Updated: February 5, 2008

SYNONYM(S): megestrol acetate¹

Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

MECHANISM OF ACTION:

PHARMACOKINETICS:

Adapted from standard reference¹ unless specified otherwise.

USES:

*Health Canada approved indication

SPECIAL PRECAUTIONS:

Caution:

• history of thrombophlebitis¹
• adrenocortical insufficiency¹; see paragraph following the Side Effects table
• diabetes (due to risk of hyperglycemia)⁶
• should not be used as a diagnostic test for pregnancy¹
• HIV infected women (due to risk of breakthrough bleeding)¹
• should not be used prophylactically to avoid weight loss⁶

Carcinogenicity: An increased incidence of benign and malignant breast tumours has been reported in female dogs treated for up to seven years; an increased incidence has not been noted in monkeys when treated for up to ten years.¹ Dogs treated with 10-25 times the human dose, on a mg/kg basis, have developed mammary carcinoma with metastasis.¹ Pituitary tumours have occurred in female rats treated for 2 years.¹ Malignant lymphoma in mice may be stimulated.¹ The relevance of these findings to humans has not been established.¹

Mutagenicity: studies not performed to date^1,3

Fertility: In monkeys, megestrol caused decreased mean uterine weights and estrogen activity and a dose-related reduction in menses with near cessation of cyclic activity at 5 times the human dose on a mg/kg basis.¹ Impaired fertility in male offspring of female rats and dogs receiving doses equivalent to less than the recommended human dose has also been reported.^1,3 No information has been found regarding fertility in male animals.³

Pregnancy: FDA Pregnancy Category X.⁴ Studies in animals or humans have shown fetal abnormalities,¹ or there is evidence of fetal risk based on human experience, or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Breastfeeding is not recommended due to the potential secretion into breast milk.¹

SIDE EFFECTS:

The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be clinically important.⁷

Adapted from standard reference¹ unless specified otherwise.

Adrenal insufficiency: Megestrol may rarely suppress the pituitary-adrenal axis during chronic administration.¹ Glucose intolerance, new onset diabetes, exacerbation of preexisting diabetes, and Cushing’s syndrome have been reported.⁶ Consider the possibility of adrenal insufficiency in patients being withdrawn from chronic therapy.¹ Symptoms may include fatigue, anorexia, hypotension, and asthenia.¹¹ Replacement therapy with a rapid-acting glucocorticoid should be considered.⁴

INTERACTIONS:

SUPPLY AND STORAGE:

Tablets: Apotex and Bristol-Myers Squibb supply megestrol as 40 mg and 160 mg scored tablets. Selected non-medicinal ingredients: lactose.^1,6 Store at room temperature.^1,6

Additional information: Bristol-Myers Squibb supplies megestrol as a 240 ml bottle of 40 mg/mL suspension (only indicated for the treatment of anorexia in patients with a diagnosis of acquired immunodeficiency syndrome).⁶

MEGACE® ES 125 mg/mL (USA) is not equivalent on a mg per mg basis with other megestrol formulations due to its increased bioavailability^3,10 (625 mg MEGACE® ES is equivalent to 800 mg megestrol tablets or suspension).

DOSAGE GUIDELINES:

Refer to protocol by which patient is being treated.

Adults:

Children:

References:

1. Apotex Inc. Apo-Megestrol Product Monograph. Weston, Ontario; 18 June 1998.

2. National Institute for Occupational Safety and Health (NIOSH). Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. Cincinnati, Ohio: NIOSH - Publications Dissemination; September 2004. p. 31-40.

3. McEvoy GK, editor. AHFS 2007 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc. p. 1123-1125.

4. Rose BD editor. Megestrol acetate. UpToDate 15.2 ed. Waltham, Massachusetts: UpToDate®; 2007.

5. MARTINDALE- The Complete Drug Reference (database on the Internet). Megestrol acetate. Thomson MICROMEDEX®, 2007. Available at: http://www.micromedex.com/. Accessed 24 September 2007.

6. Bristol-Myers Squibb Canada Inc. MEGACE® AND MEGACE® OS Product Monograph. Cote de Liesse Rd, Montreal; 22 September 1999.

7. Nicol Macpherson MD. Personal communication. BC Cancer Agency Breast Tumour Group; 17 December 2007.

8. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.

9. Solimando Jr DA. Aminoglutethimide and megestrol. Hospital Pharmacy 1999;34(3):271-276.

10. DRUGDEX® Evaluations (database on the Internet). Megestrol. Thomson MICROMEDEX®, 2007. Available at: http://www.micromedex.com/. Accessed 24 September 2007.

11. Rose BD editor. Diagnosis of adrenal insufficiency in adults. UpToDate 15.3 ed. Waltham, Massachusetts: UpToDate®; 2008.

12. Drug Interaction Facts (database on the Internet). Megestrol acetate monograph. Facts and Comparisons 4.0, 2007. Available at: http://online.factsandcomparisons.com. Accessed 24 August 2007.

13. BC Cancer Agency Breast Tumour Group. (BRAVMEG) BCCA Protocol Summary for Palliative Therapy for Advanced Breast Cancer Using Megestrol. Vancouver, British Columbia: BC Cancer Agency; 1 December 2002.

14. Azcona C, Castro L, Crespo E, et al. Megestrol acetate therapy for anorexia and weight loss in children with malignant solid tumours. Aliment.Pharmacol.Ther. 1996;10(4):577-586.