Megestrol is a synthetic oral progestin. The drug has slight glucocorticoid and mineralocorticoid activity, but is not estrogenic, androgenic, or anabolic. Megestrol acetate suspensions are used for the treatment of anorexia, cachexia, or unexplained, significant weight loss in adult patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Megestrol is also used off-label as an appetite stimulant in pediatric patients with chronic conditions. Due to dosage differences, the concentrated 125 mg/mL megestrol acetate ES suspension is not substitutable with other strengths (e.g., 40 mg/mL oral suspension). Megestrol acetate tablets are indicated for the palliative treatment of advanced breast cancer or endometrial cancer and have been used off-label for advanced prostate cancer; megestrol not be used in lieu of currently accepted procedures such as surgery, radiation, or chemotherapy. Megestrol is considered second- or third-line therapy in the treatment of breast cancer; it is less effective than tamoxifen but as effective as aminoglutethimide. Megestrol is also used off-label for treating endometriosis and has some utility in treating hot flashes that occur from androgen-deprivation therapy for hormonally-dependent cancers.
General Administration Information
NOTE: The correct dose of megestrol for the treatment of neoplastic disease will vary from protocol to protocol. Clinicians should consult the appropriate references to verify the dose.
For storage information see specific product information, within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Megestrol acetate oral tablets:
-It is unknown whether the tablets are affected by food.
Oral Liquid Formulations
Megestrol Acetate Oral Suspension:
-Shake well prior to administration. Measure dosage with calibrated cup, spoon, or oral syringe.
-Megestrol suspension (40 mg/mL) and megestrol ES suspension (125 mg/mL) are available in different strengths and the dosage for the treatment of cachexia and anorexia in AIDS patients is different for these 2 formulations. It is imperative that health care providers inform patients of these differences to prevent errors in dosage. This Megace ES suspension (125 mg/mL) is not substitutable with other strengths (e.g., 40 mg/mL).
-Recommendations on the administration of the original 40 mg/mL suspension with food have NOT been made.
-The concentrated 125 mg/mL ES suspension can be taken without regard to meals.
Long-term treatment with megestrol may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a two-year chronic toxicity study of megestrol acetate conducted in rats. Pneumonia was reported in up to 2% of patients receiving megestrol oral suspension at dosages of 400 to 1200 mg/day in clinical trials; however, it was not reported at a greater frequency than in placebo patients. General infection and candidiasis were reported in 1 to 3% of patients; however, the incidences were not significantly different than placebo.
Weight gain is a frequent side effect of megestrol, even at doses used for the treatment of cancer. Weight gain has been associated with increased appetite and is not necessarily associated with fluid retention. Appetite stimulation and weight gain are generally considered to be beneficial to patients with cachexia and anorexia associated with cancer or HIV infection. Gastrointestinal (GI) adverse reactions that were reported in patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials include nausea (0 to 5%), vomiting (0 to 6%), diarrhea (6% to 15%), dyspepsia (3% to 4%), and flatulence (1% to 10%). Other GI adverse reactions reported in 1% to 3% of patients were abdominal pain, constipation, dry mouth (xerostomia), hepatomegaly, increased salivation (hypersalivation), and oral candidiasis; however, the incidences were not significantly different than placebo.
Vaginal discharge and breakthrough bleeding (menstrual) have occurred commonly in females being treated with megestrol for breast or endometrial carcinoma. In the ten females included in the trial for HIV-related anorexia/cachexia, all reported breakthrough menstrual bleeding during the trial. Other types of menstrual irregularity may occur during megestrol treatment. Hot flashes have also been reported with megestrol.
Rash (unspecified) was reported in 2 to 12% of patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials. Other dermatologic adverse reactions reported in 1 to 3% of patients include alopecia, herpes, pruritus, vesicular rash, sweating (diaphoresis), and skin disorder; however, the incidences were not significantly different than placebo.
Hypertension was reported in 8% of patients receiving megestrol oral suspension at a dose of 800 mg/day in clinical trials. Other cardiovascular adverse reactions reported in 1 to 3% of patients include chest pain (unspecified), cardiomyopathy, edema, peripheral edema, and palpitations; however, the incidences were not significantly different than placebo. Heart failure has also been reported. Thrombo-phlebitis and thromboembolism, including deep vein thrombosis and pulmonary embolism (some cases fatal), have been reported in post-marketing surveillance.
