Letrozole Information
Letrozole (Letrozole) Indications And Usage
Letrozole (Letrozole) tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.
Letrozole (Letrozole) Dosage And Administration
In the adjuvant setting, the optimal duration of treatment with Letrozole (Letrozole) is unknown. The planned duration of treatment in the study was 5 years with 73% of the patients having completed adjuvant therapy. Treatment should be discontinued at relapse []
Letrozole (Letrozole) Dosage Forms And Strengths
2.5 mg tablets – dark-yellow, standard convex round, film-coated tablet, debossed with “TEVA” on one side and “B1” on the other side of the tablet.
Letrozole (Letrozole) Contraindications
Letrozole (Letrozole) tablets may cause fetal harm when administered to a pregnant woman and the clinical benefit to premenopausal women with breast cancer has not been demonstrated. Letrozole (Letrozole) tablets are contraindicated in women who are or may become pregnant. If Letrozole (Letrozole) tablets are 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 []
Letrozole (Letrozole) Warnings And Precautions
This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Use of Letrozole (Letrozole) may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Results of a substudy to evaluate safety in the adjuvant setting comparing the effect on lumbar spine (L2 to L4) bone mineral density (BMD) of adjuvant treatment with Letrozole (Letrozole) to that with tamoxifen showed at 24 months a median decrease in lumbar spine BMD of 4.1% in the Letrozole (Letrozole) arm compared to a median increase of 0.3% in the tamoxifen arm (difference = 4.4%) (
In the adjuvant trial the incidence of bone fractures at any time after randomization was 13.8% for Letrozole (Letrozole) and 10.5% for tamoxifen. The incidence of osteoporosis was 5.1% for Letrozole (Letrozole) and 2.7% for tamoxifen []. In the extended adjuvant trial the incidence of bone fractures at any time after randomization was 13.3% for Letrozole (Letrozole) and 7.8% for placebo. The incidence of new osteoporosis was 14.5% for Letrozole (Letrozole) and 7.8% for placebo []
Letrozole (Letrozole) Adverse Reactions
The most serious adverse reactions from the use of Letrozole (Letrozole) are:
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Letrozole (Letrozole) Drug Interactions
Coadministration of Letrozole (Letrozole) and tamoxifen 20 mg daily resulted in a reduction of Letrozole (Letrozole) plasma levels of 38% on average. Clinical experience in the second-line breast cancer trials indicates that the therapeutic effect of Letrozole (Letrozole) therapy is not impaired if Letrozole (Letrozole) is administered immediately after tamoxifen.
A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on Letrozole (Letrozole) pharmacokinetics.
An interaction study with warfarin showed no clinically significant effect of Letrozole (Letrozole) on warfarin pharmacokinetics.
There is no clinical experience to date on the use of Letrozole (Letrozole) in combination with other anticancer agents.
Letrozole (Letrozole) Use In Specific Populations
The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64 to 65 years. About 1/3 of the patients were ≥ 70 years old. In the first-line study, patients ≥ 70 years of age experienced longer time to tumor progression and higher response rates than patients
For the extended adjuvant setting, more than 5,100 postmenopausal women were enrolled in the clinical study. In total, 41% of patients were aged 65 years or older at enrollment, while 12% were 75 or older. In the extended adjuvant setting, no overall differences in safety or efficacy were observed between these older patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
In the adjuvant setting, more than 8,000 postmenopausal women were enrolled in the clinical study. In total, 36 % of patients were aged 65 years or older at enrollment, while 12% were 75 or older. More adverse reactions were generally reported in elderly patients irrespective of study treatment allocation. However, in comparison to tamoxifen, no overall differences with regards to the safety and efficacy profiles were observed between elderly patients and younger patients.
Letrozole (Letrozole) Overdosage
Isolated cases of Letrozole (Letrozole) overdose have been reported. In these instances, the highest single dose ingested was 62.5 mg or 25 tablets. While no serious adverse reactions were reported in these cases, because of the limited data available, no firm recommendations for treatment can be made. However, emesis could be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs are also appropriate. In single-dose studies, the highest dose used was 30 mg, which was well tolerated; in multiple-dose trials, the largest dose of 10 mg was well tolerated.
Lethality was observed in mice and rats following single oral doses that were equal to or greater than 2,000 mg/kg (about 4,000 to 8,000 times the daily maximum recommended human dose on a mg/mbasis); death was associated with reduced motor activity, ataxia and dyspnea. Lethality was observed in cats following single IV doses that were equal to or greater than 10 mg/kg (about 50 times the daily maximum recommended human dose on a mg/mbasis); death was preceded by depressed blood pressure and arrhythmias.
