Usage
Megestrol acetate is a synthetic progestin, a drug that mimics the effects of the naturally occurring female hormone progesterone. It is primarily prescribed for the following conditions:
- Anorexia, cachexia, or significant weight loss in patients with AIDS: Megestrol stimulates appetite and promotes weight gain, which can be particularly beneficial for individuals experiencing these symptoms due to AIDS.
- Palliative treatment of advanced breast cancer and endometrial cancer: Although not a curative treatment, megestrol can help manage symptoms associated with these cancers.
Pharmacological classification: Appetite stimulant, antineoplastic (for cancer treatment).
Mechanism of action: Megestrol’s exact mechanism for stimulating appetite is not fully understood, but it is thought to involve interactions with the hypothalamus, a region of the brain that regulates appetite and metabolism. It also has anti-estrogenic and anti-androgenic effects, which contribute to its use in hormone-sensitive cancers.
Alternate Names
Brand names:
How It Works
Pharmacodynamics: Megestrol’s primary effect is to increase appetite and promote weight gain. In cancer treatment, its anti-estrogenic and anti-androgenic properties inhibit tumor growth.
Pharmacokinetics:
- Absorption: Megestrol is readily absorbed after oral administration.
- Metabolism: Primarily metabolized in the liver, potentially by CYP3A4 and UDP-glucuronosyltransferases (UGTs).
- Elimination: Primarily excreted in urine (57-78% within 10 days with normal renal function).
Mode of Action: Megestrol likely interacts with hypothalamic neuropeptides involved in appetite regulation, although the exact mechanism remains unclear. It binds to progesterone receptors and exerts anti-estrogenic and anti-androgenic effects.
Receptor Binding/Enzyme Inhibition: Binds to progesterone receptors. CYP3A4 may also be involved in its metabolism, leading to potential drug interactions.
Elimination Pathways: Primarily renal excretion, with some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Anorexia/Cachexia/Weight loss (AIDS):
- Megace: 800 mg orally once daily (20 mL of 40 mg/mL suspension).
- Megace ES: 625 mg orally once daily (5 mL of 125 mg/mL suspension).
- Breast cancer: 40 mg orally four times a day.
- Endometrial cancer: 40-320 mg orally per day in divided doses. Treatment should be continued for at least two months to assess efficacy. Up to 800 mg/day may be used.
Children:
The safety and effectiveness in pediatric patients have not been established. Use and dosage must be determined by a doctor. Off-label use for anorexia/cachexia: Up to 15 mg/kg/day or 800 mg/day.
Special Cases:
- Elderly Patients: Initiate therapy at the lower end of the dosing range due to the increased risk of decreased hepatic, renal, or cardiac function.
- Patients with Renal Impairment: Use with caution. Dosage adjustments may be necessary as megestrol is significantly excreted by the kidneys. Close monitoring of renal function is recommended.
- Patients with Hepatic Dysfunction: Use with caution. Dosage adjustments may be required due to potential metabolic changes.
- Patients with Comorbid Conditions (Diabetes, Cardiovascular Disease, etc.): Monitor closely due to potential exacerbation of these conditions.
Clinical Use Cases
Megestrol acetate is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary use is for appetite stimulation and treatment of certain cancers as described above.
Dosage Adjustments
Adjustments are based on patient-specific factors like renal or hepatic impairment, presence of comorbid conditions, and response to therapy. Monitor blood glucose levels in patients with diabetes.
Side Effects
Common Side Effects:
- Weight gain
- Increased appetite
- Nausea, vomiting, diarrhea, gas
- Impotence, decreased libido
- Rash, flushing
- Insomnia, weakness
- Headache
- Changes in menstrual periods/vaginal bleeding
Rare but Serious Side Effects:
- Severe allergic reactions
- Adrenal insufficiency
- Cushing’s syndrome
- Hyperglycemia/Worsening of diabetes
- Thromboembolic events (blood clots)
Long-Term Effects:
- Chronic adrenal insufficiency
- Cushing’s syndrome
- Diabetes
Adverse Drug Reactions (ADR):
- Severe allergic reactions, adrenal insufficiency, thromboembolic events require immediate medical intervention.