Although data are limited, it has been proposed that megestrol may possess glucocorticoid-like activity. Laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression has been observed. Hyperglycemia and insulin resistance may occur. In clinical trials of patients who received megestrol oral suspension at dosages of 400 to 800 mg/day, hyperglycemia was reported in up to 6% of patients. Clinical cases of new onset diabetes mellitus, exacerbation of pre-existing diabetes, and Cushing's syndrome have been reported. In small studies of pediatric patients with cystic fibrosis, 2 of 17 (12%) patients reported transient hyperglycemia and 2 of 12 (17%) patients developed diabetes while receiving megestrol for appetite stimulation. Cases of clinically apparent adrenocortical insufficiency have also been reported. In a study of 19 pediatric oncology patients receiving megestrol for appetite stimulation, a significant decrease in cortisol was reported in 10 of 11 patients tested, with 1 patient requiring inotropic support due to clinical hypoadrenalism with hemodynamic collapse. Consider the possibility of adrenal suppression in any patient taking or withdrawing from chronic megestrol therapy who presents with symptoms of adrenal insufficiency such as hypotension, nausea, vomiting, dizziness, or weakness.
Respiratory adverse reactions reported in 1 to 3% of patients receiving megestrol oral suspension in clinical trials include cough, dyspnea, pharyngitis, and lung disorder; however, the incidences were not significantly different than placebo.
Insomnia (up to 6%) was the most common central nervous system (CNS) adverse reaction reported in patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials. Other CNS adverse reactions reported in 1 to 3% of patients included confusion, headache, seizures or convulsions, depression, hypoesthesia, impaired cognition, peripheral neuropathy, and paresthesias; however, the incidences were not significantly different than placebo. Mood changes have also been reported with megestrol.
Hematologic adverse reactions reported with megestrol oral suspension in clinical trials include anemia (3 to 5%) and leukopenia (1 to 3%); however, the incidences were not significantly different than placebo.
Asthenia was reported in 3 to 6% of patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials. Generalized pain was reported in up to 6% of patients. Other musculoskeletal adverse reactions reported with megestrol include carpal tunnel syndrome and sarcoma.
Impotence (erectile dysfunction) was reported in 4 to 14% of patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials. Other reproductive/endocrine adverse effects included libido decrease in up to 5% of patients and gynecomastia in 1 to 3% of patients.
Urinary adverse reactions reported with megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials included increased urinary frequency (1 to 2%), albuminuria (1 to 3%), urinary incontinence (1 to 3%), and urinary tract infection (1 to 3%); however, the incidences were not significantly different than placebo.
Fever was reported in 2 to 5% of patients receiving megestrol oral suspension at dosages of 400 to 800 mg/day in clinical trials. Amblyopia and increased LDH were reported in 1 to 3% of patients; however, the incidences were not significantly different than placebo. Other generalized adverse reactions reported with megestrol include lethargy and malaise.
Tumor flare, with or without hypercalcemia, has been reported with megestrol therapy. A single case report in the literature implicates megestrol acetate for a rising PSA concentration in a patient with prostate cancer approximately 18 months after initiating megestrol acetate for symptomatic relief of hot flashes. The megestrol acetate was discontinued, and his PSA concentration decreased by 66%. Although a causal relationship can not be established based on a single case report, clinicians should be aware of this potential adverse effect.
Megestrol is contraindicated in those patients with a history of hypersensitivity to megestrol acetate or any component of the formulation.
Megestrol acetate is not intended for prophylactic use to avoid weight loss. Therapy with megestrol acetate oral suspension for weight loss should only be instituted after treatable causes of weight loss are sought and addressed. These treatable causes include possible malignancies, systemic infections, gastrointestinal disorders affecting absorption, endocrine disease, renal disease, or psychiatric disease.
