Giga Mechanism of Action

PHARMACOLOGY: PHARMACODYNAMICS: The major effect experienced by patients while taking megestrol acetate, particularly at high doses, is weight gain, which is usually not associated with water retention, but which is secondary to an increased appetite/food intake and an increase in fat and body cell mass.
It is this effect which forms the basis for use of megestrol acetate in patients with anorexia or weight loss. The mechanism by which megestrol acetate produces its effects in anorexia and cachexia are unclear.
PHARMACOKINETICS: Estimates of plasma levels of megestrol acetate are dependent on the measurement method used. Plasma levels depend on intestinal and hepatic inactivation of the drug, which may be affected by intestinal tract motility, intestinal bacteria, concomitant antibiotic administration, body weight, diet and hepatic function. Metabolites have accounted for only 5% to 8% of an administered dose of megestrol acetate. The major route of drug elimination in humans is urinary excretion averaging approximately 66% and faecal excretion averaging approximately 20% of the administered dose. Respiratory excretion and fat storage may account for the fraction of an administered dose not found in urine or faeces. There are no alterations in pharmacokinetic parameters when megestrol acetate is administered with zidovudine or rifabutin.
Toxicology: PRECLINICAL SAFETY DATA: The chronic administration of megestrol acetate to female dogs for up to 7 years was associated with an increased incidence of both benign and malignant tumours of the breast. Comparable studies in rats and studies in monkeys were not associated with an increased incidence of tumours. The relationship of chronic megestrol acetate exposures and associated dog tumours to cancer induction in humans is unknown, but should be considered in assessing the benefit-to-risk ratio when prescribing Giga, and in surveillance of patients on therapy Fertility and reproduction studies with high doses of megestrol acetate have shown a reversible feminising effect on some male rat foetuses.