      Document 0184
 DOCN  DRG0184
 UNIQUE IDENTIFIER        DRG-0063
 NAME OF SUBSTANCE        Megestrol acetate [USAN 1996]
 REGISTRY NUMBER          595-33-5
 RELATED REGISTRY NUMBER  3562-63-8
 STANDARD CHEMICAL NAME   Pregna-4,6-diene-3,20-dione,
                          17-(acetyloxy)-6-methyl- [USAN 1996]
 SYNONYMS                 Megace [USAN 1996]
 SYNONYMS                 Ovaban [USAN 1996]
 SYNONYMS                 Niagestin [Merck Index 1989]
 SYNONYMS                 6-Dehydro-6-methyl-17alpha-acetoxyprogesteron-
                          e [Merck Index 1989]
 SYNONYMS                 6-Methyl-Delta-4,6-pregnadien-17-alpha-ol-3,2-
                          0-dione acetate [Merck Index 1989]
 SYNONYMS                 Maygace [Merck Index 1989]
 SYNONYMS                 Megestat [Merck Index 1989]
 SYNONYMS                 Nia [Merck Index 1989]
 SYNONYMS                 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dion-
                          e acetate [USAN 1996]
 SYNONYMS                 17-Alpha-acetoxy-6-methylpregna-4,6-diene-3,2-
                          0-dione [Merck Index 1989]
 PROTOCOL ID NUMBERS      FDA 025A
 PROTOCOL ID NUMBERS      FDA 025B
 PROTOCOL ID NUMBERS      NIAID DATRI 004
 PROTOCOL ID NUMBERS      FDA 025C
 SECONDARY SOURCE ID      NSC-71423 [USAN 1996]
 SECONDARY SOURCE ID      SC 10363 [USAN 1996]
 SECONDARY SOURCE ID      5071 [USAN 1996]
 SECONDARY SOURCE ID      BDH 1298 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Megestrol acetate shares the
                          actions of the progestins: induction of
                          secretory changes in the endometrium,
                          increase in basal body temperature, pituitary
                          inhibition,and production of withdrawal
                          bleeding in the presence of estrogen.
                          Megestrol acetate has slight glucocorticoid
                          activity but no estrogenic, androgenic or
                          anabolic activities. The exact mechanism of
                          its antineoplastic action has not been
                          determined. It has been suggested that such
                          action may result fron suppression of
                          luteinizing hormone by inhibition of
                          pituitary function. The mechanism for
                          megestrol-induced weight gain has not been
                          clearly established, but the activity may be
                          related to the drug's appetite stimulant or
                          metabolic effects rather than its
                          glucocorticoid-like effects or the production
                          of edema. It may alter metabolic pathways via
                          interference with the production or action of
                          mediators such as cachectin (a hormone that
                          inhibits adipocyte lipogenic enzymes). The
                          drug is well absorbed from the GI tract; peak
                          plasma concentrations of the drug and its
                          metabolite were obtained in 1-5 hours.
                          Following daily, single 800 mg doses of
                          megestrol acetate to cachectic AIDS patients,
                          steady-state peak plasma concentration
                          occurred 5 hours after administration and
                          averaged 753 ng/ml. 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. [AHFS Drug Information
                          1995]
 DISEASES STUDIED/TREATED FDA approved 9/10/93 for treatment of
                          anorexia, cachexia, and unexplained
                          substantial weight loss in patients with AIDS
                          [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Designated an orphan drug by the FDA for this
                          use [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 CLASSIFICATION CODE      Appetite stimulant [PDR 1995]
 OTHER MAJOR USES         Palliative management of endometrial or
                          breast carcinoma. Megestrol acetate has been
                          used alone or in combination with estrogens
                          for ovulation control, in the prevention of
                          conception, and in the treatment of prostatic
                          hypertrophy, endometriosis and endometrial
                          hyperplasia (not currently in FDA-approved
                          labeling). [AHFS Drug Information 1995]
 SUBSTANCE INTERACTIONS   Possible interactions of megestrol acetate
                          with concomitant medications have not been
                          investigated. [PDR 1995]
 ADVERSE EFFECTS          Megestrol acetate is usually well tolerated.