Megestrol acetate has been used extensively in women for the treatment of breast and endometrial cancer; its use in HIV-infected females has been limited. Megestrol is a progesterone derivative, which may induce vaginal bleeding in women. In establishing the indication for the treatment of anorexia and cachexia secondary to human immunodeficiency virus (HIV), all ten females in the clinical trial reported the side effect of menstrual irregularity (breakthrough bleeding). However, vaginal bleeding can also be a sign of a serious gynecological problem. Prior to starting megestrol, females with undiagnosed abnormal vaginal bleeding or dysfunctional uterine bleeding should be evaluated.
Breast cancer in which estrogen and/or progesterone receptors are positive are more likely to respond to megestrol. The use of megestrol in other types of neoplastic disease is not recommended. Close surveillance is indicated for any patient treated for recurrent or metastatic cancer. Administration of megestrol acetate to female dogs for up to 7 years is associated with an increased incidence of both benign and malignant tumors of the breast. Comparable studies in rats and studies in monkeys are not associated with an increased incidence of tumors. Pituitary tumors were observed in female rats treated with 3.9 or 10 mg/kg/day of megestrol acetate for 2 years. The relationship of the dog tumors to humans is unknown but should be considered in assessing the benefit-to-risk ratio when prescribing megestrol and in surveillance of patients on therapy.
The glucocorticoid activity of megestrol has not been fully evaluated, clinical cases of new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia, and overt Cushing's syndrome have been reported in association with the chronic use of megestrol. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol therapy in the stressed and non-stressed state. Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealed the frequent occurrence of asymptomatic pituitary-adrenal suppression in patients treated with chronic megestrol therapy. The possibility of adrenal suppression should be considered in any patient taking or withdrawing from chronic megestrol therapy who presents with symptoms of adrenal insufficiency (e.g., hypotension, nausea, vomiting, dizziness, or weakness). Laboratory evaluation for adrenal insufficiency and replacement stress doses of a rapidly acting glucocorticoid may be indicated for such patients. Failure to recognize hypothalamic-pituitary-adrenal (HPA) suppression may result in death. Finally, in patients who are receiving or being withdrawn from chronic megestrol therapy, consideration should be given to the use of empiric therapy with stress doses or a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (e.g., surgery, infection).
Use megestrol cautiously in patients with a history of thromboembolic disease. Thromboembolism (including deep vein thrombosis and pulmonary embolism) and thrombophlebitis have been associated with megestrol therapy.
Hepatic impairment can affect the inactivation of megestrol and, thus, plasma concentrations, patients with severe hepatic disease should be monitored for adverse effects. Specific guidelines for dosage adjustments in these patients are not available.
Megestrol acetate is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with renal impairment or renal failure. Care should be taken in dose selection, and it may be useful to monitor renal function in patients with impaired renal function, especially in elderly adults.
Clinical studies of megestrol acetate for the treatment of cachexia, anorexia, or an unexplained weight loss in patients with AIDS did not include sufficient numbers of geriatric adults aged 65 years or older. Reported clinical experience has not identified differences in responses between younger and geriatric adults. Because older adults are more likely to have decreased renal function, care should be taken in dosage selection, and it may be useful to monitor renal function. According to the Beers Criteria, megestrol is considered a potentially inappropriate medication (PIM) for use in geriatric adults as a general treatment for cachexia/poor appetite and should be avoided due to a minimal effect on weight and an increased risk of thrombotic events and possibly death in older adults. The benefits and risks of treatment should be carefully considered.
Megestrol is contraindicated during pregnancy. Based on animal studies, megestrol may cause fetal harm when administered to pregnant women. There are no available human data to assess for any drug associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. Prior to use of megestrol, confirm that a female of childbearing potential is not pregnant. Females of childbearing potential should be advised to avoid becoming pregnant while receiving megestrol treatment. If megestrol is used during pregnancy, or if the patient becomes pregnant while taking megestrol, advise the patient of the potential hazard to the fetus. Reproduction studies were performed in pregnant rats at oral doses ranging from 0.05 to 12.5 mg/kg/day, which are below the maximum recommended human clinical dose (MRHD) based on body surface area. Reduction in fetal weight and number of live births were observed at 12.5 mg/kg/day (5 times lower than the MRHD) when dams were dosed on days 12 through 18 of pregnancy. Feminization of male fetuses also occurred when dams were dosed on days 13 through 20 of pregnancy at 3 mg/kg/day, approximately 22 times below the MRHD.
