What Is Megestrol Acetate (Megace)? FDA Approval, Licensing in Turkey, and Reimbursement Status

• FDA-Approved: Yes (First approval date: 1971)
• Brand Names: Megace (original product), Borea (generic/equivalent)
• Active Ingredient: Megestrol Acetate
• Method of Administration: Tablet form
• Class: Progestational agent
• Category: Hormonal therapy
• Manufacturers: Bristol-Myers Squibb, Onko İlaç San. ve Tic. A.Ş.
• Distribution in Turkey: DEVA İlaç San. ve Tic. A.Ş., ONKO İlaç San. ve Tic. A.Ş.
• Approved Indications:
  • Breast cancer
  • Endometrial cancer
  • Renal cell carcinoma (RCC)
  • Loss of appetite and weight loss associated with cancer and HIV/AIDS

What Is Megace?

Megace is a hormonal medication containing the active ingredient megestrol acetate, which belongs to the progestational agent class. It is used particularly to treat breast and endometrial cancer. It is also used as an appetite stimulant to treat weight loss and poor appetite associated with cancer and HIV/AIDS.

What Is a Progestational Agent?

Progestational agents are drugs that act similarly to the hormone progesterone and play a role particularly in maintaining hormonal balance. Through its antiestrogenic effects, megestrol acetate suppresses tumor growth in certain cancers by reducing the stability, availability, and turnover of estrogen receptors.

How Does It Work?

• Megace is a synthetic derivative of the natural hormone progesterone.
• By inhibiting the enzyme 17-hydroxysteroid dehydrogenase, it promotes the conversion of estradiol to estrone, a less active metabolite.
• By activating estrogen sulfotransferase, it accelerates the conversion of estrogen into less active metabolites.
• It lowers estrogen levels by suppressing luteinizing hormone (LH) receptors.
• At the cellular level, it reduces estrogen receptor stability and activity, slowing growth particularly in estrogen-sensitive tumors.

Through these mechanisms, Megace is used as an effective treatment for estrogen-dependent cancers such as breast and endometrial cancer. Because of its appetite-stimulating effect, it may also be prescribed to provide nutritional support for patients experiencing weight loss.

FDA (United States Food and Drug Administration) Approval History

• June 24, 1971:
  • Megestrol acetate was approved by the FDA for the palliative treatment of advanced endometrial cancer.
• November 10, 1983:
  • It was approved for the palliative treatment of advanced breast cancer.
• December 5, 1993:
  • Its use was expanded to treat anorexia, cachexia, or unexplained weight loss associated with HIV/AIDS.
• July 27, 2001:
  • The FDA formally expanded its use to treat poor appetite and weight loss associated with cancer and HIV/AIDS.
• March 1, 2005:
  • It received an additional approval for HIV-associated cachexia syndrome.
• October 18, 2012:
  • Its use was expanded to manage poor appetite and weight loss in older patients.

Licensing in Turkey

The conditions for which Megace is licensed in Turkey / its therapeutic indications are listed as follows:

It is indicated for the palliative treatment of breast cancer (e.g., recurrent, inoperable, or metastatic disease) and for the treatment of cancer-related anorexia or weight loss.

Is Megace Reimbursed?

The treatment situations in which Megace is covered by the Social Security Institution (SGK) are as follows:

It is covered by SGK when used for the palliative treatment of breast cancer (e.g., recurrent, inoperable, or metastatic disease) and for the treatment of cancer-related anorexia or weight loss.

Price:

As of January 2025, pharmacy retail prices in Turkey for medications containing megestrol acetate were:

• Megace 160 mg, 30 tablets: 905.08 TL
• Borea 160 mg, 30 tablets: 663.95 TL

Resistance Mechanisms

• Increased expression of the P-glycoprotein drug efflux transporter:
  • This transporter can reduce the intracellular effectiveness of megestrol acetate by pumping drugs taken into the cell back out.
• Reduced expression of p53-binding protein 1 (53BP1):
  • By preventing the repair of DNA double-strand breaks, this can cause cells to develop resistance to drug treatment.
• Changes in hormonal receptor regulation:
  • A decrease in progesterone receptors following long-term use may reduce the drug's effectiveness.
• Stabilization of the replication fork:
  • Changes in DNA repair processes and adaptation of cellular proliferation mechanisms may contribute to the development of resistance to megestrol acetate.

Pharmacokinetic Properties

• Absorption
  • Oral bioavailability is high. Absorption is rapid, with peak plasma concentrations reached within 2-3 hours. Taking it with food may change the rate of absorption, but bioavailability is not substantially affected.
• Distribution
  • Megestrol acetate is 90% bound to plasma proteins.
  • With daily dosing, steady-state blood levels are reached within a few days.
• Metabolism
  • It is metabolized by CYP3A4 enzymes in the liver.
  • A large proportion of the drug is converted into inactive metabolites through glucuronidation.
  • It is excreted 66% in urine and 20% in feces.
  • The terminal half-life has been determined to be approximately 34 hours.
• Dosage Range
  • For breast and endometrial cancer: 40 mg PO, 4 times daily.
  • As an appetite stimulant: 400-800 mg PO daily.

Drug Interactions

• Drugs that induce or inhibit the CYP3A4 enzyme may interact with megestrol acetate.
• Caution is required when used with anticoagulants because it may cause changes in coagulation parameters.
• Monitoring blood glucose levels is recommended when it is used with diabetes medications.

Precautions

• Risk of thromboembolic events:
  • Megestrol acetate may increase the risk of thromboembolic events. It should be used cautiously in patients with a history of thromboembolic disease or hypercoagulability disorders.
• Hyperglycemia in patients with diabetes:
  • Megestrol acetate may increase insulin resistance and cause hyperglycemia. Blood glucose levels must be monitored regularly in patients with diabetes.
• Dosage adjustment in patients with hepatic impairment:
  • In patients with impaired liver function, megestrol acetate metabolism may slow, and drug levels may increase. Dosage adjustment should therefore be made.
• Risk of weight gain and fluid retention:
  • Megestrol acetate may cause weight gain and fluid retention by increasing appetite. Patients should be informed about a low-sodium diet.
• Risk of adrenal suppression:
  • Long-term use may lead to adrenal insufficiency. Dose reduction should be carried out carefully.
• Pregnancy and breastfeeding:
  • Megestrol acetate, which is in pregnancy category D, should not be used during pregnancy. Its use is also not recommended in breastfeeding mothers because it may pass into breast milk and harm the infant.
• Hormonal adverse effects:
  • It may cause hormonal changes such as hot flashes, sweating, and mood changes.
• Menstrual irregularities:
  • Breakthrough menstrual bleeding may occur. Patients should be informed of this possibility.

Adverse Effects

• Weight gain
• Hyperglycemia and changes in blood glucose levels
• Edema and fluid retention
• Thromboembolic events (deep vein thrombosis, pulmonary embolism), (particular caution is required in patients with a history of thromboembolic or hypercoagulation disorders.)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation)
• Adrenal suppression and changes in cortisol levels
• Skin rashes and itching
• Changes in sexual desire
• Fatigue and weakness