Contraindications
- Known or suspected pregnancy
- Hypersensitivity to megestrol acetate
Drug Interactions
- Indinavir: Megestrol may significantly reduce indinavir exposure, requiring a dose adjustment of indinavir.
- Diabetes medications (e.g., insulin, metformin): Megestrol may decrease the effectiveness of these medications, leading to increased blood sugar levels.
- CYP3A4 substrates: Potential for interactions exists.
- Consult drug interaction checkers for a complete list of potential interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated)
- Fetal Risks: Megestrol may cause fetal harm, including masculinization of female fetuses.
- Breastfeeding: Megestrol is excreted in breast milk and may have adverse effects on the newborn. Breastfeeding should be discontinued if megestrol is required.
Drug Profile Summary
- Mechanism of Action: Stimulates appetite, potentially via hypothalamic interactions. Exerts anti-estrogenic and anti-androgenic effects.
- Side Effects: Weight gain, increased appetite, GI disturbances, impotence, rash, insomnia, thromboembolic events, adrenal insufficiency, hyperglycemia.
- Contraindications: Pregnancy, hypersensitivity.
- Drug Interactions: Indinavir, diabetes medications, CYP3A4 substrates.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Breastfeeding should be discontinued.
- Dosage: Varies based on indication. See detailed dosage guidelines above.
- Monitoring Parameters: Weight, blood glucose, signs of adrenal insufficiency, signs of thromboembolism.
Popular Combinations
Megestrol is not typically used in combination therapies except when managing drug interactions (e.g., adjusting indinavir dose when co-administered).
Precautions
Pre-screening for allergies, diabetes, adrenal disorders, and history of thromboembolic events is crucial. Monitor patients closely for side effects, particularly in elderly patients and those with renal or hepatic impairment. Advise patients about potential drug interactions. Women of childbearing potential should use effective contraception.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Megestrol?
A: Dosage varies depending on the condition being treated. For anorexia/cachexia/weight loss in AIDS patients, 800 mg/day of Megace or 625 mg/day of Megace ES is recommended. For breast cancer, 40 mg four times daily is common. For endometrial cancer, the range is 40-320 mg/day, often divided into multiple doses.
Q2: What are the common side effects of Megestrol?
A: Common side effects include weight gain, increased appetite, nausea, diarrhea, impotence, rash, insomnia, and changes in menstrual periods.
Q3: Is Megestrol safe during pregnancy?
A: No, Megestrol is contraindicated during pregnancy due to the risk of fetal harm.
Q4: Can Megestrol be used in children?
A: The safety and efficacy of Megestrol in children haven’t been established. However, it has been used off-label for anorexia/cachexia at doses up to 15mg/kg/day or 800mg/day.
Q5: How does Megestrol work for appetite stimulation?
A: The exact mechanism isn’t fully understood, but it is thought to involve interactions with hypothalamic neuropeptides that regulate appetite.
Q6: What are the serious side effects of Megestrol to be aware of?
A: Serious side effects can include thromboembolic events (blood clots), adrenal insufficiency, Cushing’s syndrome, and worsening of diabetes.
Q7: Does Megestrol interact with other medications?
A: Yes, significant interactions can occur with indinavir (requiring dose adjustment) and diabetes medications (decreasing their efficacy). Consult drug interaction resources for a complete list.
Q8: Should breastfeeding be discontinued when taking Megestrol?
A: Yes, Megestrol is excreted in breast milk and can potentially harm the newborn. Breastfeeding should be discontinued if Megestrol therapy is necessary.
Q9: What precautions should be taken when prescribing Megestrol to elderly patients?
A: Elderly patients often require dosage adjustments due to the potential for reduced hepatic, renal, or cardiac function. Close monitoring for side effects is essential.
Q10: How long does it take for Megestrol to show an effect on appetite and weight gain?
A: A minimum of six weeks is usually recommended for a noticeable effect in anorexia/cachexia/weight loss cases. For cancer treatment, assess the efficacy after at least two months.
