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Pronunciation
(me JES trole)
Generic Available (U.S.)
Yes: Excludes Megace® ES
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Palliative treatment of breast and endometrial carcinoma; treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS
Pregnancy Risk Factor
D (tablet) / X (suspension)
Pregnancy Considerations
Adverse effects were demonstrated in animal studies. Use during pregnancy is contraindicated (suspension).
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Due to the potential for adverse reaction in the newborn, the manufacturer recommends discontinuing breast-feeding while receiving megestrol. In addition, HIV-infected mothers are discouraged from breast-feeding to decrease the potential transmission of HIV.
Contraindications
Hypersensitivity to megestrol or any component of the formulation; pregnancy (suspension)
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Adrenal suppression: May suppress hypothalamic-pituitary-adrenal (HPA) axis during chronic administration; consider the possibility of adrenal suppression in any patient receiving or being withdrawn from chronic therapy when signs/symptoms suggestive of hypoadrenalism are noted (during stress or in unstressed state). Laboratory evaluation and replacement/stress doses of rapid-acting glucocorticoid should be considered.
Disease-related concerns:
• Diabetes: New-onset diabetes mellitus and exacerbation of pre-existing diabetes have been reported with long-term use.
• Thromboembolism: Use with caution in patients with a history of thromboembolic disease.
Special populations:
• Females: Vaginal bleeding or discharge may occur.
Dosage form specific issues:
• Concentrated suspension: Megace® ES suspension in not equivalent to other formulations on a mg-per-mg basis; Megace® ES suspension 625 mg/5 mL is equivalent to megestrol acetate suspension 800 mg/20 mL.
Adverse Reactions
Frequency not always defined.
Cardiovascular: Hypertension (≤8%), cardiomyopathy (1% to 3%), chest pain (1% to 3%), edema (1% to 3%), palpitation (1% to 3%), peripheral edema (1% to 3%), heart failure
Central nervous system: Headache (≤10%), insomnia (≤6%), fever (1% to 6%), pain (≤6%, similar to placebo), abnormal thinking (1% to 3%), confusion (1% to 3%), depression (1% to 3%), hypoesthesia (1% to 3%), seizure (1% to 3%), mood changes, malaise, lethargy
Dermatologic: Rash (2% to 12%), alopecia (1% to 3%), pruritus (1% to 3%), vesiculobullous rash (1% to 3%)
Endocrine & metabolic: Hyperglycemia (≤6%), gynecomastia (1% to 3%), adrenal insufficiency, amenorrhea, breakthrough bleeding, cervical erosion and secretions (changes), breast tenderness increased, Cushing's syndrome, diabetes, glucose intolerance, HPA axis suppression, hot flashes, hypercalcemia, menstrual flow changes, spotting, vaginal bleeding pattern changes
Gastrointestinal: Diarrhea (6% to 15%, similar to placebo), flatulence (≤10%), vomiting (≤6%), nausea (≤5%), dyspepsia (≤4%), abdominal pain (1% to 3%), constipation (1% to 3%), salivation increased (1% to 3%), xerostomia (1% to 3%), weight gain (not attributed to edema or fluid retention)
Genitourinary: Impotence (4% to 14%), decreased libido (≤5%), urinary incontinence (1% to 3%), urinary tract infection (1% to 3%), urinary frequency (≤2%)
Hematologic: Anemia (≤5%), leukopenia (1% to 3%)
Hepatic: Hepatomegaly (1% to 3%), LDH increased (1% to 3%), cholestatic jaundice, hepatotoxicity
Neuromuscular & skeletal: Weakness (2% to 6%), neuropathy (1% to 3%), paresthesia (1% to 3%), carpal tunnel syndrome
Ocular: Amblyopia (1% to 3%)
Renal: Albuminuria (1% to 3%)
Respiratory: Dyspnea (1% to 3%), cough (1% to 3%), pharyngitis (1% to 3%), pneumonia (≤2%), hyperpnea
Miscellaneous: Diaphoresis (1% to 3%), herpes infection (1% to 3%), infection (1% to 3%), moniliasis (1% to 3%), tumor flare
Postmarketing and/or case reports: Thromboembolic phenomena (including deep vein thrombosis, pulmonary embolism, thrombophlebitis)
Drug Interactions
Aminoglutethimide: May increase the metabolism of Progestins. Management: Progestin-containing contraceptives are not recommended; consider the use of alternative, nonhormonal contraceptives. Risk D: Consider therapy modification
Dofetilide: Megestrol may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid herbs with progestogenic properties (eg, bloodroot, chasteberry, damiana, oregano, and yucca); may enhance the adverse/toxic effect of megestrol.
Storage
Suspension: Store at 15°C to 25°C (59°F to 77°F); protect from heat.
Tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from heat (temperatures >40°C [>104°F])
Mechanism of Action
A synthetic progestin with antiestrogenic properties which disrupt the estrogen receptor cycle. Megestrol interferes with the normal estrogen cycle and results in a lower LH titer. May also have a direct effect on the endometrium. Megestrol is an antineoplastic progestin thought to act through an antileutenizing effect mediated via the pituitary. May stimulate appetite by antagonizing the metabolic effects of catabolic cytokines.
Pharmacodynamics/Kinetics
Absorption: Well absorbed orally
Metabolism: Hepatic (to free steroids and glucuronide conjugates)
Half-life elimination: 13-105 hours
Time to peak, serum: 1-3 hours
Excretion: Urine (57% to 78%; 5% to 8% as metabolites); feces (8% to 30%)
Dosage
Adults: Oral: Note: Megace® ES suspension is not equivalent to other formulations on a mg-per-mg basis:
Tablet: Females (refer to individual protocols):
Breast carcinoma: 40 mg 4 times/day
Endometrial carcinoma: 40-320 mg/day in divided doses; use for 2 months to determine efficacy; maximum doses used have been up to 800 mg/day
Suspension: Males/Females: HIV-related cachexia:
Megace®: Initial dose: 800 mg/day; daily doses of 400 and 800 mg/day were found to be clinically effective
Megace® ES: 625 mg/day
Dosing adjustment in renal impairment: No data available; however, the urinary excretion of megestrol acetate administered in doses of 4-90 mg ranged from 57% to 78% within 10 days
Administration: Oral
Megestrol acetate (Megace®) oral suspension is compatible with water, orange juice, apple juice, or Sustacal H.C. for immediate consumption. Shake suspension well before use.
Monitoring Parameters
Observe for signs of thromboembolic events; blood pressure, weight; serum glucose
Test Interactions
Altered thyroid and liver function tests
Patient Education
May cause sensitivity to sunlight, dizziness, anxiety, depression, change in appetite, decreased libido or increased body hair (reversible when drug is discontinued), or hot flashes. Report swelling of face, lips, or mouth; absent or altered menses; abdominal pain; vaginal itching, irritation, or discharge; heat, warmth, redness, or swelling of extremities; or sudden onset change in vision.
Geriatric Considerations
Elderly females may have vaginal bleeding or discharge and need to be forewarned of this side effect and inconvenience. No specific changes in dose are required for the elderly. Megestrol has been used in the treatment of the failure to thrive syndrome in cachectic elderly in addition to proper nutrition. Data does not support the use of megestrol for weight gain. The increase in weight tends to be mostly fat instead of lean body mass. Also, this agent is associated with DVTs.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause insomnia or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause myelosuppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Monitor for hypertension, CNS changes (confusion, insomnia), rash, changes in menses, gastrointestinal upset, jaundice, and thrombophlebitis regularly during therapy. Teach patient importance of adequate hydration and importance of avoiding pregnancy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, oral, as acetate: 40 mg/mL (10 mL, 20 mL, 237 mL, 240 mL, 473 mL, 480 mL)
Megace®: 40 mg/mL (240 mL) [contains ethanol 0.06%, sodium benzoate; lemon-lime flavor]
Megace® ES: 125 mg/mL (150 mL) [contains ethanol 0.06%, sodium benzoate; lemon-lime flavor]
Tablet, oral, as acetate: 20 mg, 40 mg
Pricing: U.S. (www.drugstore.com)
Suspension (Megace ES)
625 mg/5 mL (150): $640.01
Suspension (Megace Oral)
40 mg/mL (240): $167.99
Suspension (Megestrol Acetate)
40 mg/mL (240): $131.99
Tablets (Megestrol Acetate)
20 mg (100): $37.99
40 mg (100): $52.99
References
Canetta R, Florentine S, Hunter H, et al, “Megestrol Acetate,” Cancer Treat Rev, 1983, 10(3);141-57.
Chang AY, "Megestrol Acetate as a Biomodulator," Semin Oncol, 1998, 25(2 Suppl 6):58-61.
Farrar DJ, "Megestrol Acetate: Promises and Pitfalls," AIDS Patient Care STDS, 1999, 13(3):149-52.
Fietkau R, Riepl M, Kettner H, et al, “Supportive Use of Megestrol Acetate in Patients With Head and Neck Cancer During Radio(Chemo)Therapy,” Eur J Cancer, 1997, 33(1):75-9.
Lentz SS, Brady MF, Major FJ, et al, “High-Dose Megestrol Acetate in Advanced or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study,” J Clin Oncol, 1996, 14(2):357-61.
Schacter L, Rozencweig M, Canett R, et al, “Megestrol Acetate: Clinical Experience,” Cancer Treat Rev, 1989, 16(1):49-63.
Strang P, “The Effect of Megestrol Acetate on Anorexia, Weight Loss and Cachexia in Cancer and AIDS Patients,” Anticancer Res, 1997, 17(1B):657-62.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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