Letrozol
Letrozol Uses, Dosage, Side Effects, Food Interaction and all others data.
Letrozol 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. Letrozol selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis. Letrozol 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.
Letrozol 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.
Letrozol 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 | Letrozol |
| Availability | Prescription only |
| Generic | Letrozole |
| Letrozole Other Names | Letrozol, Letrozole |
| Related Drugs | Arimidex, Ibrance, Femara, Aromasin, Faslodex, Verzenio, Afinitor, tamoxifen, paclitaxel, Xeloda |
| Type | |
| 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 | |
| Available Country | Netherlands |
| 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.
Letrozol 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 Letrozol works
Letrozol 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
Letrozol dosage
The recommended dose is one 2.5 mg tablet administered once a day, regardless to meals. In patients with advanced disease, treatment with Letrozol 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 Letrozol Tablet do not require glucocorticoid or mineralocorticoid replacement therapy.
Side Effects
Letrozol 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 Letrozol 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 Letrozol pharmacokinetics. In in-vitro experiments, Letrozol & diazepam showed no significant inhibition in the metabolism of each other. Coadministration of Letrozol and tamoxifen 20 mg daily resulted in a reduction of Letrozol plasma levels of 38% on average. Clinical experience in the second-line breast cancer pivotal trials indicates that the therapeutic effect of Letrozol therapy is not impaired if Letrozol is administered immediately after tamoxifen.
Food Interaction
- Take with or without food. Food slows absorption without decreasing the quantity absorbed.
Letrozol 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.,
Letrozol 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
Letrozol Disease Interaction
Volume of Distribution
The volume of distribution of letrozole is 1.87L/kg.
Elimination Route
Letrozol 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
Letrozol 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 Letrozol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Letrozol is administered to a nursing woman.
Contraindication
Letrozol may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Letrozol 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 Letrozol 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 Letrozol 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 Letrozol
Letrozol contains Letrozole see full prescribing information from innovator Letrozol Monograph, Letrozol MSDS, Letrozol FDA label
FAQ
How safe is Letrozol?
Letrozol 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 Letrozol?
Letrozol is generally safe to take long term, however, your specialist team will monitor your health carefully. This is because Letrozol reduces levels of oestrogen that your body needs for strong and healthy bones.
How does Letrozol work?
Letrozol works by decreasing the amount of estrogen produced by the body.
What are the common side effects of Letrozol?
Common side effects of Letrozol 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 Letrozol safe during pregnancy?
Letrozol cannot be taken during pregnancy. Research shows it may cause damage to developing embryos.
Is Letrozol safe during breastfeeding?
The manufacturer recommends that breastfeeding be discontinued during Letrozol therapy and for 3 weeks after the last dose.
Can I drink alcohol with Letrozol?
There is no evidence that drinking alcohol causes any problems when taking Letrozol. Some people taking Letrozol may get hot flushes or redness when they drink alcohol. In this case, avoiding alcohol may help.
Can I drive after taking Letrozol?
You should know that Letrozol 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 Letrozol ?
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 Letrozol on an empty stomach?
Letrozol may be taken with food or on an empty stomach. If you miss a dose of Letrozol , 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 Letrozol without food?
Letrozol comes as a tablet to take by mouth once a day with or without food.
Can I take Letrozol for a long time?
Most people are given Letrozol for 5 years, but some will take it for up to 10 years.
How long does Letrozol take to work ?
Letrozol takes several weeks or months for the medicine to work fully.
How long does Letrozol stay in my system?
Letrozol 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 Letrozol?
Side effects usually improve after a few months as your body gets used to the medicine.
How do I know if Letrozol is working?
You may be asked to have a blood test during the menstrual cycle in which you are taking Letrozol.
How does Letrozol make me feel?
Letrozol can sometimes cause headaches, nausea and vomiting.
Does Letrozol put on weight?
Weight gain is one of the occasional side effects that can occur when taking Letrozol 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 Letrozol?
You should know that Letrozol 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. Letrozol may harm the fetus. you should know that Letrozol 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 Letrozol can I take?
Letrozol daily dose of 2.5-7.5 mg starting day 3-5 of the cycle for 5 days.
Can I overdose on Letrozol ?
If you accidentally take too much Letrozol, contact a doctor or hospital straight away. You might need medical treatment.
What happen If I stop taking Letrozol?
Some people worry about stopping their treatment, but there's evidence that Letrozol 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 Letrozol affect my fertility?
Letrozol increases the chances of natural conception.
Can Letrozol affects my heart?
Hormone therapy may increase heart problems.
