Mezoxia

Approved Indications:

• Anorexia, cachexia, or unexplained significant weight loss in patients with AIDS
• Palliative treatment of advanced breast cancer (hormone-dependent)
• Palliative treatment of endometrial carcinoma
• Endometriosis (in selected cases as part of hormonal management)

Clinically Accepted Off-Label Uses:

• Appetite stimulation in cancer-induced cachexia
• Palliative care to promote weight gain or improve nutritional status
• Hot flashes in postmenopausal women unresponsive to other therapies
• Advanced prostate cancer (as hormonal manipulation)

Route of Administration: Oral (tablet or oral suspension)

Adults:

• Anorexia/Cachexia in AIDS or Cancer:
• 400 mg to 800 mg/day orally in a single daily dose (oral suspension)
• Duration: Continue as long as benefit is observed and adverse effects are tolerable
• Breast Cancer (Palliative):
• 160 mg/day orally in divided doses (e.g., 40 mg four times daily)
• Endometrial Cancer (Palliative):
• 40–320 mg/day orally in divided doses
• Evaluate periodically for clinical response and tolerance

Geriatrics:

• Same as adult dosing; monitor for thromboembolic and fluid retention risks

Pediatrics:

• Safety and efficacy not well established

Renal Impairment:

• Use with caution; monitor fluid status due to risk of edema

Hepatic Impairment:

• Use cautiously; dose adjustment may be needed based on tolerance

Megestrol acetate is a synthetic derivative of progesterone with potent progestational and antiestrogenic properties. It binds to progesterone receptors, exerting an antigonadotropic effect by inhibiting the secretion of gonadotropins (LH and FSH), which suppresses estrogen production. In cancer, this reduces hormone-stimulated tumor growth. Additionally, it has appetite-stimulating effects, possibly by influencing neuropeptide Y and other appetite-related pathways in the hypothalamus. Its anti-inflammatory and glucocorticoid-like effects may further contribute to weight gain and improved appetite.

• Absorption: Well absorbed orally; bioavailability increases with food
• Peak Plasma Time: ~1 to 3 hours after oral administration
• Bioavailability: Variable; oral suspension better absorbed than tablets
• Protein Binding: High (>98%)
• Metabolism: Hepatic via reduction and conjugation pathways
• Half-life: 20 to 50 hours (depending on formulation and patient factors)
• Excretion: Primarily fecal (~66%), some renal excretion (~20%)

• Pregnancy: Category X – Contraindicated due to teratogenic and abortifacient potential
• Lactation: Not recommended; drug is excreted in breast milk and may affect infant hormonal balance. Breastfeeding should be avoided during therapy.

• Primary Class: Progestin
• Subclass: Antineoplastic hormone / Appetite stimulant

• Known hypersensitivity to megestrol acetate or any component of the formulation
• Pregnancy (Category X)
• Active or recent history of thromboembolic disease (e.g., DVT, PE)
• Uncontrolled diabetes mellitus or adrenal suppression (use caution)

• Thromboembolic Risk: Increased risk of DVT, pulmonary embolism; use cautiously in at-risk populations
• Adrenal Suppression: Chronic high doses may suppress adrenal function; tapering may be necessary when stopping
• Fluid Retention/Edema: Monitor in patients with cardiac, renal, or hepatic impairment
• Hyperglycemia: May worsen blood glucose control in diabetics
• Weight Gain: May be significant; monitor in patients where fluid overload is a concern
• Use in Men: Gynecomastia and sexual dysfunction can occur

Common Adverse Effects:

• Metabolic: Weight gain, increased appetite
• Endocrine: Adrenal suppression, gynecomastia (in men), menstrual changes
• GI: Nausea, diarrhea, flatulence
• General: Fatigue, rash

Serious Adverse Effects:

• Thromboembolism: DVT, PE, stroke
• Hyperglycemia or new-onset diabetes
• Hypertension
• Mood disturbances (e.g., depression, irritability)
• Adrenal insufficiency after abrupt withdrawal

• Indinavir: Decreased indinavir levels; avoid or monitor closely
• Warfarin: Possible increased anticoagulant effect; monitor INR
• Diabetic medications (e.g., insulin, metformin): May require adjustment due to hyperglycemia risk
• Glucocorticoids: Additive adrenal suppression or Cushingoid effects

Metabolic Pathway:

• Primarily hepatic; not a significant CYP450 inducer or inhibitor

• FDA labeling updates highlight thrombosis and adrenal suppression risks with long-term or high-dose use
• Clinical practice guidelines (e.g., ASCO, NCCN) include megestrol acetate as a supportive option for cancer-related cachexia, though recommend caution due to thrombotic risk
• EMA recommends re-evaluation of megestrol therapy if no clinical benefit is observed within 2 months of initiation

• Storage Temperature: 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C
• Humidity & Light: Store in a dry place, protect from light
• Oral Suspension Handling: Shake well before use
• Do Not Freeze: Especially oral suspension formulations
• Shelf Life: Follow manufacturer’s label (commonly 2–3 years)