Note: Megace ES is not equivalent mg per mg with other megestrol formulations.
Appetite stimulant/anorexia associated with chronic illness (eg, cancer, cystic fibrosis, HIV): Limited data available: Infants ≥8 months, Children, and Adolescents: Oral: Tablets or 40 mg/mL suspension: Initial dose: 7.5 to 10 mg/kg/day in 1 to 2 divided doses; titrate dose to response, decrease dose if weight gain is excessive. Reported duration was 3 to 11 months. Maximum daily dose: 800 mg/day or 15 mg/kg/day
Dosing based on several prospective and retrospective trials and case series. Clinical trials show benefit for weight gain and body mass (Azcona 1996; Brady 1994; Clarick 1997; Cuvelier 2014; Eubanks 2002; Hobbs 2010; Marchand 2000; Nasr 1999; Orme 2003).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, the urinary excretion of megestrol acetate is substantial, use caution.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Megestrol acetate: Drug information")
Note: Megestrol suspensions are not equivalent on a mg-per-mg basis.
Anorexia or cachexia associated with AIDS: Suspension: Initial: Oral: 625 mg daily (of the 125 mg/mL suspension) or 800 mg daily (of the 40 mg/mL suspension); daily doses of 400 mg to 800 mg have been found to be effective.
Breast cancer, advanced: Tablet: Oral: 160 mg per day in divided doses of 40 mg 4 times daily for at least 2 months.
Cancer-related cachexia (off-label use): Oral: 200 to 600 mg/day; duration of treatment depends on treatment goals and risk/benefit assessment (ASCO [Roeland 2020]). In studies, doses ranging from 160 to 800 mg/day were effective in achieving weight gain; higher doses (>160 mg) were associated with more weight gain (Beller 1997; Loprinzi 1990; Loprinzi 1993; Loprinzi 1999; Vadell 1998).
Endometrial cancer, advanced: Tablet: Oral: 40 to 320 mg daily in divided doses for at least 2 months.
Endometrial hyperplasia, alternative therapy (off-label use): Tablet: Oral: 40 to 200 mg/day for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia; megestrol may be administered continuously or cyclical. The optimal dose and duration have not been established (ACOG 2015). Surgical treatment is recommended if response is not observed within 6 months (Concin 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, the urinary excretion of megestrol acetate is substantial, use with caution.
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Oral, as acetate:
Megace ES: 625 mg/5 mL (150 mL [DSC]) [contains alcohol, usp, sodium benzoate; lemon-lime flavor]
Generic: 40 mg/mL (10 mL, 240 mL, 480 mL); 400 mg/10 mL (10 mL); 625 mg/5 mL (5 mL, 150 mL)
Tablet, Oral, as acetate:
Generic: 20 mg, 40 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 160 mg
Tablet, Oral, as acetate:
Generic: 40 mg
Oral: Oral suspension (40 mg/mL): Shake oral suspension well before administering; the effect of food on the bioavailability of MEGACE Oral Suspension has not been evaluated
Oral: Shake suspension well before use.
The 625 mg/5 mL suspension may be administered without regard to meals.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Suspension: Store at 15°C to 25°C (59°F to 77°F); protect from heat. Store/dispense in a tight container.
Tablet: Store at 15°C to 30°C (59°F to 86°F); protect from light. Protect from temperatures above 40°C (104°F).
Oral suspension: Treatment of anorexia; cachexia; or an unexplained, significant weight loss in patients with AIDS (FDA approved in adults)
Note: Treatment of AIDS-related weight loss should only be initiated after addressing the treatable causes for weight loss (eg, malignancy, infection, malabsorption, endocrine disease, renal disease, psychiatric disorder). Megestrol is not intended to prevent weight loss.
Tablet: Treatment (palliative) of advanced breast cancer and advanced endometrial carcinoma (FDA approved in adults); has also been used for the treatment of cachexia
Megace may be confused with Reglan
Megestrol may be confused with mesalamine
Megestrol is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to an increased risk of thrombotic events and potentially death in older adults, with minimal effects on weight (Beers Criteria [AGS 2019]).
Pharmacy Quality Alliance (PQA): Megestrol is identified as a high-risk medication in patients 65 years and older on the PQA’s Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not always defined.
