Femara® (letrozole) EDITED

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Femara® (letrozole)

Quick Overview
Active Life: 2-4 days
Drug Class: Anti-estrogen/inhibitor (Oral)
Average Dose: 0.62 - 2.5 mg/day
Acne: No
Water Retention: No
High Blood Pressure: May reduce bp when using aronatizable steroids
Liver Toxic: Yes, dose dependant
Decrease HPTA function: No


Femara®(generic name is letrozole) is a new drug developed for the treatment of advanced breast cancer in women. Femara is the second in a new class of third-generation selective oral aromatase inhibitors.. It acts by blocking the enzyme aromatase, subsequently blocking the production of estrogen. Since many forms of breast cancer cells are stimulated by estrogen, it is hoped that by reducing amounts of estrogen in the body the progression of such a disease can be halted. This is the basic premise behind Nolvadex, except this drug blocks the action and not production of estrogen. The effects of Femara can be quite dramatic to say the least. A daily dose of one tablet (2.5 mg) can produce estrogen suppression greater than 80 % in treated patients. With the powerful effect this drug has on hormone levels, it is only to be used (clinically) by post-menopausal women whose disease has progressed following treatment with Nolvadex. Side effects like hot flushes and hair thinning can be present, and would no doubt be much more severe in pre-menopausal patients.

For the steroid using male athlete, Femara shows great potential. Up to this point, drugs like Nolvadex and Proviron have been our weapons against excess estrogen. These drugs, especially in combination, do prove quite effective. But Femara appears able to do the job much more efficiently, and with less hassle. Its use is only now catching on, but early reports have been excellent. A single tablet daily, the same dose use clinically, seems to be all one needs for an exceptional effect (some even report excellent results with only 1/4 tablet daily). When used with strong, readily aromatizing androgens such as Dianabol or testosterone, gynecomastia and water retention can be effectively blocked. In combination with Propecia (finasteride), we have a great advance. With the one drug halting estrogen conversion and the other blocking 5-alpha reduction (testosterone, methyltestosterone and Halotestin only), related side effects can be effectively minimized. Here the strong androgen testosterone could theoretically provide incredible muscular growth, while at the same time being as tolerable as nandrolone. Additionally the quality of the muscle should be greater, the athlete appearing harder and much more defined without holding excess water.

There are some concerns with using an aromatase inhibitor such as this during prolonged steroid treatment however. While it will effectively reduce estrogenic side effects, it will also block the beneficial properties of estrogen from becoming apparent (namely its effect on cholesterol values). Studies have clearly shown that when an aromatase inhibitor is used in conjunction with a steroid such as testosterone, suppression of HDL (good) cholesterol becomes much more pronounced. Apparently estrogen plays a role in minimizing the negative impact of steroid use. Since the estrogen receptor antagonist Nolvadex does not display an anti-estrogenic effect on cholesterol values, it is the preferred from of estrogen maintenance for those concerned with cardiovascular health.

Femara has another principle drawback, namely the great price of this drug. Tablets can be quite costly with regular use, but it can ward off the side effects of strong androgens much better than Nolvadex and/or Proviron, making heavy cycles much more comfortable. As the number of countries manufacturing this drug increases, we may be able to look forward to a reduction in price. Privately compounded versions of "liquid Femara have also been formulated "for research purposes" and are currently circulating the black market. Generic tabs are also available and these two forms represent a very cost-effective alternative for buying the brand name drug.
 
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Im sure hhajdo will. He's actually putting up all the profiles this weekend and I have told him to edit any part of the characteristics that he feels need to be changed. Im sure he'll throw in the active life of letro for us.
 
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.

Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM.

Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. abuzdar@mdanderson.org

BACKGROUND: The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first-line treatments and compared with megestrol acetate as second-line therapy in postmenopausal women with advanced breast carcinoma. In an open-label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles. METHODS: In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane. RESULTS: At clinically administered doses, the plasma half-lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41-48 hours, 2-4 days, and 27 hours, respectively. The time to steady-state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis. CONCLUSIONS: All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long-term clinical significance of these differences remains to be elucidated. Copyright 2002 American Cancer Society.
 
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