i.e. blurred vision, difficulty with focusing, contact lens intolerance, refractive disorders requiring correction; increase in the number of red blood cells and platelets, reversible polycythemia, eosinophilia, leukopenia, thrombocytopenia and spontaneous purpura; increase in serum transaminases, cholestatic jaundice (rare), hepatic adenomas and pancreatitis, hepatic purpura (very rarely), malignant liver tumors (very rarely); emotional instability, anxiety, depressed mood, nervousness; decrease in T4 thyroid hormone globulin concentration, with increased T3 uptake, but without thyroid stimulating hormone levels and without changes in the free thyroxin ratio; nausea, epigastric pain; weariness; hematuria (rarely with prolonged use in patients with hereditary angioedema); interstitial pneumonitis, pleural pain.
Dosage:
Orally. Doses should be determined individually depending on the severity of the disease and the rate of regression of clinical symptoms. The recommended doses are 200-800 mg daily, the duration of treatment should not exceed 6 months. Treatment should be started during menstrual bleeding, preferably the first day.
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