Version May 2024
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 (Ref). 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 (Ref).
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 (Ref). Surgical treatment is recommended if response is not observed within 6 months (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl >30 mL/minute: No dosage adjustment necessary (Ref).
CrCl ≤30 mL/minute: Note: Megestrol is primarily eliminated in the urine; use with caution.
Oral: Initial: Start with doses at the lower end of the recommended indication-specific dose range; may titrate to the usual recommended indication-specific dose based on response and tolerability. Monitor frequently for adverse effects (eg, edema, hyperglycemia, adrenal insufficiency, venous thromboembolism). Doses of up to 800 mg/day taken for up to 6 months have been used for the treatment of cachexia in patients with severe kidney disease (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (Ref): Oral: Dose as for CrCl ≤30 mL/minute (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzable (Ref): Oral: Dose as for CrCl ≤30 mL/minute (Ref).
CRRT: Oral: Dose as for CrCl ≤30 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral: Dose as for CrCl ≤30 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Avoid use (Ref).
(For additional information see "Megestrol acetate: Pediatric drug information")
Note: Megestrol oral suspension is available in 2 concentrations (40 mg/mL and 125 mg/mL [eg, Megace ES]); they are not equivalent on a mg-per-mg basis; precautions should be taken to verify and avoid confusion between the different concentrations; in pediatric trials including liquid formulations, only the 40 mg/mL has been used.
Appetite stimulant/anorexia associated with chronic illness (eg, cancer, cystic fibrosis, HIV): Limited data available; efficacy results variable:
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; in patients >10 years, daily doses divided into 4 doses have been used; titrate dose to response; maximum daily dose: 15 mg/kg/day not to exceed 800 mg/day. Monitor patients closely for adverse effects, particularly adrenal suppression.
Dosing based on several prospective and retrospective trials and case series. Clinical trials show benefit for weight gain and body (non-muscle) mass (Ref).
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.
Megestrol may be associated with hypothalamic-pituitary-adrenal (HPA)-axis suppression that may be difficult to differentiate due to comorbid conditions or concurrent therapies (Ref). HPA-axis suppression may be life threatening, but discontinuation of megestrol and/or treatment with a corticosteroid typically resolves symptoms (Ref). Symptom resolution in case reports varies from days to months (Ref).
Mechanism: Dose- and time-related; megestrol activates both progesterone and glucocorticoid receptors (GR) and has a stronger binding affinity than its endogenous counterparts (Ref). Dual agonist/antagonist behavior is exhibited by megestrol binding to the GR as a weak agonist, then simultaneously blocking endogenous glucocorticoids to the GR (Ref).
Onset: Varied; reports range from days to months and has been reported during therapy and following discontinuation (Ref).
Risk factors:
• Abrupt discontinuation of megestrol (Ref)
• Concurrent therapies that may impair HPA (Ref)
• Intercurrent acute stress or illness (Ref)
Megestrol may be associated with venous thromboembolism (VTE); the exact incidence is difficult to quantify, given confounding risk factors such as concurrent chemotherapy/radiotherapy and tumor-induced hypercoagulability, but has been cited as <5% to 11% (Ref). Megestrol is on the Beers List of Potentially Inappropriate Medication Use in Older Adults due to concerns of thrombosis (Ref).
Mechanism: Unknown; etiology of hypercoagulability has not been elucidated (Ref). Postmarketing reports contain a variety of dosing regimens resulting in insufficient evidence to correlate dose with VTE risk (Ref).
Onset: Varied; reports range from 10 days to months of megestrol use (Ref).
