indication

For the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries.

pharmacology

Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.

mechanism of action

The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes.

toxicity

No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362].

biotransformation

Primarily hepatic. Megestrol metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified.

absorption

Variable, but well absorbed orally.

half life

34 hours

route of elimination

The major route of drug elimination in humans is urine. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.

drug interactions

Amobarbital: The enzyme inducer, amobarbital, decreases the effect of the hormone agent, megestrol.

Aprobarbital: The enzyme inducer, aprobarbital, decreases the effect of the hormone agent, megestrol.

Butabarbital: The enzyme inducer, butabarbital, decreases the effect of the hormone agent, megestrol.

Butalbital: The enzyme inducer, butalbital, decreases the effect of the hormone agent, megestrol.

Butethal: The enzyme inducer, butethal, decreases the effect of the hormone agent, megestrol.

Ethotoin: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, megestrol.

Fosphenytoin: The enzyme inducer, fosphenytoin, may decrease the effect of the hormone, megestrol.

Griseofulvin: The enzyme inducer, griseofulvin, may decrease the effect of the hormone, megestrol.

Heptabarbital: The enzyme inducer, heptabarbital, decreases the effect of the hormone agent, megestrol.

Hexobarbital: The enzyme inducer, hexobarbital, decreases the effect of the hormone agent, megestrol.

Mephenytoin: The enzyme inducer, mephenytoin, decreases the effect of the hormone agent, megestrol.

Methohexital: The enzyme inducer, methohexital, decreases the effect of the hormone agent, megestrol.

Methylphenobarbital: The enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, megestrol.

Pentobarbital: The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, megestrol.

Phenobarbital: The enzyme inducer, phenobarbital, may decrease the effect of the hormone, megestrol.

Phenytoin: The enzyme inducer, phenytoin, may decrease the effect of megestrol.

Primidone: The enzyme inducer, primidone, may decrease the effect of the hormone, megestrol.

Secobarbital: The enzyme inducer, secobarbital, decreases the effect of the hormone agent, megestrol.

Talbutal: The enzyme inducer, talbutal, decreases the effect of the hormone agent, megestrol.