Letrozole (Letrozole) Description
Letrozole (Letrozole) tablets USP for oral administration contain 2.5 mg of Letrozole (Letrozole) , a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis). It is chemically described as 4,4'-(1-1,2,4-triazol-1-ylmethylene)dibenzonitrile, and its structural formula is
CHN M.W. 285.31
Letrozole (Letrozole) is a white to yellowish crystalline powder, freely soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water. It has a melting range of 184° to 185°C.
Letrozole (Letrozole) tablets USP are available as 2.5 mg tablets for oral administration.
Inactive Ingredients: colloidal silicon dioxide, FD&C blue #2 aluminum lake, FD&C yellow #5 aluminum lake, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium starch glycolate, starch, talc, and titanium dioxide.
Letrozole (Letrozole) Clinical Pharmacology
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 progestational agents). These interventions lead to decreased 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.
Letrozole (Letrozole) 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, Letrozole (Letrozole) 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 Letrozole (Letrozole) does not lead to an increase in serum FSH. Letrozole (Letrozole) selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.
Letrozole (Letrozole) 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 Letrozole (Letrozole) 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.
In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg Letrozole (Letrozole) suppress plasma concentrations of estradiol, estrone, and estrone sulfate by 75% to 95% from baseline with maximal suppression achieved within two to three days. Suppression is dose-related, with doses of 0.5 mg and higher giving many values of estrone and estrone sulfate that were below the limit of detection in the assays. Estrogen suppression was maintained throughout treatment in all patients treated at 0.5 mg or higher.
Letrozole (Letrozole) is highly specific in inhibiting aromatase activity. There is no impairment of adrenal steroidogenesis. No clinically-relevant changes were found in the plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxy-progesterone, ACTH or in plasma renin activity among postmenopausal patients treated with a daily dose of Letrozole (Letrozole) 0.1 mg to 5 mg. The ACTH stimulation test performed after 6 and 12 weeks of treatment with daily doses of 0.1, 0.25, 0.5, 1, 2.5, and 5 mg did not indicate any attenuation of aldosterone or cortisol production. Glucocorticoid or mineralocorticoid supplementation is, therefore, not necessary.
No changes were noted in plasma concentrations of androgens (androstenedione and testosterone) among healthy postmenopausal women after 0.1, 0.5, and 2.5 mg single doses of Letrozole (Letrozole) or in plasma concentrations of androstenedione among postmenopausal patients treated with daily doses of 0.1 mg to 5 mg. This indicates that the blockade of estrogen biosynthesis does not lead to accumulation of androgenic precursors. Plasma levels of LH and FSH were not affected by Letrozole (Letrozole) in patients, nor was thyroid function as evaluated by TSH levels, T3 uptake, and T4 levels.
In a pharmacokinetic study, subjects with liver cirrhosis and severe hepatic impairment (Child-Pugh classification C, which included bilirubins about 2 to 11 times ULN with minimal to severe ascites) had two-fold increase in exposure (AUC) and 47% reduction in systemic clearance. Breast cancer patients with severe hepatic impairment are thus expected to be exposed to higher levels of Letrozole (Letrozole) than patients with normal liver function receiving similar doses of this drug []
Letrozole (Letrozole) Nonclinical Toxicology
A conventional carcinogenesis study in mice at doses of 0.6 to 60 mg/kg/day (about 1 to 100 times the daily maximum recommended human dose on a mg/mbasis) administered by oral gavage for up to 2 years revealed a dose-related increase in the incidence of benign ovarian stromal tumors. The incidence of combined hepatocellular adenoma and carcinoma showed a significant trend in females when the high dose group was excluded due to low survival. In a separate study, plasma AUC levels in mice at 60 mg/kg/day were 55 times higher than the AUC level in breast cancer patients at the recommended dose. The carcinogenicity study in rats at oral doses of 0.1 to 10 mg/kg/day (about 0.4 to 40 times the daily maximum recommended human dose on a mg/mbasis) for up to 2 years also produced an increase in the incidence of benign ovarian stromal tumors at 10 mg/kg/day. Ovarian hyperplasia was observed in females at doses equal to or greater than 0.1 mg/kg/day. At 10 mg/kg/day, plasma AUC levels in rats were 80 times higher than the level in breast cancer patients at the recommended dose.
Letrozole (Letrozole) was not mutagenic in tests (Ames and E.coli bacterial tests) but was observed to be a potential clastogen in assays (CHO K1 and CCL 61 Chinese hamster ovary cells). Letrozole (Letrozole) was not clastogenic (micronucleus test in rats).
