<b>Megestrol acetate  [Megace]</b>

Megestrol acetate, a synthetic progesterone, has a normalizing effect upon the uterine endometrium. It inhibits recurrence of atypical hyperplasia as well as adenocarcinoma in situ. These conditions, when left untreated, often progress to invasive adenocarcinoma. Additional studies have shown that megestrol acetate is effective in the treatment of endometrial adenocarcinoma in inoperable patients and increases survival in patients with recurrent endometrial cancer. 

Estrogen and progesterone receptor studies are recommended in all cases of cancers of endometrial origin.  Hormonal therapy can be given either alone or with chemotherapy agents, to enable resection of previously inoperable uterine endometrial tumors as neoadjuvant treatment. Hormonal therapy can be used as adjuvant treatment, when the cancer is in remission. Hormonal therapy can also be used palliatively to diminish symptomatology and increase survival. Sometimes progesterone might promote growth in a tumor [tumor flare], in which case removal of the progestogen might result in diminution of the tumor. 

More Information &&url
Search Pubmed for &&url
Search Pubmed for &&url
Search Pubmed for &&url

<b>General Information about Megestrol Acetate (meh-JESS-troll  AH-set-tate)</b> 

It is essential that the package insert be consulted for detailed information on the usual cautions, precautions, contraindications, and exhaustive list of side effects.

Megestrol acetate is a synthetic progesterone (female hormone) and one of its uses is the palliative management of recurrent, inoperable, or metastatic endometrial carcinoma or breast cancer. The drug is also used as an adjunct to surgery or radiation. 

It possesses anti-estrogenic effects, inducing the activities of hormones that convert estrogen to less active metabolites.  It also inhibits the release of luteinizing hormone receptors resulting in a decrease in estrogen levels, and  inhibits stability, availability, and turnover of estrogen receptors.   Megestrol acetate shares the actions of the progestins: induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. It has slight glucocorticoid activity and a very slight degree of mineralocorticoid activity. Megestrol acetate has no estrogenic, androgenic, or anabolic activity. 

<b>The exact mechanism of the antineoplastic action of megestrol acetate has not been determined,</b> but might result from suppression of luteinizing hormone by inhibition of pituitary function. Results of one study suggested that megestrol acetate produced a local effect on the cancerous cell by converting the actively growing stroma into decidua [sloughed off tissue that forms some of the menstrual discharge].  Megestrol acetate has shown a marked suppressive effect on the colony formation of endometrial cancer cells. 

It is absorbed rapidly and completely from an oral dose, with peak plasma concentrations within 1 to 3 hours. A large percentage of megestrol is stored in body fat. About 70% of drug is metabolized in the liver to inactive steroid metabolites. Sixty to 80% of the parent drug and metabolites is excreted by the kidneys within 10 days after administration. 

Elimination half-life varies from 15-105 hours with an average of 34 hours.  The usual dosage of megestrol acetate in the palliative treatment of advanced endometrial carcinoma is between 40 and 320 mg daily, depending on body weight and the type of cancer being treated, administered in divided doses.

Megestrol acetate tablets should be stored in well-closed containers at room temperature and megestrol acetate oral suspension should be stored in tight containers at a temperature of 25C or less. An adequate trial period for determining the effectiveness of megestrol acetate is 2 months. 

Megestrol acetate is also used in the management of significant weight loss in cancer and AIDS patients. The exact mechanism by which megestrol acetate works to stimulate appetite and weight gain is unknown at this time. Weight gain seems to be from increased fat storage. Megestrol acetate is not intended for prophylactic use to avoid weight loss.

<b>Use with caution in patients with either a history of thromboembolic or hypercoagulable disorders as megestrol acetate has been associated with an increased incidence of thromboembolic events. 

Use with caution in patients with diabetes, cardiac failure, epilepsy, migraines, asthma, hyperlipidemia, mental depression, or renal dysfunction.

Use with caution in patients with abnormal liver function. Dose reduction is recommended in this setting.
 
Caution patients on the risk of weight gain and fluid retention. Patients should be advised to go on a low-salt diet.</b>
 
Do not use if you are pregnant, plan to become pregnant or while breastfeeding. Do not use if there is abnormal, undiagnosed vaginal bleeding or incomplete abortion.  Caution with history of ectopic pregnancy. Because of increased genital abnormalities caused by progestins in both male and female fetuses, the manufacturer states that megestrol acetate is not recommended during pregnancy.  If a woman becomes pregnant while receiving megestrol acetate or is inadvertently exposed to the drug during pregnancy, she should notify her physician and should be advised of the potential risks to the fetus.  Women of childbearing potential should be advised not to become pregnant while receiving megestrol acetate therapy, and they should be advisedto use an effective form of contraception while receiving the drug.  Because of the potential for serious adverse reactions to megestrol acetate in nursing infants, women receiving the drug should discontinue nursing.

