Megace

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Megace

Method of action: Endocrine Therapy

Treatment option: Anorexia, Cachexia, Cancer, Breast Cancer

Medically reviewed

Laura Arias

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Megace

Megace Quick Facts

Property Description
Active Ingredient Megestrol acetate
Form Tablet, Oral Suspension
Pharmacological Class Progestin, Antineoplastic agent
Route of Administration Oral
Origin Synthetic derivative

Megace: Definition and Pharmacological Class

Megace is a prescription-only medicine containing the active substance Megestrol acetate. This compound is a synthetic derivative of the natural steroid progesterone, classifying the drug within the field of hormone therapy. It is primarily classified as a progestin, a type of steroid agent that interacts with the body's hormone receptors.

Composition and General Purpose

The medication is a single-ingredient product administered via the oral route. A key feature is its availability as both a solid tablet and a liquid oral suspension; the suspension utilizes an aqueous suspension base, offering an essential option for patients with swallowing difficulties. The general therapeutic intent relies on the drug's dual mechanism: hormonal modulation and a potent influence on metabolism. A core property of Megestrol acetate is its ability to serve as a significant appetite stimulant. This action is used for managing progressive, involuntary body tissue loss, or cachexia, by promoting increased caloric intake and aiding in weight maintenance.

Regulatory References

  1. FDA DailyMed Label

What side effects are possible with Megace?

Adverse reaction scope

The official regulatory documents, such as the FDA Prescribing Information and European SmPC, classify the possible side effects of Megace (megestrol acetate) based on frequency and affected body system.

Feature Details
Frequency classification Very Common (ge 1/10): Weight increase. Common: Gastrointestinal effects (nausea, vomiting, diarrhea, flatulence), asthenia (weakness), headache, pain, dyspnoea, hot flushes, vaginal bleeding, and impotence (in male patients).
System-organ classes involved Vascular Disorders (e.g., thromboembolic phenomena); Endocrine Disorders (e.g., adrenal suppression, changes in glucose tolerance); Gastrointestinal Disorders (e.g., nausea, diarrhea, abdominal pain).
Serious adverse reactions The regulatory labels document risks of thromboembolic phenomena, including deep vein thrombosis (DVT) and pulmonary embolism. Adrenal insufficiency following withdrawal, particularly after chronic use, is also recognized as a serious endocrine concern.

Safety classifications (high-level)

Feature Details
Population-specific safety considerations The medicine is contraindicated in pregnancy and should be discontinued during breastfeeding. Patients with pre-existing diabetes require close monitoring due to the potential for decreased glucose tolerance and increased blood sugar levels.
Dose- or exposure-related patterns The development of Cushing's Syndrome and clinically significant adrenal suppression is explicitly associated with long-term exposure to the medication.
Safety-related restrictions or limitations A specific safety constraint is the potential for the oral suspension to cause a significant decrease in the plasma levels of Indinavir when co-administered.

Resulting safety structure

Regulatory safety summary:

  • The most frequently documented effect is weight increase, which is classified as very common in official sources.
  • The regulatory framework highlights potential serious vascular risks, specifically thromboembolic events, and endocrine risks, including adrenal suppression.
  • System-specific effects are documented across the Gastrointestinal and Reproductive Systems.

Connection to the overall safety profile:

The official safety profile provides a descriptive framework by classifying adverse reactions based on frequency and body system involved. This approach differentiates common, often anticipated effects (like weight gain) from less frequent but clinically significant risks (like blood clots and HPA axis suppression), strictly defining the drug's safety characteristics as determined by government authorities.

Overdose and Emergency Response

Overdose and When to Seek Help

The official regulatory profile for Megestrol acetate overdose is based on clinical reports and historical toxicological studies.

Classification Regulatory Definition
Antidote Availability No specific antidote is known for overdose with Megace.
Required Action Appropriate supportive measures should be taken in the event of an overdose.