In female patients of childbearing potential, discuss the reproductive risk of megestrol and the contraception requirements during use including the need for pregnancy testing before therapy. Advise female patients of childbearing potential to contact their physician immediately if they become pregnant or suspect they may be pregnant. If a pregnancy test is positive, counsel the patient on the potential risk to the fetus and discuss options. To prevent pregnancy, females of reproductive potential must use acceptable contraception methods during treatment.
Megestrol should not be used during breast-feeding since its effect on the breastfed infant or the effects on milk production are not known. Alternate forms of feeding are recommended if megestrol therapy is essential to the mother. Megestrol is known to be excreted in human breast milk; the amount that an infant absorbs systemically per day is estimated to be 0.1% of the maternal daily ingested dose based on available data. The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed to avoid risking postnatal transmission of HIV-1 to the breastfed child.
For the treatment of anorexia, cachexia, or unexplained weight loss:
-in adult patients with acquired immunodeficiency syndrome (AIDS):
Oral dosage (125 mg/mL suspension, e.g., Megace ES):
Adults: 625 mg PO once daily. This oral suspension strength (125 mg/mL) is not substitutable with other strengths (e.g., 40 mg/mL), due to dosage differences for this indication.
Oral dosage (40 mg/mL suspension):
Adults: 800 mg PO once daily. Doses of 400 to 800 mg/day were effective in clinical trials.
-in pediatric patients with chronic conditions (e.g., cancer, cystic fibrosis, chronic kidney disease, human immunodeficiency virus [HIV])*:
Oral dosage (40 mg/mL suspension or tablets):
Infants, Children, and Adolescents 6 months to 17 years: 7.5 to 10 mg/kg/day PO in 1 to 2 divided doses; adjust to individual response. Max: 15 mg/kg/day or 800 mg/day. Reported treatment duration: 1 to 11 months. A higher initial dose of 14 mg/kg/day was used and tapered to 10 mg/kg/day over 5 to 6 months in a retrospective review of pediatric patients (n = 25; age range: 1.7 to 19.7 years) with chronic kidney disease.
For the palliative treatment of advanced, inoperable, recurrent metastatic breast cancer:
Oral dosage (tablets):
Adults: 40 mg PO given 4 times per day. At least 2 months of therapy is considered an adequate period for determining the antineoplastic effectiveness of megestrol.
For the palliative treatment of advanced, inoperable, recurrent metastatic endometrial cancer:
Oral dosage (tablets):
Adults: 40 to 320 mg/day PO, given in divided doses. At least 2 months of therapy is adequate for determining the antineoplastic effectiveness of megestrol.
For the treatment of advanced hormone-refractory prostate cancer*:
Oral dosage (tablets):
Adult males: Dosage has not been established. In a randomized study that compared low-doses of 160 mg PO once daily to high-doses of 640 mg PO once daily in 149 patients with progressive prostate cancer following androgen ablation and 1 prior hormone therapy, there was no significant difference in response rate (2 partial responses (PR) vs. 1 PR), median overall survival time (11.2 vs. 12.1 months), or progression-free survival time (3.8 vs. 4.3 months) between the 2 treatment arms. Toxicity was similar in both study arms and 7% of patients experienced a pain flare. In another randomized phase II trial of 58 patients, 40 mg PO 4 times daily resulted in an objective response rate of 10% compared with 7% in patients who received dexamethasone 0.75 mg PO twice daily. A separate randomized trial was closed early after enrolling 22% of the planned patient accrual; no complete or PR were observed in 86 patients with HRPC who received 1 of 4 treatments: megestrol 40 mg PO 3 times per day as monotherapy, megestrol 40 mg PO given 3 times per day plus diethylstilbestrol 0.1 mg PO once daily, stilphostrol, or streptozotocin.
For the for the treatment of metastatic renal cell cancer*:
Oral dosage (tablets):
Adults: Dosage has not been established. In a randomized, 4-arm phase II study in 144 evaluable patients, 1 partial response (PR) was reported in 37 patients who received initial treatment with megestrol acetate 150 mg/m2/day PO in 3 divided doses; additionally, 2 PR were reported in 48 patients who crossed over to the megestrol arm after failing initial therapy with one of the other 3 study treatments (etoposide, cyclophosphamide, or dianhydrogalactitol). In another phase II trial, no complete response or PR was observed in 15 patients who received megestrol 80 mg PO twice daily plus interferon alpha-2b (10 million international units/m2 subcutaneously 5 days/week). Stable disease was achieved in 5 patients; 12 patients discontinued therapy due to fatigue.
