What Are the Most Common Letrozole Side Effects?

Letrozole is an indication for adjuvant treatment of patients with postmenopausal early breast cancer, who have a positive estrogen or progesterone receptor or unknown receptor status. Adjuvant therapy for patients with early postmenopausal breast cancer who have received adjuvant treatment with tamoxifen for 5 years. These patients have positive estrogen or progesterone receptor status or unknown receptor status. Treatment of patients with advanced breast cancer after menopause, estrogen receptor-positive progesterone receptor positive or unknown receptor status, these patients should be natural menopause or artificially induced menopause.

Letrozole is an indication for adjuvant treatment of patients with postmenopausal early breast cancer, who have a positive estrogen or progesterone receptor or unknown receptor status. Adjuvant therapy for patients with early postmenopausal breast cancer who have received adjuvant treatment with tamoxifen for 5 years. These patients have positive estrogen or progesterone receptor status or unknown receptor status. Treatment of patients with advanced breast cancer after menopause, estrogen receptor-positive progesterone receptor positive or unknown receptor status, these patients should be natural menopause or artificially induced menopause.

Drug Name

Letrozole tablets

Drug type

Prescription drugs, medicines for medical workers' injuries

Special medicine

Doping

Use classification

Aromatase inhibitor

Letrozole warnings

Athletes use with caution

Letrozole Tablets Ingredients

Chemical name: 4,4 '[(1H-1,2,4-triazol-1-yl) -methylene] -bis-benzonitrile Chemical structural formula:

Molecular formula: C ₁₇ H ₁₁ N ₅
Molecular weight: 285.3

Letrozole Tablet Properties

This product is a film-coated tablet, which appears white after removing the coating.

Letrozole tablets indications

Adjuvant therapy for patients with early postmenopausal breast cancer. These patients have positive estrogen or progesterone receptors or unknown receptor status.
Adjuvant therapy for patients with early postmenopausal breast cancer who have received adjuvant treatment with tamoxifen for 5 years. These patients have positive estrogen or progesterone receptor status or unknown receptor status.
Treatment of patients with advanced breast cancer after menopause, estrogen receptor-positive progesterone receptor positive or unknown receptor status, these patients should be natural menopause or artificially induced menopause.

Letrozole Tablet Specifications

2.5mg

Letrozole tablets dosage

Adjuvant therapy with this product should be taken for 5 years or until the disease relapses.
For patients who have received adjuvant treatment with tamoxifen for 5 years, this product should be continuously taken until the disease relapses.
The recommended dose of this product is 2.5 mg once daily. Do not consider eating time when taking (see [ Pharmacokinetics ]-absorption). For advanced breast cancer, the treatment of this product should continue until the tumor progression is confirmed.
Dose for patients with liver and / or renal dysfunction Patients with liver and / or renal dysfunction (creatinine clearance 10ml / min) do not need to adjust the dose.

Letrozole tablets adverse reactions

This product shows good safety in all first-line and second-line treatment of patients with advanced breast cancer, as well as adjuvant therapy in early patients and follow-up intensive adjuvant therapy after receiving tamoxifen standard treatment. Approximately 75% received adjuvant therapy (this product and tamoxifen control group, with a median duration of 60 months), and 80% of patients received subsequent intensive adjuvant therapy (this product and placebo control group, with median duration of treatment 60 months) and one-third of patients with advanced metastases treated with this product and neoadjuvant treatment experienced adverse reactions. Adverse reactions observed in clinical studies were mild to moderate. Most adverse reactions are caused by estrogen deficiency.
The most common adverse reactions in clinical trials were hot flushes, joint pain, nausea and fatigue. Many adverse reactions are due to the normal pharmacological effects of estrogen deficiency (eg, hot flushes, hair loss, and vaginal bleeding). The adverse reactions listed in Table 1 are derived from clinical studies and post-marketing reports.
Table 1
The adverse reactions are classified according to the frequency of occurrence. The most common are the first. They are expressed using the following habits: very common: 1 / 10; common: 1 / 100, <1/10; uncommon: 1 / 1000, <1 / 100; rare: 1 / 10,000, <1/1000; rare: <1 / 10,000

