Megace ES
Par Pharmaceutical, Inc
Par Pharmaceutical, Inc
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Megace ES safely and effectively. See full prescribing information for MegaceES. Megace ES (megestrol acetate, USP) Oral SuspensionInitial U.S. Approval: 1993INDICATIONS AND USAGEMegace® ES oral suspension is a progestin indicated for the treatment of anorexia, cachexia, or an unexplained significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS) (1).DOSAGE AND ADMINISTRATIONThe recommended adult initial dosage of Megace® ES oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). Shake the container well before using (2).DOSAGE FORMS AND STRENGTHSOral suspension containing 125 mg of megestrol acetate per mL (3). CONTRAINDICATIONS •History of hypersensitivity to megestrol acetate or any component of the formulation (4.1). •Known or suspected pregnancy (4.2) (8.1). WARNINGS AND PRECAUTIONS •Women of childbearing potential should be advised to avoid becoming pregnant (5.2). •Use with caution in patients with a history of thromboembolic disease (5.1). •Clinical cases of 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 In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate in the stressed and non-stressed state (5.3). •New onset and exacerbation of pre-existing diabetes have been reported (5.4). Side EffectsThe most common adverse events occurring in > 5% of all patients receiving 800mg/20mL of megestrol acetate oral suspension in the two clinical efficacy trials were nausea, diarrhea, impotence, rash, flatulence, hypertension, and asthenia (6.2). To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical, Inc. at 1-800-828-9393, option 3 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONSDue to a significant decrease in indinavir exposure, administration of a higher dose of indinavir should be considered when coadministering with megestrol acetate (7.1, 12.3).USE IN SPECIFIC POPULATIONS • Geriatrics: 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 therapy (8.5). • Nursing Mothers: Because of the potential for adverse effects on the newborn, nursing should be discontinued if Megace® ES oral suspension is required (8.3).
FULL PRESCRIBING INFORMATION: CONTENTS*
- 1 MEGACE ES INDICATIONS AND USAGE
- 2 MEGACE ES DOSAGE AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 MEGACE ES CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 6 MEGACE ES ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 10 OVERDOSAGE
- 11 MEGACE ES DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Limitations of Use
Other Treatable Causes
Prophylactic Use
2 DOSAGE AND ADMINISTRATION
The recommended adult initial dosage of Megace® ES oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). Shake the container well before using.
This strength (125 mg/mL) is not substitutable with other strengths (e.g., 40 mg/mL). Refer to the prescribing information of the 40 mg/mL product for dosage recommendations for the 40 mg/mL strength.
3 DOSAGE FORMS AND STRENGTHS
Megace® ES is a milky white, lemon-lime flavored oral suspension containing 125 mg of megestrol acetate per mL. Megace® ES does not contain the same amount of megestrol acetate as Megace® oral suspension or any of the other megestrol acetate oral suspensions (2).
4 CONTRAINDICATIONS
4.1 Hypersensitivity Reaction
4.2 Pregnancy
5 WARNINGS AND PRECAUTIONS
5.1 General
-
• Effects on HIV viral replication have not been determined. -
• Use with caution in patients with a history of thromboembolic disease.
5.2 Fetal Effects
Megestrol acetate may cause fetal harm when administered to a pregnant woman. For animal data on fetal effects, see NonClinical Toxicology: Impairment of Fertility (13.1). 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.
5.3 Adrenal Insufficiency
5.4 Diabetics
6 ADVERSE REACTIONS
6.1 Serious and Otherwise Important Side Effects
-
-
• Hypersensitivity [see Contraindications (4.1)] -
• Pregnancy [see Contraindications (4.2)] -
• Fetal Effects [see Warnings and Precautions (5.2)] -
• Thromboembolic Disease [see Warnings and Precautions (5.1)] -
• Adrenal Insufficiency [see Warnings and Precautions (5.3)]
6.2 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Megace® ES (megestrol acetate oral suspension, 125 mg/mL) was based on three studies of megestrol acetate oral suspension (40 mg/mL). The adverse reaction profile of these 3 studies are presented below.
Adverse events which occurred in at least 5% of patients in any arm of the two clinical efficacy trials and the open trial for megestrol acetate oral suspension are listed below by treatment group. All patients listed had at least one post baseline visit during the 12 study weeks.