For the treatment of pain due to endometriosis*:
Oral dosage (tablets):
Adults: 40 mg PO once daily for 3 to 6 months has been used and appear to relieve dysmenorrhea, noncyclic pelvic pain, and dyspareunia. Treatment guidelines recommend progestin therapy as a treatment option; however, megestrol is not commonly prescribed as there is more evidence supporting use of other progestogens.
For the treatment of hot flashes* in women with a history of breast cancer or in men with prostate cancer who have undergone androgen-deprivation therapy:
Oral dosage (tablets):
Adults: Dosage not established. A double-blind, cross over study of 4 weeks of megestrol 20 mg PO twice daily compared to placebo was studied in 97 females with breast cancer and 66 males with prostate cancer who had hot flashes. During the first 4 weeks, 74% of the megestrol group vs. 20% of the placebo group had a 50% decrease in hot flashes compared to baseline. In general, 2 to 3 weeks of therapy was needed to achieve optimal effect. Cross over data demonstrated a carry-over effect of the megestrol and therefore this data was not included in the data analysis.
Maximum Dosage Limits:
-Adults
Specific maximum dose information is not available for oncologic treatments; see indications. 800 mg/day PO (40 mg/mL suspension) or 625 mg/day PO (125 mg/mL suspension) for anorexia/cachexia.
-Geriatric
Specific maximum dose information is not available for oncologic treatments; see indications. 800 mg/day PO (40 mg/mL suspension) or 625 mg/day PO (125 mg/mL suspension) for anorexia/cachexia.
-Adolescents
Safety and efficacy have not been established; however, doses up to 15 mg/kg/day PO or 800 mg/day PO have been used off-label for anorexia/cachexia.
-Children
Safety and efficacy have not been established; however, doses up to 15 mg/kg/day PO or 800 mg/day PO have been used off-label for anorexia/cachexia.
-Infants
6 to 11 months: Safety and efficacy have not been established; however, doses up to 15 mg/kg/day PO or 800 mg/day PO have been used off-label for anorexia/cachexia.
1 to 5 months: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Hepatic impairment can affect megestrol plasma concentrations; however, specific guidelines for dosage adjustments in hepatic impairment are not available.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, megestrol is substantially excreted by the kidney and the risk of toxic reactions may be greater in patients with impaired renal function.
Intermittent hemodialysis
Megestrol acetate has not been tested for dialyzability; however, due to its low solubility it is postulated that hemodialysis is not an effective means of drug removal. No supplemental dosages are needed.
*non-FDA-approved indication
Dofetilide: (Contraindicated) All inhibitors of renal cationic secretion, including megestrol, are contraindicated with dofetilide. In a population pharmacokinetic analysis of plasma dofetilide concentrations, the mean clearance of dofetilide was 15% lower in patients receiving inhibitors of tubular organic cation transport.
Entecavir: (Minor) Entecavir and megestrol are eliminated by active renal tubular secretion. In theory, coadministration of these drugs may increase the serum concentrations of either drug due to competition for the drug elimination pathway. Coadministration of entecavir with antiviral drugs known to be eliminated by active tubular secretion did not result in significant drug interactions in studies.
Indinavir: (Major) Due to the significant decrease in the exposure of indinavir by megestrol acetate, administration of a higher dose of indinavir should be considered when coadministering with megestrol acetate. Specific adjustment recommendations are not available, but should be determined by viral response. In one pharmacokinetic study of healthy male subjects, co-administration of megestrol acetate (675 mg/day for 14 days) and indinavir (a single dose 800 mg) resulted in a 32% decrease in the Cmax of indinavir and a 21% decrease in the AUC of indinavir.
Trospium: (Minor) Trospium is metabolized by ester hydrolysis and excreted by the kidneys through a combination of tubular secretion and glomerular filtration. Some drugs which are actively secreted by the kidney, including megestrol, may interact with trospium by competing for renal tubular secretion. Be alert for increased effect of either trospium ( anticholinergic effects) or megestrol.