(1) Including neuroticism, excitement (2) Including paresthesia, dullness (3) Including superficial or deep thrombophlebitis (4) Including erythema, maculopapular psoriasis, vesicular rash (5) Including fatigue, discomfort (6 ) Appear only in metastatic / neo-adjuvant therapy (7) In adjuvant therapy, regardless of causality, the frequency of the following adverse reactions in the letrozole and tamoxifen groups were: thrombus (2.1% vs. 3.6%) , Angina pectoris (1.1% vs. 1.0%), myocardial infarction (1.0% vs. 0.5%), and heart failure (0.8% vs. 0.5%).
(8) In the case of subsequent intensive adjuvant therapy, the median duration of treatment was 60 months in the letrozole group and 37 months in the placebo group. The following adverse reactions were reported in letrozole and placebo (excluding Patients replaced with trazozole): new or worsening angina (1.4% vs. 1.0%); angina requiring surgery (0.8% vs. 0.6%); myocardial infarction (1.0% vs. 0.7%); thromboembolic events ( 0.9% vs. 0.3%); stroke / transient ischemia (1.5% vs. 0.8%).

Letrozole taboo

Patients who are allergic to the active drug and / or any of the excipients. Premenopausal, pregnant, lactating women.

Letrozole tablets precautions

Athletes use with caution < br For patients with unknown menopausal status, the patients' LH, FSH and / or estradiol levels must be checked to determine their menopausal status before treatment.
This product should not be used with other estrogen-containing drugs at the same time, because estrogen will offset the pharmacological effects of this product.
This product can reduce the level of estrogen in the blood circulation. Long-term use may lead to lower bone density.
For women with osteoporosis or at risk for osteoporosis, before using this product for adjuvant therapy, bone density dosimeter should be used to evaluate bone density, and regular inspections should be performed afterwards.
It is recommended to test the overall bone health during treatment, and if necessary, to check at any time to prevent or treat osteoporosis, and to closely observe the patients who have problems.
Renal insufficiency Letrozole is not used in women with creatinine clearance <10 mL / min, and the possible benefits and potential risks of treatment with this product should be carefully weighed in these patients.
Liver insufficiency < br In patients with severe liver insufficiency, the systemic drug concentration and the terminal half-life of the drug are nearly twice that of healthy volunteers, so these patients should be closely observed (see Pharmacokinetics ). No clinical experience with repeated medications.
Impact on the ability to drive and operate the machine . Fatigue and dizziness related to medication can be observed during the application of this product. Occasionally, lethargy is observed. Therefore, patients should be reminded to pay attention when driving the vehicle or operating the machine.

Letrozole tablets for pregnant and lactating women

For women at risk of pregnancy, including premenopausal or short-term menopause, physicians should inform these patients of the need for adequate contraception until the patient has fully reached the postmenopausal state.
Oral administration of letrozole in pregnant rats can lead to a slight increase in the incidence of teratogenicity in treated animals. However, it is difficult to determine whether this is the result of an indirect effect of pharmacological properties (inhibition of estrogen biosynthesis) or a direct effect of letrozole itself.
Preclinical studies are limited to those with known pharmacological effects. Safety data for human use are derived from animal studies, and it is recommended that letrozole be contraindicated during pregnancy and lactation.

Letrozole tablets for children

Letrozole should not be used in children or adolescents.

Letrozole tablets for elderly

There is no need to adjust the dosage in elderly patients.

