Anastrozole Arimidex

Anonymous

Arimidex (Anastrozole) aka: A-Dex / Liquidex (liquid form)

DESCRIPTION

Arimidex is not a steroid. It is a tablet or liquid form anti-aromitase that is used by many body builders to help prevent bloating (edema) and Gynecomastia (bitch tit) associated with the use of testosterone and androgens. It can be used in place of Nolvadex, Clomid, etc. Bodybuilders are using around .25mg to 1mg per day or .5mg to 1mg every other day and are having good success with it. Its approved uses are for the treatment of breast cancer in post-menopausal women with disease progression following tamoxifen therapy. Hypersensitivity to anastrozole are reasons not to use this drug. If you have these problems please inform your doctor. Common side effects are: shortness of breath, dizziness, diarrhea, vomiting, headache, hot flashes, weakness, cough, dry mouth, skin rash, sweating, abdominal pain and bone pain. Some less common symptoms are vaginal bleeding, weight gain, tiredness, chills, fever, breast pain, and itching. In case of an overdose, it is recommended to contact your poison control center.

Breast cancer is the most frequently diagnosed malignancy and the second most common cause of cancer-related deaths in women. Hormonal therapies that inhibit estrogen action or production have been used successfully for various stages of breast cancer. Tamoxifen is the most widely used hormonal manipulation and has been shown to prolong survival when given as adjuvant therapy or in combination with chemotherapy. When patients fail tamoxifen therapy, a second hormonal manipulation may be considered. Traditionally, progestins (i.e., megestrol, medroxyprogesterone acetate) or aminoglutethimide have been used. Approximately 30% of patients respond to megestrol therapy. Aminoglutethimide, a nonspecific aromatase inhibitor, produces response rates ranging from 28% to 43%. It may also significantly inhibit desmolase complex enzymes which are responsible for the initial step in the production of adrenal steroids. Therefore, hydrocortisone and fludrocortisone supplementation is sometimes necessary in patients receiving aminoglutethimide.
The aromatase inhibitors, anastrozole and letrozole, were developed to be more specific and potent than aminoglutethimide. Anastrozole (Arimidex) and letrozole (Femera) are indicated for the treatment of advanced breast cancer in postmenopausal women who have disease progression following previous antiestrogen therapy.
Pharmacology
Anastrozole and letrozole are highly potent and selective nonsteroidal aromatase enzyme complex inhibitors. Aromatase is responsible for the peripheral conversion of androgens to estrogens. In postmenopausal women, the majority of estrogen production comes from aromatization of adrenal androgens to estrone or estradiol. Anastrozole reduces estradiol serum concentrations to 70%-80% of baseline values within 24 hours. These effects are dose-dependent and persist for approximately 6 days after the drug is discontinued. Anastrozole has no effect on other circulating adrenal steroids (e.g., cortisol, androstenedione, dehydroepiandrosterone). Similar reductions in estrone or estradiol concentrations, with no changes in other hormones, are seen following letrozole administration.
Pharmacokinetics
Anastrozole is rapidly absorbed from the gastrointestinal tract, and peak plasma concentrations are obtained within two hours of oral administration. Administration with food decreases the rate, but not the extent, of absorption. The elimination half-life is 30 to 60 hours with no differences reported between female volunteers and female breast cancer patients. Anastrozole is extensively metabolized by the liver ( 85%), and only 10% of the drug is excreted unchanged in the urine. Letrozole is also rapidly absorbed following oral administration and is extensively metabolized by the cytochrome P450 3A4 and 2A6 isoenzymes. The elimination half-life of letrozole is approximately two days, and 6% of the drug is excreted unchanged in the urine. Advanced age does not appear to affect the pharmacokinetics of letrozole, and steady-state concentrations are not significantly affected by changes in renal function. The area under the plasma-concentration-time curve (AUC) is increased in patients with hepatic dysfunction, but remains within the range seen in patients without liver dysfunction. It is not known if severe liver disease affects the pharmacokinetics of letrozole.
Selected Clinical Studies
Two randomized, single-blinded trials have compared 1 mg and 10 mg of anastrozole daily to 160 mg of megestrol daily in postmenopausal breast cancer patients who failed or whose disease progressed after initial hormonal therapy (Table 1). In both trials, the major clinical endpoints at 6 months were time to disease progression, time to treatment failure, and time to death. In these trials, the objective response rates were not different between treatment groups. Quality-of-life scores were better in the physical domain for anastrozole 1 mg daily and better in the psychological domain for anastrozole 10 mg daily when compared to megestrol (p < 0.025 for both). In a follow-up analysis at 31 months, patients treated with anastrozole 1 mg daily had a significantly prolonged overall survival (hazard ratio 0.78, p = 0.02) and a longer two-year survival (56.1%) compared to megestrol (46.3%).