Studies to investigate the effect of Letrozole (Letrozole) on fertility have not been conducted; however, repeated dosing caused sexual inactivity in females and atrophy of the reproductive tract in males and females at doses of 0.6, 0.1 and 0.03 mg/kg in mice, rats and dogs, respectively (about one, 0.4 and 0.4 the daily maximum recommended human dose on a mg/mbasis, respectively).
Letrozole (Letrozole) administered to young (postnatal day 7) rats for 12 weeks duration at 0.003, 0.03, 0.3 mg/kg/day by oral gavage, resulted in adverse skeletal/growth effects (bone maturation, bone mineral density) and neuroendocrine and reproductive developmental perturbations of the hypothalamic-pituitary axis at exposures less than exposure anticipated at the clinical dose of 2.5 mg/day. Decreased fertility was accompanied by hypertrophy of the hypophysis and testicular changes that included degeneration of the seminiferous tubular epithelium and atrophy of the female reproductive tract. Young rats in this study were allowed to recover following discontinuation of Letrozole (Letrozole) treatment for 42 days. Histopathological changes were not reversible at clinically relevant exposures.
Letrozole (Letrozole) is embryotoxic at doses equal to or greater than 0.002 mg/kg and fetotoxic when administered to rabbits at 0.02 mg/kg (about 1/100,000 and 1/10,000 the daily maximum recommended human dose on a mg/mbasis, respectively). Fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs.
Letrozole (Letrozole) Clinical Studies
In a multicenter study enrolling over 8,000 postmenopausal women with resected, receptor-positive early breast cancer, one of the following treatments was randomized in a double-blind manner:
The study in the adjuvant setting, BIG 1-98 was designed to answer two primary questions: whether Letrozole (Letrozole) for 5 years was superior to tamoxifen for 5 years (Primary Core Analysis) and whether switching endocrine treatments at 2 years was superior to continuing the same agent for a total of 5 years (Sequential Treatments Analysis). Selected baseline characteristics for the study population are shown in . The primary endpoint of this trial was disease-free survival (DFS) (i.e., interval between randomization and earliest occurrence of a local, regional, or distant recurrence, or invasive contralateral breast cancer, or death from any cause). The secondary endpoints were overall survival (OS), systemic disease-free survival (SDFS), invasive contralateral breast cancer, time to breast cancer recurrence (TBR) and time to distant metastasis (TDM).
The Primary Core Analysis (PCA) included all patients and all follow-up in the monotherapy arms in both randomization options, but follow-up in the two sequential treatments arms was truncated 30 days after switching treatments. The PCA was conducted at a median treatment duration of 24 months and a median follow-up of 26 months. Letrozole (Letrozole) was superior to tamoxifen in all endpoints except overall survival and contralateral breast cancer [e.g., DFS: hazard ratio, HR 0.79; 95% CI (0.68, 0.92); = 0.002; SDFS: HR 0.83; 95% CI (0.70, 0.97); TDM: HR 0.73; 95% CI (0.60, 0.88); OS: HR 0.86; 95% CI (0.70, 1.06).
In 2005, based on recommendations by the independent Data Monitoring Committee, the tamoxifen arms were unblinded and patients were allowed to complete initial adjuvant therapy with Letrozole (Letrozole) (if they had received tamoxifen for at least 2 years) or to start extended adjuvant treatment with Letrozole (Letrozole) (if they had received tamoxifen for at least 4.5 years) if they remained alive and disease-free. In total, 632 patients crossed to Letrozole (Letrozole) or another aromatase inhibitor. Approximately 70% (448) of these 632 patients crossed to Letrozole (Letrozole) to complete initial adjuvant therapy and most of these crossed in years 3 to 4. All of these patients were in Option 1. A total of 184 patients started extended adjuvant therapy with Letrozole (Letrozole) (172 patients) or with another aromatase inhibitor (12 patients). To explore the impact of this selective crossover, results from analyses censoring follow-up at the date of the selective crossover (in the tamoxifen arm) are presented for the Monotherapy Arms Analysis (MAA).
The PCA allowed the results of Letrozole (Letrozole) for 5 years compared with tamoxifen for 5 years to be reported in 2005 after a median follow-up of only 26 months. The design of the PCA is not optimal to evaluate the effect of Letrozole (Letrozole) after a longer time (because follow-up was truncated in two arms at around 25 months). The Monotherapy Arms Analysis (ignoring the two sequential treatment arms) provided follow-up equally as long in each treatment and did not over-emphasize early recurrences as the PCA did. The MAA thus provides the clinically appropriate updated efficacy results in answer to the first primary question, despite the confounding of the tamoxifen reference arm by the selective crossover to Letrozole (Letrozole) . The updated results for the MAA are summarized in . Median follow-up for this analysis is 73 months.