Letrozole Drug Interactions

Letrozole and a substrate of the CYP3A4 enzyme. Although letrozole does not appear to affect drugs metabolized by the CYP3A4 enzyme, these drugs may affect the biotransformation of the letrozole by the CYP3A4 enzyme.
In vitro studies have found that letrozole can inhibit cytochrome P450 isoenzyme 2A6 and slightly inhibit 2C19. When the activity of the applied drug mainly depends on these isoenzymes, it should be used with caution when using these drugs with a narrow therapeutic index. The CYP2A6 enzyme does not play a major role in drug metabolism. In vitro experiments found that when the concentration of letrozole was close to 100 times the steady-state plasma concentration, it did not significantly affect the metabolism of diazepam (the substrate of CYP2C19). Therefore, it is unlikely that clinically related interactions with CYP2C19 will occur.
Clinical studies of interactions with cimetidine and warfarin have shown that the combination of these drugs with letrozole does not produce clinically significant drug interactions.
After letrozole and tamoxifen (20 mg / day) combined, plasma letrozole levels decreased by an average of 38%. Letrozole has no effect on the plasma concentration of tamoxifen.
There is no data on the clinical experience of letrozole in combination with other antitumor drugs.

Letrozole tablets overdose

There have been cases of letrozole overdose. No specific treatment is known at this time, and treatment should be systemic and supportive.

Letrozole clinical trials

The following clinical trial data are mainly from clinical studies conducted abroad.
Adjuvant therapy < br A randomized, double-blind study of more than 8,000 patients with postmenopausal receptor-positive early breast cancer was randomized into patients; tamoxifen or letrozole had been monotherapy for 5 years; tamoxifen After 2 years of treatment with fenfen or letrozole, sequential letrozole or tamoxifen continued treatment for 3 years. All patients were evaluated before switching to treatment.
Effectiveness results at a median follow-up period of 26 months. The data in Table 2 reflect the main core analysis (PCA) results, including data from two non-changeover groups and two changeover groups up to 30 days after the changeover. The analysis was performed at a median treatment duration of 24 months and a median follow-up of 26 months. The letrozole group was superior to the tamoxifen group in all efficacy endpoints, and the advantages in disease-free survival, time to metastasis, and systemic disease-free survival were statistically significant.
Table 2 Disease-free and overall survival at a median follow-up of 26 months (PCAITT population)

Results of effectiveness of the monotherapy group analysis (MAA) at a median follow-up of 73 months. <Br A monotherapy analysis that includes data from the monotherapy group only. Letrozole and tamoxifen monotherapy are provided. Comparison of long-term clinical latest results of treatment efficacy (Table 3). At a median follow-up of 73 months and a median duration of treatment of 60 months, the risk of DFS in the letrozole group was significantly lower than in the tamoxifen group (MAA ITT population analysis: hazard ratio 0.88; 95% CI 0.78, 0.99: P = 0.03), confirming the 2005 PCA results. DFS showed similar benefits in truncated populations (risk ratio 0.85; 95% CI 0.75, 0.96). Similarly, the updated analysis confirms that letrozole has the advantage of reducing the risk of distant metastasis (risk ratio 0.87 0.76, 1.00) and extending the time to distant metastasis (risk ratio 0.85; 95% CI 0.72, 1.00). In addition, the letrozole group in the ITT analysis population tended to improve overall survival. The overall survival in the censored population showed a significantly greater benefit (risk ratio 0.82 0.70, 0.96) in support of letrozole.

