U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H30O3
Molecular Weight 342.4726
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MEGESTROL

SMILES

CC1=C[C@]2([H])[C@]([H])(CC[C@@]3(C)[C@@]2([H])CC[C@@]3(C(=O)C)O)[C@@]4(C)CCC(=O)C=C14

InChI

InChIKey=VXIMPSPISRVBPZ-NWUMPJBXSA-N
InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=23395103

Megestrol acetate is a progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. MEGACE Oral Suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time. But its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes. The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5% to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7% to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%). Megestrol acetate metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. Plasma steady-state pharmacokinetics of megestrol acetate were evaluated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of MEGACE Oral Suspension for 21 days. Plasma concentration data obtained on day 21 were evaluated for up to 48 hours past the last dose.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
MEGACE

Approved Use

Megestrol acetate oral suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

Launch Date

7.4761922E11
Palliative
MEGACE

Approved Use

Megestrol acetate oral suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

Launch Date

7.4761922E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
753 ng/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
490 ng/mL
750 mg 1 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1133 ng/mL
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1618 ng/mL
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
1364 ng/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
187 ng/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10476 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6779 ng × h/mL
750 mg 1 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
12095 ng × h/mL
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
16268 ng × h/mL
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
18625 ng × h/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8942 ng × h/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
33.68 h
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
39.75 h
625 mg single, oral
dose: 625 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
32.84 h
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
31.38 h
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEGESTROL ACETATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day multiple, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 54-68 years
n = 2
Health Status: unhealthy
Age Group: 54-68 years
Sex: F
Population Size: 2
Sources:
Disc. AE: Osteoporosis...
AEs leading to
discontinuation/dose reduction:
Osteoporosis (2 patients)
Sources:
625 mg 1 times / day multiple, oral
Recommended
Dose: 625 mg, 1 times / day
Route: oral
Route: multiple
Dose: 625 mg, 1 times / day
Sources:
unhealthy, 65 years
n = 1
Health Status: unhealthy
Age Group: 65 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Adrenal insufficiency...
AEs leading to
discontinuation/dose reduction:
Adrenal insufficiency (1 patient)
Sources:
40 mg 2 times / day multiple, oral
Dose: 40 mg, 2 times / day
Route: oral
Route: multiple
Dose: 40 mg, 2 times / day
Sources:
unhealthy, 85 years
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 85 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Deep vein thrombosis...
AEs leading to
discontinuation/dose reduction:
Deep vein thrombosis (1 patient)
Sources:
400 mg 2 times / day multiple, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 86 years
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 86 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Deep vein thrombosis...
AEs leading to
discontinuation/dose reduction:
Deep vein thrombosis (1 patient)
Sources:
1600 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1600 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: advanced breast cancer
Sex: F
Sources:
AEs

