Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1554
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MEGACE (Suspension)
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| dailymed-instance:dosage |
The recommended adult initial dosage of MEGACE Oral Suspension
is 800 mg/day (20 mL/day). Shake container well before using. In clinical trials evaluating different dose schedules, daily doses
of 400 and 800 mg/day were found to be clinically effective. A plastic dosage cup with 10 mL and 20 mL markings is provided
for convenience.
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| dailymed-instance:descripti... |
MEGACE (megestrol acetate, USP) Oral
Suspension contains megestrol acetate, a synthetic derivative of the naturally
occurring steroid hormone, progesterone. Megestrol acetate is a white, crystalline
solid chemically designated as 17��-(acetyloxy)-6-methylpregna-4,6-diene-3,20-dione.
Solubility at 37��C in water is 2��g per mL, solubility in plasma is 24��g
per mL. Its molecular weight is 384.51. The empirical formula is CHOand
the structural formula is represented as follows: MEGACE Oral Suspension is supplied as an oral suspension containing
40 mg of micronized megestrol acetate per mL. MEGACE Oral Suspension contains the following inactive ingredients:
alcohol (max. 0.06% v/v from flavor), citric acid, lemon-lime flavor, polyethylene
glycol, polysorbate 80, purified water, sodium benzoate, sodium citrate, sucrose
and xanthan gum.
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Several investigators have reported on the appetite enhancing property
of megestrol acetate and its possible use in cachexia. The precise mechanism
by which megestrol acetate produces effects in anorexia and cachexia is unknown
at the present time. There are several analytical methods used to estimate megestrol
acetate plasma concentrations, including gas chromatography-mass fragmentography
(GC-MF), high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA).
The GC-MF and HPLC methods are specific for megestrol acetate and yield equivalent
concentrations. The RIA method reacts to megestrol acetate metabolites and
is, therefore, non-specific and indicates higher concentrations than the GC-MF
and HPLC methods. Plasma concentrations are dependent, not only on the method
used, but also on intestinal and hepatic inactivation of the drug, which may
be affected by factors such as intestinal tract motility, intestinal bacteria,
antibiotics administered, body weight, diet and liver function. 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 (megestrol acetate,
USP) Oral Suspension for 21 days. Plasma concentration data obtained on day
21 were evaluated for up to 48 hours past the last dose. Mean (��1SD) peak plasma concentration (C)
of megestrol acetate was 753 (��539) ng/mL. Mean area under the concentration
time-curve (AUC) was 10476 (��7788) ng��hr/mL. Median Tvalue
was five hours. Seven of 10 patients gained weight in three weeks. Additionally, 24 adult, asymptomatic HIV seropositive male subjects
were dosed once daily with 750 mg of MEGACE Oral Suspension. The treatment
was administered for 14 days. Mean Cand AUC values
were 490 (��238) ng/mL and 6779 (��3048) hr��ng/mL, respectively. The median
Tvalue was three hours. The mean Cvalue
was 202 (��101) ng/mL. The mean percent of fluctuation value was 107 (��40). The effect of food on the bioavailability of MEGACE Oral Suspension
has not been evaluated.
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History of hypersensitivity to megestrol acetate or any component
of the formulation. Known or suspected pregnancy.
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| dailymed-instance:supply |
MEGACE (megestrol acetate, USP) Oral
Suspension is available as a lemon-lime flavored oral suspension containing
40 mg of micronized megestrol acetate per mL. NDC 0015-0508-42 Bottles of 240 mL
(8 fl. oz.)
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| dailymed-instance:inactiveI... |
dailymed-ingredient:alcohol,
dailymed-ingredient:citric_acid,
dailymed-ingredient:lemon-lime_flavor,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:polysorbate_80,
dailymed-ingredient:sodium_benzoate,
dailymed-ingredient:sodium_citrate,
dailymed-ingredient:sucrose,
dailymed-ingredient:water,
dailymed-ingredient:xanthan_gum
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| dailymed-instance:precautio... |
General: Therapy with MEGACE Oral Suspension for weight loss should only
be instituted after treatable causes of weight loss are sought and addressed.
These treatable causes include possible malignancies, systemic infections,
gastrointestinal disorders affecting absorption, endocrine disease and renal
or psychiatric diseases. Effects on HIV viral replication have not been determined. Use with caution in patients with a history of thromboembolic disease.<br/>Use in Diabetics: Exacerbation of preexisting diabetes with increased insulin requirements
has been reported in association with the use of MEGACE.<br/>Information for Patients: Patients using megestrol acetate should receive the following instructions:<br/>Drug Interactions: Pharmacokinetic studies show that there are no significant alterations
in pharmacokinetic parameters of zidovudine or rifabutin to warrant dosage
adjustment when megestrol acetate is administered with these drugs. The effects
of zidovudine or rifabutin on the pharmacokinetics of megestrol acetate were
not studied.<br/>Animal Toxicology: Long-term treatment with MEGACE may increase the risk of respiratory
infections. A trend toward increased frequency of respiratory infections,
decreased lymphocyte counts and increased neutrophil counts was observed in
a two-year chronic toxicity/carcinogenicity study of megestrol acetate conducted
in rats.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Carcinogenesis: Data on carcinogenesis were obtained from studies conducted in
dogs, monkeys and rats treated with megestrol acetate at doses 53.2, 26.6
and 1.3 times lower than the proposed dose (13.3 mg/kg/day)
for humans. No males were used in the dog and monkey studies. In female beagles,
megestrol acetate (0.01, 0.1 or 0.25 mg/kg/day) administered for up to 7 years
induced both benign and malignant tumors of the breast. In female monkeys,
no tumors were found following 10 years of treatment with 0.01, 0.1 or 0.5
mg/kg/day megestrol acetate. Pituitary tumors were observed in female rats
treated with 3.9 or 10 mg/kg/day of megestrol acetate for 2 years. The relationship
of these tumors in rats and dogs to humans is unknown but should be considered
in assessing the risk-to-benefit ratio when prescribing MEGACE Oral Suspension
and in surveillance of patients on therapy.<br/>Mutagenesis: No mutagenesis data are currently available.<br/>Impairment of Fertility: Perinatal/postnatal (segment III) toxicity studies were performed
in rats at doses (0.05���12.5 mg/kg) less than
that indicated for humans (13.3 mg/kg); in these low dose studies, the reproductive
capability of male offspring of megestrol acetate-treated females was impaired.