Two randomized, single-blinded studies have compared letrozole 0.5 mg or 2.5 mg daily to either megestrol or aminoglutethimide in postmenopausal women who failed or whose disease progressed after initial hormonal manipulation (Table 1). At the 35-month follow-up period, patients who received letrozole 2.5 mg daily had a significantly improved objective response rate, a longer response duration, and a longer time to treatment failure compared to megestrol. In addition, 2.5 mg of letrozole was superior to 0.5 mg of the drug in terms of objective response rate, time to treatment failure, and time to disease progression. When compared to aminoglutethimide, the relative risk of disease progression was significantly lower with letrozole 2.5 mg daily. The time to disease progression, time to treatment failure, and duration of clinical benefit were significantly longer with letrozole 2.5 mg daily when compared to either letrozole 0.5 mg daily or aminoglutethimide at the 33-month follow-up period. Letrozole 2.5 mg daily, but not 0.5 mg daily, was associated with significantly prolonged survival when compared to aminoglutethimide (RR 0.68, p = 0.02). There are no published studies directly comparing anastrozole to letrozole.
Adverse Effects
Both anastrozole and letrozole are well tolerated. The principal adverse effects associated with anastrozole are asthenia, headache, nausea, hot flushes, and pain. Nausea and vomiting are more common with the 10-mg dose than the 1-mg dose. The nausea is generally mild and improves with continued therapy. Compared to megestrol, anastrozole is associated with more gastrointestinal disturbances, but weight gain, peripheral edema, and dyspnea are less frequent. The most common adverse effects associated with letrozole include nausea, musculoskeletal pain, headache, peripheral edema, hot flushes, and fatigue. Compared to megestrol, letrozole is associated with fewer adverse cardiovascular events, less weight gain, fewer thromboembolic events, and less vaginal bleeding.
Drug Interactions
In vitro, anastrozole inhibits cytochrome P450 1A2, 2C8, 2C9, and 3A4 isoenzymes. Anastrozole does not inhibit enzymes that metabolize dextromethorphan or coumarins. Concentrations that are 30 times higher than those expected from a daily 1-mg dose can cause 50% inhibition of enzymes that metabolize nifedipine, tolbutamide, and phenacetin. Letrozole is a potent inhibitor of cytochrome P450 2A6 and a moderate inhibitor of cytochrome P450 2C19. Letrozole does not appear to interact signifigantly with either cimetidine or warfarin.
Contraindications and Precautions
Both anastrozole and letrozole are teratogenic, embryotoxic, and fetotoxic and are classified as FDA pregnancy Category D. There are no controlled studies using either drug in pregnant women. Pregnancy should be ruled out in patients before initiating anastrozole or letrozole therapy. Letrozole has been associated with decreases in lymphocyte counts, and periodic monitoring of complete blood counts should be considered. Both anastrozole and letrozole have been associated with elevations in some liver function tests in patients with and without liver metastases. For this reason, periodic monitoring of liver function should be considered. Despite decreased clearance in elderly patients and those with mild to moderate hepatic disease, no dose modifications for anastrozole or letrozole are suggested at this time. For patients with renal impairment, dosage modifications are not necessary for those with creatinine clearances greater than 10 mL/min.
Dosage and Administration
The recommended dose of anastrozole for advanced breast cancer in postmenopausal women is 1 mg once daily. For letrozole, the recommended dose is 2.5 mg once daily. Patients treated with either anastrozole or letrozole do not require glucocorticoid or mineralocorticoid replacement therapy.
MedicationDoseDaily Cost*Aminoglutethimide500 mg daily$1.33Megestrol acetate160 mg daily $1.46Anastrozole1 mg daily$5.27Letrozole2.5 mg daily$3.90 *Based on Federal Supply ScheduleConclusion
Oral therapy with either anastrozole or letrozole results in an equivalent or improved response rate when compared to standard secondary therapy (megestrol or aminoglutethimide) for postmenopausal women with progressive breast cancer. Although there are no direct comparative studies, anastrozole and letrozole appear to be therapeutically equivalent. Both medications are well tolerated and appear to have fewer adverse effects than either megestrol or aminoglutethimide. Ongoing studies will determine whether these agents have a role as initial hormonal therapy in patients with breast cancer.