Sequential therapy analysis < br At a median follow-up of 48 months, a comparison between conversion therapy and monotherapy was performed. For example, after 2 years of data in the tamoxifen monotherapy group, compared with the tamoxifen-treated letrozole group. , DFS risk ratio 0.93 97.5% CI 0.68, 1.15. Data from the letrozole monotherapy group two years later were compared with the tamoxifen-treated letrozole group, with a DFS hazard ratio of 0.93 97.5% CI 0.71, 1.22. At a median follow-up of 67 months, there were no significant differences in all endpoints after randomization in the sequential treatment analysis (e.g., 2 years after tamoxifen treatment and 3 years after trazozole versus 5 years with letrozole monotherapy DFS hazard ratio 1.10 99% CI 0.86, 1.41; tamoxifen treatment 3 years after letrozole treatment 2 years compared to letrozole monotherapy 5 years, DFS hazard ratio 0.96 99% CI 0.74, 1.24) . There is no evidence that sequential use of letrozole and tamoxifen is superior to letrozole monotherapy for 5 years.
Safety data at a median treatment duration of 60 months <br The median treatment duration was 60 months. The observed side effects were consistent with the safety characteristics of this product. The majority of adverse events reported (approximately 75% of patients reported one or more AEs) were grades 1 and 2. Based on all levels of adverse events during the study period, the incidence of the letrozole group was higher than that of the tamoxifen group: hypercholesterolemia (52% vs. 29%), fractures (10.1% vs. 7.1%), and myocardial infarction (1.0 % Vs. 0.5%), osteoporosis (5.1% vs. 2.7%) and joint pain (25.2% vs. 20.4%); tamoxifen group was higher than that of letrozole group: hot flashes (38% vs. 33%), Night sweats (17% vs. 15%), vaginal bleeding (13% vs. 52%), constipation (29% vs. 2.0%), thromboembolic events (3.6% vs. 2.1%), endometrial hyperplasia / cancer (2.9% vs. 0.3) %), And endometrial hyperplasia (1.8% vs. 0.3%).
Adjuvant treatment of early breast cancer in 262 menopausal women with hormone-sensitive primary breast cancer resection randomized to receive letrozole 2.5 mg daily for 5 years or tamoxifen 20 mg daily for 2 years, and then received letrozole 2.5 mg daily for 3 years . At 24 months, BMD in the lumbar spine (L2-L4) showed a median decrease of 4.1% in the letrozole group and a median increase of 0.3% in the tamoxifen group (a 4.4% difference). The median difference was statistically significant and supported tamoxifen (P <0.0001). The current data show that at 2 years, none of the patients with normal baseline BMD had osteoporosis, and only one patient with baseline osteopenia (T score 1.9) had osteoporosis during treatment.
Total hip BMD results are similar to lumbar spine BMD results, but there is no significant difference. At 2 years, significant differences in total BMD were observed in the safety population and in all stratified categories, supporting tamoxifen (P <0.0001). Fractures were reported in 2 years (20 cases (15%) in the letrozole group and 22 cases (17%) in the tamoxifen group).
Compared to baseline, the median total cholesterol level was reduced by 16% after 6 months in the tamoxifen group, and a similar decrease was seen after visits up to 24 months. The median total cholesterol level in the letrozole group was relatively high over time. Stable, no significant increase in single diagnosis. There were statistically significant differences between the two groups at each time point, supporting tamoxifen (P <0.0001).
Follow-up intensive adjuvant therapy was performed on 5,100 recipient-positive or unknown primary breast cancers. Postmenopausal patients with no disease progression after completion of tamoxifen adjuvant therapy (4.5-6 years) were randomized to receive letrozole or placebo. A primary analysis at a median follow-up of 28 months (25% of patients to 38 months) showed that letrozole significantly reduced the risk of recurrence by 42% compared to placebo (risk ratio 0.58; P = 0.00003). Regardless of lymph node status, significant statistically significant DFS support for letrozole was observed: a hazard ratio of 0.48, P = 0.002 for lymph node-negative populations, and a hazard ratio of 0.61, P = 0.002 for lymph node-positive populations.
The Independent Data and Safety Monitoring Committee recommended that women who had no relapses in the placebo group at the time of blindness in 2003 were allowed to switch to trazozole for up to 5 years. In a final analysis of the update performed in 2008, at a median 31 months after completion of tamoxifen adjuvant therapy, 1551 women (60% of eligible dressing change patients) were switched from placebo to letrozole. The median duration of treatment after switching to trzozole was 40 months.
An updated final analysis with a median follow-up of 62 months confirmed a significantly lower risk of breast cancer recurrence in the letrozole group compared with the placebo group, although 60% of eligible patients in the placebo group switched to letrozole after blinding. The median duration of treatment in the letrozole group was 60 months and the placebo group was 37 months.