Similar results were obtained in dogs. Pregnant rats treated with megestrol
acetate showed a reduction in fetal weight and number of live births, and
feminization of male fetuses. No toxicity data are currently available on
male reproduction (spermatogenesis).<br/>Pregnancy: Pregnancy Category X. (See WARNINGS and PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility:
Impairment of Fertility.) No adequate animal teratology information
is available at clinically relevant doses.<br/>Nursing Mothers: Because of the potential for adverse effects on the newborn, nursing
should be discontinued if MEGACE Oral Suspension is required.<br/>Use in HIV-Infected Women: Although megestrol acetate has been used extensively in women for
the treatment of endometrial and breast cancers, its use in HIV-infected women
has been limited. All 10 women in the clinical trials reported breakthrough bleeding.<br/>Pediatric Use: Safety and effectiveness in pediatric patients have not been established.<br/>Geriatric Use: Clinical studies of MEGACE Oral Suspension in the treatment of
anorexia, cachexia, or an unexplained, significant weight loss in patients
with AIDS did not include sufficient numbers of patients aged 65 years and
older to determine whether they respond differently than younger patients.
Other reported clinical experience has not identified differences in responses
between elderly and younger patients. In general, dose selection for an elderly
patient should be cautious, usually starting at the low end of the dosing
range, reflecting the greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease or other drug therapy. Megestrol acetate is known to be substantially excreted by the
kidney, and the risk of toxic reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients are more likely to
have decreased renal function, care should be taken in dose selection, and
it may be useful to monitor renal function.
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No serious unexpected side effects have resulted from studies involving
MEGACE Oral Suspension administered in dosages as high as 1200 mg/day. Megestrol
acetate has not been tested for dialyzability; however, due to its low solubility
it is postulated that dialysis would not be an effective means of treating
overdose.
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MEGESTROL ACETATE
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MEGACE (Suspension)
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| dailymed-instance:adverseRe... |
Clinical Adverse Events: Adverse events which occurred in at least 5% of patients in any
arm of the two clinical efficacy trials and the open trial are listed below
by treatment group. All patients listed had at least one post baseline visit
during the 12 study weeks. These adverse events should be considered by the
physician when prescribing MEGACE (megestrol acetate, USP) Oral Suspension. Adverse events which occurred in 1% to 3% of all patients enrolled
in the two clinical efficacy trials with at least one follow-up visit during
the first 12 weeks of the study are listed below by body system. Adverse events
occurring less than 1% are not included. There were no significant differences
between incidence of these events in patients treated with megestrol acetate
and patients treated with placebo. Body as a Whole: abdominal pain, chest pain, infection,
moniliasis and sarcoma Cardiovascular System: cardiomyopathy and palpitation Digestive System: constipation, dry mouth, hepatomegaly,
increased salivation and oral moniliasis Hemic and Lymphatic System: leukopenia Metabolic and Nutritional: LDH increased, edema and
peripheral edema Nervous System: paresthesia, confusion, convulsion,
depression, neuropathy, hypesthesia and abnormal thinking Respiratory System: dyspnea, cough, pharyngitis and
lung disorder Skin and Appendages: alopecia, herpes, pruritus,
vesiculobullous rash, sweating and skin disorder Special Senses: amblyopia Urogenital System: albuminuria, urinary incontinence,
urinary tract infection and gynecomastia<br/>Postmarketing: Postmarketing reports associated with MEGACE Oral Suspension include
thromboembolic phenomena including thrombophlebitis and pulmonary embolism,
and glucose intolerance .
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| dailymed-instance:warning |
Megestrol acetate may cause fetal harm when administered to a pregnant
woman. For animal data on fetal effects, see PRECAUTIONS:
Carcinogenesis, Mutagenesis, Impairment of Fertility: Impairment of Fertility.
There are no adequate and well-controlled studies in pregnant women. If this
drug is used during pregnancy, or if the patient becomes pregnant while taking
(receiving) this drug, the patient should be apprised of the potential hazard
to the fetus. Women of childbearing potential should be advised to avoid becoming
pregnant. Megestrol acetate is not intended for prophylactic use to avoid
weight loss. (See also PRECAUTIONS: Carcinogenesis,
Mutagenesis, Impairment of Fertility.) The glucocorticoid activity of MEGACE Oral Suspension 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 MEGACE. In addition, clinical cases
of adrenal insufficiency have been observed in patients receiving or being
withdrawn from chronic MEGACE 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 MEGACE therapy. Therefore, the possibility of adrenal
insufficiency should be considered in any patient receiving or being withdrawn
from chronic MEGACE therapy who presents with symptoms and/or signs suggestive
of hypoadrenalism (e.g., 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
MEGACE 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 (e.g., surgery, infection).
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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).
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MEGACE
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