DrugindexOnline^{2nd edition}

Pronouncation: (me-JES-trole AS-eh-tate)
Class: Progestin

Trade Names:
Megace
- Suspension 40 mg/mL

Trade Names:
Megace ES
- Suspension 125 mg/mL

Trade Names:
Megestrol
- Tablets 20 mg
- Tablets 40 mg

Apo-Megestrol (Canada)
Linmegestrol (Canada)
Megace OS (Canada)
Nu-Megestrol (Canada)

Mechanism of Action

Pharmacology

Inhibits secretion of pituitary gonadotropins with a resultant decrease in estrogen secretion; exerts a direct cytotoxic effect on tumor cells; mechanism of effect on anorexia and cachexia is unknown.

Pharmacokinetics

Absorption

C _max is 10 to 56 ng/mL; T _max is 1 to 3 h for tablets. C _max is approximately 753 ng/mL, and T _max is approximately 5 h for suspension.

Metabolism

The megestrol acetate metabolites are negligible.

Elimination

The major route for elimination is urine; minor routes are feces and respiratory, as CO ₂ . The t _½ is 13 to 104.9 h (mean, 34.2 h) for tablets.

Indications and Usage

Oral suspension

Treatment of anorexia, cachexia, or an unexplained weight loss in patients diagnosed with AIDS.

Tablets

Palliative treatment of advanced inoperable, recurrent, or metastatic carcinoma of breast or endometrium.

Contraindications

Hypersensitivity to progestins or any component of these formulations; known or suspected pregnancy (suspension).

Dosage and Administration

Breast Cancer
Adults

PO 40 mg 4 times daily.

Endometrial Cancer
Adults

PO 40 to 320 mg/day in divided doses.

Anorexia, Cachexia, Unexplained Weight Loss in AIDS patients
Adults

PO 800 mg/day. PO 625 mg/day ( Megace ES ).

General Advice

• Shake suspension well before using.

Storage/Stability

Store tablet in dry, cool place at room temperature (59° to 86°F).

Store suspension between 59° and 77°F. Dispense in tight container. Protect from light.

Drug Interactions

Dofetilide

Elevated dofetilide plasma concentrations may occur. Do not use concurrently.

Indinavir

Coadministration results in a significant decrease in C _max and AUC of indinavir.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (8%); cardiomyopathy, palpitation (1% to 3%); heart failure, thromboembolic phenomena, including pulmonary embolism and thrombophlebitis.

CNS

Headache (10%); asthenia (6%); abnormal thinking, confusion, convulsion, depression, hyperesthesia, neuropathy, paresthesia (1% to 3%); hot flashes, lethargy, malaise, mood changes.

Dermatologic

Rash (2%); alopecia, pruritus, skin disorder, sweating, vesiculobullous rash (2%).

EENT

Amblyopia, pharyngitis (2%).

GI

Diarrhea (15%); flatulence (10%); vomiting (6%); nausea (5%); dyspepsia (4%); abdominal pain or discomfort, constipation, dry mouth, increased salivation, oral moniliasis (1% to 3%).

Genitourinary

Impotence (14%); decreased libido (5%); urinary frequency (2%); albuminemia, breakthrough bleeding, gynecomastia, urinary incontinence, UTI (1% to 3%).

Hematologic-Lymphatic

Leukopenia (1% to 3%).

Hepatic

Anemia (5%); hepatomegaly (1% to 3%).

Metabolic-Nutritional

Hyperglycemia (6%); increased LDH, peripheral edema (1% to 3%); glucose intolerance.

Respiratory

Pneumonia (2%); cough, dyspnea, lung disorder (1% to 3%).

Miscellaneous

Fever, pain (6%); chest pain, edema, herpes, infection, moniliasis, sarcoma (1% to 3%); carpal tunnel syndrome, increased appetite, tumor flare, weight gain.

Precautions

Pregnancy

Tablets

Category D .

Suspension

Category X .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased cardiac, hepatic, or renal function, and concomitant diseases or other drug therapy.

Adrenal insufficiency

Adrenal insufficiency may occur in patients receiving or being withdrawn from chronic megestrol acetate therapy.

Cushing syndrome

Has occurred.

Diabetes mellitus

New onset diabetes mellitus and exacerbation of preexisting diabetes mellitus has occurred.

Thromboembolic disease

Use with caution in patients with history of thromboembolic disease.

Overdosage

Symptoms

No data.

Patient Information

• Explain potential significance of breakthrough bleeding, irregular menstrual cycles, and possible lack of menstrual cycle. Tell patient to notify health care provider of heavy or continuous menstrual flow.
• Encourage patients with diabetes to monitor blood glucose more frequently until effect on diabetes control has been determined.
• Instruct patient to report these symptoms to health care provider: chest pain; clay-colored stools; dark urine; dyspnea; edema; jaundice; numbness in extremities; pain in calves of legs with redness, warmth, and swelling; sudden severe headache; visual disturbances.
• Inform patient about the product differences in dosages. Depending on the indications for use, the various oral suspensions contain different amounts of megestrol acetate in 5 mL.
• Instruct patient to report any adverse reactions.
• Advise women of childbearing potential to use contraception and avoid becoming pregnant while taking this drug.