Danazol dosing

It has been demonstrated that Danazol [17230-88-5] C22H2yN02, is highly effective in post-coital regimens, and has a very low incidence of side effects. Danazol is marketed in many countries for the treatment of endometriosis and its availabiUty is unrestricted. It does not appear that there is a significant difference in effectiveness when doses of 800 to 1200 mg have been utilized daily for three days (64,65). When utilized in the post-coital mode, the precise mechanism of action of Danazol is not weU-understood. 

Cyclosporine alone fewer remissions than combination with ATG Androgens (such as Danazol—see dosing in ITP section)—can take 3 or more months to show effect... 

Recently, a Japanese research group published preclinical safety and efficacy data of an oral antiestrogen (TZE-5323) (Saito et al. 2003). This drug has been shown to have a strong affinity for human ERa and ER/i and a dose-dependent capacity to inhibit estradiol-stimulated transcriptional activation (Saito et al. 2003). In the experimental endometriosis model in rats, TZE-5323 dose-dependently reduced the volume of the endometrial implant with an effectiveness similar to that of danazol and leuprorelin acetate without causing significant changes in bone mineral density and in serum estradiol levels (Saito et al. 2003). 

The synthesis of Lp(a) can be influenced by hormones, as is reported by Albers et al. (A7), who observed a reduction of Lp(a) concentrations in nor-molipidemic postmenopausal women treated during 6 weeks with the anabolic steroid stanazolol. The same effect was reported for norethisterone (FI) and danazol (Cl2). Exogenous estrogens, as used in treatment of postmenopausal complaints and in oral contraceptives, induce a decrease of Lp(a) (D9, H27, K13, KAO, L21, S37). This effect is dose-related and dependent on Lp(a) levels before treatment (F2). Watanabe (W9) investigated the influence of progestogen (alone) and detected a decrease of Lp(a) during treatment. 

Experience with long-term therapy with danazol is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intra-abdominal hemorrhage. Therefore, alert the physician to this possibility. Attempts should be made to determine the lowest dose that will provide... 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

The synthetic androgen danazol has also been evaluated for post-coital use, but with inconsistent results (8) doses of twice 400 mg or twice 600 mg seem to be reliable while a single dose of 600 mg seems to be insufficient. A 10% incidence of vomiting, headache, and breast tenderness has been reported and a lower incidence (1-2%) of vomiting (10). 

Figure 5.9 The fraction of dose dissolved as a function of time for the danazol data [126], Symbols represent experimental points and the lines represent the fittings of (5.21) to data. Key (% sodium lauryl sulfate in water as dissolution medium) 1.0 0.75 0.50 T 0.25 0.10.

Gestrinone is licensed to be taken continuously for up to six months. It has similar actions to danazol but has a longer half-life, allowing twice weekly instead of daily dosing. 

Danazol 200-400 mg/day in divided doses at onset of breast pain until first day of menses (for mastalgia or... 

Serotonin reuptake inhibitor (intermittent or continuous with increase in dose during luteal phase) Alternative danazol or gonadotropin-releasing hormone agonist for 2-3 cycles (if longer treatment, estradiol progesterone add-back therapy may be required)... 

By inducing anovulation with various hormonal therapies, the cyclicity of PMS disappears. Anovulation can be induced by estradiol implants, high doses of progesterones, OCs, GnRH-As, and danazol. For the perimenopausal syndrome, the replacement of hormones such as 17/S-estradiol, progesterone (if the uterus is intact), and testosterone is used to stabilize the deficiency and fluctuations in hormone levels. 

Danazol 600-800 mg orally daily in divided doses Androgenic side effects limit use not preferred in adolescent patients secondary to side-effect profile... 

The chance of pregnancy can be reduced by 75% by a high dose of oral contraceptives taken within 72 h (under a doctor s supervision) after unprotected intercourse.43 This usually consists of taking one set of pills followed by a second set 12 h later. The use of a product containing only lev-onorgestrel has cut the side effect of nausea by over 50%.44 Additional work is needed to improve the efficacy and to reduce the side effect of nausea further. Inclusion of an antinausea drug may help. Danazol (16.6) may be the answer. It is said to be highly effective with few side effects. 

Danazol is a sex hormone that suppresses the pituitary-ovarian axis by inhibiting output of pituitary gonadotropins has weak, dose-related androgenic activity with no estrogenic or progestational activity. Danazol is indicated in treatment of endometriosis symptomatic treatment of fibrocystic breast disease and in prevention of attacks of hereditary angioedema. 

A pharmacokinetic study in one kidney transplant patient found that danazol 200 mg three times daily for 16 days reduced the ciclosporin clearance by 50%, prolonged its half-life by 66%, and raised its AUC by 65%. A patient with aplastic anaemia taking ciclosporin was given danazol 200 mg daily for pancytopenia and endometriosis. Within 4 days the patient had epigastric pain and elevated serum ciclosporin and creatinine levels. Danazol was stopped and the ciclosporin dose was halved. Two weeks later abrupt severe hepatic injury occurred and the patient died of hepatic failure, although this was thought to be due to danazol toxicity rather than the interaction. ... 

These appear to be the only reports of this apparent interaction, but the pharmacokinetic basis of the interaction seems to be established. The US manufacturers of lovastatin suggest that the dose should not exceed 20 mg daily in the presence of danazol. Similarly the manufacturers of simvastatin suggest that the dose should not exceed 10 mg daily in the presence of danazol. It would seem prudent to reinforce the symptoms of myopathy and tell patients to report any unexplained muscle pain, tenderness or weakness. The authors of the lovastatin report point out that, as in this case, severe lovastatin muscle toxicity may be very slow to develop. See also muscle toxicity , (p.l086), for further guidance on monitoring, and risk factors for muscle toxicity. 

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