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megestrol
megestrol
SYNONYM(S): BDH 1298; MEG; megestrol acetate
COMMON TRADE NAME(S): Megace® (multiple brands available)
Megestrol was initially developed as a contraceptive and was first evaluated in breast cancer treatment in 1967. It is a synthetic progestin and has the same physiologic effects as natural progesterone. Megestrol has direct cytotoxic effects on breast cancer cells in tissue culture and suppresses luteinizing hormone release from the pituitary. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown.
| Bioavailability |
Oral: Variable, but well absorbed |
Found in breast milk.
| Cross blood brain barrier? | No information found |
| Volume of distribution | No information found |
Mainly in liver to free steroids and glucuronide conjugates.
| Active metabolites | no |
| Inactive metabolites | yes |
Predominantly excreted by kidneys, 19.8% within 10 days in feces.
| Urine | 66.4% within 10 days |
| Half-life | 34 hours |
- Anorexia, cachexia or weight loss secondary to metastatic cancer
- Adjunctive or palliative treatment of recurrent, inoperable or advanced breast and endometrial cancer.
- Palliative treatment of hormone responsive advanced (stage D2) carcinoma of the prostate
Emetogenic Potential:
Extravasation Potential: Not applicable
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Auditory | Hearing impaired (less common) | E D | |||
| Cardiovascular | Hypertension (unusual) | E | |||
| Venous thromboembolism | D | ||||
| Dermatological | Alopecia (mild, rare) | D | |||
| Hirsutism | E | ||||
| Rash (unusual) | I E | ||||
| Skin discolouration (chloasma) | E | ||||
| Gastrointestinal | Appetite improved | E | |||
| Constipation | E | ||||
| Diarrhea (unusual) | E | ||||
| Nausea, vomiting (2%) | I | ||||
| Weight gain | E | ||||
| General | Edema (mild fluid retention) | E | |||
| Fatigue | E | ||||
| Tumour flare | E | ||||
| Hepatobiliary | Cholecystitis (rare) | D | |||
| ↑ LFTs (rare) | E D | ||||
| Metabolic / Endocrine | Adrenal insufficiency (adrenocortical suppression - rare) | L | |||
| Cushingoid | D | ||||
| Hyperglycemia | E | ||||
| Musculoskeletal | Other (carpal tunnel syndrome - rare) | E | |||
| Nervous System | Insomnia (less common) | E D | |||
| Memory impairment | E | ||||
| Mood changes (unusual) | D | ||||
| Reproductive and breast disorders | Erectile dysfunction | E | |||
| Gynecomastia | E | ||||
| Vaginal bleeding (2%) | D | ||||
| Respiratory | Dyspnea | E | |||
| Urinary | Urinary frequency | E | |||
| Vascular | Hot flashes (rare) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
Weight gain has been reported in one third of patients on megestrol 160mg daily. Weight gain is associated with an increase in fat and body cell mass. This effect has been used therapeutically in the treatment of cachexia.
Spotting may occur during treatment with megestrol. Vaginal bleeding is not uncommon following withdrawal of megestrol. May cause tumour flare with increased pain and hypercalcemia. There is a theoretical risk of adrenal insufficiency after prolonged treatment.
Breast Cancer: 160mg or 125mg/m2 PO daily as a single or divided daily dose(s)
Endometrial Cancer: 80-320 mg or 125mg/m2 daily in divided doses
Prostate Cancer: 120 mg (93.8 mg/m2) daily as a single daily dose (Continued on next page)
Megestrol is contraindicated in patients who are sensitive to megestrol or any ingredients in the dosage forms. It should be used with caution in patients with arterial or venous thromboembolic disorders. Tablets contain lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
The mutagenic potential of megestrol is not known. An increased incidence of breast (benign and malignant) and pituitary tumours have been observed in animals after prolonged megestrol use. Megestrol is fetotoxic. Contraindicated in pregnancy. Detectable amounts excreted in breast milk; therefore, breast feeding is not recommended. Fertility may be affected in females.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Dofetilide | ↑ dofetilide effect | Megestrol ↓ renal secretion | Avoid combination |
| Monitor Type | Monitor Frequency |
|---|---|
| Clinical toxicity assessment for venous thromboembolism, edema and GI effects. |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
| Monitor Type | Monitor Frequency |
|---|---|
| Liver function tests | Baseline and regular |
Canetta R, Florentine S, Hunter H, et al. Megestrol Acetate, Cancer Treat Rev 1983;10(3):141-57.
Foitl DR, Hyman G, Lefkowitch JH. Jaundice and intrahepatic cholestasis following high dose megestrol acetate for breast cancer. Cancer 1989;63:438-9.
Megestrol: The Merck Manual [Internet]; 2011 [cited 2012 April 3]. Available from:
http://www.merckmanuals.com/professional/lexicomp/megestrol.html
Product Monograph: Megestrol. AA Pharma Inc., May 28, 2010.
Product Monograph: Megestrol. Aspen Pharma Pty Ltd (Australia), April 2011.
Prescribing information: Megace® OS, Bristol-Myers Squibb (US)., March 2011.
October 2017 Added public funding info; revised April 2012
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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