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# Megestrol Acetate (Megace ES, Megace OS)
## Overview
Megestrol acetate is a synthetic progestin with anti-androgenic and anti-estrogenic properties. It is thought to exert its effects by inhibiting gonadotropins and adrenal androgens, as well as by directly affecting hormone-sensitive target tissues.
## Primary Indications
* **Cachexia, anorexia, or unexplained significant weight loss:** Associated with conditions like acquired immunodeficiency syndrome (AIDS) or advanced malignancy.
* **Palliative treatment of advanced breast cancer.**
* **Palliative treatment of advanced endometrial cancer.**
## Adult Dosing
* **Weight Loss/Appetite Stimulation:**
* Suspension (40 mg/mL): 625 mg (15.6 mL) orally once daily.
* Tablet (20 mg or 40 mg): 800 mg orally once daily.
* *Note:* Doses may range from 100 mg to 800 mg daily. Some sources suggest starting with lower doses and titrating up. A maximum dose of 800 mg daily is commonly cited.
* **Advanced Breast Cancer:** 160 mg orally once daily.
* **Advanced Endometrial Cancer:** 40 mg orally 4 times daily (160 mg total daily dose). May be increased to 40 mg orally 6 times daily (240 mg total daily dose).
## Pediatric Dosing
There is no established pediatric dosing for megestrol acetate. Its use in pediatric patients is not recommended.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustments are established. Use with caution.
* **Hepatic Impairment:** No specific dose adjustments are established. Use with caution.
## Contraindications
* Known hypersensitivity to megestrol acetate or any component of the formulation.
* Pregnancy.
* Undiagnosed abnormal vaginal bleeding.
* Thrombophlebitis, thrombosis, or a history of these conditions.
* Cerebral apoplexy.
* Known or suspected hormone-dependent neoplasia (e.g., breast cancer in men).
## Adverse Effects
* **Common:** Weight gain, increased appetite, hypertension, hot flashes, nausea, vomiting, diarrhea, rash, shortness of breath, edema, bleeding, amenorrhea, vaginal discharge, impotence, decreased libido.
* **Serious:** Adrenal insufficiency (especially with abrupt discontinuation after prolonged use), thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction), hyperglycemia, Cushing's syndrome, tumor flare.
## Key Drug Interactions
* **CYP3A4 Inducers:** May decrease the efficacy of megestrol acetate (e.g., rifampin, phenytoin, carbamazepine).
* **CYP3A4 Inhibitors:** May increase the concentration of megestrol acetate (e.g., ketoconazole, itraconazole, clarithromycin).
* **Aminoglutethimide:** May decrease megestrol acetate levels.
* **Insulin and Oral Hypoglycemic Agents:** Megestrol acetate can cause hyperglycemia; dose adjustments of antidiabetic medications may be necessary.
## Monitoring
* Blood pressure.
* Weight and appetite.
* Signs and symptoms of thromboembolic events (leg pain, swelling, sudden shortness of breath, chest pain).
* Signs and symptoms of adrenal insufficiency (fatigue, weakness, dizziness, nausea, vomiting, low blood pressure), particularly upon withdrawal.
* Blood glucose levels in diabetic patients.
* Liver function tests (periodically).
## Clinical Pearls
* Gradual withdrawal is recommended after prolonged therapy to avoid potential adrenal insufficiency.
* The oral suspension contains sugar and alcohol; caution in diabetic patients and those with alcohol sensitivities.
* Effectiveness for weight gain may take several weeks to become apparent.
* Women of childbearing potential should be advised to use effective contraception.
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**Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive patient management. This response does not constitute medical advice.