Documented Overdose Presentations

Reports received in the postmarketing setting have included the following signs and symptoms in the context of overdose:

  • Gastrointestinal: Diarrhoea, nausea, abdominal pain.
  • Constitutional/Neurological: Unsteady gait, listlessness.
  • Respiratory/Cardiovascular: Shortness of breath, cough, chest pain.

Toxicological studies cited in regulatory documentation reported no acute toxicological effects when Megestrol acetate was administered in high dosages, up to 1600 mg/day for six months or longer. The official labeling does not specify distinct life-threatening outcomes, monitoring requirements, or population-specific risks in the Overdose section. The regulatory guidance mandates that supportive measures should be taken.

Therapeutic Uses of Megace

This medication is generally used across two distinct therapeutic domains, both involving symptoms that interfere with daily functioning. The primary applications involve providing symptomatic support for anorexia and cachexia (wasting syndrome), and is relevant in the management of specific advanced malignancies, including breast cancer and endometrial cancer.


Wasting Syndrome (Cachexia) and Severe Appetite Loss

This domain is relevant for managing symptoms of severe, involuntary weight loss and a profound loss of appetite. The medication is commonly applied in clinical settings marked by heightened systemic burden, such as in patients with Acquired Immunodeficiency Syndrome (AIDS), where severe wasting symptoms create noticeable physiological strain. The core benefit is supporting appetite stimulation to promote increased caloric intake, which supports general well-being during symptomatic phases. This support provides relief when symptoms interfere with routine activities.

Quick Fact: Relief for Nutritional Stress

Focus Symptom Category Therapeutic Goal
Primary Use Severe loss of appetite (anorexia) Supports appetite and assists with maintaining weight
Context Wasting syndrome (cachexia) Contributes to easing nutritional strain and increasing caloric intake

Palliative Treatment for Advanced Hormone-Sensitive Cancers

The medication is relevant in therapeutic contexts involving specific advanced cancers for the palliative management of advanced or recurrent breast cancer and endometrial cancer. This application is relevant in conditions characterized by periods of heightened symptoms associated with metastatic or recurrent disease. The therapeutic benefit in this context is offering symptomatic relief that helps manage challenging manifestations and contributes to easing the overall symptom load during advanced stages of the illness.

Regulatory References

  1. NIH MedlinePlus overview

Eligibility and Restrictions for Use

Eligibility Map: Who can and cannot use Megace

The eligibility profile for Megace (megestrol acetate) is strictly defined by regulatory warnings and absolute contraindications. Its use is primarily established for adult patients with anorexia, cachexia, unexplained significant weight loss (such as that associated with AIDS), or advanced breast or endometrial cancer.


Classification Population Eligibility Status
Absolute Contraindication Patients with a history of hypersensitivity to megestrol acetate, and those with known or suspected pregnancy (use is prohibited).
Not Recommended Pediatric patients (safety and effectiveness have not been established). The drug is also not intended for prophylactic use to avoid weight loss.
Use with Caution Patients with a history of thromboembolic disease (e.g., blood clots) and those with diabetes mellitus. Caution is also advised for patients with impaired renal or hepatic function, reflecting the drug's excretion pathway.

Females of reproductive potential must be advised to avoid becoming pregnant during treatment. For older adults, the regulatory label recommends using caution, often starting at a lower dose, due to the increased frequency of age-related decline in organ function.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Official regulatory information identifies specific drug interactions that require careful management or modification of therapy.


Documented Interacting Medicines and Classes

Interacting Product Category Specific Drug Listed Interaction Context / Constraint
HIV Protease Inhibitors Indinavir Co-administration results in a significant decrease in Indinavir exposure; administration of a higher dose of Indinavir should be considered.
Anticoagulants Warfarin May increase the effects of Warfarin, requiring careful monitoring of coagulation indices.
Antidiabetic Agents Insulin, oral agents May decrease the therapeutic efficacy of these agents due to megestrol's inherent ability to impair glucose tolerance.

