Megestrol

Megestrol is also sometimes used to treat malnutrition in patients with cancer, prostatic hypertrophy (enlargement of a male reproductive gland called the prostate), endometriosis (condition in which the type of tissue that lines the uterus grows in other areas of the body), and endometrial hyperplasia (overgrowth of the lining of the uterus). Talk to your doctor about the risks of using this medication for your condition.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Megestrol is part of the drug class:

• Pregnadien derivatives

You should not use megestrol if you are allergic to it, or if you are pregnant.

To make sure megestrol is safe for you, tell your doctor if you have:

• diabetes;

• an adrenal gland disorder; or

• a history of stroke or blood clot.

This medication can harm an unborn baby or cause birth defects. Do not use megestrol if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use effective birth control and follow your doctor's instructions about how long to prevent pregnancy after your treatment ends.

It is not known whether megestrol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while taking megestrol.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these side effects during or after your treatment with megestrol:

• weight gain (especially in your waist and upper back), stretch marks;

• thinning skin, easy bruising, increased acne or facial hair;

• menstrual problems, impotence or loss of interest in sex;

• high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss);

• pain, swelling, warmth, or redness (especially in one or both legs); or

• chest pain, sudden cough, wheezing, rapid breathing, coughing up blood,

Common side effects may include:

• nausea, gas, diarrhea;

• unusual vaginal bleeding;

• mild skin rash; or

• weakness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Megestrol Acetate Oral Suspension, USP contains Megestrol acetate, a synthetic derivative of the naturally occurring steroid hormone, progesterone. Megestrol acetate is a white, crystalline solid chemically designated as 17α-(acetyloxy)-6-methylpregna-4,6-diene-3,20-dione. Solubility at 37°C in water is 2 µg per mL, solubility in plasma is 24 µg per mL. Its molecular weight is 384.51.

The empirical formula is C24H32O4 and the structural formula is represented as follows:

Megestrol acetate, USP

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: citric acid, natural and artificial lemon-lime flavor, polyethylene glycol, polysorbate 80, purified water, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

The clinical efficacy of Megestrol acetate oral suspension was assessed in two clinical trials. One was a multicenter, randomized, double-blind, placebo-controlled study comparing Megestrol acetate (MA) at doses of 100 mg, 400 mg, and 800 mg per day versus placebo in AIDS patients with anorexia/cachexia and significant weight loss. Of the 270 patients entered on study, 195 met all inclusion/exclusion criteria, had at least two additional post baseline weight measurements over a 12-week period, or had one post baseline weight measurement but dropped out for therapeutic failure. The percent of patients gaining five or more pounds at maximum weight gain in 12 study weeks was statistically significantly greater for the 800 mg (64%) and 400 mg (57%) MA-treated groups than for the placebo group (24%). Mean weight increased from baseline to last evaluation in 12 study weeks in the 800 mg MA-treated group by 7.8 pounds, the 400 mg MA group by 4.2 pounds, the 100 mg MA group by 1.9 pounds, and decreased in the placebo group by 1.6 pounds. Mean weight changes at 4, 8, and 12 weeks for patients evaluable for efficacy in the two clinical trials are shown graphically. Changes in body composition during the 12 study weeks as measured by bioelectrical impedance analysis showed increases in non-water body weight in the MA-treated groups (see clinical studies table). In addition, edema developed or worsened in only 3 patients.

Greater percentages of MA-treated patients in the 800 mg group (89%), the 400 mg group (68%), and the 100 mg group (72%), than in the placebo group (50%), showed an improvement in appetite at last evaluation during the 12 study weeks. A statistically significant difference was observed between the 800 mg MA-treated group and the placebo group in the change in caloric intake from baseline to time of maximum weight change. Patients were asked to assess weight change, appetite, appearance, and overall perception of well-being in a 9-question survey. At maximum weight change, only the 800 mg MA-treated group gave responses that were statistically significantly more favorable to all questions when compared to the placebo-treated group. A dose response was noted in the survey with positive responses correlating with higher dose for all questions.

The second trial was a multicenter, randomized, double-blind, placebo-controlled study comparing Megestrol acetate 800 mg/day versus placebo in AIDS patients with anorexia/cachexia and significant weight loss. Of the 100 patients entered on study, 65 met all inclusion/exclusion criteria, had at least two additional post baseline weight measurements over a 12-week period or had one post baseline weight measurement but dropped out for therapeutic failure. Patients in the 800 mg MA-treated group had a statistically significantly larger increase in mean maximum weight change than patients in the placebo group. From baseline to study week 12, mean weight increased by 11.2 pounds in the MA-treated group and decreased 2.1 pounds in the placebo group. Changes in body composition as measured by bioelectrical impedance analysis showed increases in non-water weight in the MA-treated group (see clinical studies table). No edema was reported in the MA-treated group. A greater percentage of MA-treated patients (67%) than placebo-treated patients (38%) showed an improvement in appetite at last evaluation during the 12 study weeks; this difference was statistically significant. There were no statistically significant differences between treatment groups in mean caloric change or in daily caloric intake at time to maximum weight change. In the same 9-question survey referenced in the first trial, patients' assessments of weight change, appetite, appearance, and overall perception of well-being showed increases in mean scores in MA-treated patients as compared to the placebo group.

In both trials, patients tolerated the drug well and no statistically significant differences were seen between the treatment groups with regard to laboratory abnormalities, new opportunistic infections, lymphocyte counts, T4 counts, T8 counts, or skin reactivity tests (see ADVERSE REACTIONS)

Megestrol Acetate Oral Suspension, USP

Clinical Efficacy Trials

Trial 1 Trial 2

Study Accrual Dates Study Accrual Dates

11/88 to 12/905/89 to 4/91

Megestrol Acetate, mg/day 0 100 400 800 0 800

Entered Patients 38 82 75 75 48 52

Evaluable Patients 28 61 53 53 29 36

Mean Change in Weight (lb.)

Baseline to 12 Weeks 0.0 2.9 9.3 10.7 -2.1 11.2

% Patients ≥5-Pound Gain at

Last Evaluation in 12 Weeks 21 44 57 64 28 47

Mean Changes in Body Composition*

Fat Body Mass (lb.) 0.0 2.2 2.9 5.5 1.5 5.7

Lean Body Mass (lb.) -1.7 -0.3 1.5 2.5 -1.6 -0.6

Water (liters) -1.3 -0.3 0.0 0.0 -0.1 -0.1

% Patients With Improved Appetite

At Time of Maximum Wt. Change 50 72 72 93 48 69

At Last Evaluation in 12 Weeks 50 72 68 89 38 67

Mean Change in Daily Caloric Intake:

Baseline to Time of Maximum

Weight Change -107 326 308 646 30 464

*Based on bioelectrical impedance analysis determinations at last evaluation in 12 weeks

Presented below are the results of mean weight changes for patients evaluable for efficacy in Trials 1 and 2.

Megestrol tablets are indicated for use in the palliative treatment of advanced carcinoma of the breast: 160 mg/day (40 mg of oral tablets four times a day)

Megestrol oral suspension is indicated for use in the treatment of cachexia at a dose of 800 mg/day.

Alternatively, 625 mg/5 mL of the concentrated formula (Megace ES formula) may be given.

Note: 800 mg/20 mL of the regular formula is equivalent to 625 mg/ 5 mL of the concentrated formula.

Megestrol oral suspension is indicated for use in the treatment of unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS) at a dose of 800 mg/day.

Alternatively, 625 mg/5 mL of the concentrated formula (Megace ES formula) may be given.

Note: 800 mg/20 mL of the regular formula is equivalent to 625 mg/ 5 mL of the concentrated formula.