Warfarin: (Moderate) At high doses, megestrol may be associated alterations in warfarin pharmacokinetics that may increase warfarin exposure. Carefully monitor the INR when these drugs are used together. Lower doses of warfarin may be necessary when megestrol is given. In one study, a small change in the rate of warfarin clearance was see with concomitant administration of high doses of megestrol; a minor decrease observed in warfarin clearance may be of clinical importance. Additionally, a 71% increase in warfarin's half-life was seen.
Megestrol shares the properties of the progestins. The drug induces endometrial secretory changes, increases basal body temperature, inhibits pituitary function, and precipitates bleeding when estrogen is present. The mechanism of its antineoplastic activity is not known, but it has been suggested that megestrol-induced suppression of luteinizing hormone release from the pituitary may have a negative effect on cancerous tissues of the breast and endometrial lining. Megestrol enhances estrogen metabolism, which suppresses estrogen-dependent tumors by lowering plasma estrogen concentrations. Megestrol also may change the actively growing cancer cell stroma into decidua. Because megestrol promotes the differentiation and maintenance of endometrial tissue, it is effective in the therapy of endometriosis and endometrial cancer.
The reported weight gain associated with megestrol therapy is believed to be due to the drug's metabolic and appetite-stimulatory effects rather than to its glucocorticoid activity. Megestrol, or its metabolites, may interfere with cachexin, the hormone that inhibits adipocyte lipogenic enzymes and leads to the wasting syndrome of AIDS or cancer. Weight gain occurs within 3 weeks in most patients who receive megestrol for this purpose.
Megestrol is administered orally. The drug is highly bound to plasma proteins, chiefly transcortin. Megestrol tends to concentrate in adipose tissue. Megestrol is inactivated by the liver; however, metabolites account for only 5% to 8% of the administered dose and are considered negligible. The major route of drug elimination in humans is the urine with a minor portion excreted in the feces; the urinary excretion within 10 days after administration ranges from 56.5% to 78.4% and fecal excretion ranges from 7.7% to 30.3%. Respiratory excretion and fat storage of metabolites may account for at least part of the radioactivity not found in urine and feces. During a pharmacokinetic evaluation of megestrol in healthy subjects, the mean elimination half-life ranged from 20 to 50 hours.
-Route-Specific Pharmacokinetics
Oral Route
-Tablets: Megestrol appears to be rapidly absorbed across the GI tract, with a bioavailability of greater than 90%, although this varies significantly among individual patients. Peak concentrations for the tablets occur in 1 to 3 hours. Whether the tablets are affected by food has not been established. The relative bioavailability of the oral tablets to oral suspension has not been determined.
-Oral suspension (40 mg/mL): The median Tmax for the 40 mg/mL suspension was 5 hours. The effect of food on the absolute bioavailability of megestrol acetate oral suspension has not been evaluated.
-Oral suspension ES (125 mg/mL; e.g., Megace ES suspension): Mean plasma concentrations of megestrol acetate after administration of 625 mg dose (125 mg/mL) of Megace ES oral suspension are equivalent under fed conditions to a 800 mg dose (40 mg/mL) of the original megestrol acetate oral suspension in healthy volunteers. Per the product label, the 125 mg/mL megestrol ES oral suspension is not substitutable with other suspension strengths (e.g., 40 mg/mL); the dosage recommendations differ by product concentration. The mean Cmax and AUC when administered after a high-fat meal were increased by 48% and 36% respectively, compared to the Cmax and AUC under the fasting conditions. This food effect on Cmax and AUC is significantly less than that seen for the original megestrol 40 mg/mL oral suspension where administration with a high-fat meal significantly increased AUC and Cmax of megestrol acetate to 2-fold and 7-fold, respectively, compared to the fasting condition. There was no difference in safety following administration of the megestrol ES suspension in the fed states; therefore, megestrol ES suspension may be taken without regard to meals.
-Special Populations
Hepatic Impairment
The pharmacokinetics of megestrol in patients with hepatic impairment have not been evaluated.
Renal Impairment
The pharmacokinetics of megestrol in patients with renal impairment have not been evaluated.
Pediatrics
The pharmacokinetics of megestrol in pediatric patients have not been evaluated.