Interaction-Related Constraints

  • Dofetilide: Use with this antiarrhythmic medicine is generally not recommended.
  • Pharmacodynamic Impact: Megestrol's intrinsic progestational/glucocorticoid activity is the mechanistic basis for its caution statement concerning antidiabetic agents. The drug's influence on glucose metabolism necessitates the monitoring and potential adjustment of antidiabetic therapy, particularly in patients with pre-existing diabetes mellitus.
  • Monitoring Requirement: Due to potential alterations in drug levels and/or effects, close clinical and laboratory monitoring is required when megestrol is co-administered with narrow therapeutic index drugs like Warfarin or when combined with Indinavir.

This structure reflects mandated regulatory information concerning how the co-administration of megestrol acetate affects the concentration or action of select other medicinal products.

Mechanism of Action

Megace (megestrol acetate) is a synthetic progestin that functions as an agonist at the nuclear progesterone receptor (PR). Upon binding, the ligand-receptor complex translocates into the nucleus, where it binds to specific DNA response elements to modulate the transcription of target genes. This genomic signaling pathway alters the synthesis of various proteins, subsequently modifying cell proliferation and differentiation in tissues expressing the PR, such as the endometrium.

Megestrol also exhibits weak agonist activity at the glucocorticoid receptor (GR). Activation of the GR initiates a separate intracellular cascade that also leads to the altered expression of genes involved in metabolic regulation. System-level physiological consequences of these receptor-mediated actions include an antigonadotropic effect, where pituitary luteinizing hormone (LH) release is suppressed via a negative feedback loop. Reduced LH then decreases ovarian estrogen synthesis. Additionally, megestrol is hypothesized to modulate the production or action of metabolic mediators, such as pro-inflammatory cytokines (e.g., TNF-alpha and IL-6) and Neuropeptide Y levels within the hypothalamus, leading to changes in systemic energy balance.

Dosage and Administration Information

Megestrol acetate is administered exclusively via the oral route, available as both a tablet (e.g., 20 mg and 40 mg) and as an oral suspension in two concentrations (40 mg/mL and 125 mg/mL). The specific daily dose and frequency pattern are defined by the intended use.


Official Dosing Schedules

For the palliative management of advanced breast carcinoma, the total daily dose is typically 160 mg, administered in divided amounts. The total daily dose for advanced endometrial carcinoma ranges from 40 mg to 320 mg, also taken in divided doses. Conversely, for the treatment of anorexia or cachexia, the oral suspension is prescribed as a single daily dose (QD) of 800 mg (conventional strength) or 625 mg (concentrated strength).


Administration Requirements

The container for the oral suspension must be shaken well before each dose is measured. A crucial instruction is that the 125 mg/mL concentrated suspension is not substitutable with the 40 mg/mL conventional suspension on a milligram-per-milligram basis due to differing absorption. While the concentrated form can be taken without regard to meals, the conventional suspension's absorption is enhanced with food. A minimum of two months of continuous treatment is often specified to adequately assess the drug's effect in advanced cancer indications. Dose selection for older adults requires caution, typically beginning at the low end of the dosing range, and the drug should not be used prophylactically to prevent weight loss.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Megace

Evidence for Use in Wasting Syndrome (Cachexia and Anorexia)

Megace has been studied extensively in Randomized Controlled Trials (RCTs) to examine outcomes in patients with severe, involuntary weight loss, a condition sometimes called cachexia or wasting syndrome. Research focused on adults experiencing this condition, primarily in the context of Acquired Immunodeficiency Syndrome (AIDS) or advanced malignancies. These trials were designed to use placebo controls and examined short-term symptom changes over intervals of around eight to twelve weeks.

