Megestrol Acetate

1. Health Canada Product Monograph — Megestrol Acetate

• Megestrol acetate is used for the adjunctive or palliative treatment of recurrent, inoperable, or metastatic breast cancer.
• Megestrol acetate is used for the adjunctive or palliative treatment of recurrent, inoperable, or metastatic endometrial cancer.
• Megestrol acetate is used for the palliative treatment of hormone-responsive advanced (Stage D2) prostate cancer.
• Megestrol acetate is used to treat anorexia, cachexia, or significant unexplained weight loss associated with cancer.
• Megestrol acetate is not a substitute for standard treatments such as surgery or radiation, and it should not be used as a pregnancy test.

• Use of megestrol acetate during the first four months of pregnancy is not recommended.
• Progestational agents used in early pregnancy have been linked to genital abnormalities in the fetus, including an increased risk of hypospadias in male infants and possible mild virilization of female fetuses.
• Women of childbearing potential should avoid becoming pregnant while taking megestrol acetate and should use effective contraception.
• If pregnancy occurs or is suspected while taking megestrol acetate, the patient should notify her physician promptly to discuss the potential risks to the fetus.

• Breastfeeding should be discontinued during megestrol acetate therapy, because many drugs pass into human breast milk and could cause adverse effects in a nursing infant.

• Specific dosing guidance for older adults is not established in the product monograph; general caution and monitoring for adverse effects, including thromboembolic events and fluid retention, is appropriate given the population typically treated with this drug.

• The safety and effectiveness of megestrol acetate in children have not been established, and it is not authorized for pediatric use.

• For palliative or adjunctive treatment of breast cancer, the usual dose is 160 mg daily, given as 40 mg four times daily or 160 mg once daily.
• For endometrial cancer, the usual dose is 80 to 320 mg daily in divided doses.
• For hormone-responsive advanced prostate cancer, the usual dose is 120 mg once daily, given together with diethylstilbestrol 0.1 mg.
• For anorexia, cachexia, or significant weight loss related to cancer, the usual dose is 400 to 800 mg once daily.
• At least two months of continuous treatment is recommended to properly assess response for the cancer indications.
• No formal dose adjustment guidance is provided for renal or hepatic impairment; patients with these conditions should be monitored closely.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• The Health Canada product monograph does not describe a specific overdose toxidrome for megestrol acetate; studies using doses as high as 1600 mg per day for 6 months or longer did not identify any unexpected or serious effects beyond its usual safety profile.
• Usual safety measures should still be taken as with overdose of any medication.
• Because megestrol acetate has low solubility, dialysis is not expected to be an effective way to remove it from the body.

• Weight gain, usually associated with increased appetite, is a frequent effect and is the basis for its use in anorexia and cachexia.
• Nausea may occur.
• Vomiting may occur.
• Fluid retention (edema) may occur.
• Hot flashes may occur.
• Mood changes may occur.
• Hair loss (alopecia) may occur.
• Diarrhea may occur.
• Fatigue (lethargy) may occur.
• Skin rash may occur.
• Breast enlargement in males (gynecomastia) may occur.
• Constipation may occur, particularly at higher doses.
• Increased urinary frequency may occur, particularly at higher doses.
• Gas (flatulence) may occur.
• Reduced sexual function (impotence) may occur in men.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Breakthrough uterine bleeding can occur.
• Blood clots, including thrombophlebitis and pulmonary embolism, have been reported and can be fatal.
• Heart failure or worsening of existing heart failure has been reported.
• High blood pressure (hypertension) may occur.
• Shortness of breath (dyspnea) has been reported.
• Cushingoid features (rounded "moon" face, easy bruising) and Cushing's syndrome can develop, related to the drug's glucocorticoid-like activity.
• Adrenal gland suppression can occur, particularly with high-dose or prolonged therapy, and may become apparent when the drug is stopped; replacement corticosteroid doses may be needed during periods of stress.
• Tumour flare, sometimes with high blood calcium (hypercalcemia), can occur.
• High blood sugar (hyperglycemia), reduced glucose tolerance, and new-onset or worsening diabetes have been reported.
• Hearing loss has been reported.
• Carpal tunnel syndrome has been reported.
• Seek urgent medical attention for sudden shortness of breath or chest pain (possible blood clot), signs of heart failure such as swelling or difficulty breathing, or symptoms of very high blood sugar.

• Use with caution in patients with a history of blood clots (thrombophlebitis), given the reported risk of thromboembolic events.
• Use with caution in patients with diabetes or risk factors for diabetes, since megestrol acetate can raise blood sugar and impair glucose tolerance.
• Use with caution in patients with heart failure or fluid retention, since megestrol acetate can cause edema and worsen heart failure.
• Use with caution in patients being withdrawn from long-term therapy, and monitor for signs of adrenal suppression; replacement corticosteroid doses may be needed.
• Investigate and treat other possible causes of weight loss, such as infection, malignancy, gastrointestinal disease, or endocrine or kidney disease, before starting megestrol acetate for anorexia or cachexia.
• Use with caution in women with HIV infection, who reported breakthrough uterine bleeding in clinical experience.
• Close, routine monitoring is recommended, as with any patient being treated for recurrent or metastatic cancer.

• Contraindicated in patients with known hypersensitivity to megestrol acetate or to any ingredient in the tablet formulation.
• Megestrol acetate should not be used as a diagnostic test for pregnancy.

• Formal drug interaction studies with megestrol acetate have not been conducted.
• Because megestrol acetate can raise blood sugar, it may reduce the effectiveness of insulin or oral diabetes medications, and blood sugar should be monitored closely when starting or stopping therapy.
• As a steroid hormone that can affect clotting factors, megestrol acetate may alter the effect of anticoagulants such as warfarin, and closer monitoring is reasonable when these are combined.
• Since megestrol acetate is metabolized in the liver, drugs that strongly induce or inhibit hepatic drug-metabolizing enzymes could theoretically alter megestrol acetate blood levels, although this has not been formally studied.

• No specific food interactions have been established for megestrol acetate; it may be taken without regard to meals.

• Megestrol acetate for cancer indications is typically taken in divided doses through the day; for anorexia or cachexia, the full daily dose is usually taken once daily.

• Store at room temperature (15°C to 30°C) in a well-closed container.

• Megestrol acetate is a progestin tablet used either to palliate certain hormone-sensitive cancers or to stimulate appetite and reduce weight loss related to cancer.
• Weight gain and increased appetite are expected effects when used for anorexia or cachexia; nausea, hot flashes, and fluid retention are also common.
• Tell your healthcare professional about any history of blood clots, diabetes, or heart failure before starting, and seek urgent care for sudden shortness of breath, chest pain, or leg swelling.
• Megestrol acetate is not recommended in the first four months of pregnancy and should not be used while breastfeeding; store tablets at room temperature.