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Megestrol

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
Brands: Megace

Medically reviewed by Drugs.com on Oct 6, 2021. 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.

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

Does not replace appropriate methods of treatment of advanced breast cancer (e.g., surgery, radiation, chemotherapy).

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

Endometrial Cancer

Palliative management of recurrent, inoperable, or metastatic endometrial carcinoma.

Does not replace appropriate methods of treatment of advanced endometrial carcinoma (e.g., surgery, radiation, chemotherapy).

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

Cachexia

Management of anorexia, cachexia, or an unexplained, substantial weight loss in HIV-infected individuals (designated an orphan drug by FDA for this use).

Also has been used to stimulate appetite and promote weight gain in a limited number of patients with cachexia associated with neoplastic disease.

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.

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

Megestrol Dosage and Administration

Administration

Oral Administration

Administer orally.

Manufacturer makes no specific recommendations regarding administration with meals.

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). (See Plasma Concentrations under Pharmacokinetics.)

Dosage

Available as megestrol acetate; dosage expressed in terms of the salt.

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.

Dosages of 480-1600 mg daily in divided doses have been used in clinical trials.

Endometrial Carcinoma
Oral (Tablets)

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

Cachexia
Treatment in HIV-infected Individuals
Oral (Oral Suspension)

Initially, 800 mg daily (20 mL per day).

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

Oral (Concentrated Oral Suspension [Megace ES])

Initially, 625 mg daily.

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

Treatment in Individuals with Neoplastic Disease†
Oral

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

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time. (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.

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

Cautions for Megestrol

Contraindications

  • Known hypersensitivity to megestrol or any ingredient in the formulation.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

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

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. Adrenal insufficiency reported in patients receiving or being withdrawn from chronic therapy.

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).

Glucocorticoid activity of megestrol not fully evaluated.

Endocrine Effects

May increase insulin requirements and aggravate or precipitate diabetes mellitus.

Administration over a prolonged period may produce hypercorticism (Cushing’s syndrome).

General Precautions

Cardiovascular Effects

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

HIV Viral Replication

Effect of megestrol therapy on HIV viral replication not evaluated.

Respiratory Effects

Possible increased risk of respiratory infections associated with chronic therapy.

Specific Populations

Pregnancy

Category X (Oral Suspensions); Category D (Tablets). (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Discontinue nursing because of potential risk to nursing infants.

Pediatric Use

Safety and efficacy not established.

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. (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.

Renal Impairment

Substantially eliminated by kidneys; possible increased risk of toxicity.

Common Adverse Effects

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

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

Interactions for Megestrol

Specific Drugs

Drug

Interaction

Comments

Indinavir

Decreased plasma concentrations and AUC of indinavir

Effect of indinavir on megestrol pharmacokinetics not evaluated

If used with megestrol, consider increasing indinavir dosage

Rifabutin

Pharmacokinetics of rifabutin not significantly altered

Effect of rifabutin on megestrol pharmacokinetics not evaluated

Dosage adjustments not required

Zidovudine

Pharmacokinetics of zidovudine not significantly altered

Effect of zidovudine on megestrol pharmacokinetics not evaluated

Dosage adjustments not required

Megestrol Pharmacokinetics

Absorption

Bioavailability

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

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.

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%).

Stability

Storage

Oral

Tablets

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

Suspension

Tight containers at 15–25°C; protect from heat.

Actions

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

  • 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.

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

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

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

  • 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); however precise mechanism for weight gain not clearly established.

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.

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • 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.

  • Importance of informing patients of other important precautionary information. (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

Megestrol Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

200 mg/5 mL*

Megace (with alcohol 0.06% v/v, polyethylene glycol, polysorbate [Tween] 80, and xanthan gum)

Bristol-Myers Squibb

Megestrol Acetate Suspension

Barr, Morton Grove, Par, Roxane, Teva

625 mg/5 mL

Megace ES (with alcohol 0.06% v/v, docusate sodium, and hydroxypropyl methylcellulose)

Par

Tablets

20 mg*

Megestrol Acetate Tablets

Barr, Par, Roxane, Teva

40 mg*

Megestrol Acetate Tablets

Barr, Par, Roxane, Teva

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 16, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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