The primary outcomes was studied for included objective change in total body weight and patient-reported outcomes describing perceived appetite improvement. Studies reported measurements indicating a pattern of increased appetite and weight gain in the groups receiving Megace compared to those receiving a placebo. What remains uncertain is the composition of the weight gained, as research has not consistently established that the weight gained is lean body mass (muscle).


Evidence for Use in Advanced Hormone-Sensitive Carcinomas

The evidence for Megace in advanced breast carcinoma was evaluated in controlled clinical trials, including Phase III dose-response studies. The main outcomes studies monitored were objective measures related to the cancer itself, such as the Objective Tumor Response Rate (ORR), and time-related events like Time to Disease Progression (TTP) and Overall Survival (OS). One long-term trial reported no significant differences in TTP or survival between different dose arms, highlighting complexity in interpreting the data.

For advanced endometrial carcinoma, research primarily examined the compound as a palliative hormonal therapy. Findings indicate that tumor response rates was observed in some studies to be higher in patients whose tumors were well-differentiated (lower grade). However, much of this evidence is derived from smaller Phase II trials, which means the evidence quality varies across studies for certain long-term outcomes.

Key Evidence Gaps and Scientific Uncertainty

The research highlights several areas where uncertainty remains. Evidence is limited and often mixed regarding the compound's influence on functional status or overall quality of life for the general cachexia population. In the cancer domain, evidence regarding the optimal dose is complex, with some large studies indicating that escalating the dose did not provide a benefit on progression time or survival compared to lower doses.

Key Studies & References

  1. Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a meta-analysis

Frequently Asked Questions (FAQ)

Common questions about Megace (FAQ)


Q: Is Megace considered a chemotherapy drug?

A: Megace is classified as a synthetic progestin, which is a type of hormonal agent. Official labeling indicates that the medicine is used for the palliative treatment of advanced carcinoma and should not be used in lieu of standard procedures such as chemotherapy, radiation, or surgery.


Q: Can Megace be used as a primary cancer treatment?

A: According to regulatory documents, this medicine is indicated for the palliative treatment of advanced (recurrent, inoperable, or metastatic) carcinoma. It should not be used in place of primary treatments such as surgery or radiation.


Q: What is the difference between Megace and Megestrol Acetate?

A: Megace is the brand name for the active substance known as Megestrol Acetate. Megestrol Acetate is the chemical compound that acts as the medication's active ingredient.


Q: How quickly does Megace usually start to affect appetite?

A: Studies and clinical data suggest that the onset of weight gain, which is associated with increased appetite, may begin within two to four weeks of starting treatment.


Q: Does Megace work by the same method as other hormone-based medicines?

A: The medicine is a synthetic progestin, meaning it works by stimulating the body's progesterone receptors. While it exhibits this classical progestational activity, its precise anti-cancer mechanism and its full anti-estrogenic effects are not entirely understood in regulatory documents.


Q: Does taking Megace increase the risk of developing diabetes?

A: Regulatory warnings state that clinical cases of new onset diabetes mellitus have been reported in association with the chronic use of this medicine. The regulatory label also indicates that it may worsen a pre-existing diabetic condition.


Q: Are there any signs of blood clots that patients should be aware of?

A: Official product information indicates that the medicine carries a risk of thromboembolic phenomena (blood clots). Symptoms such as sudden difficulty breathing, chest pain, or swelling, redness, and pain in one leg are listed as adverse effects that require prompt medical attention.


Q: Does Megace cause changes to mood or mental state?

A: Mood changes have been reported as an adverse reaction. Additionally, symptoms such as depression and anxiety are associated with the risk of Cushing's syndrome, which has been reported with the medicine’s chronic use.


Q: Is it common to have fluid retention or swelling in the legs with Megace?

A: Edema (fluid retention) has been reported as an adverse reaction. However, official labeling notes that the common weight gain observed with the medicine is not necessarily due to fluid retention.


Q: Is it safe to take Megace with a blood thinner like Warfarin?

