Megestrol acetate, also known as Megace, is a type of medicine called an anticachectic. Anticachectics are drugs that cause weight gain.
HIV/AIDS-Related Uses
Megestrol acetate was approved by the FDA on September 10, 1993, for use in the treatment of significant AIDS-related weight loss. This medicine does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.
Dosage Form/Administration
Megestrol acetate comes in tablet and oral suspension form and is taken by mouth.
Contraindications
Individuals should tell a doctor about any medical problems before taking this medicine.
Possible Side Effects
Along with its desired effects, megestrol acetate can cause some unwanted effects. Serious side effects of this medicine include high blood pressure, diabetes, inflammation of the blood vessels, congestive heart failure, seizures, and pneumonia. Individuals should tell a doctor if they have symptoms of any of these side effects.Other side effects may not be serious and may lessen or disappear with continued use of the medicine. Less serious side effects of this medicine include diarrhea, excess gas, nausea, vomiting, constipation, heartburn, dry mouth, increased salivation, and thrush; impotence or decreased sex drive; frequent urination, urinary incontinence, urinary tract infection, and vaginal bleeding and discharge (including breakthrough bleeding); disease of the heart muscle, palpitation, chest pain, chest pressure, and swelling; shortness of breath, cough, sore throat, lung disorders, and rapid breathing; trouble sleeping; headache; weakness; numbness; and confusion, seizures, depression, and abnormal thinking. Individuals should tell a doctor if these side effects continue or are bothersome.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Megestrol acetate.
Manufacturer Information
Megace ES
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
Phone: 800-828-9393
Megace Oral Suspension
Bristol - Myers Squibb Co
PO Box 4500
Princeton, NJ 08543-4500
Phone: 800-321-1335
Megestrol acetate
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
Phone: 800-828-9393
Last Updated: April 9, 2007
Drug Description
Megestrol acetate is a synthetic derivative of the naturally occurring steroid hormone, progesterone. [1]
References
[1] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, p. 1. Available at: http://www.bms.com. Accessed 03/27/07.
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. [1]
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. [2]
References
[1] AHFS Drug Information 2007; p. 1123
[2] AHFS Drug Information 2007; p. 1123
Dosing Information
Mode of Delivery
Oral. [1]
Dosage Form
Oral suspension containing micronized megestrol acetate 40 mg/ml. [2]
Concentrated oral suspension containing megestrol acetate 125 mg/ml. [3]
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). [4]
Store oral suspension in tight containers at 25 C (77 F) or less. [5]
Store concentrated oral suspension between 15 C and 25 C (59 F to 77 F), dispense in a tight container, and protect from heat. [6]
References
[1] USP DI 2005; p. 2474
[2] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, p. 12. Available at: http://www.bms.com. Accessed 03/27/07.
[3] FDA Megace ES Oral Suspension Prescribing Information, May 2005, p. 10. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021778s002s003lbl.pdf. Accessed 03/27/07.
[4] AHFS Drug Information 2007; p. 1125
[5] AHFS Drug Information 2007; p. 1125
[6] FDA Megace ES Oral Suspension Prescribing Information, May 2005, p. 11. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021778s002s003lbl.pdf. Accessed 03/27/07.
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). [1]
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. [2]
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. [3]
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. [4] [5]
Progestins, including megestrol acetate, are distributed into breast milk. [6] 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. [7]
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. [8]
References
[1] AHFS Drug Information 2007; p. 1125
[2] AHFS Drug Information 2007; p. 1125
[3] AHFS Drug Information 2007; p. 1125
[4] USP DI 2005; p. 2467
[5] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, p. 9. Available at: http://www.bms.com. Accessed 03/27/07.
[6] USP DI 2005; p. 2467
[7] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, p. 9. Available at: http://www.bms.com. Accessed 03/27/07.
[8] AHFS Drug Information 2007; p. 1125
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. [1]
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. [2]
Postmarketing reports associate megestrol acetate with thrombophlebitis, pulmonary embolism, glucose intolerance, and diabetes mellitus. [3]
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. [4]
References
[1] AHFS Drug Information 2007; pp. 1124-5
[2] AHFS Drug Information 2007; p. 1124
[3] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, pp. 6, 11. Available at: http://www.bms.com. Accessed 03/27/07.
[4] AHFS Drug Information 2007; p. 1124
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. [1]
References
[1] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, pp. 7, 11. Available at: http://www.bms.com. Accessed 03/27/07.
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. [1]
References
[1] Bristol-Myers Squibb Megace Oral Suspension Prescribing Information, January 2005, pp. 6, 11. Available at: http://www.bms.com. Accessed 03/27/07.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use Acetato de megestrol.
Chemistry
CAS Name
Pregna-4,6-diene-3,20-dione, 17-(acetyloxy)-6-methyl-, acetate [1]
CAS Number
595-33-5 [2]
Molecular Formula
C24-H32-O4
Elemental Composition
C74.97%, H8.39%, O16.64%
Molecular Weight
384.51
Melting Point
214-216 C
Physical Description
White crystalline solid. [3]
Solubility
2 mcg/ml in water (37 C); 24 mcg/ml in plasma. [4]
References
[1] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 03/27/07.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 03/27/07.
[3] FDA Megace ES Oral Suspension Prescribing Information, May 2005, p. 1. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021778s002s003lbl.pdf. Accessed 03/27/07.
[4] Merck Index 2006; p. 1003
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.
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.
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.
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.
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.
Manufacturer Information
Megace ES
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
Phone: 800-828-9393
Megace Oral Suspension
Bristol - Myers Squibb Co
PO Box 4500
Princeton, NJ 08543-4500
Phone: 800-321-1335
Megestrol acetate
Par Pharmaceutical, Inc
One Ram Ridge Road
Spring Valley, NY 10977
Phone: 800-828-9393
Last Updated: April 9, 2007