Percentage of Patients Reporting Adverse Events |
|||||||
Trial 1 (N=236) |
Trial 2 (N=87) |
Open Label Trial |
|||||
Placebo |
Placebo |
||||||
Megestrol Acetate mg/day |
0 |
100 |
400 |
800 |
0 |
800 |
1200 |
No. of Patients |
N=34 |
N=68 |
N=69 |
N=65 |
N=38 |
N=49 |
N=176 |
Diarrhea |
15 |
13 |
8 |
15 |
8 |
6 |
10 |
Impotence |
3 |
4 |
6 |
14 |
0 |
4 |
7 |
Rash |
9 |
9 |
4 |
12 |
3 |
2 |
6 |
Flatulence |
9 |
0 |
1 |
9 |
3 |
10 |
6 |
Hypertension |
0 |
0 |
0 |
8 |
0 |
0 |
4 |
Asthenia |
3 |
2 |
3 |
6 |
8 |
4 |
5 |
Insomnia |
0 |
3 |
4 |
6 |
0 |
0 |
1 |
Nausea |
9 |
4 |
0 |
5 |
3 |
4 |
5 |
Anemia |
6 |
3 |
3 |
5 |
0 |
0 |
0 |
Fever |
3 |
6 |
4 |
5 |
3 |
2 |
1 |
Libido Decreased |
3 |
4 |
0 |
5 |
0 |
2 |
1 |
Dyspepsia |
0 |
0 |
3 |
3 |
5 |
4 |
2 |
Hyperglycemia |
3 |
0 |
6 |
3 |
0 |
0 |
3 |
Headache |
6 |
10 |
1 |
3 |
3 |
0 |
3 |
Pain |
6 |
0 |
0 |
2 |
5 |
6 |
4 |
Vomiting |
9 |
3 |
0 |
2 |
3 |
6 |
4 |
Pneumonia |
6 |
2 |
0 |
2 |
3 |
0 |
1 |
Urinary Frequency |
0 |
0 |
1 |
2 |
5 |
2 |
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.
6.3 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Indinavir
7.2 Zidovudine and Rifabutin
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
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.
8.6 Use in Women
Megestrol acetate has had limited use in HIV infected women.
All 10 women in the clinical trials reported breakthrough bleeding. Megace® ES is a progesterone derivative, which may induce vaginal bleeding in women.
10 OVERDOSAGE
11 DESCRIPTION
Figure 1: Megestrol Acetate Chemical Structure
Megace® ES is an oral suspension containing 125 mg of megestrol acetate per mL.
Megace® ES oral suspension contains the following inactive ingredients: alcohol (max 0.06% v/v from flavor), artificial lime flavor, citric acid monohydrate, docusate sodium, hydroxypropyl methylcellulose (hypromellose), natural and artificial lemon flavor, purified water, sodium benzoate, sodium citrate dihydrate, and sucrose.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
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.
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility
13.2 Animal Pharmacology and/or Toxicology
14 CLINICAL STUDIES
Trial 1
Trial 2
Megestrol Acetate Oral Suspension Clinical Efficacy Trials |
||||||
Trial 1 Study Accrual Dates 11/88 to 12/90 |
Trial 2 Study Accrual Dates 5/89 to 4/91 |
|||||
Megestrol Acetate, mg/day |
0 |
100 |
400 |
800 |
0 |
800 |
|
38 |
82 |
75 |
75 |
48 |
52 |
|
28 |
61 |
53 |
53 |
29 |
36 |
Mean Change in Weight (kg) |
||||||
|
0.0 |
1.3 |
4.2 |
4.9 |
-1.0 |
5.1 |
|
21 |
44 |
57 |
64 |
28 |
47 |
|
||||||
|
0.0 |
1.0 |
1.3 |
2.5 |
0.7 |
2.6 |
|
-0.8 |
-0.1 |
0.7 |
1.1 |
-0.7 |
-0.3 |
|
-1.3 |
-0.3 |
0.0 |
0.0 |
-0.1 |
-0.1 |
|
||||||
|
||||||
|
50 |
72 |
72 |
93 |
48 |
69 |
|
50 |
72 |
68 |
89 |
38 |
67 |
|
||||||
|
||||||
|
-107 |
326 |
308 |
646 |
30 |
464 |
*Based on bioelectrical impedance analysis determinations at last evaluation in 12 weeks. |
Figure 2: Mean Weight Change for Patients Evaluable for Efficacy in Trial 1
Figure 3: Mean Weight Change for Patients Evaluable for Efficacy in Trial 2
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage
16.3 Safe Handling
Health Hazard Data
17 PATIENT COUNSELING INFORMATION
-
-
-
• This medication is to be used as directed by the physician. -
• Megace® ES (625 mg/5 mL) does not contain the same amount of megestrol acetate as Megace® oral suspension or any of the other megestrol acetate oral suspensions. Megace® ES contains 625 mg of megestrol acetate per 5 mL (125mg/mL) whereas Megace® oral suspension and other megestrol acetate oral suspensions contain 800 mg per 20 mL (40 mg/mL). -
• Report any adverse reaction experiences while taking this medication. -
• Use contraception while taking this medication if you are a woman capable of becoming pregnant. -
• Notify your physician if you become pregnant while taking this medication.
Manufactured by:
PAR PHARMACEUTICAL COMPANIES, INC.
Spring Valley, New York 10977
U.S. Patent No.:
Revised: 03/14 OS949-01-1-09
Megace® is a registered trademark of Bristol-Myers Squibb Company licensed to Par Pharmaceutical, Inc.
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
Megace ESmegesterol acetate SUSPENSION
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