A: The medicine may increase the effects of the blood thinner Warfarin. Regulatory documents indicate that co-administration is associated with a requirement for close clinical and laboratory monitoring of blood clotting indices.


Q: Are there certain over-the-counter pain relievers that interact with Megace?

A: Official information indicates that the metabolism of Megestrol Acetate may be increased when combined with certain common non-prescription pain relievers like Acetaminophen. Regulatory labels include advice for patients to inform their provider of all over-the-counter medicines they are using.


Q: Can Megace be taken alongside Indinavir, an HIV medicine?

A: Co-administration of the medicine with the HIV drug Indinavir may significantly decrease the concentration of Indinavir in the body. The regulatory label states that the healthcare provider may need to consider adjusting the Indinavir dose if these two medicines are taken together.


Q: Is there a concern about combining Megace with other hormonal therapies?

A: Since this medicine is a hormonal agent, regulatory labels include advice for patients to inform their healthcare provider about all hormonal therapies they are currently taking. This includes those that contain estrogen, such as contraceptives or hormone replacement therapy (HRT).


Q: Why is Megace sometimes associated with 'moon face' or a rounded facial appearance?

A: Overt Cushing's syndrome, a condition that can cause a characteristic rounded or 'moon face' appearance, has been reported in association with the chronic use of the medicine.


Q: Is Megace known to interact with herbal supplements?

A: Official patient safety advisories include the statement that patients should inform their healthcare provider about all substances they are taking. This includes prescription medicines, over-the-counter products, and any herbal products or other supplements.


Q: What is the risk of having a change in vision while on Megace?

A: Visual disturbances are listed as a reported adverse reaction in clinical trial data.


Q: Does Megace affect sleep patterns, such as causing insomnia?

A: Trouble sleeping or insomnia is listed as a reported adverse reaction in official product information.


Q: Is there a common reason for Megace treatment to be stopped by the healthcare team?

A: Discontinuation is often considered due to the development of serious side effects, such as a thromboembolic event (blood clot). Treatment may also be stopped to manage the risk of adrenal insufficiency that can occur upon medicine withdrawal.


Q: Does Megace cause hair loss or thinning?

A: Alopecia, which is the medical term for hair loss or thinning, is listed as a reported adverse reaction in official product information.


Q: What kind of monitoring (blood tests, etc.) is typically done while taking Megace?

A: Official documentation mentions the need for close surveillance for cancer patients. Monitoring may involve checking for changes in blood sugar (due to diabetes risk) and evaluating for adrenal insufficiency or changes in blood clotting ability (if taking Warfarin).


Q: If someone forgets to take a dose, what is the general guidance on catching up?

A: General patient guidance indicates that if a dose is missed, it should be taken as soon as it is remembered. However, if it is close to the next scheduled dose, the guidance is to skip the missed dose, and not to take double or extra doses.


Q: Does Megace affect blood pressure levels?

A: High blood pressure, known medically as hypertension, is listed as a reported adverse reaction in official product information.


Q: Are there specific symptoms that require immediate medical attention while taking Megace?

A: Symptoms that require immediate medical attention include signs of a blood clot, such as sudden difficulty breathing or swelling and pain in a leg. Signs of a serious allergic reaction, such as swelling of the face, lips, or tongue, also require immediate attention as described in the warnings.

How should Megace be stored and disposed of?

Official Storage and Disposal Requirements

Megace (megestrol acetate) must be stored according to regulatory mandates to maintain its quality and ensure safety. Storage conditions differ slightly by formulation:

  • Oral Suspension: Store at controlled room temperature, specifically between 15 C and 25 C (59 F and 77 F). The suspension must be protected from heat above 40 C and kept from freezing. The container should be shaken well before use.
  • Tablets: Store below 25 C in the original package to protect them from moisture.

All forms must be stored out of the sight and reach of children. Unused or expired Megace product must be disposed of in accordance with local regulations and must not be discarded via household waste or wastewater, consistent with its classification as a Hazardous Agent.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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