Risk factors:
• Cancer patients, especially pancreatic cancer (Ref)
• Limited mobility (Ref)
• Preexisting hypercoagulable states (Ref)
• Older adults (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash (12%)
Genitourinary: Impotence (4% to 14%)
1% to 10%:
Cardiovascular: Hypertension (8%)
Endocrine & metabolic: Decreased libido (2% to 5%), hyperglycemia (6%)
Gastrointestinal: Dyspepsia (3%), flatulence (10%), nausea (4%), vomiting (6%)
Genitourinary: Urinary frequency (1% to 2%)
Nervous system: Asthenia (6%), insomnia (4% to 6%), pain (6%)
Miscellaneous: Fever (4% to 5%)
Frequency not defined:
Cardiovascular: Heart failure
Dermatologic: Alopecia, diaphoresis
Endocrine & metabolic: Hot flash
Genitourinary: Breakthrough bleeding
Hematologic & oncologic: Tumor flare
Nervous system: Lethargy, malaise, mood changes
Respiratory: Dyspnea
Postmarketing:
Cardiovascular: Edema (Ruiz 2013), venous thromboembolism (including pulmonary embolism, thrombophlebitis) (Oberhoff 2001)
Endocrine & metabolic: Adrenocortical insufficiency (Mehta 2015), Cushing syndrome (Delitala 2013), decreased glucose tolerance, diabetes mellitus (Jain 1996), exacerbation of diabetes mellitus, HPA-axis suppression (Mehta 2015), weight gain (Ruiz 2013)
Hypersensitivity to megestrol or any component of the formulation; known or suspected pregnancy (suspension).
Concerns related to adverse effects:
• Bleeding irregularities: Vaginal bleeding or discharge may occur.
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.
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]
Generic: 40 mg/mL (10 mL [DSC], 240 mL, 480 mL); 400 mg/10 mL (10 mL); 800 mg/20 mL (20 mL); 625 mg/5 mL (5 mL, 150 mL)
Tablet, Oral, as acetate:
Generic: 20 mg, 40 mg
Yes
Suspension (Megestrol Acetate Oral)
40 mg/mL (per mL): $0.60
625 mg/5 mL (per mL): $5.99
Tablets (Megestrol Acetate Oral)
20 mg (per each): $0.69 - $1.04
40 mg (per each): $0.28 - $1.71
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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: Shake suspension well before use.
The 625 mg/5 mL suspension may be administered without regard to meals.
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.
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).
Anorexia or cachexia: Suspension: Treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS
Limitations of use: Treatment of AIDS-related weight loss should only be initiated after addressing the treatable causes (eg, malignancy, infection, malabsorption, endocrine disease, renal disease, psychiatric disorder) for weight loss. Megestrol is not intended to prevent weight loss.
Breast cancer: Tablet: Treatment (palliative) of advanced breast cancer
Endometrial cancer: Tablet: Treatment (palliative) of advanced endometrial carcinoma
Cancer-related cachexia; Endometrial hyperplasia (alternative therapy)
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 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Chlorprothixene: Progestins may enhance the adverse/toxic effect of Chlorprothixene. Progestins may enhance the therapeutic effect of Chlorprothixene. 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
Flotufolastat F18: Antiandrogens may diminish the diagnostic effect of Flotufolastat F18. Management: Therapies targeting the androgen pathway may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of these therapies on the performance of flotufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider therapy modification
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 (gozetotide) in prostate cancer. The impact on the performance of gallium Ga 68 PSMA-11 (gozetotide) 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
MetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modification
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.
Megestrol is present in breast milk.
Information is available from 5 breastfeeding women, ~8 weeks postpartum, who were administered megestrol 4 mg in combination with ethinyl estradiol 50 mcg daily for contraception. Maternal serum and milk samples were obtained over 5 days, beginning 10 days after therapy began. The highest concentrations of megestrol were found at the samples taken 3 hours after the maternal dose. Mean concentrations of megestrol were 6.5 ng/mL (maternal serum; range: 3.7 to 10.8 ng/mL), 4.6 ng/mL (foremilk; range: 1.1 to 12.7 ng/mL), and 5.6 ng/mL (hindmilk; range: 1.2 to 18.5 ng/mL) (Nilsson 1977).
Due to the potential for adverse reaction in the breastfed newborn, the manufacturer recommends discontinuing breastfeeding while receiving megestrol for the treatment of cancer. Due to the potential for HIV transmission, breastfeeding is not recommended when treating anorexia or cachexia associated with HIV infection.
Observe for signs of thromboembolic events; blood pressure, weight; serum glucose; signs/symptoms suggestive of adrenal insufficiency with chronic use. Evaluate pregnancy status prior to treatment in patients who may become pregnant.
Endometrial hyperplasia (off-label use): Assess response to treatment every 3 to 6 months (ACOG 2015; Concin 2021).
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
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