Monograph: |
MEGESTROL ACETATE
An odourless or almost odourless, white to creamy-white, crystalline powder. Practically insoluble in water; sparingly soluble in alcohol; very soluble in chloroform; soluble in acetone; slightly soluble in ether and in fixed oils. Protect from light.
Adverse Effects and Precautions
As for progestogens in general, like progesterone. The weight gain that may be observed with megestrol acetate appears to be associated with an increased appetite and food intake rather than with fluid retention.
Severe pain of the hands reminiscent of carpal tunnel syndrome occurred in 4 women while taking megestrol acetate and melphalan;1 megestrol appeared to be responsible.
Effects on carbohydrate metabolism. Megestrol therapy has been associated with hyperglycaemia1 or diabetes mellitus3 in AIDS patients being treated for cachexia. It has been suggested that megestrol produces peripheral insulin resistance due to a glucocorticoid action.
Effects on the respiratory system. Two cases of hyperp-noea in patients receiving megestrol acetate 80 mg three times daily.
Glucocorticoid effects. Megestrol appears to have gluco-corticoid-like properties which can result in adrenocortical insufficiency severe enough to require replacement therapy with hydrocortisone.
Interactions
As for progestogens in general, like Progesterone.
Pharmacokinetics
Absorption of megestrol acetate from the gastro-in-testinal tract is variable following oral administration; peak drug concentrations in plasma occur 1 to 3 hours after a dose by mouth. Megestrol acetate is highly protein bound in plasma. It undergoes hepatic metabolism, with 57 to 78% of a dose being excreted in the urine and 8 to 30% in the faeces.
Uses and Administration
Megestrol acetate is a progestogen structurally related to progesterone that is used for the palliative treatment of various cancers. It is given by mouth in endometrial carcinoma in doses of 40 to 320 mg daily in divided doses, and in doses of 40 mg four times daily or 160 mg once daily in breast'cancer.
Megestrol acetate is used in the treatment of anorexia and cachexia in patients with cancer or AIDS. The usual dose is 800 mg daily, as oral suspension, for one month, followed by a maintenance dose of 400 to 800 mg daily.
Anorexia and cachexia. Double-blind, placebo-controlled trials have confirmed the efficacy of high dose megestrol (800 mg per day) in patients with cancer-related cachexia1 and HIV-related cachexia. Megestrol was also associated with weight gain in children with HP/ infection.
Hot flushes. Megestrol has been used in female patients with breast cancer who were experiencing hot flushes (to avoid the potentially tumour-stimulating effects of an oestrogen, as well as in men with hot flushes after orchidectomy or anti-androgen therapy for prostate cancer. Therapy, which involved low doses of 20 mg twice daily, was associated with a decrease in frequency of flushes of 50% or more in about three-quarters of all patients.
Malignant neoplasms. Like some other progestogens megestrol acetate is used in endometrial cancer (p.487), and it has been reported to have similar efficacy to anastrozole1 and tamoxifen2 in postmenopausal women with advanced breast cancer.
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