Megestrolacetaat

Uses

Megestrolacetaat is used in anorexia, cachexia or a significant weight loss. Megestrolacetaat is also used for the palliative treatment of advanced carcinoma of the breast (i.e. recurrent, inoperable or metastatic diseases). It should not be used in lieu of currently accepted procedures such as surgery, radiation or chemotherapy.

Megestrolacetaat is also used to associated treatment for these conditions: Advanced Breast Cancer, Advanced Endometrial Cancer, Cachexia, Loss of Appetite

How Megestrolacetaat works

The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes.

Dosage

Megestrolacetaat dosage

For the following indications, at least two months of continuous treatment is considered an adequate period for determining the efficacy of megestrol acetate tablets.

For palliative or adjunctive treatment of breast carcinoma: 160 mg or 125 mg/m² daily (40 mg q.i.d. or 160 mg q.d.)

For endometrial carcinoma: 80 - 320 mg or 62.5 - 250 mg/m² daily in divided doses (40 - 80 mg one to four times daily or one to two 160 mg tablets daily).

For palliative treatment of hormone responsive advanced (Stage D2) carcinoma of the prostate: 120 mg (93.8 mg/m²) as a single daily dose in combination with diethylstilbestrol tablet, 0.1 mg.

For anorexia, cachexia, or significant weight loss in patients with cancer: usual adult dose: 400 to 800 mg as a single daily dose.The recommended adult initial dosage of megestrol acetate oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). Shake container well before using

Side Effects

Side Effects: Nausea, vomiting, edema occur in approximately 1% to 2% of patients. Dyspnea, pain, hypertension, hot flashes, sweating mood changes, hyperglycemia, alopecia, asthenia, malaise, lethargy, rash, flatulence, diarrhoea and impotence have been reported. Constipation and urinary frequency have been reported in patients who received high doses of Megestrol acetate in clinical trials.

Adverse effects:

• Thromboembolic phenomena: Thromboembolic phenomena including thrombophlebitis and pulmonary embolism (in some cases fatal) have been reported.
• Other adverse reactions: Breakthrough uterine bleeding occur in approximately 1% to 2% of patients. Heart failure, cushingoid facies, tumor flare (with or without hypercalcemia), carpal tunnel syndrome and urticaria have been reported.

Toxicity

No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362].

Precaution

History of thrombophlebitis, mild to moderate hepatic impairment, risk of fluid retention, history of depression, diabetes, hypertension, renal or cardiac dysfunction.

Interaction

Concentrations of indinavir may be reduced. Possible reduced efficacy of cisplatin. Warfarin half life may be increased. Megestrol concentration may be decreased by aminoglutethimide and enzyme-inducing drugs.

Food Interaction

• Take with food.

Elimination Route

Variable, but well absorbed orally.

Half Life

34 hours

Elimination Route

The major route of drug elimination in humans is urine. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.

Pregnancy & Breastfeeding use

Pregnancy category D. Megestrolacetaat can cause fetal abnormalities and risks, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Nursing mothers: Very small amounts (approximately 0.1%) are excreted in mother's milk. It is however, not known whether these amounts exert any harmful effect on the newborn. Because of the potential for adverse effects on the new born, nursing should be discontinued during treatment with Megestrolacetaat.

Contraindication

Allergy to Megestrol acetate or any of the excipients. Women of child bearing potential should be advised to avoid becoming pregnant.

Special Warning

Pediatric use: The safety and efficacy of Megestrolacetaat has not been established in pediatric cases. In general, dose selection for a pediatric patient should be cautious.

Geriatric use: Insufficient data from clinical studies of Megestrol acetate are available for patients 65 years of age and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious.

Hepatic impairment: Dose selection for a hepatic impaired patient should be cautious.

Renal impairment: Dose selection for a renal impaired patient should be cautious.

Innovators Monograph

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