Cardiovascular: Hypertension (4% to 8%), cardiomyopathy (1% to 3%), chest pain (1% to 3%), edema (1% to 3%), palpitations (1% to 3%), peripheral edema (1% to 3%), cardiac failure
Central nervous system: Headache (3% to 10%), pain (4% to 6%, similar to placebo), insomnia (1% to 6%), abnormality in thinking (1% to 3%), confusion (1% to 3%), convulsions (1% to 3%), depression (1% to 3%), hypoesthesia (1% to 3%), neuropathy (1% to 3%), paresthesia (1% to 3%), carpal tunnel syndrome, lethargy, malaise, mood changes
Dermatologic: Skin rash (6% to 12%), alopecia (1% to 3%), dermatological disease (1% to 3%), diaphoresis (1% to 3%), pruritus (1% to 3%), vesicobullous dermatitis (1% to 3%)
Endocrine & metabolic: Hyperglycemia (6%), decreased libido (1% to 5%), albuminuria (1% to 3%), gynecomastia (1% to 3%), increased lactate dehydrogenase (1% to 3%), adrenocortical insufficiency, amenorrhea, Cushing's syndrome, diabetes mellitus, hot flash, HPA-axis suppression, hypercalcemia, weight gain (not attributed to edema or fluid retention)
Gastrointestinal: Diarrhea (10%, similar to placebo), flatulence (6% to 10%), vomiting (4% to 6%), nausea (4% to 5%), dyspepsia (2% to 3%), abdominal pain (1% to 3%), constipation (1% to 3%), oral moniliasis (1% to 3%), sialorrhea (1% to 3%), xerostomia (1% to 3%)
Genitourinary: Impotence (4% to 14%), urinary incontinence (1% to 3%), urinary tract infection (1% to 3%), urinary frequency (1% to 2%), breakthrough bleeding
Hematologic & oncologic: Leukopenia (1% to 3%), sarcoma (1% to 3%), tumor flare
Hepatic: Hepatomegaly (1% to 3%)
Infection: Candidiasis (1% to 3%), herpes virus infection (1% to 3%), infection (1% to 3%)
Neuromuscular & skeletal: Weakness (5% to 6%)
Ophthalmic: Amblyopia (1% to 3%)
Respiratory: Cough (1% to 3%), dyspnea (1% to 3%), pharyngitis (1% to 3%), pulmonary disorder (1% to 3%), pneumonia (1%), hyperventilation
Miscellaneous: Fever (1% to 6%)
Postmarketing and/or case reports: Decreased glucose tolerance, thromboembolic phenomena (including deep vein thrombosis, pulmonary embolism, thrombophlebitis)
Hypersensitivity to megestrol or any component of the formulation; known or suspected pregnancy (suspension).
Documentation of allergenic cross-reactivity for progestins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Adrenal suppression: May suppress hypothalamic-pituitary-adrenal (HPA) axis during chronic administration; consider the possibility of adrenal suppression in any patient receiving or being withdrawn from chronic therapy when signs/symptoms suggestive of hypoadrenalism are noted (during stress or in unstressed state). Laboratory evaluation and replacement/stress doses of rapid-acting glucocorticoid should be considered.
• Bleeding irregularities: Vaginal bleeding or discharge may occur.
• Cushing syndrome: Has been reported with long-term use.
Disease-related concerns:
• AIDS-related cachexia: The effects on HIV viral replications are unknown.
• Diabetes: New-onset diabetes mellitus and exacerbation of preexisting diabetes have been reported with long-term use.
• Thromboembolism: Use with caution in patients with a history of thromboembolic disease.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
None known.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Dofetilide: Megestrol may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Gallium Ga 68 PSMA-11: Antiandrogens may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 in prostate cancer. The impact of these therapies on the performance of gallium Ga 68 PSMA-11 is unknown; consider use of alternative agents. Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Antiandrogens may diminish the diagnostic effect of Piflufolastat F18. Management: Therapies targeting the androgen pathway may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of these therapies on the performance of piflufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider therapy modification
Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Megestrol may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Evaluate pregnancy status prior to treatment in patients who may become pregnant; effective contraception should be used when treating anorexia or cachexia in patients with HIV infection. In clinical studies, megestrol was shown to cause breakthrough vaginal bleeding.
Megestrol may be used for the nonsurgical management of endometrial intraepithelial neoplasia/atypical endometrial hyperplasia in patients who desire fertility (ACOG 2015; Concin 2021). Pregnancy rates are favorable in patients who respond to treatment (Shikeli 2020; Wang 2019; Yang 2020). Close monitoring is recommended; surgery may be required following pregnancy or in case of treatment failure (Concin 2021).
Based on data from animal reproduction studies, megestrol may cause fetal harm if administered during pregnancy.
Use is contraindicated for the treatment of anorexia or cachexia in pregnant patients with HIV infection.
Monitor for signs of thromboembolic phenomena and adrenal axis suppression
Appetite stimulation: Weight, caloric intake, basal cortisol level, serum glucose
Antineoplastic: Tumor response
Megestrol is a synthetic progestin with antiestrogenic properties which disrupt the estrogen receptor cycle. Megestrol interferes with the normal estrogen cycle and results in a lower LH titer. May also have a direct effect on the endometrium. Megestrol is an antineoplastic progestin thought to act through an antileutenizing effect mediated via the pituitary. May stimulate appetite by antagonizing the metabolic effects of catabolic cytokines.
Onset of action: Breast or endometrial cancer: At least 2 months of continuous therapy; Weight gain: 2 to 4 weeks
Absorption: Well absorbed
Metabolism: Hepatic (to free steroids and glucuronide conjugates)
Half-life elimination: Suspension: 20 to 50 hours; Tablet: Mean: 34.2 hours (range: 13 to 105 hours)
Time to peak, serum: Suspension: 5 hours; Tablet: 2.2 hours (range: 1 to 3 hours)
Excretion: Urine (57% to 78%; 5% to 8% as metabolites); feces (8% to 30%) within 10 days
Suspension (Megestrol Acetate Oral)
40 mg/mL (per mL): $0.60 - $0.68
625 mg/5 mL (per mL): $5.89 - $5.99
Tablets (Megestrol Acetate Oral)
20 mg (per each): $0.69 - $1.04
40 mg (per each): $1.23 - $1.71
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