What to Know About Megace (Megestrol acetate)

Megace (megestrol acetate) is an appetite stimulant used in adults with severe weight loss due to advanced HIV infection. Available as an oral solution, Megace is a man-made chemical similar to the female hormone progesterone that can help achieve weight gain in people with HIV wasting syndrome, an AIDS-defining condition.

Available as a generic, Megace is also often used to treat anorexia (loss of appetite), cachexia (wasting), and severe weight loss in people with advanced cancer. While the exact mechanism of action of Megace is unclear, the drug is known to induce non-fluid weight gain by increasing body fat as opposed to muscle mass.

Uses

Megace is licensed for use by the Food and Drug Administration (FDA) to treat unexplained, severe weight loss in adults with AIDS. This is the stage of HIV where the immune system is fully compromised, increasing a person's vulnerability to an ever-widening range of opportunistic infections.

The Centers for Disease Control and Prevention (CDC) further defines AIDS as having a CD4 count under 200 or any one of 24 AIDS-defining conditions, of which HIV wasting is one.

Unexplained, severe weight loss is the central feature of HIV wasting syndrome. This is defined as loss of more than 10% of a person's body weight, along with diarrhea or weakness and fever that lasts for more than 30 days, and that is independent of any infection or disease.

HIV wasting syndrome is not as common as it used to be due to the widespread use of antiretroviral therapy. Even so, an estimated one in 10 people with HIV will have some evidence of HIV-associated weight loss.

Off-Label Uses

Megace is commonly used off-label to treat cachexia and anorexia in people with advanced cancer. In addition to stimulating weight gain, Megace has antineoplastic (anti-tumor) properties and is often used for the palliative treatment of advanced breast cancer and endometrial cancer.

Megace has also been widely used off-label to treat anorexia and cachexia in people with:

• Endometriosis
• Geriatric wasting syndrome
• Hepatocellular carcinoma (liver cancer)
• Ovarian cancer
• Prostate cancer

Before Taking

Megace is a Pregnancy Category X drug, meaning that it is contraindicated for use in pregnancy. Animal studies have shown that megestrol acetate, even at low doses, affects fetal development and increases the risk of stillbirth, miscarriage, low birth weight, and the feminization of male fetuses.

Before Megace is prescribed, women of childbearing age are given a pregnancy test to ensure they are not pregnant. They will also be advised to use approved forms of contraception to avoid pregnancy. Breastfeeding must also be discontinued once Megace is prescribed.

Megace is also contraindicated for use in people with a known hypersensitivity to megestrol acetate or any of the inactive ingredients in the product (including citric acid or sodium benzoate).

Megace should also be used with caution in people with diabetes or prediabetes. The chronic use of Megace has been linked to cases of new-onset diabetes as well as the loss of blood sugar control in people with pre-existing diabetes. If used, blood glucose levels must be closely monitored.

Other Treatments for HIV Wasting

There is no standardized approach for treating HIV wasting syndrome. Megace is one option that may be used in combination with:

• Increased caloric intake
• Appropriate exercise, including resistance training
• Nutritional support, including micronutrient supplements and protein drinks
• Anti-diarrheal treatment, including the drug Mytesi (crofelemer) used to treat HIV-associated diarrhea
• Testosterone replacement therapy
• Human growth hormone (HGH)
• Medical marijuana

Dosage

Megace is an oral solution available in 150-milliliter (mL) bottles. It is milky white in color and has a sweetened lemon-lime flavor. There are two formulations available:

• Megace oral solution, which contains 40 milligrams (mg) of megestrol acetate per milliliter
• Megace ES oral solution, which contains 125 mg of megestrol acetate per milliliter

The recommended adult dose is 625 mg per day. For Megace oral solution, that translates to roughly three tablespoons. For Megace ES oral solution, that translates to roughly one tablespoon.

Megace is not used in children.

How to Take and Store

Be sure to shake the bottle well before use. Rather than "eyeballing" the dose, use a measuring spoon or syringe to ensure you take no more or less than the prescribed dose.

Megace can be stored safely at room temperature, ideally between 59 and 77 degrees F (15 to 25 degrees C). Keep Megace in its original light-resistant container and well away from heat sources (including sunny windowsills). Discard contents that have expired.

Side Effects

As with all drugs, Megace can cause side effects. Some are more common than others, and, on rare occasions, severe side effects can develop. Call your doctor if side effects seem unusual, are persistent, or get worse.

Common

Many of the side effects of Megace are transient and resolve over time as your body adapts to treatment. Others occur with long-term use of the drug, typically due to the hormonal effects it exerts on the body

Some of the more common side effects of Megace include (by order of frequency):

• Diarrhea (10%)
• Skin rash (6% to 12%)
• Hyperglycemia (6%)
• Impotence or decreased libido (4% to 14%)
• High blood pressure (4% to 8%)
• Headache (3% to 10%)
• Fever (1% to 6%)
• Insomnia (1% to 6%)
• Cough (1% to 3%)
• Chest pain (1% to 3%)
• Palpitations (1% to 3%)
• Depression (1% to 3%)
• Neuropathy (1% to 3%)
• Itchiness (1% to 3%)
• Gynecomastia (1% to 3%)
• Constipation (1% to 3%)
• Urinary incontinence (1% to 3%)

Severe

On rare occasions, severe side effects can develop, typically with ongoing use. This includes the new onset of diabetes or the worsening of diabetes symptoms.

The chronic use of Megace has also been known to cause Cushing's syndrome, a disorder caused by the overactivation of the adrenal glands and the overproduction of the stress hormone cortisol. Symptoms include fatigue, extreme thirst, menstrual changes, hirsutism (abnormal body hair), purple stretch marks, erectile dysfunction, and "moon face."

Warnings and Interactions

Megace can cause a contrary reaction called adrenal insufficiency when the drug is abruptly stopped after long-term use. Also known as Addison's disease, adrenal insufficiency is characterized by a severe drop in cortisol levels, causing low blood pressure, excessive urination, weight loss, muscle weakness, loss of libido, and the absence of menstruation.

In rare cases, the sudden discontinuation of Megace can lead to an acute adrenal crisis requiring emergency care. Call 911 if you experience:

• High fever
• Lightheadedness or dizziness
• Nausea or vomiting
• Profuse sweating
• Abdominal pain
• Rapid heartbeat
• Rapid respiratory rate
• Confusion
• Loss of consciousness

Drug Interactions

Megace causes few drug interactions, and those that occur rarely require a dose adjustment or change of treatment. The one exception is the antiretroviral drug Crixivan (indinavir), used to treat HIV, the combined use of which can cause Crixivan levels to drop in the bloodstream.

Crixivan was voluntarily discontinued by the manufacturer in March 2020 and is no longer in use.