Full Prescribing Info
Megestrol acetate.
Each tablet contains megestrol acetate 40 mg or 160 mg, respectively
Pharmacology: The precise mechanism of action by which megestrol acetate produces its antineoplastic effects is unknown at present. Pharmacologic doses of megestrol acetate exerted a direct cytotoxic effect on human breast cancer cells in vitro and proved capable of modifying and abolishing the stimulatory effects of estrogen on breast cancer cell lines. Megestrol acetate interacts with progesterone receptors to stimulate cell maturation through a progestin-inducing mechanism. It has also been shown to have certain androgenic properties and may also modify glucocorticoid action by binding to the glucocorticoid receptor.
In previously untreated breast cancer patients with ER+ PR+ receptor status, endocrine therapy has been shown to produce responses in up to 81% of patients.
Inhibition of persistent endometrial hyperplasia and of persistent endometrial adenocarcinoma was observed upon administration of megestrol acetate in doses of 160 mg/day and megestrol acetate partially inhibited expression of estrogen dependent secretory proteins and certain constituent proteins in the rat uterine epithelium.
Metastatic carcinoma of the prostate responds to a variety of hormone manipulations that decrease the level of androgens in androgen-sensitive tissue.
The primary mechanism of action of megestrol acetate and DES is the suppression of luteinizing hormone from the pituitary gland, which leads to suppression of serum androgens arising from the testicle.
Megestrol acetate may have other mechanisms of action as well, including an antiandrogen activity, suppression of adrenal androgens, and possibly the inhibition of enzymes, eg. 5 -reductase, critical to androgen metabolism within the prostate.
APO-MEGESTROL (megestrol acetate) is indicated for adjunctive or palliative treatment of recurrent, inoperable or metastatic carcinoma of the breast and endometrium and for palliative treatment of hormone responsive advanced (Stage D2) carcinoma of the prostate. APO-MEGESTROL should not be used in lieu of currently accepted procedures such as surgery and radiation. Objective or subjective responses or arrest of tumour growth may occur for one to several months while on therapy.
Dosage/Direction for Use
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 as a single daily dose in combination with diethylstilbestrol tablet, 0.1 mg.
At least two months of continuous treatment is considered an adequate period for determining the efficacy of APO-MEGESTROL (megestrol acetate).
Usual safety measures as with the overdose of any medication should be instituted. However, no serious side effects have resulted from studies involving megestrol acetate administered in dosages as high as 800 mg/day.
APO-MEGESTROL (megestrol acetate) is contraindicated in those people who are sensitive to megestrol acetate or any ingredients in the dosage form. It should not be used as a diagnostic test for pregnancy.
The use of progestational agents during the first four months of pregnancy is not recommended.
Progestational agents have been used beginning within the first trimester of pregnancy in an attempt to prevent habitual abortion or treat threatened abortion. There is no adequate evidence that such use is effective and there is evidence of potential harm to the fetus when such drugs are given during the first four months of pregnancy. Furthermore, in the vast majority of women, the cause of abortion is a defective ovum, which progestational agents could not be expected to influence. In addition, the use of progestational agents, with their uterine-relaxant properties, in patients with fertilized defective ova may cause a delay in spontaneous abortion.
Therefore, the use of such drugs during the first four months of pregnancy is not recommended.
Several reports suggest an association between intrauterine exposure to female sex hormones and congenital anomalies, including congenital heart defects and limb reduction defects. One study estimated a 4.7-fold increased risk of limb reduction defects in infants exposed in utero to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy, or attempted treatment for threatened abortion). Some of these exposures were very short and involved only a few days of treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat less than 1 in 1,000. If the patient is exposed to APO-MEGESTROL (megestrol acetate) during the first four months of pregnancy or if she becomes pregnant while taking the drug, she should be apprised of the potential risks to the fetus.
Administration for up to 7 years of megestrol acetate to female dogs is associated with an increased incidence of both benign and malignant tumours of the breast. Comparable studies in the monkey are not associated with an increased incidence of malignant tumours. The relationship of the dog tumours to humans is unknown but should be considered in assessing the benefit-to-risk ratio when prescribing megestrol acetate and in surveillance of patients on therapy.
Special Precautions
There are no specific precautions identified for the use of APO-MEGESTROL (megestrol acetate) when used as recommended. Close, customary surveillance is indicated as in any patient being treated for recurrent or metastatic cancer. Use with caution in patients with a history of thrombophlebitis. Patients receiving large doses of progestational agents such as APO-MEGESTROL continuously for prolonged periods should be observed closely for possible adrenal cortical suppression.
Use In Pregnancy & Lactation
It should not be used as a diagnostic test for pregnancy.
Adverse Reactions
Untoward reactions that have been reported to occur in patients receiving megestrol acetate include gynecomastia, carpal tunnel syndrome, deep vein thrombophlebitis, alopecia, loss of hearing, hyperglycemia, pulmonary embolism and dyspnea. The relationship of these reactions to megestrol acetate therapy is not known at this time. Weight gain is frequently reported. Vaginal bleeding occurs occasionally following withdrawal of megestrol acetate.
Drug Interactions
Possible interactions of megestrol with concomitant medications have not been investigated.
ATC Classification
L02AB01 - megestrol ; Belongs to the class of progestogens.
Tab 40 mg (light blue, round, flat-faced, bevelled-edged, scored, engraved "APO" over "40" on one side) x 100's. 160 mg (white, oval, biconvex, scored, engraved "APO 160" on one side) x 100's.
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