Megestrol

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Megestrol
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Overview

Megestrol is a progestin that is FDA approved for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).. Common adverse reactions include Hypertension, Rash, Hot sweats, Weight gain, Diarrhea, Mood swings, Erectile dysfunction.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • MEGACE Oral Suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

Dosage

  • The recommended adult initial dosage of MEGACE Oral Suspension is 800 mg/day (20 mL/day). Shake container well before using.

In clinical trials evaluating different dose schedules, daily doses of 400 and 800 mg/day were found to be clinically effective.

A plastic dosage cup with 10 mL and 20 mL markings is provided for convenience.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Megestrol in adult patients.

Non–Guideline-Supported Use

  • Cachexia - Cancer[1]
  • Cachexia - Cystic fibrosis[2]
  • Carcinoma of prostate, Advanced hormone-refractory[3]
  • Endometrial hyperplasia[4]
  • Endometriosis[5]
  • Hot sweats, In women with a history of breast cancer[6]
  • Malignant melanoma[7]
  • Malignant neoplasm of liver[8]
  • Mullerian mixed tumor, Adenosarcoma[9]
  • Ovarian carcinoma[10]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Megestrol in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Megestrol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Megestrol in pediatric patients.

Contraindications

  • History of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy.

Warnings

  • Megestrol acetate may cause fetal harm when administered to a pregnant woman. For animal data on fetal effects, see PRECAUTIONS: CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: IMPAIRMENT OF FERTILITY. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Megestrol acetate is not intended for prophylactic use to avoid weight loss.

(See also PRECAUTIONS: CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY.)

The glucocorticoid activity of MEGACE (megestrol acetate, USP) Oral Suspension has not been fully evaluated. Clinical cases of new onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and overt Cushing’s syndrome have been reported in association with the chronic use of MEGACE. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic MEGACE therapy in the stressed and non-stressed state. Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealed the frequent occurrence of asymptomatic pituitary-adrenal suppression in patients treated with chronic MEGACE therapy. Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic MEGACE therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (eg, hypotension, nausea, vomiting, dizziness, or weakness) in either the stressed or non-stressed state. Laboratory evaluation for adrenal insufficiency and consideration of replacement or stress doses of a rapidly acting glucocorticoid are strongly recommended in such patients. Failure to recognize inhibition of the hypothalamic-pituitary-adrenal axis may result in death. Finally, in patients who are receiving or being withdrawn from chronic MEGACE therapy, consideration should be given to the use of empiric therapy with stress doses of a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (eg, surgery, infection).

Precautions

General Therapy with MEGACE Oral Suspension for weight loss should only be instituted after treatable causes of weight loss are sought and addressed. These treatable causes include possible malignancies, systemic infections, gastrointestinal disorders affecting absorption, endocrine disease, and renal or psychiatric diseases.

Effects on HIV viral replication have not been determined.

Use with caution in patients with a history of thromboembolic disease.

Use in Diabetics Exacerbation of preexisting diabetes with increased insulin requirements has been reported in association with the use of MEGACE.

Animal Toxicology Long-term treatment with MEGACE may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a 2-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats.

Adverse Reactions

Clinical Trials Experience

  • Clinical Adverse Events

Adverse events which occurred in at least 5% of patients in any arm of the two clinical efficacy trials and the open trial are listed below by treatment group. All patients listed had at least one post baseline visit during the 12 study weeks. These adverse events should be considered by the physician when prescribing MEGACE Oral Suspension.

Adverse events which occurred in 1% to 3% of all patients enrolled in the two clinical efficacy trials with at least one follow-up visit during the first 12 weeks of the study are listed below by body system. Adverse events occurring less than 1% are not included. There were no significant differences between incidence of these events in patients treated with megestrol acetate and patients treated with placebo.

Body as a Whole: abdominal pain, chest pain, infection, moniliasis and sarcoma

Cardiovascular System: cardiomyopathy and palpitation

Digestive System: constipation, dry mouth, hepatomegaly, increased salivation and oral moniliasis

Hemic and Lymphatic System: leukopenia

Metabolic and Nutritional: LDH increased, edema and peripheral edema

Nervous System: paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking

Respiratory System: dyspnea, cough, pharyngitis and lung disorder

Skin and Appendages: alopecia, herpes, pruritus, vesiculobullous rash, sweating and skin disorder

Special Senses: amblyopia

Urogenital System: albuminuria, urinary incontinence, urinary tract infection and gynecomastia

Postmarketing Experience

  • Postmarketing reports associated with MEGACE Oral Suspension include thromboembolic phenomena including thrombophlebitis and pulmonary embolism, and glucose intolerance

Drug Interactions

  • Pharmacokinetic studies show that there are no significant alterations in pharmacokinetic parameters of zidovudine or rifabutin to warrant dosage adjustment when megestrol acetate is administered with these drugs. The effects of zidovudine or rifabutin on the pharmacokinetics of megestrol acetate were not studied.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): X

  • No adequate animal teratology information is available at clinically relevant doses.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Megestrol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Megestrol during labor and delivery.

Nursing Mothers

  • Because of the potential for adverse effects on the newborn, nursing should be discontinued if MEGACE Oral Suspension is required.

Pediatric Use

  • Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

Clinical studies of MEGACE Oral Suspension in the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with AIDS did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

  • Megestrol acetate is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Gender

  • Breakthrough bleeding was observed in all 10 female patients participating in the clinical trials. Megace is a progesterone derivative, which may induce vaginal bleeding in women.

