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megestrol acetate suspension
Megestrol Acetate Oral Suspension USP
Study Accrual Dates
11/88 to 12/90
Study Accrual Dates
5/89 to 4/91
|*Based on bioelectrical impedance analysis determinations at last evaluation in 12 weeks|
|Megestrol Acetate, mg/day||0||100||400||800||0||800|
|Mean Change in Weight (lb.)
Baseline to 12 Weeks
|% Patients ≥ 5 Pound Gain
at Last Evaluation in 12 Weeks
|Mean Changes in Body Composition*
Fat Body Mass (lb.)
Lean Body Mass (lb.)
|% Patients With Improved Appetite
At Time of Maximum Wt. Change
At Last Evaluation in 12 Weeks
|Mean Change in Daily Caloric Intake:
Baseline to Time of Maximum
Presented below are the results of mean weight changes for patients evaluable for efficacy in trials 1 and 2.
Megestrol acetate 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).
History of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy.
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.
The glucocorticoid activity of megestrol acetate oral suspension has not been fully evaluated. Clinical cases of new onset diabetes mellitus, exacerbation of pre-existing 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 In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate therapy in the stressed and non-stressed state.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 (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 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 (e.g., surgery, infection).
Therapy with megestrol acetate 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.
Exacerbation of preexisting diabetes with increased insulin requirements has been reported in association with the use of megestrol acetate.
Patients using megestrol acetate should receive the following instructions:
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.
Long-term treatment with megestrol acetate 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.
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 megestrol acetate oral suspension and in surveillance of patients on therapy. (See WARNINGS.)
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).
Pregnancy Category X.
(See WARNINGSand PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility: Impairment of Fertility.) No adequate animal teratology information is available at clinically relevant doses.
Because of the potential for adverse effects on the newborn, nursing should be discontinued if megestrol acetate oral suspension is required.
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.
Clinical studies of megestrol acetate 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.
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 megestrol acetate oral suspension.
|% of Patients Reporting|
No. of Patients
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
Cardiomyopathy and palpitation
Constipation, dry mouth, hepatomegaly, increased salivation and oral moniliasis
Hemic and Lymphatic System
Metabolic and Nutritional
LDH increased, edema and peripheral edema
Paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking
Dyspnea, cough, pharyngitis and lung disorder
Skin and Appendages
Alopecia, herpes, pruritus, vesiculobullous rash, sweating and skin disorder
Albuminuria, urinary incontinence, urinary tract infection and gynecomastia
No serious unexpected side effects have resulted from studies involving megestrol acetate 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.
The recommended adult initial dosage of megestrol acetate 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.
Megestrol Acetate Oral Suspension USP, 40 mg/mL is available as a lemon-lime flavored oral suspension containing 40 mg of micronized megestrol acetate per mL.
NDC 60505-0368-1 Bottles of 240 mL (8 fl. oz.)
Store at 20º - 25ºC (68º - 77ºF) [see USP Controlled Room Temperature]. Dispense in a tight container and protect from heat.
Keep this and all drugs out of the reach of children.
Manufactured by: Manufactured for:
Apotex Inc. Apotex Corp.
Toronto, Ontario Weston, Florida
Canada M9L 1T9 33326
272549 June 2008
megestrol acetate suspension
Revised: 09/2008 Apotex Corp.
Reproduced with permission of U.S. National Library of Medicine
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