Megestrol is a synthetic, orally active progestin derived from 17α-hydroxyprogesterone. It is primarily used for the palliative treatment of advanced carcinoma of the breast or endometrium in postmenopausal women and for the management of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS. It exerts its antineoplastic effects via multiple mechanisms, including direct cytotoxic effects, induction of apoptosis, and downregulation of estrogen receptors. Its appetite-stimulating and weight-gain effects are mediated through neuropeptide modulation, cytokine inhibition, and potential glucocorticoid-like activity.
Adult: Breast Cancer: 160 mg/day (40 mg QID) as a single dose or in divided doses. Endometrial Cancer: 40-320 mg/day in divided doses. AIDS-related Cachexia: 400-800 mg/day (10-20 tablets of 40mg) as a single dose or in divided doses. Initiation at 400 mg/day is common.
Note: Administer orally with or without food, but consistency is key (preferably with food to enhance absorption). Tablets should be swallowed whole with a glass of water. For patients with difficulty swallowing, tablets can be crushed and mixed with a small amount of soft food (e.g., yogurt, pudding). Doses are usually given once daily or in divided doses (twice daily) as per physician advice.
Megestrol acetate is a synthetic progestogen with multiple mechanisms. In cancer therapy, it binds to progesterone receptors, leading to a negative feedback on the hypothalamic-pituitary axis, reducing gonadotropin secretion and consequently estrogen production. It may also downregulate estrogen receptors in tumor cells, induce cellular differentiation, and directly inhibit tumor cell growth. For cachexia, it stimulates appetite via central effects on the hypothalamus (increasing neuropeptide Y), antagonizes the action of cachectic cytokines like TNF-α and IL-6, and may have glucocorticoid-like activity promoting lipogenesis and weight gain.
Pregnancy: Pregnancy Category D (US FDA). Contraindicated. May cause fetal harm. Progestins have been associated with minor birth defects, including cardiovascular and limb reduction defects. If used during pregnancy or patient becomes pregnant, apprise of potential hazard to fetus.
Driving: May cause dizziness, vertigo, or fatigue. Patients should not drive or operate machinery if they experience these effects.
| Warfarin, Acenocoumarol | Megestrol may decrease anticoagulant effect; monitor INR closely. | Major |
| Indinavir, Ritonavir, other CYP3A4 Inhibitors | May increase megestrol plasma concentrations, increasing risk of toxicity. | Moderate |
| Rifampicin, Carbamazepine, Phenytoin (CYP3A4 Inducers) | May decrease megestrol plasma concentrations, reducing efficacy. | Moderate |
| Insulin, Sulfonylureas (e.g., Glimepiride) | Megestrol can cause hyperglycemia, potentially increasing antidiabetic drug requirements. | Moderate |
| Corticosteroids (e.g., Prednisolone) | Additive risk of adrenal suppression, hyperglycemia, fluid retention, and immunosuppression. | Major |
| Diuretics (e.g., Furosemide) | Megestrol may cause fluid retention, counteracting diuretic effect. | Moderate |