Race

There is no FDA guidance on the use of Megestrol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Megestrol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Megestrol in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Megestrol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Megestrol in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

  • Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

IV Compatibility

There is limited information regarding IV Compatibility of Megestrol in the drug label.

Overdosage

  • No serious unexpected side effects have resulted from studies involving MEGACE Oral Suspension administered in dosages as high as 1200 mg/day. In post-marketing experience, limited reports of overdose have been received. Signs and symptoms reported in the context of overdose included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain. There is no specific antidote for overdose with MEGACE Oral Suspension. In case of overdose, appropriate supportive measures should be taken. Megestrol acetate has not been tested for dialyzability; however, due to its low solubility, it is postulated that dialysis would not be an effective means of treating overdose.

Pharmacology

There is limited information regarding Megestrol Pharmacology in the drug label.

Mechanism of Action

Structure

File:Megestrol01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Megestrol in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Megestrol in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis

Data on carcinogenesis were obtained from studies conducted in dogs, monkeys, and rats treated with megestrol acetate at doses 53.2, 26.6, and 1.3 times lower than the proposed dose (13.3 mg/kg/day) for humans. No males were used in the dog and monkey studies. In female beagles, megestrol acetate (0.01, 0.1, or 0.25 mg/kg/day) administered for up to 7 years induced both benign and malignant tumors of the breast. In female monkeys, no tumors were found following 10 years of treatment with 0.01, 0.1, or 0.5 mg/kg/day megestrol acetate. Pituitary tumors were observed in female rats treated with 3.9 or 10 mg/kg/day of megestrol acetate for 2 years. The relationship of these tumors in rats and dogs to humans is unknown but should be considered in assessing the risk-to-benefit ratio when prescribing MEGACE Oral Suspension and in surveillance of patients on therapy. (See WARNINGS.)

Mutagenesis

No mutagenesis data are currently available.

Impairment of Fertility

Perinatal/postnatal (segment III) toxicity studies were performed in rats at doses (0.05–12.5 mg/kg) less than that indicated for humans (13.3 mg/kg); in these low dose studies, the reproductive capability of male offspring of megestrol acetate-treated females was impaired. Similar results were obtained in dogs. Pregnant rats treated with megestrol acetate showed a reduction in fetal weight and number of live births, and feminization of male fetuses. No toxicity data are currently available on male reproduction (spermatogenesis).

Clinical Studies

There is limited information regarding Clinical Studies of Megestrol in the drug label.

How Supplied

Storage

There is limited information regarding Megestrol Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Patients using megestrol acetate should receive the following instructions:

This medication is to be used as directed by the physician. Report any adverse reaction experiences while taking this medication. Use contraception while taking this medication if you are a woman capable of becoming pregnant. Notify your physician if you become pregnant while taking this medication..

Precautions with Alcohol

  • Alcohol-Megestrol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Loprinzi CL, Ellison NM, Schaid DJ, Krook JE, Athmann LM, Dose AM; et al. (1990). "Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia". J Natl Cancer Inst. 82 (13): 1127–32. PMID 2193166.
  2. ↑ Marchand V, Baker SS, Stark TJ, Baker RD (2000). "Randomized, double-blind, placebo-controlled pilot trial of megestrol acetate in malnourished children with cystic fibrosis". J Pediatr Gastroenterol Nutr. 31 (3): 264–9. PMID 10997370.
  3. ↑ Bonomi P, Pessis D, Bunting N, Block M, Anderson K, Wolter J; et al. (1985). "Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer". Semin Oncol. 12 (1 Suppl 1): 36–9. PMID 3975650.
  4. ↑ Gal D (1986). "Hormonal therapy for lesions of the endometrium". Semin Oncol. 13 (4 Suppl 4): 33–6. PMID 3798126.
  5. ↑ Schlaff WD, Dugoff L, Damewood MD, Rock JA (1990). "Megestrol acetate for treatment of endometriosis". Obstet Gynecol. 75 (4): 646–8. PMID 2314784.
  6. ↑ Goodwin JW, Green SJ, Moinpour CM, Bearden JD, Giguere JK, Jiang CS; et al. (2008). "Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: Southwest Oncology Group Study 9626". J Clin Oncol. 26 (10): 1650–6. doi:10.1200/JCO.2006.10.6179. PMID 18375894.
  7. ↑ Creagan ET, Schutt AJ, Ahmann DL, Green SJ (1982). "Phase II study of high-dose megestrol acetate in patients with advanced malignant melanoma". Cancer Treat Rep. 66 (5): 1239–40. PMID 7083227.
  8. ↑ Villa E, Ferretti I, Grottola A, Buttafoco P, Buono MG, Giannini F; et al. (2001). "Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors". Br J Cancer. 84 (7): 881–5. doi:10.1054/bjoc.2000.1534. PMC 2363845. PMID 11286465.
  9. ↑ Hines BJ, Porges RF, Mittal K, Muggia FM, Curtin JP (2002). "Use of medroxyprogesterone acetate in the treatment of Müllerian adenosarcoma: a case report". Gynecol Oncol. 85 (1): 192–5. doi:10.1006/gyno.2002.6585. PMID 11925144.
  10. ↑ Wilailak S, Linasmita V, Srisupundit S (2001). "Phase II study of high-dose megestrol acetate in platinum-refractory epithelial ovarian cancer". Anticancer Drugs. 12 (9): 719–24. PMID 11593052.
  11. ↑ Empty citation (help)
  12. ↑ "http://www.ismp.org". External link in |title= (help)

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