Megestrol acetate dosing

High-dose progestins are used as last-line endocrine therapy [223]. They inhibit the adrenal steroid biosynthesis. The decrease of estrogen levels is comparable to that caused by the administration of aromatase inhibitors. In post-menopausal women, the progestin megestrol acetate (MGA) decreases serum plasma level of DEAH, androstenedione and cortisol to less than 10% [223,224]. 

Megestrol acetate has also proved of value in patients with metastatic prostatic cancer, epithelial ovarian cancer, or malignant melanoma and is therefore used in both sexes. The adverse effects are very similar in men to those seen with oncological doses in women loss of libido and potency is likely to occur in male patients. In one clinical study of 43 men with recurrent and metastatic cancer of the prostate given megestrol acetate 160 mg/ day orally, five developed a symptomatic rise in liver... 

Tchekmedyian NS, Tait N, Aisner J. High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer. Semin Oncol 1986 13(4 Suppl 4)20-5. 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Progestin activity is further enhanced when a doubie bond is introduced between positions 6 and 7, as is found in megestrol acetate (Fig. 46.13). Megestrol is used primarily in the treatment of breast and endometrial carcinomas and in postmenopausal women with advanced hormone-dependent carcinoma. Less than 10% of an oral dose undergoes metabolism. Several major metabolites appear in the urine (e.g., 2-hydroxy and 6-hydroxymethyl megestrol and their glucuronide conjugates). 

R9. Rose, D, P., and Adams, P. W., Oral contraceptives and tryptophan metabolism. Effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone. J. Clin. Pathol. 25, 252-258 (1972). 

In 12 asymptomatic HIV-positive subjects megestrol acetate 800 mg daily for 13 days had no effect on the steady-state pharmacokinetics of zidovudine or its glucuronide metabolite. Megestrol does not appear to aifect the metabolism of zidovudine. No dose adjustments appear necessary. 

The data indicate that the oral bioavailability of nanoparticulate megestrol acetate was 54.8% higher in the fed state when dosed at 450mg and 43.3% higher when dosed at 675 mg in the fed state than the respective values in the fasted state. However, the 800-mg dose of drug in the micronized form was more than 100% more bioavadable in the fed state than in the fasted state. The reduced variability... 

Although the evidence is limited, what is known suggests that it would be prudent to monitor prothrombin times in patients taking warfarin who are high-dose medroxyprogesterone acetate or megestrol, being alert for any increased warfarin effects. 

Doses of medroxyprogesterone acetate or megestrol used for malignant disease do not appear to interact with digitoxin to a clini-caiiy relevant extent. 

Both interactions appear to be established and are possibly clinically important. A 50% reduction in the plasma levels of medroxyprogesterone and megestrol should be expected during concurrent use, and this may reduce the adrenal suppressive effect. The authors of one report say that to achieve adequate plasma medroxyprogesterone acetate levels in breast cancer (above 100 nanograms/mL) a daily dose of 800 mg of Provera is probably necessary in the presence of aminoglutethimide 125 or 250 mg twice daily. This is double the usual recommended dose for this condition. 

---