AEs

AESignificanceDosePopulation
Osteoporosis 2 patients
Disc. AE
400 mg 2 times / day multiple, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 54-68 years
n = 2
Health Status: unhealthy
Age Group: 54-68 years
Sex: F
Population Size: 2
Sources:
Adrenal insufficiency 1 patient
Disc. AE
625 mg 1 times / day multiple, oral
Recommended
Dose: 625 mg, 1 times / day
Route: oral
Route: multiple
Dose: 625 mg, 1 times / day
Sources:
unhealthy, 65 years
n = 1
Health Status: unhealthy
Age Group: 65 years
Sex: M
Population Size: 1
Sources:
Deep vein thrombosis 1 patient
Disc. AE
40 mg 2 times / day multiple, oral
Dose: 40 mg, 2 times / day
Route: oral
Route: multiple
Dose: 40 mg, 2 times / day
Sources:
unhealthy, 85 years
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 85 years
Sex: F
Population Size: 1
Sources:
Deep vein thrombosis 1 patient
Disc. AE
400 mg 2 times / day multiple, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 86 years
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 86 years
Sex: F
Population Size: 1
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
mild [Inhibition 50 uM]
mild [Inhibition 50 uM]
moderate [Inhibition 50 uM]
moderate [Inhibition 50 uM]
no
no
no
yes [Activation 50 uM]
yes [Activation 50 uM]
yes [Inhibition 50 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Effect of nomegestrol acetate on human estrogen sulfotransferase activity in the hormone-dependent MCF-7 and T-47D breast cancer cell lines.
2003 Nov-Dec
Nomegestrol acetate: a progestin that deserves recognition.
2004 Apr
The role of MRI in the conservative management of endometrial cancer.
2004 Apr
A comparison of the central effects of different progestins used in hormone replacement therapy.
2004 Aug 20
Osteoporosis associated with megestrol acetate.
2004 Dec
[Nome gesrol (lutenyl) induced severe acute hepatitis].
2004 Jan
Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy.
2004 Jul-Aug
Therapy for unresectable hepatocellular carcinoma: review of the randomized clinical trials-II: systemic and local non-embolization-based therapies in unresectable and advanced hepatocellular carcinoma.
2004 Jun
Aromatase inhibition in the treatment of advanced breast cancer: is there a relationship between potency and clinical efficacy?
2004 May 4
Cost utility and budget impact of third-generation aromatase inhibitors for advanced breast cancer: a literature-based model analysis of costs in the Italian National Health Service.
2004 Sep
Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies.
2005
The science of megestrol acetate delivery: potential to improve outcomes in cachexia.
2005
Retrospective review of megestrol use for weight loss in an elderly veteran population.
2005 Apr
Effects of the combined treatment with thalidomide, megestrol and interleukine-2 in cirrhotic patients with advanced hepatocellular carcinoma. A pilot study.
2005 Apr
Treatment with inhibitors of angiogenesis in advanced hepatocellular carcinoma: a new tool in our hands or simply a hope?
2005 Apr
The effects of aromatase inhibitors on lipids and thrombosis.
2005 Aug
Bone loss and the aromatase inhibitors.
2005 Aug
Role of aromatase inhibitors in breast cancer.
2005 Aug
[Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate].
2005 Feb
Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells.
2005 Jan
Control of sulfatase activity by nomegestrol acetate in normal and cancerous human breast tissues.
2005 Jul-Aug
Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period.
2005 Jun
Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer.
2005 Jun
Antigenotoxic effects of ascorbic acid against megestrol acetate-induced genotoxicity in mice.
2005 Mar
Hormonal treatment of a recurrent granulosa cell tumor of the ovary: case report and review of the literature.
2005 Mar
Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer.
2005 May 9
Benign metastasizing leiomyoma responsive to megestrol: case report and review of the literature.
2005 Nov-Dec
The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment.
2005 Oct 4
[Isolation and identification of two new epimer from the mother liquid of megestrol acetate].
2005 Sep
Review of cost-effectiveness analyses in hormonal therapies in advanced breast cancer.
2005 Sep
Bleeding patterns during continuous estradiol with different sequential progestogens therapy.
2005 Sep-Oct
Progestogens: effects on clinical and biochemical parameters in postmenopausal women.
2005 Sep-Oct
Letrozole: a pharmacoeconomic review of its use in postmenopausal women with breast cancer.
2006
Megestrol attenuates the hormonal response to CCK-4-induced panic attacks.
2006
Hepatocellular carcinoma--Pathological complete response to oral capecitabine, megestrol and thalidomide.
2006
Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year.
2006 Dec
Durable response of metastatic endometrial carcinoma to treatment with fulvestrant (Faslodex) after prior progestin and anastrozole therapy.
2006 Feb
Effects of estrogen, raloxifene, and hormone replacement therapy on serum C-reactive protein and homocysteine levels.
2006 Feb 20
Nanoparticles of poorly water-soluble drugs prepared by supercritical fluid extraction of emulsions.
2006 Jan
Short-term progestin treatments prevent estrous induction by a GnRH agonist implant in anestrous bitches.
2006 Jan 20
Orchiectomy or androgen receptor blockade attenuates baroreflex-mediated bradycardia in conscious rats.
2006 Jan 23
A successful live birth through in vitro fertilization program after conservative treatment of FIGO grade I endometrial cancer.
2006 Jun
Characterization of related impurities in megestrol acetate.
2006 Jun 16
Second- and third-generation aromatase inhibitors as first-line endocrine therapy in postmenopausal metastatic breast cancer patients: a pooled analysis of the randomised trials.
2006 Jun 19
Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimenopausal women.
2006 Mar-Apr
New progestagens for contraceptive use.
2006 Mar-Apr
[Pharmacological therapy of cancer anorexia-cachexia].
2006 May
Activation of nitric oxide synthesis in human endothelial cells using nomegestrol acetate.
2006 Oct
Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.
2007 Feb
Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women.
2007 May-Jun
Patents

Patents

Sample Use Guides

Oral Suspension is 800 mg/day (20 mL/day). In clinical trials evaluating different dose schedules, daily doses of 400 and 800 mg/day.
Route of Administration: Oral
Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC (50) of 260 uM (24-h incubation)
Name Type Language
MEGESTROL
HSDB   INN   VANDF   WHO-DD  
INN  
Official Name English
MEGESTROL [WHO-DD]
Common Name English
MEGESTROL [VANDF]
Common Name English
MEGESTROL [HSDB]
Common Name English
MEGESTROL ACETATE SPECIFIED IMPURITY B [EP]
Common Name English
17-HYDROXY-6-METHYLPREGNA-4,6-DIENE-3,20-DIONE
Systematic Name English
CHRONOPIL
Brand Name English
MEGESTROL [INN]
Common Name English
Classification Tree Code System Code
WHO-VATC QG03AC05
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03AC05
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
LIVERTOX 593
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03FB04
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
CFR 21 CFR 520.1341
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
NCI_THESAURUS C776
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QG03DB02
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03FA08
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC L02AB01
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QG03FA08
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03AB01
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QG03AB01
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
NDF-RT N0000175602
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03DB02
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QL02AB01
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
NDF-RT N0000011301
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QG03FB04
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-ATC G03AA04
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
WHO-VATC QG03AA04
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
Code System Code Type Description
INN
1529
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
NCI_THESAURUS
C630
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
RXCUI
6703
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY RxNorm
HSDB
3233
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
FDA UNII
EA6LD1M70M
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201139
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
WIKIPEDIA
MEGESTROL
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
CAS
3562-63-8
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
EVMPD
SUB08712MIG
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
PUBCHEM
19090
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
ECHA (EC/EINECS)
222-628-6
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY
MESH
D008535
Created by admin on Sat Jun 26 01:14:24 UTC 2021 , Edited by admin on Sat Jun 26 01:14:24 UTC 2021
PRIMARY