megestrol

Megestrol is a synthetic form of progesterone, one of the female sex hormones, and has effects similar to the natural hormone. Megestrol is used to treat extreme weight loss and muscle wasting syndrome (cachexia) associated with acquired immunodeficiency syndrome (AIDS), the advanced stage of human immunodeficiency virus (HIV) infection, and advanced breast and endometrial cancers.

Megestrol appears to stimulate appetite in the treatment of cachexia, and its antiestrogenic property may help retard the growth of estrogen-dependent cancers.

The precise way in which megestrol works to stimulate appetite and increase body mass is not clear. Megestrol may interfere with the activity of inflammatory molecules (catabolic cytokines) that cause appetite loss and the breakdown of proteins leading to weight loss. It is believed to also increase the synthesis and release of neuropeptide Y, a substance in the hypothalamus region of the brain that stimulates appetite.

In breast and endometrial cancer treatments, megestrol interferes with the normal estrogen cycle, reducing the release of estrogen and luteinizing hormone from the pituitary gland, which slows down the growth of estrogen-dependent cancers. Megestrol induces endometrial secretary changes and may also have a direct protective effect on the endometrium.

Uses of megestrol include:

FDA-approved:

• Anorexia or cachexia associated with AIDS
• Palliative treatment of advanced breast cancer
• Palliative treatment of advanced endometrial cancer

Off-label:

• Cancer-related cachexia
• Endometriosis
• Endometrial overgrowth (hyperplasia)
• Ovarian cancer
• Advanced prostate cancer

• Do not use megestrol in patients with hypersensitivity to any of the components in the formulation.
• Do not administer megestrol to pregnant women. Test and rule out pregnancy before initiating treatment. Advise women of pregnancy potential to practice effective contraception. If a patient becomes pregnant while on megestrol therapy apprise them of the hazards to the fetus.
• Do not use megestrol as a prophylaxis to prevent weight loss. Megestrol should be used only after treatable causes for weight loss are assessed and treated.
• Do not administer megestrol to patients with:
  • Blood clots with vein inflammation (thrombophlebitis)
  • Blood clot blocks (thromboembolic disorders)
  • Undiagnosed abnormal genital bleeding
• Megestrol may induce breakthrough vaginal bleeding or discharge in women.
• Prolonged administration of megestrol may cause hypothalamus-pituitary-adrenal (HPA) axis suppression. Monitor patients and if signs of adrenal suppression occur, treat appropriately.
• Chronic use of megestrol can cause Cushing’s syndrome, a disorder caused by excessive buildup of cortisol, the stress hormone.
• Long-term megestrol therapy can cause new onset or exacerbation of diabetes.
• The effects of megestrol treatment on HIV viral replications are not known.

Common side effects of megestrol include:

• Diarrhea
• Gas (flatulence)
• Nausea
• Vomiting
• Indigestion (dyspepsia)
• Abdominal pain
• Constipation
• Oral Candida yeast infection (moniliasis)
• Dry mouth (xerostomia)
• Excessive salivation (sialorrhea)
• Skin rash
• Hair loss (alopecia)
• Itching (pruritus)
• Skin disease
• Dermatitis with blisters (vesicobullous dermatitis)
• Excessive sweating (diaphoresis)
• Impotence
• Breakthrough bleeding
• Decreased libido
• Breast tissue growth in males (gynecomastia)
• Absence of menstruation (amenorrhea)
• Hot flash
• Urinary incontinence
• Urinary frequency
• Urinary tract infection
• Weakness
• Headache
• Pain
• Lethargy
• Fever
• Feeling unwell (malaise)
• Carpal tunnel syndrome
• Reduced skin sensation (hypoesthesia)
• Abnormal skin sensation (paresthesia)
• Nerve damage (neuropathy)
• Convulsions
• Insomnia
• Confusion
• Abnormality in thinking
• Depression
• Mood changes
• Lazy eye (amblyopia)
• High blood pressure (hypertension)
• Heart muscle disease (cardiomyopathy)
• Chest pain
• Cardiac failure
• Palpitations
• Swelling (edema)
• Swelling of extremities (peripheral edema)
• Cough
• Throat inflammation (pharyngitis)
• Shortness of breath (dyspnea)
• Rapid breathing (hyperventilation)
• Pulmonary disorder
• Pneumonia
• High blood glucose levels (hyperglycemia)
• Diabetes mellitus
• High blood calcium levels (hypercalcemia)
• Increase in lactate dehydrogenase (LDH) enzyme
• Albumin in urine (albuminuria)
• Adrenocortical insufficiency
• Hypothalamus-pituitary-adrenal axis suppression
• Cushing’s syndrome, a disorder caused by excessive levels of the stress hormone, cortisol
• Weight gain
• Liver enlargement (hepatomegaly)
• Low blood count of leukocyte immune cells (leukopenia)
• Cancer of bone and connective tissue (sarcoma)
• Tumor flare
• Infection
• Herpes virus infection
• Candida yeast infection

Less common side effects of megestrol include:

• Reduced glucose tolerance
• Blood clot block-related (thromboembolic) conditions including:
  • Deep vein thrombosis (DVT)
  • Pulmonary embolism
  • Thrombophlebitis

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 20 mg
• 40 mg

Oral Suspension

• 200 mg/5mL
• 625 mg/5mL

Adult:

AIDS-Related Cachexia

• Megace: 800 mg/day orally
• Megace ES: 312.5-625 mg/day orally

Breast Cancer

• 40 mg orally every 6 hours

Endometrial Cancer

• 40-320 mg/day orally in divided doses; evaluate efficacy after 2 months of treatment; up to 800 mg/day may be used

Cancer-Related Cachexia (Off-label)

• 480-600 mg/day orally

Dosing Modifications

• Renal impairment: Use with caution; in normal renal function, 57-78% is excreted in urine within 10 days

Pediatric:

• Safety and efficacy not established

Overdose

• Megestrol overdose of up to 1200 mg/day has not resulted in unexpected serious adverse effects. Overdose may be treated with symptomatic and supportive care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Megestrol has no known severe interactions with other drugs.
• Serious interactions of megestrol include:
  • mavacamten
• Moderate interactions of megestrol include:
  • insulin degludec
  • insulin degludec/insulin aspart
  • insulin inhaled
  • siponimod
  • warfarin
• Mild interactions of megestrol include:
  • maitake
  • taurine

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on the use of megestrol in pregnant women. Animal studies indicate megestrol can cause fetal harm if administered to pregnant women.
• Women of childbearing potential should be tested for pregnancy before initiating megestrol treatment. Megestrol should not be administered to pregnant women.
• Women of pregnancy potential should use effective contraception while on megestrol treatment.
• Megestrol is excreted in breast milk. Nursing mothers should discontinue nursing while being treated with megestrol, because of the potential for serious adverse reactions in the breastfed infant.

• Take megestrol exactly as prescribed.
• Do not use the brands Megace and Megace ES interchangeably.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.