Megestrol Acetate

MEGACE Oral Suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

No serious unexpected side effects have resulted from studies involving MEGACE 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 MEGACE 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.

The prescriber should inform the patient about the product differences to avoid overdosing or underdosing of megestrol acetate. The recommended adult dosage of Megace® ES is one teaspoon (5 mL) once a day [see table in DOSAGE AND ADMINISTRATION].

Patients using Megace® ES should receive the following instructions:

• 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.

Megestrol can harm an unborn baby or cause birth defects. Do not use megestrol if you are pregnant.

Before you take megestrol, tell your doctor if you have diabetes or a history of stroke or blood clot.

Your dosage needs may change if you have surgery, are ill, are under stress, or have an infection. Do not change your medication dose or schedule without your doctor's advice.

Megace ES contains a higher concentration of megestrol than Megace. Ask your pharmacist if you have any questions about the medicine you receive at the pharmacy.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Serious And Otherwise Important Adverse Reactions

The following serious reactions and otherwise important adverse drug reactions are discussed in greater detail in other sections of the labeling:

• Hypersensitivity [see CONTRAINDICATIONS]
• Pregnancy [see CONTRAINDICATIONS]
• Fetal Effects [see WARNINGS AND PRECAUTIONS]
• Thromboembolic Disease [see WARNINGS AND PRECAUTIONS]
• Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]

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 1 2 study weeks.

Table 1: Adverse Events

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 1 2 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 Experience

Postmarketing reports associated with megestrol acetate oral suspension include thromboembolic phenomena including thrombophlebitis, deep vein thrombosis, and pulmonary embolism; and glucose intolerance [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Megace ES (Megestrol Acetate)

Breast Cancer

Palliative management of recurrent, inoperable, or metastatic breast cancer.b c

Estrogen and/or progesterone receptor-positive breast cancer is more likely to respond to megestrol therapy.b

Does not replace appropriate methods of treatment of advanced breast cancer (e.g., surgery, radiation, chemotherapy).b c

Not recommended for treatment of other types of neoplastic disease; use only for treatment of breast cancer or endometrial cancer.b

Endometrial Cancer

Palliative management of recurrent, inoperable, or metastatic endometrial carcinoma.b c

Does not replace appropriate methods of treatment of advanced endometrial carcinoma (e.g., surgery, radiation, chemotherapy).b c

Not recommended for treatment of other types of neoplastic disease; use only for treatment of endometrial cancer or breast cancer.b

Cachexia

Management of anorexia, cachexia, or an unexplained, substantial weight loss in HIV-infected individuals (designated an orphan drug by FDA for this use).102 104 106 107 108 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 138 a

Also has been used to stimulate appetite and promote weight gain in a limited number of patients with cachexia associated with neoplastic disease†.100 101 103 108 116 117 118 119 134 135

Therapy should be initiated only after treatable causes (e.g., possible malignancies; systemic infections; GI disorders affecting absorption; endocrine, renal, or psychiatric diseases) of the condition have been evaluated.121

Manufacturer states that megestrol should not be used prophylactically to avoid weight loss.

• Induces secretory changes in the endometrium, increases basal body temperature, inhibits pituitary function, and produces withdrawal bleeding in the presence of estrogen.c

• In animals, suppresses ovulation and produces antigonadotropic, antiuterotropic, and antiandrogenic/antimyotropic effects; has slight glucocorticoid activity and a very slight degree of mineralocorticoid activity; and has no estrogenic, androgenic, or anabolic activity.c

• Antineoplastic effect may result from inhibition of pituitary gonadotropin production which results in decreased estrogen secretion.b

• Decreases the number of hormone-dependent breast cancer cells and eliminates the stimulatory effect that estrogen has on these cells.b

• May produce a local effect on cancerous cells by converting the actively growing stroma into decidua.c

• May directly or indirectly stimulate appetite or may alter metabolic pathways via interference with the production or action of mediators such as cachectin (a hormone that inhibits adipocyte lipogenic enzymes);100 101 103 109 110 111 however precise mechanism for weight gain not clearly established.100 101 103 108 109 116 121

• Importance of taking megestrol exactly as prescribed.

• Importance of informing patients that the more concentrated oral suspension containing 625 mg/5 mL (Megace ES) does not contain the same amount of megestrol as oral suspensions containing 200 mg/5 mL and therefore are not interchangeable.138

• Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.128 135 c

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.138 a b

• Importance of informing patients of other important precautionary information.138 a b (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name