Additional studies were conducted in 1975 and 1978, followed by others thereafter. However, results of MGA therapy for prostate cancer have been "disappointing", and the medication has not been approved for the treatment of prostate cancer in the United States or elsewhere.Clinical studies of very high dosages of MGA for breast cancer conducted in the 1980s observed markedly increased appetite and weight gain in treated patients despite them having advanced cancer. This led to potential interest in MGA as an appetite stimulant, and in 1986, a paper was published proposing the study and potential use of MGA in cachexia. MGA was subsequently studied for this indication and, following completion of phase III clinical trials, was approved as an oral suspension for the treatment of anorexia–cachexia syndrome due to cancer and other chronic conditions such as HIV/AIDS in the United States in 1993. Thereafter, the branded product, Megace ES, has been heavily promoted by its maker, Par Pharmaceutical, for treatment of unintentional weight loss in elderly patients, especially those living in long-term care facilities. In March 2013, Par settled a $45 million federal and multi-state criminal and civil lawsuit in which the company was accused of promoting the branded version of MGA, over the generic version, for use in treating non-AIDS-related geriatric wasting. This use was not approved as safe and effective by the Food and Drug Administration (FDA), and not covered by federal health care programs.
Pharmacokinetics
The oral bioavailability of MGA is approximately 100%. After a single low oral dose of 4 mg MGA, peak serum concentrations of MGA were about 7 ng/dL (18 nmol/L) and occurred after 3 hours. Following a single high oral dose of 160 mg micronized MGA in men, peak circulating levels of MGA were 125 ng/mL (325 nmol/L) and occurred after 6.3 hours. This study found that micronized MGA at this dose showed considerably improved absorption relative to its conventional tablet form. In terms of plasma protein binding, MGA is bound mostly to albumin (82.4%) and is not bound to sex hormone-binding globulin or to corticosteroid-binding globulin. MGA metabolized in the liver mainly by hydroxylation of the C21, C2α, and C6 positions, as well as by reduction and conjugation. Its elimination half-life is 34 hours on average, with a range of 13 to 105 hours. MGA is excreted 57 to 78% in urine and 8 to 30% in feces.At high doses, MGA appears to have far greater bioavailability and potency than medroxyprogesterone acetate, regardless of whether the route of administration of the latter is oral or parenteral. Following oral administration of 80 to 160 mg MGA or 500 to 1,000 mg medroxyprogesterone acetate, circulating levels of MGA were 2- to 10-fold higher than those of medroxyprogesterone acetate. Similar findings have been found for oral MGA relative to medroxyprogesterone acetate administered via intramuscular injection. MGA also reaches steady-state levels more quickly than medroxyprogesterone acetate.