Megestrol Acetate is a synthetic, antineoplastic and progestational drug. While the precise mechanism by which Megestrol Acetate produces its antineoplastic effects against endometrial carcinoma is unknown at the present time, inhibition of pituitary gonadotrophin production and resultant decrease in estrogen secretion may be factors. The antineoplastic action of megestrol acetate on carcinoma of the breast is effected by modifying the action of other steroid hormones and by exerting a direct cytotoxic effect on tumor cells. In metastatic cancer, hormone receptors may be present in some tissues but not others. The receptor mechanism is a cyclic process whereby estrogen produced by the ovaries enters the target cell, forms a complex with cytoplasmic receptor and is transported into the cell nucleus. There it induces gene transcription and leads to the alteration of normal cell functions. Pharmacologic doses of megestrol acetate not only decrease the number of hormone-dependent human breast cancer cells but also are capable of modifying and abolishing the stimulatory effects of estrogen on these cells.
Estimates of plasma levels of Megestrol Acetate are dependent on the measurement method used. Peak plasma concentrations occur 2 to 3 hours after a single oral dose 160 mg tablets. The plasma half-life of Megestrol Acetate is 33 to 38 hours. Approximately 66% of an administered dose is excreted in the urine and approximately 20% in the faeces.
Weight Gain: Weight gain is a frequent side effect of Megestrol Acetate. This gain has been associated with increased appetite and is not necessarily associated with fluid retention.
Thromboembolic Phenomena: Thromboembolic phenomena including thrombophlebitis and pulmonary embolism (in some cases fatal) have been reported.
Glucocorticoid Effects: The glucocorticoid activity of Megestrol Acetate has not been fully evaluated. Clinical cases of new onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and overt Cushing’s syndrome have been reported in association with the chronic use of Megestrol Acetate. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic Megestrol Acetate therapy in the stressed and non-stressed state.
Other: Nausea, dyspnea, tumor flare, hyperglycemia, glucose intolerance, alopecia, hypertension, carpal tunnel syndrome, mood changes, hot flashes, malaise, asthenia, lethargy, sweating and rash.
General: Close surveillance is indicated for any patient treated for recurrent or metastatic cancer. Use with caution in patients with a history of thromboembolic disease.
Use in Diabetics: Exacerbation of preexisting diabetes with increased insulin requirements has been reported in association with the use of Megestrol Acetate.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Geriatric Use: In the dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.