<b>Side Effects:</b>
<b>GI effects:</b> occur in at least 5% of patients and include diarrhea, flatulence, nausea, and vomiting. Constipation, dyspepsia, dry mouth, increased salivation, and oral candidiasis have been reported in about 1--4% of patients. Weight gain results from a combination of fluid retention and increased appetite.  

<b>GU effects:</b>   Impotence and decreased libido have been reported. Frequency, incontinence, and infection of the urine have been reported. Vaginal bleeding & irregular periods have occurred in patients receiving the drug for breast cancer management. 

<b>Cardiovascular effects:</b> Increases in blood pressure have been reported in patients receiving high doses (480 to 1600 mg daily) of megestrol acetate. Cardiomyopathy, palpitations, chest pain, chest pressure, edema, peripheral edema, and congestive heart failure have been reported. These side effects were generally mild, and resolved following initiation of treatment for them. 

<b>Respiratory effects:</b> Dyspnea, cough, pharyngitis, and lung disorder occurred in about 1 to 3% of patients receiving megestrol.  Megestrol, like other progestins, may stimulate respiration in patients receiving high doses. 

<b>Nervous System effects:</b> reported in patients with AIDS-related cachexia include insomnia, headache, asthenia, paresthesia, confusion, seizures, depression, neuropathy, hypesthesia, and abnormal thinking. 

<b>Endocrine effects</b>: Tumor flare (with or without hypercalcemia). Development or worsening of diabetes mellitus, hyperglycemia or glucose intolerance, hot flashes, sweating, mood changes. Adrenal suppression might possibly occur.

<b>Other Side Effects:</b>

Carpal tunnel syndrome, clotting problems (e.g., deep-vein thrombophlebitis, pulmonary embolism), gynecomastia, rash, feeling of coldness, and hair loss also have been reported in patients receiving megestrol therapy. 
Weight gain and increased appetite have been reported in some patients; some evidence suggests that such effects may be dose-related. 
Also unusual tiredness, weakness, weight loss, galactorrhea, gallbladder obstruction, hepatitis, breast tenderness, chloasma, fever, hirsutism, and trouble sleeping have been reported.   
Mutagenicity studies of megestrol acetate have not been performed. The drug should be used only when the potential benefits justify the possible risks to the patient.

<b>Notify your Doctor Promptly IF: 
This medication can cause changes in appetite, thirst or weight, diarrhea, constipation, frequent urination, swelling of ankles or feet, increased rate or difficulty breathing. If any of these effects persist or worsen, inform your doctor promptly. 

Notify your doctor if you experience: changes in vaginal bleeding or discharge, severe or sudden vision changes, headache, loss of coordination, slurred speech, trouble breathing, weakness or numbness in arms or legs, skin rash or itching, pain (in the stomach, side, chest, groin, arm, leg, or especially calf pain).</b> If you notice other effects not listed above, contact your doctor or pharmacist.  

<b>Drug Interactions:</b>
Aminoglutethimide - Aminoglutethimide enhances the hepatic metabolism of megestrol resulting in decreased serum levels.  
dofetilide-contraindicated.

Consult your doctor before taking this drug. Tell your doctor your medical history, especially: liver disease, congestive heart failure, depression, incomplete abortion,ectopic pregnancy, unusual vaginal bleeding, suspected pregnancy, blood clotting problems, diabetes, any allergies. 

This drug may decrease adrenal gland activity. Therefore, tell your doctors and dentists of your megestrol use and when you stopped using it. After stopping this drug, additional corticosteroids (e.g., hydrocortisone) may be necessary in stress situations such as trauma, major surgery or serious infection. Consult your doctor or pharmacist for details. Symptoms of adrenal problems include unusual weakness, fever, dizziness, nausea and rapid weight loss. 

Contraceptive (birth control) measures are recommended for use while using this medication. Megestrol is not recommended for use during pregnancy. . Megestrol may be excreted into breast milk. Because of the potential of harm to the infant, nursing should be stopped while using this drug. 

Tell your doctor of any nonprescription or prescription medication, or herbal or other supplement you may take. Do not start or stop any medicine without doctor or pharmacist approval. Never begin taking a new medication, prescription or nonprescription, without asking your doctor or nurse if it will interact with alcohol, foods or other medications. 

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up. Store at room temperature, and away from heat and moisture. Keep this and all medications out of the reach of children. 

Your condition can cause complications in a medical emergency. For information on enrollment call Medic Alert(TM) at 1-800-854- 1166. In Canada call 1-800-668-1507. 
