Letrozole
Letrozole Uses, Dosage, Side Effects, Food Interaction and all others data.
Letrozole is a nonsteroidal aromatase inhibitor. It inhibits the conversion of androgen to estrogen. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum FSH. Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis. 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 significantly lowers serum estrone, estradiol and estrone sulfate and has not been shown to significantly affect the adrenal corticosteroid synthesis, ldosterone synthesis, or synthesis of thyroid hormones.
Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue.
Letrozole is a third generation type II aromatase inhibitor used to treat estrogen dependant breast cancers. It has a long duration of action as it has a half life of over 42 hours in breast cancer patients. Patients should be counselled regarding the risk of interstitial lung disease, pneumonitis, QT prolongation, elevated transaminase levels, neutropenia, and embryo-fetal toxicity.
| Trade Name | Letrozole |
| Availability | Prescription only |
| Generic | Letrozole |
| Letrozole Other Names | Letrozol, Letrozole |
| Related Drugs | Arimidex, Ibrance, Femara, Aromasin, Faslodex, Verzenio, Afinitor, tamoxifen, paclitaxel, Xeloda |
| Weight | 2.5mg |
| Type | Oral tablet |
| Formula | C17H11N5 |
| Weight | Average: 285.3027 Monoisotopic: 285.101445377 |
| Protein binding | Letrozole is 60% bound to proteins. 55% is bound to albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | Hormonal Chemotherapy |
| Manufacturer | Dr, Reddys Laboratories (UK) Ltd |
| Available Country | United Kingdom, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
- Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.
- Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy.
- First-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer.
- Treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
Letrozole is also used to associated treatment for these conditions: Advanced Breast Cancer, Anovulatory cycle, Early Breast Cancer, Ovarian Epithelial Cancer, Advanced HR + HER2 - breast cancer, Metastatic HR + HER2 - breast cancer
How Letrozole works
Letrozole is a non-steroidal type II aromatase inhibitor. It blocks the active site, and therefore the electron transfer chain of CYP19A1. This competitive inhibition prevents the conversion of androgens to estrogen. This action leads to a reduction in uterine weight and elevated leuteinizing hormone. In postmenopausal women, the action of aromatase is responsible for the majority of estrogen production. With reduced availability of estrogen, estrogen-dependant tumors regress. Third generation aromatase inhibitors do not significantly affect cortisol, aldosterone, and thyroxine levels.
Dosage
Letrozole dosage
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Letrozole Tablet should be continued until tumor progression is evident. Treatment should be discontinued at tumor relapse. No dose adjustment is required for elderly patients. Patients treated with Letrozole Tablet do not require glucocorticoid or mineralocorticoid replacement therapy.
Side Effects
Letrozole is generally well tolerated. The observed adverse reactions are mild or moderate in nature including hot flashes, night sweats, weight increase, nausea, vaginal bleeding & irritation, endometrial proliferation disorders etc.
Toxicity
Overdose data in humans is not readily available, however 1 reported case was not associated with serious adverse reactions. Animal studies do not report serious adverse effects with high dose treatment. Patients experiencing and overdose should be treated with symptomatic and supportive measures.
Oral doses over 2000mg/kg were associated with reduced motor activity, ataxia, dyspnea, and death in mice and rats.
Precaution
Since fatigue and dizziness have been observed with the use of Letrozole and somnolence was uncommonly reported, caution is advised when driving or using machinery.
Interaction
A pharmacokinetic interaction study with cimetidine & warfarin showed no clinically significant effect on Letrozole pharmacokinetics. In in-vitro experiments, Letrozole & diazepam showed no significant inhibition in the metabolism of each other. Coadministration of Letrozole and tamoxifen 20 mg daily resulted in a reduction of Letrozole plasma levels of 38% on average. Clinical experience in the second-line breast cancer pivotal trials indicates that the therapeutic effect of Letrozole therapy is not impaired if Letrozole is administered immediately after tamoxifen.
Food Interaction
- Take with or without food. Food slows absorption without decreasing the quantity absorbed.
Letrozole Cholesterol interaction
[Moderate] In an adjuvant clinical trial hypercholesterolemia was reported in 52.3% of letrozole patients and 28.6% of tamoxifen patients.
CTC grade 3-4 hypercholesterolemia was reported in 0.4% of letrozole patients and 0.1% of tamoxifen patients.
Also in the adjuvant setting, an increase of >=1.5 X ULN in total cholesterol (generally non-fasting) was observed in patients on monotherapy who had baseline total serum cholesterol within the normal range (i.e.,
Letrozole Drug Interaction
Unknown: aspirin, aspirin, calcium / vitamin d, calcium / vitamin d, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, palbociclib, palbociclib, metoprolol, metoprolol, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine
Letrozole Disease Interaction
Volume of Distribution
The volume of distribution of letrozole is 1.87L/kg.
Elimination Route
Letrozole is 99.9% orally bioavailable. A 2.5mg oral dose reaches a Cmax of 104nmol/L with a Tmax of 8.10h, and an AUC of 7387nmol*h/L.
Half Life
The terminal elimination half life of letrozole is approximately 42h in healthy volunteers, but longer in breast cancer patients.