The Sequential Treatments Analysis (STA) addresses the second primary question of the study. The primary analysis for the Sequential Treatments Analysis (STA) was from switch (or equivalent time-point in monotherapy arms) + 30 days (STA-S) with a two-sided test applied to each pair-wise comparison at the 2.5% level. Additional analyses were conducted from randomization (STA-R) but these comparisons (added in light of changing medical practice) were under-powered for efficacy.
ITT analysis ignores selective crossover in tamoxifen arms
Censored analysis censors follow-up at the date of selective crossover in 632 patients who crossed to Letrozole (Letrozole) or another aromatase inhibitor after the tamoxifen arms were unblinded in 2005
Figure 1
DFS events defined as loco-regional recurrence, distant metastasis, invasive contralateral breast cancer, or death from any cause (i.e., definition excludes second non-breast primary cancers).
The medians of overall survival for both arms were not reached for the Monotherapy Arms Analysis (MAA). There was no statistically significant difference in overall survival. The hazard ratio for survival in the Letrozole (Letrozole) arm compared to the tamoxifen arm was 0.87, with 95% CI (0.75, 1.02) (see ). There were no significant differences in DFS, OS, SDFS, and Distant DFS from switch in the Sequential Treatments Analysis with respect to either monotherapy (e.g., [Tamoxifen 2 years followed by] Letrozole (Letrozole) 3 years versus tamoxifen beyond 2 years, DFS HR 0.89; 97.5% CI 0.68, 1.15 and [Letrozole (Letrozole) 2 years followed by] tamoxifen 3 years versus Letrozole (Letrozole) beyond 2 years, DFS HR 0.93; 97.5% CI 0.71, 1.22).
There were no significant differences in DFS, OS, SDFS, and Distant DFS from randomization in the Sequential Treatments Analyses.
A double-blind, randomized, placebo-controlled trial of Letrozole (Letrozole) was performed in over 5,100 postmenopausal women with receptor-positive or unknown primary breast cancer who were disease free after 5 years of adjuvant treatment with tamoxifen.
The planned duration of treatment for patients in the study was 5 years, but the trial was terminated early because of an interim analysis showing a favorable Letrozole (Letrozole) effect on time without recurrence or contralateral breast cancer. At the time of unblinding, women had been followed for a median of 28 months, 30% of patients had completed 3 or more years of follow-up and less than 1% of patients had completed 5 years of follow-up.
Selected baseline characteristics for the study population are shown in .
shows the study results. Disease-free survival was measured as the time from randomization to the earliest event of loco-regional or distant recurrence of the primary disease or development of contralateral breast cancer or death. DFS by hormone receptor status, nodal status and adjuvant chemotherapy were similar to the overall results. Data were premature for an analysis of survival.
CI = confidence interval for hazard ratio. Hazard ratio of less than 1.0 indicates difference in favor of Letrozole (Letrozole) (lesser risk of recurrence); hazard ratio greater than 1.0 indicates difference in favor of placebo (higher risk of recurrence with Letrozole (Letrozole) ).
Updated analyses were conducted at a median follow-up of 62 months. In the Letrozole (Letrozole) arm, 71% of the patients were treated for a least 3 years and 58% of patients completed at least 4.5 years of extended adjuvant treatment. After the unblinding of the study at a median follow-up of 28 months, approximately 60% of the selected patients in the placebo arm opted to switch to Letrozole (Letrozole) .
In this updated analysis shown in , Letrozole (Letrozole) significantly reduced the risk of breast cancer recurrence or contralateral breast cancer compared with placebo (HR 0.75; 95% CI 0.63, 0.89; = 0.001). However, in the updated DFS analysis (interval between randomization and earliest event of loco-regional recurrence, distant metastasis, contralateral breast cancer, or death from any cause) the treatment difference was heavily diluted by 60% of the patients in the placebo arm switching to Letrozole (Letrozole) and accounting for 64% of the total placebo patient- years of follow-up. Ignoring these switches, the risk of DFS event was reduced by a non-significant 11% (HR 0.89; 95% CI 0.77, 1.03). There was no significant difference in distant disease-free survival or overall survival.
A randomized, double-blind, multinational trial compared Letrozole (Letrozole) 2.5 mg with tamoxifen 20 mg in 916 postmenopausal patients with locally advanced (Stage IIIB or loco-regional recurrence not amenable to treatment with surgery or radiation) or metastatic breast cancer. Time to progression (TTP) was the primary endpoint of the trial. Selected baseline characteristics for this study are shown in .
