Brand name: Megace
Drug class: Progestins
VA class: AN500
Chemical name: 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate
Molecular formula: C₂₄H₃₂O₄
CAS number: 595-33-5

Medically reviewed by Drugs.com on Oct 6, 2023. Written by ASHP.

Introduction

Synthetic progestin; antineoplastic agent and appetite stimulant.

Uses for Megestrol

Breast Cancer

Palliative management of recurrent, inoperable, or metastatic breast cancer.^{b c}

Estrogen and/or progesterone receptor-positive breast cancer is more likely to respond to megestrol therapy.^b

Does not replace appropriate methods of treatment of advanced breast cancer (e.g., surgery, radiation, chemotherapy).^{b c}

Not recommended for treatment of other types of neoplastic disease; use only for treatment of breast cancer or endometrial cancer.^b

Endometrial Cancer

Palliative management of recurrent, inoperable, or metastatic endometrial carcinoma.^{b c}

Does not replace appropriate methods of treatment of advanced endometrial carcinoma (e.g., surgery, radiation, chemotherapy).^{b c}

Not recommended for treatment of other types of neoplastic disease; use only for treatment of endometrial cancer or breast cancer.^b

Cachexia

Management of anorexia, cachexia, or an unexplained, substantial weight loss in HIV-infected individuals (designated an orphan drug by FDA for this use).^{102 104 106 107 108 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 138 a}

Also has been used to stimulate appetite and promote weight gain in a limited number of patients with cachexia associated with neoplastic disease^{† [off-label]}.^{100 101 103 108 116 117 118 119 134 135}

Therapy should be initiated only after treatable causes (e.g., possible malignancies; systemic infections; GI disorders affecting absorption; endocrine, renal, or psychiatric diseases) of the condition have been evaluated.¹²¹

Manufacturer states that megestrol should not be used prophylactically to avoid weight loss.

Megestrol Dosage and Administration

Administration

Oral Administration

Administer orally.^{138 a b}

Manufacturer makes no specific recommendations regarding administration with meals.^a

Oral suspensions containing 200 mg/5 mL are not bioequivalent or interchangeable on a mg-per-mg basis with the oral suspension containing 625 mg/5 mL (Megace ES).¹³⁸ (See Plasma Concentrations under Pharmacokinetics.)

Dosage

Available as megestrol acetate; dosage expressed in terms of the salt.^{138 a b}

Adults

Breast Cancer

Oral (Tablets)

160 mg daily in 4 equally divided doses (40 mg 4 times daily); continue therapy for at least 2 months to determine antineoplastic effectiveness.^b

Dosages of 480-1600 mg daily in divided doses have been used in clinical trials.^{100 108 110 114}

Endometrial Carcinoma

Oral (Tablets)

40–320 mg daily in divided doses; continue therapy for at least 2 months to determine antineoplastic effectiveness.^b

Cachexia

Treatment in HIV-infected Individuals

Oral (Oral Suspension)

Initially, 800 mg daily (20 mL per day).^{121 122 126 127 128 130 a}

In clinical trials, 400 mg daily also has been used effectively.^a

Oral (Concentrated Oral Suspension [Megace ES])

Initially, 625 mg daily.¹³⁸

Clinically effective dosages are expected to range from 312.5–625 mg daily.¹³⁸

Treatment in Individuals with Neoplastic Disease† [off-label]

Oral

480–600 mg daily generally have been used.^c However, some patients may exhibit weight gain with dosages as low as 160 mg daily.^c

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.^{138 a b}

Renal Impairment

No specific dosage recommendations at this time.^{138 a b} (See Renal Impairment under Cautions.)

Geriatric Patients

Treatment of cachexia in HIV-infected individuals: Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹³⁸

Treatment of breast cancer or endometrial cancer: No specific dosage recommendations at this time.^b

Cautions for Megestrol

Contraindications

• Known hypersensitivity to megestrol or any ingredient in the formulation.^{138 a c}

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

May cause fetal harm; animal studies indicate dose-related feminization of male fetuses.^{138 a c} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.^{138 a c}

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Asymptomatic pituitary-adrenal suppression occurs frequently in patients receiving chronic therapy; suppression of HPA function may be fatal if not recognized.^{138 a b} Adrenal insufficiency reported in patients receiving or being withdrawn from chronic therapy.^{138 a b}

