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Brand Name: Megace Oral Suspension, Megace ES  |
Drug Class: Opportunistic Infection and Other Drugs
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Drug Description |
| Megestrol acetate is a synthetic derivative of the naturally occurring steroid hormone, progesterone.[1] |
HIV/AIDS-Related Uses |
Megestrol acetate was approved by the FDA on September 10, 1993, for use in the management of anorexia, cachexia, and unexplained substantial weight loss in patients with HIV and AIDS. The FDA has designated it an orphan drug for this use.[2]
In clinical trials, megestrol acetate in 800 mg daily doses experienced appetite and weight gain, despite caloric intakes similar to those of control groups. Weight gain was associated with nonwater body weight. HIV patients also reported subjective improvement in their sense of well-being during megestrol therapy.[3] |
Non HIV/AIDS-Related Uses |
| Megestrol acetate is used in palliative management of recurrent, inoperable, or metastatic endometrial or breast carcinoma. Megestrol acetate is also used as an adjunct to surgery or radiation. Megestrol acetate is not currently recommended for use in other neoplastic disease, but additional studies are underway.[4] |
Dosing Information |
Mode of Delivery |
| Oral.[5] |
Dosage Form |
Oral suspension containing micronized megestrol acetate 40 mg/ml.[6]
Concentrated oral suspension containing megestrol acetate 125 mg/ml.[7] |
Storage |
Store tablets in well-closed containers at less than 40 C (104 F), preferably between 15 C and 30 C (59 F to 86 F).[8]
Store oral suspension in tight containers at 25 C (77 F) or less.[9]
Store concentrated oral suspension between 15 C and 25 C (59 F to 77 F), dispense in a tight container, and protect from heat.[10] |
Pharmacology |
Weight gain is induced by megestrol acetate and is likely related to the drug's appetite-stimulant and/or metabolic effects. Megestrol acetate and/or its metabolites may either directly or indirectly stimulate appetite, resulting in weight gain, or may alter metabolic pathways via interference with the production or action of mediators such as cachectin (a hormone that inhibits adipocyte lipogenic enzymes).[11]
The exact mechanism of the antineoplastic action of megestrol acetate has not been determined. The antineoplastic effect may result from suppression of luteinizing hormone by inhibition of pituitary function. Results of one clinical study suggested that megestrol acetate produced a local effect on the cancerous cell by converting the actively growing stroma into decidua.[12]
The drug is well absorbed from the gastrointestinal (GI) tract; peak plasma concentrations (Cmax) of the drug were obtained in 1 to 5 hours. Following daily single 800 mg doses of megestrol acetate to cachectic AIDS patients, steady-state Cmax on day 21 occurred 5 hours after administration and averaged 753 ng/ml.[13]
Megestrol acetate oral suspension is in FDA Pregnancy Category X; the tablet form is in Category D. The drug may cause fetal harm when administered to a pregnant woman. Although there have been no adequate or well-controlled studies in pregnant women, results from studies in pregnant rats given high doses of megestrol acetate showed decreased fetal birth weight, fewer live births, and reversible feminization of some male fetuses.[14][15]
Progestins, including megestrol acetate, are distributed into breast milk.[16] Because of the potential for transmission of HIV from the mother and for serious adverse effects from megestrol acetate to the breast-fed infant, women should be instructed not to breast-feed while taking megestrol acetate.[17]
The drug is completely metabolized in the liver to free steroids and glucuronides of steroidal metabolites. The major route of elimination appears to be urinary excretion. Following oral administration of radiolabeled megestrol acetate, about 66% of the dose was excreted in urine and about 20% was excreted as feces within 10 days.[18] |
Adverse Events/Toxicity |
Because of increased genital abnormalities caused by progestins in male and female fetuses, the manufacturer states that megestrol acetate is not recommended during pregnancy. Women of childbearing potential who are receiving megestrol acetate therapy should be advised not to become pregnant and to use an effective form of contraception while receiving the drug.[19]
Megestrol acetate is usually well tolerated. Adverse reactions occurring in more than 5% of patients include diarrhea, flatulence, nausea, vomiting, impotence, decreased libido, rash, and hypertension. Hypertension has been reported to resolve following initiation of diuretic therapy or adjustment of patient's pre-existing antihypertensive regimen.[20]
Postmarketing reports associate megestrol acetate with thrombophlebitis, pulmonary embolism, glucose intolerance, and diabetes mellitus.[21]
Pneumonia has been reported in 2% of patients receiving megestrol acetate for AIDS-related cachexia. Nervous system effects reported in patients receiving megestrol acetate for AIDS-related cachexia include insomnia, headache, asthenia, paresthesia, confusion, seizure, depression, neuropathy, hypesthesia, and abnormal thinking. Other adverse effects reported among patients being treated for AIDS-related cachexia include fever, anemia, leukopenia, hepatomegaly, abdominal pain, infections, candidiasis, herpes, pruritus, vesiculobullous rash, sweating, skin disorders, amblyopia, increase in LDH, and sarcoma.[22] |
Drug And Food Interactions |
| Pharmacokinetic studies show that there are no significant alterations in the pharmacokinetic parameters of zidovudine or rifabutin that would warrant dosage adjustment when megestrol acetate is coadministered. The effects of zidovudine or rifabutin on the pharmacokinetics of megestrol were not studied.[23] |
Contraindications |
| Megestrol acetate should not be used in individuals with a history of hypersensitivity to megestrol acetate or to any component of the formulations. In addition, it should not be used during pregnancy or while nursing. It is contraindicated as a test for pregnancy.[24] |
Clinical Trials |
| Click here to search ClinicalTrials.gov for trials that use Megestrol acetate. |
Chemistry |
CAS Name |
| Pregna-4,6-diene-3,20-dione, 17-(acetyloxy)-6-methyl-, acetate[25] |
CAS Number |
| 595-33-5[26] |
Molecular Formula |
| C24-H32-O4[27] |
Elemental Composition |
| C74.97%, H8.39%, O16.64%[28] |
Molecular Weight |
| 384.51[29] |
Melting Point |
| 214-216 C[30] |
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Physical Description |
| White crystalline solid.[31] |
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Solubility |
| 2 mcg/ml in water (37 C); 24 mcg/ml in plasma.[32] |
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Further Reading |
Megace Tablets - FDA Oncology Tools Product Label [html]. A more current version may be available on the manufacturer's Web site.