                          Adverse GI effects occurring in at least 5%
                          of patients include diarrhea, flatulence,
                          nausea and vomiting. Genitourinary effects
                          such as impotence and decreased libido were
                          reported in 5% of AIDS patients receiving the
                          drug for cachexia. Hypertension and mild
                          elevation in blood pressure have been
                          reported in patients receiving high doses
                          (480-1600 mg daily). Among other effects,
                          fever, anemia, leukopenia, hepatomegaly,
                          pain, infections, candidiasis, herpes,
                          pruritus, sweating, skin disorders and
                          increase in LDH were reported. [AHFS Drug
                          Information 1995]
 CONTRAINDICATIONS        Contraindicated as a diagnostic test for
                          pregnancy. Should not be used during
                          pregnancy. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic derivative of
                          the naturally occurring steroid hormone
                          progesterone [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C24H32O4 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 384.5 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 214-216 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: (37 C) water, 2 mcg/ml; plasma,
                          24 mcg/ml [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White crystalline solid
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C74.97%, H8.39%,
                          O16.65% [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Lemon-lime flavored suspension
                          containing 40 mg megestrol acetate per ml.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at or below 25 C. Protect from
                          heat. [PDR 1995]
 MANUFACTURERS            Bristol-Myers
 MANUFACTURERS            Mead Johnson
 MANUFACTURERS            Schering Plough
 REFERENCES               Von Roenn JH. Randomized trials of megestrol
                          acetate for AIDS-associated anorexia and
                          cachexia. Oncology. 1994 Oct;51 Suppl
                          1:19-24.
 REFERENCES               Von Roenn JH, Armstrong D, Kotler DP, Cohn
                          DL, Klimas NG, Tchekmedyian NS, Cone L,
                          Brennan PJ, Weitzman SA. Megestrol acetate in
                          patients with AIDS-related cachexia. Ann
                          Inter Med. 1994 Sep 15;121(6)393-9.
 REFERENCES               Oster MH, Enders SR, Samuels SJ, Cone LA,
                          Hooton TM, Browder HP, Flynn NM. Megestrol
                          acetate in patients with AIDS and cachexia.
                          Ann Inter Med. 1994 Sep 15;121(6):400-8.
 REFERENCES               Vigano M, Danise A, Novati R, Finazzi R,
                          Gaiera G, Lazzarin A. A pilot Italian study
                          with megestrol acetate (MA) in AIDS-related
                          cachexia. Int Conf AIDS. 1994 Aug
                          7-12;10(2):224 (abstract no. PB0908).
 REFERENCES               Graham KK, Mikolich DJ, Fisher AE, Posner MR,
                          Dudley MN. Pharmacologic evaluation of
                          megestrol acetate oral suspension in
                          cachectic AIDS patients. J Acquir Immune
                          Defic Syndr. 1994 Jun;7(6):580-6.
 REFERENCES               Engelson ES, Tierney AR, Pi-Sunyer FX, Kotler
                          DP. Effects of megestrol acetate therapy upon
                          body composition and serum testosterone in
                          AIDS. Int Conf AIDS. 1994 Aug 7-12;10(2):222
                          (abstract no. PB0900).
 REFERENCES               Berman S, Katz K, Ho M, Nakasato S. Megestrol
                          acetate produces weight gain in HIV+
                          patients. Int Conf AIDS 1993 Jun
                          6-11;9(1):499 (abstract no. PO-B29-2186).
 REFERENCES               Oster M, Enders S, Samuels S, Cone L, Hooton
                          T, Browder H, Flynn N. Randomized
                          double-blind study comparing high-dose
                          megestrol acetate and placebo in cachectic
                          patients with acquired immunodeficiency
                          syndrome (AIDS). Int Conf AIDS. 1993 Jun
                          6-11;9(1):528 (abstract mp/ PO-B36-2360).
 REFERENCES               Orzechowski A, del Rio C, Tellez I. Weight
                          gain with the use of megace in patients with
                          AIDS in Mexico. Int Conf AIDS. 1992 Jul
                          19-24;8(3):115 (abstract no. PuB 7397).
 REFERENCES               Flynn N, Enders S, Oster M, Cone L, Hooten T.
                          Megestrol acetate 800 mg/day vs placebo for
                          treatment of weight loss and anorexia in AIDS
                          patients. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B205 (abstract no. PoB 3687).
 ENTRY MONTH              8911
 LAST REVISION DATE       951107
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
