1. Clinical Overview
Megestrol is a synthetic, orally active progestin derived from 17α-hydroxyprogesterone. The 160mg oral suspension formulation is specifically indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of AIDS. It acts as an appetite stimulant and promotes weight gain, primarily by increasing fat mass and improving overall sense of well-being. It is not indicated for use as a contraceptive.
| Onset | Duration | Bioavailability |
|---|---|---|
| Appetite stimulation may be observed within 1-2 weeks of therapy initiation. Significant weight gain typically requires several weeks of continuous treatment. | The pharmacological effects persist for the duration of therapy. The terminal half-life is approximately 20-50 hours. | Approximately 60-70% following oral administration of the suspension. |
2. Mechanism of Action
The precise mechanism for appetite stimulation and weight gain is not fully elucidated. It is believed to involve multiple pathways: 1) Direct stimulation of appetite via hypothalamic neuropeptide Y (NPY) activity. 2) Antagonism of cachectic cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). 3) Inhibition of pro-inflammatory cytokine production. 4) Modulation of lipid metabolism. Its progestational activity is also significant, mediated through binding to progesterone and glucocorticoid receptors.
3. Indications & Uses
- Treatment of anorexia, cachexia, or unexplained significant weight loss in patients with Acquired Immunodeficiency Syndrome (AIDS).
- Palliative treatment of advanced hormone-dependent breast carcinoma (typically using tablet formulations like 40mg).
4. Dosage & Administration
Adult Dosage: For AIDS-related cachexia/anorexia: 160 mg (10 mL of 160mg/10mL oral suspension) once daily. Some patients may respond to 80 mg/day. For breast cancer: 160 mg/day in divided doses (tablet formulation).
Administration: Shake the oral suspension well before each use. Use the provided measuring cup or oral syringe for accurate dosing. Can be taken with or without food. Administer once daily, preferably at the same time each day.
5. Side Effects
Common side effects may include:
- Nausea
- Diarrhea or constipation
- Flatulence
- Headache
- Insomnia or somnolence
- Rash
- Mild peripheral edema
- Weight gain
- Hyperglycemia
- Libido changes
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin and other Coumarin Anticoagulants | 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-induced hyperglycemia may antagonize the effect of hypoglycemic agents. | Moderate |
| Corticosteroids (e.g., Prednisolone) | Additive risk of adrenal suppression, hyperglycemia, and fluid retention. | Major |
7. Patient Counselling
- DO shake the bottle well before every use.
- DO use the provided measuring device for an accurate dose.
- DO take it at the same time each day.
- DO inform all your doctors and pharmacists that you are taking this medicine.
- DO report any signs of blood clots (leg pain/swelling, chest pain, shortness of breath, sudden vision changes, severe headache).
- DONT stop taking this medicine suddenly without consulting your doctor, especially after long-term use.
- DONT use it if you are or plan to become pregnant.
- DONT breastfeed while on this medication.
8. Toxicology & Storage
Overdose: Acute overdose is unlikely to be life-threatening. Symptoms may include nausea, vomiting, dizziness, drowsiness, diarrhea, and abdominal discomfort. Chronic overdose would manifest as exaggerated pharmacological effects: severe fluid retention, hypertension, profound hyperglycemia, and signs of Cushing's syndrome.
Storage: Store at room temperature (15-30°C). Protect from light and excessive heat. Do not freeze. Keep the bottle tightly closed. Keep out of reach of children. Discard any unused suspension 60 days after opening the bottle (check manufacturer's instructions).