Megestrol

Name: Megestrol

Do I need a prescription for megestrol?

Yes

What are the side effects of megestrol?

The most common side effects are:

  • diarrhea,
  • weight gain,
  • nausea,
  • rash,
  • impotency,
  • insomnia,
  • mood swings,
  • sweating,
  • breakthrough menstrual bleeding,
  • high blood pressure, and
  • excess gas (flatulence).

Blood clots in legs and lungs may occur.

Megestrol may worsen existing diabetes or lead to new onset diabetes.

What Is Megace (Megestrol)?

Megace is the brand name of the prescription drug megestrol, which is used to treat advanced breast cancer and advanced endometrial cancer.

The medicine is given in a concentrated liquid form (Megace ES) to prevent weight loss and improve appetite in people with acquired immunodeficiency syndrome (AIDS).

It's also sometimes used to relieve symptoms of other cancers, an enlarged prostate, endometriosis (a condition where tissue that lines the uterus grows in other places), or endometrial hyperplasia (overgrowth of the lining of the uterus).

Megace is a man-made form of the human hormone progesterone.

It helps breast and endometrial cancers by affecting the hormones involved in cancer growth. It helps AIDS patients gain weight by increasing appetite.

The Food and Drug Administration (FDA) first approved the medicine in 1971. Megace is manufactured by Bristol-Myers Squibb and Megace ES by Par Pharmaceutical Companies, Inc.

Megace Warnings

Megace shouldn't be given to prevent weight loss or improve appetite in people who don't have AIDS or those who haven't yet developed the disease.

Before taking Megace, tell your doctor if you have or have ever had:

  • An adrenal gland disorder
  • Diabetes
  • Stroke
  • Blood clot
  • Liver disease
  • Kidney disease
  • Allergies to medications

Megace may cause changes in a woman's normal menstrual period. Talk to your doctor if this is a concern.

Tell your doctor you're taking this drug before having any type of surgery, including a dental procedure.

Your dose of Megace may need to be changed if you have surgery, become ill, have an infection, or are under a lot of stress. Don't change your dose without first talking to your physician.

Megace can pass into body fluids such as urine, feces, vomit, semen, and vaginal fluid. Wear rubber gloves when cleaning up these fluids or changing a diaper. Wash your hands before and after.

Pregnancy and Megace

Megace can harm an unborn baby or cause birth defects. Don't take this medicine if you're pregnant.

Also, pregnant women shouldn't handle the body fluids of someone who takes Megace.

Be sure to use effective birth control methods to prevent pregnancy while taking Megace. Talk to your doctor about birth control options.

It's not known whether the medicine passes into breast milk or could harm a breastfeeding baby. Don't breastfeed while taking Megace without talking to your doctor first.

Megace for Dogs and Cats

The medicine is sometimes used in dogs and cats to treat certain medical conditions. It's prescribed by veterinarians under the brand name Ovaban.

The drug is used to help control heat cycles in dogs and cats.

It's also used to treat false pregnancies, behavioral problems, skin disorders, and other health issues in pets.

Side Effects of Megestrol

Serious side effects have been reported with megestrol. See the "Drug Precautions" section.

Common side effects of megestrol include the following:

  • impotence (the inability to develop or maintain an erection of the penis during sexual activity)
  • insomnia (difficulty falling asleep or staying asleep)
  • gas
  • decreased sexual desire
  • rash
  • dyspepsia (indigestion)

This is not a complete list of megestrol side effects. Ask your doctor or pharmacist for more information.

Tell your doctor is you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What is the most important information I should know about megestrol?

Megestrol can harm an unborn baby or cause birth defects. Do not use megestrol if you are pregnant. Use birth control to prevent pregnancy.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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 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 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 x 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 percent of fluctuation value was 107 (±40).

The effect of food on the bioavailability of Megestrol acetate oral suspension has not been evaluated.

Adverse Reactions

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 Megestrol acetate oral suspension.

ADVERSE EVENTS

% of Patients Reporting

Megestrol Acetate, mg/day

No. of Patients

Trial 1

(N=236)

Placebo

0 100 400 800

N=34 N=68 N=69 N=65

Trial 2

(N=87)

Placebo

0 800

N=38 N=49

Open Label Trial

1200

N=176

Diarrhea

Impotence

Rash

Flatulence

Hypertension

Asthenia

Insomnia

Nausea

Anemia

Fever

Libido Decreased

Dyspepsia

Hyperglycemia

Headache

Pain

Vomiting

Pneumonia

Urinary Frequency

15 13 8 15

3 4 6 14

9 9 4 12

9 0 1 9

0 0 0 8

3 2 3 6

0 3 4 6

9 4 0 5

6 3 3 5

3 6 4 5

3 4 0 5

0 0 3 3

3 0 6 3

6 10 1 3

6 0 0 2

9 3 0 2

6 2 0 2

0 0 1 2

8 6

NaN 4   3 2   3 10 NaN 0   8 4 NaN 0   3 4 NaN 0   3 2 NaN 2   5 4 NaN 0   3 0   5 6   3 6   3 0   5 2

10

7

6

6

4

5

1

5

0

1

1

2

3

3

4

4

1

1

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

Postmarketing

Postmarketing reports associated with Megestrol acetate oral suspension include thromboembolic phenomena including thrombophlebitis and pulmonary embolism, and glucose intolerance (see WARNINGS and PRECAUTIONS).

Index Terms

  • 5071-1DL(6)
  • Megestrol Acetate

Use Labeled Indications

Anorexia or cachexia: Suspension: Treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS

Limitations of use: Treatment of AIDS-related weight loss should only be initiated after addressing the treatable causes (eg, malignancy, infection, malabsorption, endocrine disease, renal disease, psychiatric disorder) for weight loss. Megestrol is not intended to prevent weight loss.

Breast cancer: Tablet: Treatment (palliative) of advanced breast cancer

Endometrial cancer: Tablet: Treatment (palliative) of advanced endometrial carcinoma

Off Label Uses

Treatment of cancer-related cachexia

Data from randomized, placebo controlled studies [Loprinzi 1990], [Vadell 1998]; support the use of megestrol to promote weight gain in cachectic patients with cancer. A meta-analysis of megestrol for the management of anorexia/cachexia showed benefit with the use of megestrol; higher doses were associated with more weight gain, however, data was insufficient to determine an optimal dose [Ruiz Garcia 2013]. Data from dose finding studies suggest higher doses are associated with higher weight gain [Beller 1997], [Loprinzi 1993].

Usual Adult Dose for Endometrial Carcinoma

Megestrol tablets are indicated for use in the palliative treatment of advanced carcinoma of the endometrium: 40 to 320 mg/day of oral tablets in divided doses

Dialysis

Data not available

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