Laboratory evaluation recommended if signs/symptoms of adrenal insufficiency (e.g., hypotension, nausea, vomiting, dizziness, weakness) occur in patients receiving or being withdrawn from chronic therapy; administration of replacement or stress dosages of a rapidly acting glucocorticoid may be required, especially in patients subjected to stress (e.g., surgery, infection).^{138 a b}

Glucocorticoid activity of megestrol not fully evaluated.^{138 a b}

Endocrine Effects

May increase insulin requirements and aggravate or precipitate diabetes mellitus.^{138 a b}

Administration over a prolonged period may produce hypercorticism (Cushing’s syndrome).^{138 a b}

General Precautions

Cardiovascular Effects

Thromboembolic events (e.g., deep-vein thrombophlebitis, pulmonary embolism), sometimes fatal, reported.^b Use with caution in patients with a history of thromboembolic disease.^{138 a b}

HIV Viral Replication

Effect of megestrol therapy on HIV viral replication not evaluated.^{138 a}

Respiratory Effects

Possible increased risk of respiratory infections associated with chronic therapy.^{138 a}

Specific Populations

Pregnancy

Category X (Oral Suspensions);^{138 a} Category D (Tablets).^b (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Discontinue nursing because of potential risk to nursing infants.^{138 a b}

Pediatric Use

Safety and efficacy not established.^{138 a b}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients with cachexia respond differently than younger adults; select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.¹³⁸ (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; assess renal function periodically since geriatric patients are more likely to have decreased renal function.¹³⁸

Renal Impairment

Substantially eliminated by kidneys; possible increased risk of toxicity.¹³⁸

Common Adverse Effects

In patients with breast cancer or endometrial cancer: Weight gain,^b nausea,^b vomiting,^b hypertension,^b vaginal bleeding and discharge (including breakthrough bleeding),^{108 b} hyperglycemia,^b asthenia,^b rash.^b

In patients with cachexia: Diarrhea, flatulence, nausea, vomiting, hypertension, impotence, decreased libido, asthenia, rash, insomnia, anemia, fever, hyperglycemia, pain.^{138 a}

Drug Interactions

Specific Drugs

Megestrol Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration usually attained within 1–5 hours.^c

Plasma Concentrations

Plasma concentrations achieved with a 625-mg dose of the concentrated oral suspension (Megace ES 625 mg/5 mL) are equivalent to those achieved with an 800-mg dose of the original formulation (200 mg/5 mL) under fed conditions.¹³⁸

Elimination

Metabolism

Completely metabolized in the liver to free steroids and glucuronide conjugates.

Elimination Route

Excreted principally in urine (about 66%) and in feces (about 20%).^{138 a b}

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15-30°C); protect from heat.^b

Suspension

Tight containers at 15–25°C; protect from heat.^{138 a}

Actions

• Induces secretory changes in the endometrium, increases basal body temperature, inhibits pituitary function, and produces withdrawal bleeding in the presence of estrogen.^c

• In animals, suppresses ovulation and produces antigonadotropic, antiuterotropic, and antiandrogenic/antimyotropic effects; has slight glucocorticoid activity and a very slight degree of mineralocorticoid activity; and has no estrogenic, androgenic, or anabolic activity.^c

• Antineoplastic effect may result from inhibition of pituitary gonadotropin production which results in decreased estrogen secretion.^b

• Decreases the number of hormone-dependent breast cancer cells and eliminates the stimulatory effect that estrogen has on these cells.^b

• May produce a local effect on cancerous cells by converting the actively growing stroma into decidua.^c

• May directly or indirectly stimulate appetite or may alter metabolic pathways via interference with the production or action of mediators such as cachectin (a hormone that inhibits adipocyte lipogenic enzymes);^{100 101 103 109 110 111} however precise mechanism for weight gain not clearly established.^{100 101 103 108 109 116 121}

Advice to Patients

• Importance of taking megestrol exactly as prescribed.

• Importance of informing patients that the more concentrated oral suspension containing 625 mg/5 mL (Megace ES) does not contain the same amount of megestrol as oral suspensions containing 200 mg/5 mL and therefore are not interchangeable.¹³⁸

• Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{128 135 c}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.^{138 a b}

• Importance of informing patients of other important precautionary information.^{138 a b} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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