The secondary endpoint was overall survival, with a total of 113 deaths reported, 51 [2%] in the letrozole group, and 62 [2.4%] in the placebo group. Overall, there were no significant differences between the two groups. (Hazard ratio 0.82; P = 0.292; CI95%: 0.56, 1.19). In higher-risk lymph node-positive patients, letrozole significantly reduced the risk of death by about 40% (risk ratio 0.61; P = 0.035; CI95%: 0.38, 0.97), and there was no significant difference between the two groups of lymph node-negative patients (risk Ratio 1.36; P = 0.385; CI95%: 0.68, 2.71).
In the updated analysis, compared with the placebo group, although 60% of patients in the placebo group switched to letrozole, the chance of contralateral aggressive breast cancer in the letrozole group was significantly reduced. There was no significant difference in overall survival.
An exploratory analysis of censored follow-up time on the switching day showed that the all-cause mortality risk was significantly lower in the letrozole group than in the placebo group.
There were no significant differences in safety and effectiveness between patients 65 years of age and younger.
The incidence of adverse reactions was significantly higher in the letrozole group than in the placebo group: hot flashes (49.7% vs. 43.3%), joint pain / arthritis (27.7% vs. 22.2%), and myalgia (9.5% vs. 6.7%). ). The incidence of osteoporosis in the letrozole group was higher than in the placebo group (6.9% vs 5.5%), and the incidence of clinical fractures was slightly higher than in the placebo group (5.9% vs 5.5%).
From the preliminary results of the bone mineral density study (median follow-up time of 18 months), it can be seen that compared with baseline, patients taking letrozole reduced hip bone mineral density by an average of 3% compared with 0.4% in the placebo group (P = 0.048). ). Bone mineral density in the spine decreased 4.6% in the letrozole group and 2% in the placebo group, but there was no significant difference. Newly diagnosed osteoporosis was 5.7% in the letrozole group and 4.5% in the placebo group (P = 0.07). Some patients are treated with calcium and bisphosphate.
Lipid renewal study results (median follow-up time 62 months) showed no significant difference between letrozole and placebo. The incidence of cardiovascular ischemic events in the two groups was 9.8% and 7.8%, respectively, which was statistically significant.
In the quality of life analysis (SF-36), there were no clinically relevant differences in the physical health, pain, and mobility of the letrozole and placebo groups.
First-line therapy < br A comparative study of letrozole and tamoxifen as first-line therapy was performed in 907 patients with locally advanced or metastatic breast cancer. Analysis shows that letrozole is superior to the following research indicators: Tamoxifen: the time to disease progression as the main indicator, the median time to disease progression was 9.4 months to 6.0 months (risk ratio 0.7, p = 0.0001); total objective response rate (CR + PR), 30% versus 20% (odds ratio 1.71, p = 0.001); in terms of time to treatment failure, 9.1 months to 5.7 months (P = 0.0001).
Letrozole is superior to tamoxifen in terms of objective response rate and time to disease progression, both in the hormone receptor (+) and in a subgroup of patients with unknown receptor status.
In a subgroup of patients who have previously been treated with anti-estrogens, letrozole is still superior to tamoxifen in terms of remission rate and time to disease progression.
In patients older than 70 years, the letrozole group was significantly better than the tamoxifen-treated group in terms of time to disease progression, 12.2 months to 5.8 months (risk ratio 0.72, p = 0.0001), and the letrozole group The chance of obtaining an objective response rate was also significantly higher than that of the control group (odds ratio 1.68, p = 0.0009).
Letrozole has a clear advantage in survival (40 months: 30 months).
Second-line therapy < br Two controlled studies in postmenopausal patients with advanced breast cancer who have previously received anti-estrogen therapy compared two doses of letrozole (0.5 mg and 2.5 mg) with mediacetate Efficacy of Progesterone and Anlumet.
Compared with megestrol acetate 2.5mg, letrozole showed statistically significant differences in response rate (24% vs. 16%, p = 0.04) and time to treatment failure (p = 0.04). There was no significant difference in disease progression time between the 2.5 mg letrozole treatment group and megestrol group (p = 0.07), and the overall survival rate was not significantly different between the two treatment groups (p = 0.2).
In the second study, there was no significant difference in remission rate between 2.5 mg letrozole and alumetide (p = 0.06).
The 2.5 mg letrozole treatment group was significantly better than the alumetide treatment group in terms of disease progression time (p = 0.008), treatment failure time (p = 0.003), and overall survival (p = 0.002).

