Class: Antineoplastic Agents
VA Class: AN500
Chemical Name: 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate
Molecular Formula: C24H32O4
CAS Number: 595-33-5
Synthetic progestin; antineoplastic agent and appetite stimulant.
Uses for Megestrol Acetate
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
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
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†.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 Acetate Dosage and 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.)
Available as megestrol acetate; dosage expressed in terms of the salt.138 a b
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
40–320 mg daily in divided doses; continue therapy for at least 2 months to determine antineoplastic effectiveness.b
Treatment in HIV-infected IndividualsOral (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.aOral (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†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
No specific dosage recommendations at this time.138 a b
No specific dosage recommendations at this time.138 a b (See Renal Impairment under Cautions.)
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 Acetate
Known hypersensitivity to megestrol or any ingredient in the formulation.138 a c
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
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
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
Possible increased risk of respiratory infections associated with chronic therapy.138 a
Category X (Oral Suspensions);138 a Category D (Tablets).b (See Fetal/Neonatal Morbidity under Cautions.)
Discontinue nursing because of potential risk to nursing infants.138 a b
Safety and efficacy not established.138 a b
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
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
Interactions for Megestrol Acetate
Decreased plasma concentrations and AUC of indinavir138
Effect of indinavir on megestrol pharmacokinetics not evaluated138
If used with megestrol, consider increasing indinavir dosage138
Pharmacokinetics of rifabutin not significantly altered138
Effect of rifabutin on megestrol pharmacokinetics not evaluated138
Dosage adjustments not required138
Pharmacokinetics of zidovudine not significantly altered138
Effect of zidovudine on megestrol pharmacokinetics not evaluated138
Dosage adjustments not required138
Megestrol Acetate Pharmacokinetics
Well absorbed following oral administration, with peak plasma concentration usually attained within 1–5 hours.c
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
Completely metabolized in the liver to free steroids and glucuronide conjugates.
Excreted principally in urine (about 66%) and in feces (about 20%).138 a b
25°C (may be exposed to 15-30°C); protect from heat.b
Tight containers at 15–25°C; protect from heat.138 a
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.)
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
200 mg/5 mL*
Megace (with alcohol 0.06% v/v, polyethylene glycol, polysorbate [Tween] 80, and xanthan gum)
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)
Megestrol Acetate Tablets
Barr, Par, Roxane, Teva
Megestrol Acetate Tablets
Barr, Par, Roxane, Teva
AHFS DI Essentials. © Copyright 2017, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
Only references cited for selected revisions after 1984 are available electronically.
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119. Raub W. Possible antianorexia/cachexia therapy for cancer patients. JAMA. 1990; 264:1086. [PubMed 2117074]
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121. Mead Johnson. Megace oral suspension (megestrol acetate) prescribing information. Princeton, NJ; 1993 Sep.
122. Oster M, Enders S, Samuels S et al. Randomized, double-blind study comparing high-dose megestrol acetate and placebo in cachectic patients with acquired immunodeficiency syndrome (AIDS). Int Conf AIDS. 1993; 9:528.
123. Berman S, Katz K, Ho M et al. Megestrol acetate produces weight gain in HIV+ patients. Int Conf AIDS. 1993; 9:499.
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125. Scevola D, Bottari G, Oberto L et al. Changes in caloric intake, anthropometric parameters and TNF levels induced by megestrol acetate in AIDS patients. Int Conf AIDS. 1992; 8:133.
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129. Scevola D, Barbarini G, Bottari G et al. Prevalence, etiology and management of AIDS malnutrition. Int Conf AIDS. 1991; 7:224.
130. Tierney A, Cuff P, Kotler DP. The effect of megestrol acetate (Megace) on appetite, nutritional repletion, and quality of life in AIDS cachexia. Int Conf AIDS. 1991; 7:247.
131. Nathwani D, Green ST, Heslop JM et al. Beneficial response to megoestrol acetate in AIDS-related cachexia and a possible megoestrol withdrawal-associated syndrome? Acta Der Venereol (Stockh). 1990; 70:520-1.
132. Von Roenn JH, Murphy RL, Wegener N. Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection. Semin Oncol. 1990; 17(Suppl 9):13-6. [PubMed 2259923]
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136. Henry K, Rathgaber S, Sullivan C et al. Diabetes mellitus induced by megestrol acetate in a patient with AIDS and cachexia. Ann Intern Med. 1992; 116:53-4. [PubMed 1727096]
137. Bristol Myers Squibb, Princeton, NJ: personal communication.
138. Bristol Myers Squibb. Megace ES (megestrol acetate) suspension prescribing information. Spring Valley, NY; 2005 May.
a. Bristol Myers Squibb. Megace oral suspension (megestrol acetate) prescribing information. Princeton, NJ; 2002 Jul.
b. Bristol Myers Squibb. Megace tablets (megestrol acetate) prescribing information. Princeton, NJ; 2002 Jul.
c. AHFS drug information 2006. McEvoy GK, ed. Megestrol Acetate. Bethesda, MD: American Society of Health-System Pharmacists; 2006:1129-31.
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