Letrozole (Letrozole) was superior to tamoxifen in TTP and rate of objective tumor response (see ).
Table 11
(All analyses are unadjusted and use 2-sided -values.)
Figure 2
Hazard ratio less than 1 or odds ratio greater than 1 favors Letrozole (Letrozole) ; hazard ratio greater than 1 or odds ratio less than 1 favors tamoxifen.
Hazard ratio less than 1 or odds ratio greater than 1 favors Letrozole (Letrozole) ; hazard ratio greater than 1 or odds ratio less than 1 favors tamoxifen.
Figure 3
Legend:
Randomized tamoxifen: n = 458, events 57%, median overall survival 32 months (95% CI 28 to 37 months)
Overall logrank = 0.5136 (i.e., there was no significant difference between treatment arms in overall survival).
The median overall survival was 35 months for the Letrozole (Letrozole) group and 32 months for the tamoxifen group, with a -value 0.5136. Study design allowed patients to cross over upon progression to the other therapy. Approximately 50% of patients crossed over to the opposite treatment arm and almost all patients who crossed over had done so by 36 months. The median time to crossover was 17 months (Letrozole (Letrozole) to tamoxifen) and 13 months (tamoxifen to Letrozole (Letrozole) ). In patients who did not cross over to the opposite treatment arm, median survival was 35 months with Letrozole (Letrozole) (n = 219, 95% CI 29 to 43 months) vs 20 months with tamoxifen (n = 229, 95% CI 16 to 26 months).
Letrozole (Letrozole) was initially studied at doses of 0.1 mg to 5.0 mg daily in six non-comparative Phase I/II trials in 181 postmenopausal estrogen/progesterone receptor positive or unknown advanced breast cancer patients previously treated with at least antiestrogen therapy. Patients had received other hormonal therapies and also may have received cytotoxic therapy. Eight (20%) of forty patients treated with Letrozole (Letrozole) 2.5 mg daily in Phase I/II trials achieved an objective tumor response (complete or partial response).
Two large randomized, controlled, multinational (predominantly European) trials were conducted in patients with advanced breast cancer who had progressed despite antiestrogen therapy. Patients were randomized to Letrozole (Letrozole) 0.5 mg daily, Letrozole (Letrozole) 2.5 mg daily, or a comparator (megestrol acetate 160 mg daily in one study; and aminoglutethimide 250 mg b.i.d. with corticosteroid supplementation in the other study). In each study over 60% of the patients had received therapeutic antiestrogens, and about one-fifth of these patients had had an objective response. The megestrol acetate controlled study was double-blind; the other study was open label. Selected baseline characteristics for each study are shown in .
Confirmed objective tumor response (complete response plus partial response) was the primary endpoint of the trials. Responses were measured according to the Union Internationale Contre le Cancer (UICC) criteria and verified by independent, blinded review. All responses were confirmed by a second evaluation 4 to 12 weeks after the documentation of the initial response.
Table 16
The Kaplan-Meier curves for progression for the megestrol acetate study are shown in .
The results for the study comparing Letrozole (Letrozole) to aminoglutethimide, with a minimum follow-up of 9 months, are shown in . (Unadjusted analyses are used.)
The Kaplan-Meier curves for progression for the aminoglutethimide study is shown in .
Letrozole (Letrozole) How Supplied/storage And Handling
Letrozole (Letrozole) tablets USP, 2.5 mg are available as follows:
2.5 mg – dark-yellow, standard convex round, film-coated tablets, debossed with “TEVA” on one side and “B1” on the other side of the tablet, in bottles of 30.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Letrozole (Letrozole) Patient Counseling Information
Pregnancy: Letrozole (Letrozole) is contraindicated in women of premenopausal endocrine status. The physician needs to discuss the necessity of adequate contraception with women who have the potential to become pregnant including women who are perimenopausal or who recently became postmenopausal, until their postmenopausal status is fully established.
Fatigue and Dizziness: Since fatigue and dizziness have been observed with the use of Letrozole (Letrozole) and somnolence was uncommonly reported, caution is advised when driving or using machinery.
Bone Effects: Consideration should be given to monitoring bone mineral density.
Manufactured In Israel By:
Jerusalem, 91010, Israel
Manufactured For:
Sellersville, PA 18960
Rev. A 8/2010
Letrozole (Letrozole) Principal Display Panel
Letrozole (Letrozole)
Tablets USP
2.5 mg
Contains FD&C Yellow No. 5 (tartrazine)
as a color additive.
Rx only
30 TABLETS
TEVA