Clearance
The average clearance after a single dose of letrozole was 1.52L/h and at steady state was 1.20L/h.
Elimination Route
Letrozole is 90% eliminated in the urine. 75% of the dose is recovered as a glucuronide metabolite, 9% is in the form of the ketone and carbinol metabolites, and 6% is recovered in urine as unchanged letrozole.
Pregnancy & Breastfeeding use
Pregnancy Category D. It is not known if Letrozole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Letrozole is administered to a nursing woman.
Contraindication
Letrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Letrozole 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.
Special Warning
Renal Impairment: No dosage adjustment is required for patients with renal impairment if creatinine clearance is 10 ml/min.
Hepatic Impairment: No dosage adjustment is recommended for patients with mild to moderate hepatic impairment. The dose of Letrozole in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50%. The recommended dose for such patients is 2.5 mg administered every other day.
Pediatric Use: The safety and effectiveness in pediatric patients have not been established.
Acute Overdose
Isolated cases of overdosage with Letrozole have been reported. No specific treatment for overdosage is known; treatment should be symptomatic and supportive.
Storage Condition
Store in a cool and dry place protected from light and moisture.
Innovators Monograph
You find simplified version here Letrozole
Letrozole contains Letrozole see full prescribing information from innovator Letrozole Monograph, Letrozole MSDS, Letrozole FDA label
FAQ
How safe is Letrozole?
Letrozole is a medicine used for treating breast cancer. It can also help prevent breast cancer coming back. It is mainly prescribed for women who have been through the menopause and have a type of cancer called "hormone-dependent" breast cancer.
How safe is Letrozole?
Letrozole is generally safe to take long term, however, your specialist team will monitor your health carefully. This is because Letrozole reduces levels of oestrogen that your body needs for strong and healthy bones.
How does Letrozole work?
Letrozole works by decreasing the amount of estrogen produced by the body.
What are the common side effects of Letrozole?
Common side effects of Letrozole are include:
- aching or pain in the joints or muscles.
- menopausal symptoms.
- low mood and depression.
- difficulty sleeping.
- fatigue.
- osteoporosis.
- high blood pressure and cholesterol.
Is Letrozole safe during pregnancy?
Letrozole cannot be taken during pregnancy. Research shows it may cause damage to developing embryos.
Is Letrozole safe during breastfeeding?
The manufacturer recommends that breastfeeding be discontinued during Letrozole therapy and for 3 weeks after the last dose.
Can I drink alcohol with Letrozole?
There is no evidence that drinking alcohol causes any problems when taking Letrozole. Some people taking Letrozole may get hot flushes or redness when they drink alcohol. In this case, avoiding alcohol may help.
Can I drive after taking Letrozole?
You should know that Letrozole may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
When should be taken of Letrozole ?
The usual dose of is 2.5mg and it is taken by mouth. It is to be taken for five days per month from day two to day six of your menstrual cycle. Day one is the first day of your period. You need to take this tablet at the same time every day for the best results.
Can I take Letrozole on an empty stomach?
Letrozole may be taken with food or on an empty stomach. If you miss a dose of Letrozole , take it as soon as you can if it is within 12 hours of the missed dose. If it is over 12 hours since your missed dose, skip the missed dose and go back to your usual dosing times.
Can I take Letrozole without food?
Letrozole comes as a tablet to take by mouth once a day with or without food.
Can I take Letrozole for a long time?
Most people are given Letrozole for 5 years, but some will take it for up to 10 years.
How long does Letrozole take to work ?
Letrozole takes several weeks or months for the medicine to work fully.
How long does Letrozole stay in my system?
Letrozole terminal elimination half-life is about 2 days and steady-state plasma concentration after daily 2.5 mg dosing is reached in 2-6 weeks.
Does your body adjust to Letrozole?
Side effects usually improve after a few months as your body gets used to the medicine.
How do I know if Letrozole is working?
You may be asked to have a blood test during the menstrual cycle in which you are taking Letrozole.
How does Letrozole make me feel?
Letrozole can sometimes cause headaches, nausea and vomiting.
Does Letrozole put on weight?
Weight gain is one of the occasional side effects that can occur when taking Letrozole but if you are finding it difficult to control then it may be worth getting in touch with your doctor to let them know.
Who should not take Letrozole?
You should know that Letrozole should only be taken by women who have experienced menopause and cannot become pregnant. However, if you are pregnant or breast-feeding, you should tell your doctor before you begin taking this medication. Letrozole may harm the fetus. you should know that Letrozole may make you drowsy.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
How much Letrozole can I take?
Letrozole daily dose of 2.5-7.5 mg starting day 3-5 of the cycle for 5 days.
Can I overdose on Letrozole ?
If you accidentally take too much Letrozole, contact a doctor or hospital straight away. You might need medical treatment.
What happen If I stop taking Letrozole?
Some people worry about stopping their treatment, but there's evidence that Letrozole continues to reduce the risk of breast cancer coming back for many years after you stop taking it. However, not taking the drug for the recommended time may increase the risk of your breast cancer coming back.
Will Letrozole affect my fertility?
Letrozole increases the chances of natural conception.
Can Letrozole affects my heart?
Hormone therapy may increase heart problems.