Megace ES Oral Suspension Prescribing Information from the FDA Web site [PDF]. A more current version may be available on the manufacturer's Web site.
PMID/11454075 Batterham MJ, Garsia R. A comparison of megestrol acetate, nandrolone decanoate and dietary counseling for HIV associated weight loss. Int J Androl 2001 Aug;24(4):232-40.
PMID/16215131 Mwamburi DM, Gerrior J, Wilson IB, Chang H, Scully E, Saboori S, Miller L, Forfia J, Albrecht M, Wanke CA. Combination megestrol acetate, oxandrolone, and dietary advice restores weight in human immunodeficiency virus. Nutr Clin Pract. 2004 Aug;19(4):395-402.
PMID/14999637 Mwamburi DM, Gerrior J, Wilson IB, Chang H, Scully E, Saboori S, Miller L, Forfia J, Albrecht M, Wanke CA. Comparing megestrol acetate therapy with oxandrolone therapy for HIV-related weight loss: similar results in 2 months. Clin Infect Dis. 2004 Mar 15;38(6):895-902. Epub 2004 Mar 01.
PMID/15050664 Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M. Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9. Review.
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Manufacturer Information |
Megestrol acetate
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
(800) 828-9393
Megace Oral Suspension
Bristol - Myers Squibb Co
PO Box 4500
Princeton, NJ 08543-4500
(800) 321-1335
Megace ES
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
(800) 828-9393
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References |
[1] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, p. 1. Available at: http://www.bms.com. Accessed 03/27/07.
[2] AHFS Drug Information - 2007; p. 1123
[3] AHFS Drug Information - 2007; p. 1123
[4] AHFS Drug Information - 2007; p. 1123
[5] USP DI - 2005; p. 2474
[6] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, p. 12. Available at: http://www.bms.com. Accessed 03/27/07.
[7] FDA - Megace ES Oral Suspension Prescribing Information, May 2005, p. 10. Available at: http://www.fda.gov/cder/foi/label/2005/021778lbl.pdf. Accessed 03/27/07.
[8] AHFS Drug Information - 2007; p. 1125
[9] AHFS Drug Information - 2007; p. 1125
[10] FDA - Megace ES Oral Suspension Prescribing Information, May 2005, p. 11. Available at: http://www.fda.gov/cder/foi/label/2005/021778lbl.pdf. Accessed 03/27/07.
[11] AHFS Drug Information - 2007; p. 1125
[12] AHFS Drug Information - 2007; p. 1125
[13] AHFS Drug Information - 2007; p. 1125
[14] USP DI - 2005; p. 2467
[15] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, p. 9. Available at: http://www.bms.com. Accessed 03/27/07.
[16] USP DI - 2005; p. 2467
[17] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, p. 9. Available at: http://www.bms.com. Accessed 03/27/07.
[18] AHFS Drug Information - 2007; p. 1125
[19] AHFS Drug Information - 2007; pp. 1124-5
[20] AHFS Drug Information - 2007; p. 1124
[21] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, pp. 6, 11. Available at: http://www.bms.com. Accessed 03/27/07.
[22] AHFS Drug Information - 2007; p. 1124
[23] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, pp. 7, 11. Available at: http://www.bms.com. Accessed 03/27/07.
[24] Bristol-Myers Squibb - Megace Oral Suspension Prescribing Information, January 2005, pp. 6, 11. Available at: http://www.bms.com. Accessed 03/27/07.
[25] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 03/27/07.
[26] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 03/27/07.
[27] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 03/27/07.
[28] Merck Index - 2006; p. 1003
[29] Merck Index - 2006; p. 1003
[30] Merck Index - 2006; p. 1003
[31] FDA - Megace ES Oral Suspension Prescribing Information, May 2005, p. 1. Available at: http://www.fda.gov/cder/foi/label/2005/021778lbl.pdf. Accessed 03/27/07.
[32] Merck Index - 2006; p. 1003
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Updated April 9, 2007
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