Absorption, Distribution and Excretion
Megestrol acetate appears to be well absorbed from the GI tract. The relative oral bioavailability of megestrol acetate suspensions and tablets has not been evaluated.
Plasma megestrol acetate concentrations achieved with a 625-mg dose of the more 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.
The effect of food on the bioavailability of Megestrol Acetate Oral Suspension has not been evaluated.
Peak concentrations and AUC were 54.8 and 43.3% higher, respectively, under fed conditions compared with fasting for the concentrated suspension and were 12.9 and 24.4% higher, respectively, under fed conditions compared with fasting for the original formulation.
For more Absorption, Distribution and Excretion (Complete) data for MEGESTROL (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
Megestrol acetate appears to be completely metabolized in the liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, and 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione.
Completely metabolized in liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, & 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione /Human, oral/

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Biological Half-Life
Plasma elimination half-life ranged from 13 to 104.9 hours (mean 34.2 hours).

Interactions
Progestins may cause amenorrhea and/or galactorrhea, interfering with effects of bromocriptine; concurrent use is not recommended. /Progestins/
/Investigators/ evaluated the multidrug resistance modulating effects of progesterone and an orally active, structurally related compound, megestrol acetate, in several multidrug resistance human cell lines. At 100 uM, both steroids inhibited the binding of a Vinca alkaloid photoaffinity analog to p-glycoprotein in multidrug resistance human neuroblastic SH-SY5Y/VCR cells (which show treater than 1500 fold resistance to vincristine in the tetrazolium dye assay). However, 100 uM markedly enhanced the binding of (3)H azidopine to p-glycoprotein. Megestrol acetate at low doses was more effective than progesterone in sensitizing cells to vincristine and enhancing their accumulation of (3)H vincristine. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that megestrol acetate may be a clinically useful modulator of multidrug resistance.

[1]. Off-Label Megestrol in Patients with Anorexia-Cachexia Syndrome Associated with Malignancy and Its Treatments. Am J Med. 2018 Jun;131(6):623-629.e1.

Therapeutic Uses
Antineoplastic Agents, Hormonal; Progestational Hormones, Synthetic
Megestrol Acetate Tablets USP are indicated for the palliative treatment of advanced carcinoma of the breast or endometrium (ie, recurrent, inoperable, or metastatic disease). It should not be used in lieu of currently accepted procedures such as surgery, radiation, or chemotherapy. /Included in US product label/
Megestrol Acetate Oral Suspension USP is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). /Included in US product label/
Anorexia is a common disorder in patients treated with regular hemodialysis and is a contributing factor to malnutrition. The aim of this study was to evaluate the effectiveness of megestrol acetate, an appetite stimulant used in cancer patients, as a treatment for anorexia in dialysis patients. ... 16 patients in /a/ hemodialysis unit, three with diabetes mellitus, were treated with megestrol (160 mg/day single dose) for anorexia defined according to a Likert scale of appetite. The schedule and dialysis dose were not changed during the study. In the third month of treatment there was, in the overall group, an increase in dry weight (60.8 vs 58.9 kg, P<.01), in albumin concentration (4.02 vs 3.8 g/dL, P<.05), in creatinine concentration (9.73 vs 8.26 mg/dL, P<.01), and protein catabolic rate (1.24 vs. 0.97 g/kg/day, P<.0001). Non-significant variations in the concentration of hemoglobin, erythropoietin dose, and lipid concentrations were found. One patient with diabetes mellitus had to increase the dose of insulin and two other patients suffered mild hyperglycaemia. Megestrol acetate did not suppress the secretion of pituitary sex hormones, but in 3 of 10 patients studied was found inhibition of ACTH secretion. The response was not homogeneous: one patient did not respond and reduced his dry weight, in 5 the weight gain was minimal (less than 1 kg) and in the remaining ten the response was good, with an increase in dry weight ranging between 1.5 and 5.5 kg. Megestrol acetate can improve appetite and nutritional parameters in patients treated with periodic hemodialysis who report anorexia. Megestrol acetate may induce hyperglycaemia and inhibit the secretion of ACTH in some patients. These side effects should be assessed when administering this treatment.
For more Therapeutic Uses (Complete) data for MEGESTROL (8 total), please visit the HSDB record page.

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Drug Warnings
The glucocorticoid activity of megestrol acetate tablets has not been fully evaluated. Clinical cases of new onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and overt Cushing's syndrome have been reported in association with the chronic use of megestrol acetate. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate 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 acetate therapy. Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic megestrol acetate therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (eg, hypotension, nausea, vomiting, dizziness, or weakness) in either the stressed or non-stressed state. Laboratory evaluation for adrenal insufficiency and consideration of replacement or stress doses of a rapidly acting glucocorticoid are strongly recommended in such patients. Failure to recognize inhibition of the hypothalamic-pituitary-adrenal axis may result in death. Finally, in patients who are receiving or being withdrawn from chronic megestrol acetate therapy, consideration should be given to the use of empiric therapy with stress doses of a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (eg, surgery, infection).
Close surveillance is indicated for any patient treated for recurrent or metastatic cancer. Use with caution in patients with a history of thromboembolic disease.
/Megestrol is contraindicated in patients with a/ history of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy.
Exacerbation of pre-existing diabetes with increased insulin requirements have been reported in association with the use of megestrol acetate.
For more Drug Warnings (Complete) data for MEGESTROL (26 total), please visit the HSDB record page.

C22H30O3

342.479

342.219

3562-63-8

Megestrol acetate;595-33-5;Megestrol-d5

19090

White to off-white solid powder

1.2±0.1 g/cm3

500.4±50.0 °C at 760 mmHg

270.5±26.6 °C

0.0±2.9 mmHg at 25°C

1.569

3.06

1

3

1

25

717

6

CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)O)C)[C@@]4(C1=CC(=O)CC4)C

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

(8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-3-one

BDH1298; BDH 1298

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~70 mg/mL (~204.40 mM)

Solubility in Formulation 1: 2.33 mg/mL (6.80 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.33 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.33 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)