2266 Sex Hormones and their Modulators sufficient to cause distress, has been described in a woman Preparations and is mainly excreted as peptide fragments in the faeces. given danazol for mastalgia. The hirsutism improved after About 20 to 30% of a dose is renally excreted. Degarelix is stopping the danazol.' ProprietaryPreparations (details are given in Volume B) injected to form a subcutaneous depot, and the I. Gately LE, Andes WA. Danazol and erythema multiforrne. Ann Intern Single-ingredient Preparations. Arg.: Ladoga!; Austral.: Azol; pharmacokinetics of the drug is strongly Influenced by the Med 1988; 109: 85. Danocrinet; Austria: Danokrin; Belg.: Danatrol; Braz.: Ladogal; concentration of the injected solution. After subcutaneous 2. Reynolds NJ, Sansom JE. Erythema multiforme during danazol therapy. Canad. : Cyclamen; China: Gong Fu Yi Kang (:g;ffl!jj>�); Cz. : injection of 240 mg at a concentration of 40 mg/mL, Clin Exp Dermato/ 1992; 17: 140. 3. Zawar V, Sankalecha C. Facial hirsutism following danazol therapy. Cutis Danoval; Fr.: Danatrol; Gr.: Danatrol; Hong Kong: Anargil; degarelix has a terminal half-life of about 43 to 53 days; after 2004; 74: 301-3. Azolt; Danocrine; Hung.: Danoval; India: Benzol; Danogen; maintenance doses of 80 mg as 20 mg/mL the half-life is Endozol; Gonablok; Gynadom; Gynazol; Gynodan; Ladoga!; about 28 days. Zendol; Indon.: Azol; Danocrine; Irl.: Danolt; Israel: Danol; Precautions Ital.: Danatrol; Jpn: Bonzol; Malaysia: Anargil; Azolt; Ladogal; Preparat ons Nazol; Mex. : Danalem; Ladogal; Novaprin; Neth.: Danatrol; NZ: i . Danazol should be used with caution in conditions that may ······························· ................................ Azol; D-Zolt; Philipp.: Ladoga!; Port. : Danatrol; Rus.: Danol ProprietaryPreparations (details are given in Volume B) be adversely affected by fluid retention, such as in (,!\aHon); Danoval (,!\aHoBaJJ); S.Afr. : Danogen; Ladazol; Singa­ Austral.: Firmagon; Austria: Fir­ cardiovascular, hepatic, and renal disorders; it should be pore: Azolt; Ladoga!; Nazol; Spain: Danatrol; Switz. : Danatrolt; Single-ingredient Preparations. magon; Belg.: Firmagon; Canad. : Firmagon; Cz.: Firmagon; avoided in marked dysfunction. It should also be used with Thai.: Anargil; Ectopal; Ladogal; Vabon; Turk. : Danasin; UK: Denm.: Firmagon; Fr.: Firmagon; Ger.: Firmagon; Gr.: Firma­ care in patients with diabetes mellitus, polycythaemia, Danol; Venez.: Danogen; Ladoga!. abnormal blood lipids, migraine, or epilepsy. Danazol gon; Irl. : Firmagon; Israel: Firmagon; Jpn: Gonax; Neth.: Fir­ magon; Norw.: Firmagon; Pol.: Firmagon; Port.: Finnagon; should not be given to patients with undiagnosed genital PharmacopoeialPreparations USP 36: Danazol Capsules. Swed. : Firmagon; Switz. : Firmagon; UK: Firmagon; USA: Fir­ bleeding or androgen-dependent tumours. As with other magon. 17a-alkylated compounds, there is an increased risk of liver disorders and liver function should be monitored during therapy. It should not be used in patients with a thromboembolic disorder or a history of thrombosis. Danazol should not be given during pregnancy because of a possible androgenic effect on the female fetus (see below), and non-hormonal contraception is recommended during treatment. Caution is required in children and adolescents since precocious sexual development may occur in boys and virilisation in girls, and premature epiphyseal closure may occur in both sexes. In the event of androgenic effects, danazol should be withdrawn, as they may prove irreversible on continued use. Breast feeding. Licensed product information warns that danazol should be avoided in breast-feeding women because of the theoretical potential for androgenic effects in the infant. Delmadinone acetate is a progestogen with anti-androgenic and anti-oestrogenic activity. It is used as an anti-androgen Porphyria. The Drug Database for Acute Porphyria, com­ in veterinary practice. piled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies danazol as prob­ ably porphyrinogenic; it should be prescribed only for compelling reasons and precautions should be considered in all patients 1 L The Drug Database for Acute Porphyria. Available at: http://www. drugs-porphyria.org {accessed 06/10/11) Pregnancy. Reports of masculinisation of female infants Uses and Administration born to mothers who had received danazol during Like cetrorelix (p. 2257.2), degarelix is a gonadorelin pregnancy.1-3 (gonadotrophin-releasing hormone) antagonist. It is used to I. Shaw RW, Farquhar JW. Female pseudohermaphroditism associated reduce testosterone concentrations in the hormonal therapy with danazol exposure in utero: case report. Br J Obstet Gynaecol l984; 91: of advanced prostate cancer (p. 712.3 ). Degarelix is given as 386-9. the acetate, but doses are expressed in terms of the base. It is 2. Kingsbury AC. Danazol and fetal masculinization: a warning. Med J Aust 1985; 143: 410-1 1. given as a subcutaneous depot injection in the abdominal 3. Brunskill PJ. The effects of fetal exposure to danazol. Br J Obstet Gynaecol area. An initial dose of degarelix 240 mg is given in two Deslorelin is an analogue of gonadorelin (p. 2280.2) that has 1992; 99: 212-1 5. separate injections of 120 mg, as a solution of 40 mg/mL. been investigated in the treatment of precocious puberty, Maintenance doses of 80 mg are then given once every 28 short stature, prostate cancer, and endometriosis. days, as a solution of 20 mg/mL. References. Interactions I. Anonymous. Deslorelin: D-Trp-LHRH-PEA, LHRH agonist analogue, Therapy with danazol may inhibit the hepatic metabolism of Van Poppel H, et a!. Degarelix: a novel gonadotropin-releasing hormone Somagard. Drugs R D 1999; 2: 420-2. several drugs including carbamazepine (see p. 517.3), (GnRH) receptor blocker-results from a 1-yr, multicentre, randomised, 2. Klein KO, et al. Increased final height in precocious puberty aher long­ term treatment with LHRH agonists: the National Institutes of Health ciclosporin (see below), and possibly tacrolirnus (see phase 2 dosage-finding study in the treatment of prostate cancer. Bur Urol 2008; 54: 805-13. experience. J Clin Endocrinol Metab 2001; 86: 471 1-16. p. 1973.2). Danazol may also enhance the effects of warfarin 2. Gittelman M, et a!. Degarelix Study Group. A 1-year, open label, 3. Yanovski JA, et al. Treatment with a luteinizing hormone-releasing (see Sex Hormones under Warfarin, p. 1535.1). Introduc­ randomized phase II dose finding study of degarelix for the treatment of hormone agonist in adolescents with short stature. N Engl J Med 2003; 348: tion of danazol appeared to reduce the maintenance prostate cancer in North America. J Urol (Baltimore) 2008; 180: 1986-92. 908-17. 4. Weise M, et a!. Determinants of growth during gonadotropin-releasing requirement for alfacalcidol (see p. 2118.1). Rhabdomyo­ 3. Klotz L, et al. The efficacy and safety of dcgarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in hormone analog therapy for precocious puberty. J Clin Endocrinol Metab Iysis has been attributed to use of danazol with statins (see patients with prostate cancer. BJU Int 2008; 102: 1531-8. 2004; 89: 103-7. p. 1495.2). 4. Frampton JE, Lyseng-Williamson KA. Degarelix. Drugs 2009; 69 1967- : 76. 5. Steinberg M. Degarelix: a gonadotropin-releasing hormone antagonist Ciclosporin. Danazol may raise ciclosporin concentrations for the management of prostate cancer. Clin Ther 2009; 31: 2312-3 1. (see p. 1955.1), possibly by inhibiting its metabolism. A case of fatal acute hepatic failure due to centrilobular massive hepatic necrosis was attributed to danazol in a Adverse Effects and Precautions patient already taking ciclosporin.1 Danazol may have raised Injection site reactions of pain and erythema are very the ciclosporin concentrations in this case, but the authors common with degarelix, while swelling, induration, and speculated that an alternative interaction between the two nodules occur less often but may still be common. Transient drugs might have played a role in this reaction to danazol. chills, fever, and flu-like symptoms may occur hours after 1. Hayashi T, et a!. Fatal acute hepatic failure induced by danazol in a dosing. Other effects commonly reported for degarelix have patient with endometriosis and aplastic anemia. J Gastroenterol2001; 36: included increases in liver enzyme values, insomnia, 783-6. dizziness, headache, and gastrointestinal disturbances. Hot flushes are a very common consequence of androgen Pharmacokinetics suppression by degarelix, while night sweats, fatigue, and weight gain are common complaints. Degarelix can also Ph. Eur. 8: (Desogestrel). A white or almost white, Danazol is absorbed from the gastrointestinal tract and contribute to loss of libido, erectile dysfunction, testicular crystalline powder. Practically insoluble in water; freely metabolised in the liver; absorption is markedly increased if atrophy, and gynaecomastia. Long-term androgen depriva­ soluble in dehydrated alcohol and in dichloromethane; very it is taken with food. A plasma elimination half-life of 3 to 6 tion therapy in general has also been associated with soluble in methyl alcohol. hours has been reported after a single dose, but is increased prolongation of the QT interval and decreases in bone to about 26 hours with repeated dosing. Ethisterone, 2- density. hydroxymethylethisterone, and I 7 -hydroxymethylethis­ Uses and Administration terone are the major metabolites, though none have Desogestrel