INDICATIONS & USAGE SECTION.
INDICATIONS AND USAGE. Megestrol acetate oral suspension, USP is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with diagnosis of acquired immunodeficiency syndrome (AIDS).
OVERDOSAGE. No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. In post-marketing experience, limited reports of overdose have been received. Signs and symptoms reported in the context of overdose included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain. There is no specific antidote for overdose with megestrol acetate oral suspension. In case of overdose, appropriate supportive measures should be taken. 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.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.
MEGESTROL ACETATE 40mg/mL SUSPENSION. NDC 33358-903-05 5mL CupNDC 33358-903-10 10mL CupNDC 33358-903-20 20mL Cup. Megestrol.
CLINICAL PHARMACOLOGY SECTION.
CLINICAL PHARMACOLOGY. 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 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 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 megestrol acetate 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 (Cmax) of megestrol acetate was 753 (+-539) ng/mL. Mean area under the concentration time-curve (AUC) was 10476 (+-7788) ng hr/mL. Median Tmax value 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 megestrol acetate oral suspension. The treatment was administered for 14 days. Mean Cmax and AUC values were 490 (+-238) ng/mL and 6779 (+-3048) hr ng/mL, respectively. The median Tmax value was three hours. The mean Cmin value was 202 (+-101) ng/mL. The mean of fluctuation value was 107 (+-40).The effect of food on the bioavailability of megestrol acetate oral suspension has not been evaluated.
CONTRAINDICATIONS. History of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy.
DESCRIPTION. Megestrol acetate oral suspension, USP contains megestrol acetate, synthetic derivative of the naturally occurring steroid hormone, progesterone. Megestrol acetate is white, crystalline solid chemically designated as 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate. Solubility at 37C in water is mcg per mL, solubility in plasma is 24 mcg per mL. Its molecular weight is 384.52.The chemical formula is C24H32O4 and the structural formula is represented as follows:Megestrol acetate oral suspension is supplied as an oral suspension containing 40 mg of micronized megestrol acetate per mL.Megestrol acetate oral suspension contains the following inactive ingredients: alcohol (max 0.06% v/v from flavor), artificial lime flavor, citric acid monohydrate, docusate sodium, glycerin, natural and artificial lemon flavor, purified water, sodium benzoate, sodium citrate dihydrate, sucrose and xanthan gum.Megestrol acetate oral suspension, 40 mg/mL complies with USP Dissolution Test 2.. structural formula.
DOSAGE & ADMINISTRATION SECTION.
DOSAGE AND ADMINISTRATION. 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.
HOW SUPPLIED SECTION.
HOW SUPPLIED. Megestrol acetate oral suspension, USP is available as milky white, lemon-lime flavored oral suspension containing 40 mg of micronized megestrol acetate per mL.
WARNINGS. Megestrol acetate may cause fetal harm when administered to 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, and Impairment of Fertility section.)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 Cushings 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 revealedthe 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 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 rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (e.g., surgery, infection).