Danazol steroid

The following reactions have been reported, a causal relationship to the administration of Danazol has neither been confirmed nor refuted; allergic: urticaria , pruritus and rarely, nasal congestion; CNS effects: headache, nervousness and emotional lability, dizziness and fainting , depression , fatigue , sleep disorders , tremor , paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension , anxiety , changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome ; gastrointestinal : gastroenteritis , nausea , vomiting, constipation, and rarely, pancreatitis ; musculoskeletal: muscle cramps or spasms, or pains, joint pain , joint lockup, joint swelling, pain in back, neck , or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; genitourinary : hematuria , prolonged posttherapy amenorrhea; hematologic: an increase in red cell and platelet count . Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia , leukopenia and thrombocytopenia have also been noted. Skin: rashes (maculopapular, vesicular , papular , purpuric, petechial), and rarely, sun sensitivity , Stevens-Johnson syndrome ; other: increased insulin requirements in diabetic patients, change in libido , elevation in blood pressure , and rarely, cataracts, bleeding gums, fever , pelvic pain, nipple discharge . Malignant liver tumors have been reported in rare instances, after long-term use.

Through its action on the pituitary, danazol indirectly reduces estrogen production by lowering the output of follicle-stimulating hormone and luteinizing hormone. There is also evidence that danazol binds to sex hormone receptors in target tissues, thereby exibiting anabolic, antiestrognic and weakly androgenic activity. With higher doses, amenorrhea generally occurs after about 6 weeks of therapy; ovulation and cyclic bleeding returns to normal 60—90 days after therapy is discontinued. Danazol is used to treat endometriosis because it causes atrophy of ectopic endometrial tissue, which relieves symptoms completely. It also decreases the growth rate of abnormal breast tissue, making it useful in fibrocystic breast disease. Heriditary angioedema is an inherited disorder characterized by a deficiency in C1 esterase inhibitor (C1 INH), a serum inhibitor of the activated first component of complement. Danazol increases circulating levels of C1 INH and therby increases C4 of the complement system, which also is deficient in hereditary angioedema. Consequently, danazol prevents attacks of hereditary angioedema in both males and females. The exact mechanism by which danazol increases C1 INH is not known. Danazol does not possess any progestogenic activity, and does not suppress normal pituitary release of corticotropin, or release of cortisol by the adrenal glands.

Danazol is metabolized in the liver by enzymes such as CYP3A4 . [1] [2] Its elimination half-life has varied across studies, but has been found to be 3 to 10 hours after a single dose and 24 to 26 hours with repeated administration. [1] [3] The major metabolites of danazol are 2-hydroxymethylethisterone (also known as 2-hydroxymethyldanazol; formed by CYP3A4 and described as inactive) and ethisterone (a progestogen and androgen), [3] [2] [36] [7] and other, minor metabolites include δ 2 -hydroxymethylethisterone, 6β-hydroxy-2-hydroxymethylethisterone, and δ 1 -6β-hydroxy-2-hydroxymethylethisterone. [37] At least 10 different metabolites have been identified. [3] Danazol is eliminated in urine and feces , with the two primary metabolites in urine being 2-hydroxymethylethisterone and ethisterone. [3]

Until more is known, caution is advised in the use of danazol in the presence of known or suspected malignant disease (see also contraindications). Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment. In the event of virilisation, Danazol should be withdrawn. Whilst androgenic reactions will generally prove reversible, continued use of danazol in the face of evident virilisation is likely to cause irreversible androgenic effects.

Danazol steroid

danazol steroid

Until more is known, caution is advised in the use of danazol in the presence of known or suspected malignant disease (see also contraindications). Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment. In the event of virilisation, Danazol should be withdrawn. Whilst androgenic reactions will generally prove reversible, continued use of danazol in the face of evident virilisation is likely to cause irreversible androgenic effects.

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