Letrozole Pharmacology and Toxicology

Pharmacological effects < br Since the growth of breast tumor tissues depends on the presence of estrogen, the elimination of estrogen-mediated stimulation is a prerequisite for tumor remission. In postmenopausal women, estrogen is mainly produced under the action of aromatase. It can convert androgens produced by the adrenal glands, mainly androstenedione and testosterone, into estrone (E1) and estradiol (E2). ). Therefore, it is possible to inhibit the biosynthesis of estrogen in surrounding tissues and tumor tissues by specifically inhibiting aromatase.
Letrozole is a selective, non-steroidal aromatase inhibitor that competitively binds to the heme of the cytochrome P450 enzyme subunit, thereby inhibiting aromatase, causing estrogen in all Biosynthesis in tissues is reduced.
In healthy postmenopausal women, a single application of letrozole at 0.1, 0.5, and 2.5 mg can reduce serum concentrations of estrone and estradiol by 75-78% and 78%, respectively, from baseline levels. The strongest effect can be achieved in 48-78 hours.
In patients with postmenopausal advanced breast cancer, all patients receiving a daily dose of 0.1-5 mg may have plasma estradiol, estrone, and estrone sulfate levels falling by 75-95% from baseline levels, respectively. When the dose reached 0.5 mg or higher, many estrone and estrone sulfate values were below the detection limit, indicating that higher inhibition rates may be obtained at this dose level. In all patients treated, the inhibitory effect of the drug on estrogen biosynthesis during treatment has remained.
No inhibitory effect on adrenocortical hormone synthesis was observed. Postmenopausal patients receiving 0.1-5 mg of letrozole daily have no clinical signs of either cortisone, aldosterone, 11-deoxycortisone, 17-hydroxyprogesterone and ACTH plasma concentrations, or plasma renin activity Related changes. Healthy postmenopausal women received 0.1, 0.25, 0.5, 1, 2.5, and 5 mg of letrozole daily for 6 and 12 weeks. ACTH stimulation experiments showed no reduction in aldosterone or cortisone synthesis. Therefore, it is not necessary to supplement glucocorticoids and mineralocorticoids.
Healthy postmenopausal women received a single 0.1, 0.5, and 2.5 mg letrozole, and no changes were found in plasma androgen concentrations (androstenedione and testosterone); postmenopausal patients received 0.1-5 mg daily letrozole No changes were found in plasma androstenedione concentrations. This indicates that inhibition of estrogen biosynthesis does not lead to the accumulation of androgen precursors. Patients receiving letrozole had no negative effects on plasma LH and FSH levels. It was confirmed by TSH, T4 and T3 uptake experiments that it did not affect thyroid function.
Toxicology studies <br In studies on young rats, the pharmacological effects of letrozole have caused changes in the bones, neuroendocrine and reproductive systems.
Male rats have reduced bone growth and maturity from the lowest dose (0.003mf / Kg / day), and female rats have increased bone growth and maturity from the lowest dose (0.003mf / Kg / day). Bone mineral density (BMD) was also reduced in female rats at this dose. In the same study, the fertility of experimental animals at all doses decreased with pituitary hypertrophy and testicular changes, including degeneration of the vas deferens and atrophy of the female rat's reproductive tract. With the exception of bone size in female rats and morphological changes in testes in male rats, all effects were (partially) reversible.
Letrozole in vitro and in vivo studies have not shown any genotoxic effects.
In a 104-week rat carcinogenicity study, no treatment-related tumors were observed in male rats. In female rats, the incidence of benign and malignant breast tumors in all letrozole test animals decreased.

