1. Clinical Overview
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.
| Onset | Duration | Bioavailability |
|---|---|---|
| Appetite stimulation: 1-2 weeks; Antineoplastic effects: Variable, often several weeks. | Approximately 24-48 hours based on its half-life. | Approximately 60-80% following oral administration. |
2. Mechanism of Action
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.
3. Indications & Uses
- Palliative treatment of advanced carcinoma of the breast (hormone receptor-positive or unknown) in postmenopausal women.
- Palliative treatment of advanced carcinoma of the endometrium (recurrent, inoperable, or metastatic).
- Treatment of anorexia, cachexia, or unexplained significant weight loss in patients with Acquired Immunodeficiency Syndrome (AIDS).
4. Dosage & Administration
Adult Dosage: 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.
Administration: 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.
5. Side Effects
Common side effects may include:
- Weight gain (due to increased appetite and fat deposition)
- Edema/peripheral edema
- Nausea
- Flatulence
- Diarrhea or constipation
- Insomnia
- Headache
- Rash
- Hyperglycemia
- Mild hypertension
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| 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 |
7. Patient Counselling
- DO take the medication exactly as prescribed, at the same time each day.
- DO inform all your doctors and dentists that you are taking this medicine before any surgery or new prescription.
- DO monitor your weight regularly and report sudden or excessive weight gain.
- DO report any signs of swelling in legs, shortness of breath, chest pain, severe headache, or vision changes immediately.
- DONT stop taking the medication abruptly without consulting your doctor, as adrenal insufficiency can occur.
- DONT use this medication if you are pregnant, planning pregnancy, or breastfeeding.
- DONT crush or chew tablets unless advised by your doctor or pharmacist for administration.
8. Toxicology & Storage
Overdose: Acute overdose is unlikely to be life-threatening. Symptoms may include nausea, vomiting, dizziness, drowsiness, diarrhea, abdominal discomfort, and possibly excessive weight gain, fluid retention, and hyperglycemia. Adrenal suppression is possible with chronic overdose.
Storage: Store at room temperature (15-30°C). Protect from light and moisture. Keep in the original container, tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the pack.