Description

The growth of some cancers of the breast is stimulated or maintained by estrogens. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) •or inhibit estrogen effects (antiestrogens and pregestational agents). These interventions lead to decrease tumor mass or delayed progression of tumor growth in some women.

In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.

lmpregnil™ is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumor-bearing female animals, lmpregnil™ is as effective as ovariectomy in reducing uterine weight, elevating serum LH, and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with lmpregnil™ does not lead to an increase in serum FSH. lmpregnil™ selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.

lmpregnil7″ inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. Treatment of women with lmpregnil™ significantly lowers serum estrone, estradiol and estrone sulfate and has not been shown to significantly affect adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones.

Indications

Impregnil is an aromatase inhibitor indicated for:

First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer

Dosage And Administration

lmpregnil”‘ tablets are taken orally without regard to meals

Recommended dose: 2.5 mg once daily

Contraindications

lmpregnil™ may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. lmpregnil1″‘ is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

Hot flashes, hair loss, joint/bone/muscle pain, tiredness, unusual sweating, nausea, diarrhea, dizziness, and trouble sleeping may occur.

Precaution

Use of Letrozole may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Updated results from the BMD sub-study demonstrated that at 2 years patients receiving lmpregnil™ had a median decrease from baseline of 3.8% in hip BMD compared to a median decrease of 2.0% in the placebo group. The changes from baseline in lumbar spine BMD jn lmpregnil™ and placebo treated groups were not statistically different.

Pharmaceutical Precaution

Store at or below 30° C. Keep out of the reach of children.