Letrozole Pharmacokinetics

Absorption of letrozole is fast and complete in the gastrointestinal tract. The average absolute bioavailability is 99.9%, while eating can slightly reduce the letrozole absorption rate, but has no effect on its absorption degree (AUC). Therefore, letrozole can be taken before, after or at the same time.
Letrozole, which is distributed in 60%, binds to plasma proteins, mainly albumin (55%). Letrozole concentration in red blood cells is 80% of its plasma concentration. After applying ¹⁴ C-labeled letrozole 2.5 mg, 82% of the radioactive substances in the plasma are the original drugs, so there are few metabolites throughout the body. Letrozole is rapidly and widely distributed in tissues, with an apparent volume of distribution at steady state of 1.87 ± 0.47 L / kg.
Metabolism and Elimination <br /> Letrozole's main elimination route is to convert to a non-pharmacologically active methanol metabolite (clearance = 2.1 L / h), which is close to 95% of total plasma clearance, but is related to liver blood flow (about 90 L / h) compared to this speed is relatively slow. Cytochrome P450 isoenzymes 3A4 and 2A6 can be converted to this metabolite in the future. The generation of small amounts of undetected metabolites, as well as drugs excreted directly through the kidneys and feces, account for only a small part of the total clearance of letrozole. After receiving 2 mg of ¹⁴ C-labeled letrozole for 2 weeks from healthy postmenopausal volunteers, the radioactive material recovered from urine was 88.2 ± 7.6% of the applied dose, while that in stool was 3.8 ± 0.9%. Until 216 hours after administration, at least 75% (84.7 ± 7.8%) of the radioactive substances collected from the urine were glucuronidated methanol metabolites, about 9% were two unmeasured metabolites, and 6% were Letrozole in its original form.
The terminal half-life of plasma is 75-110 hours. Letrozole, 2.5 mg daily, reached steady-state levels within 2-6 weeks. The plasma concentration at steady state level is nearly 7 times higher than the plasma concentration of letrozole in a single application, and 1.5-2 times higher than the steady state concentration calculated from a single administration, indicating that the daily dosage of letrozole is 2.5 mg. There is a mild non-linear relationship in dynamics. Because steady-state levels can be maintained for a long time during treatment, it is concluded that there is no sustained accumulation of letrozole.
Pharmacokinetics in special clinical situations < br Elderly patients < br Age has no effect on the pharmacokinetics of letrozole.
Renal insufficiency < br A study involving volunteers with different levels of renal function (24-hour creatinine clearance of 9-116 mL / min) showed that renal function after a single application of letrozole 2.5 mg The kinetics have no effect. In addition, in patients with advanced cancer, renal dysfunction (calculated creatinine clearance of 20-50 mL / min) has no effect on the concentration of letrozole.
Liver insufficiency In a study involving different levels of liver function, the average AUC of volunteers with moderate liver damage was 37% higher than those with normal liver function, but still within the range of normal liver function volunteers within. A study comparing the pharmacokinetics of 8 patients with cirrhosis, severe liver dysfunction, and 8 healthy volunteers after a single application of letrozole showed that the AUC and T _{1/2 of the} former group of patients increased respectively 95% and 187%. Therefore, it can be expected that the concentration of letrozole will increase in patients with breast cancer with severe liver damage compared with patients without liver damage. Since no increase in toxicity was found in patients receiving 5-10 mg letrozole daily, no dose adjustment was necessary in patients with severe liver dysfunction. However, these patients should be closely observed.

Letrozole Tablets Storage

Store below 30 to prevent children from taking it by mistake.

Letrozole tablets packaging

PVC / PE / PVDC aluminum plastic packaging.
10 tablets / box or 30 tablets / box.

Letrozole tablet expiration date

60 months

Letrozole Tablets

Import drug registration standard JX20000551 ^[1]