Letrozole 2.5 mg Tablet, Film Coated
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Aromatase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Letrozole is not chemotherapy. It's a hormone therapy, specifically an aromatase inhibitor — it works by dramatically lowering estrogen levels in your body. Some breast cancers are...
- What exactly is letrozole being used to treat — is it chemotherapy?
- Good news — you can take letrozole with or without food, whichever is easiest for you. Meals don't affect how the medication is absorbed. As for timing, pick a time of day you'll r...
- Can I take letrozole with food, and does it matter what time of day I take it?
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
10 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Letrozole 2.5 mg 69117-0004-01 | Yiling | 30 tablets | $0.109 | AB | FDA listed | — |
| Letrozole 2.5 mg 00093-7620-56 | Teva | 30 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 16729-0034-10 | Accord | 30 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 23155-0875-03 | Avet | 30 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 50268-0476-15 | AvPAK | 50 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 51991-0759-10 | Breckenridge | 1000 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 59651-0180-30 | Aurobindo | 30 tablets | $0.151 | AB | Availability likely | — |
| Letrozole 2.5 mg 62135-0491-30 | Chartwell | 30 tablets | $0.151 | AB | Availability likely | — |
| Femara 2.5 mg 00078-0249-15 | Novartis | 30 tablets | $27.116 | AB | Availability likely | — |
| Letrozole 2.5 mg 17856-0032-01 | ATLANTIC | 1 tablet | — | AB | FDA listed | — |
| Letrozole 2.5 mg 24979-0726-07 | Upsher-Smith | 90 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 42291-0374-90 | AvKARE | 90 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 50090-3474-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 51407-0986-90 | Golden | 90 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mgthis 55111-0646-78 | Dr. | 10 tablets | — | — | FDA listed | — |
| Letrozole 2.5 mg 63629-7819-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 63850-0025-01 | Natco | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 68071-2167-04 | NuCare | 40 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 68071-5264-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 71205-0587-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 71335-1526-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 71335-2396-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Letrozole 2.5 mg 80005-0139-08 | Carnegie | 30 tablets | — | — | FDA listed | — |
| Letrozole 2.5 mg 50090-8002-00 | A-S | 90 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 55111-0646-30 | 30 TABLET, FILM COATED in 1 BOTTLE (55111-646-30) | 2011-06-03 | Active |
| 55111-0646-78 You're viewing this | 10 BLISTER PACK in 1 CARTON (55111-646-78) / 10 TABLET, FILM COATED in 1 BLISTER PACK (55111-646-79) | 2011-06-03 | Active |
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Letrozole tablets are an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer (1.1) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy (1.2) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer (1.3)
1.1Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. .
1.2Extended Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy. The effectiveness of letrozole tablets in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival in patients treated with letrozole tablets for a median of 60 months [see Clinical Studies ( 14.2 , 14.3 ) ].
1.3First and Second-Line Treatment of Advanced Breast Cancer Letrozole tablets are indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. Letrozole tablets are also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy [see Clinical Studies ( 14.4 , 14.5 ) ].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Letrozole tablets are taken orally without regard to meals (2) : Recommended dose: 2.5.mg once daily (2.1) Patients with cirrhosis or severe hepatic impairment: 2.5 mg every other day ( 2.5 , 5.3 )
2.1Recommended Dose The recommended dose of letrozole tablets is one 2.5 mg tablet administered once a day, without regard to meals.
2.2Use in Adjuvant Treatment of Early Breast Cancer In the adjuvant setting, the optimal duration of treatment with letrozole tablets 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 [see Clinical Studies (14.1) ].
2.3Use in Extended Adjuvant Treatment of Early Breast Cancer In the extended adjuvant setting, the optimal treatment duration with letrozole tablets is not known. The planned duration of treatment in the study was 5 years. In the final updated analysis, conducted at a median follow-up of 62 months, the median treatment duration was 60 months.
Seventy-one percent of patients were treated for at least 3 years and 58% of patients completed least 4.5 years of extended adjuvant treatment. The treatment should be discontinued at tumor relapse [see Clinical Studies (14.2) ].
2.4Use in First and Second-Line Treatment of Advanced Breast Cancer In patients with advanced disease, treatment with letrozole tablets should continue until tumor progression is evident. [see Clinical Studies ( 14.4 , 14.5 ) ]
2.5Use in Hepatic Impairment No dosage adjustment is recommended for patients with mild to moderate hepatic impairment, although letrozole tablets blood concentrations were modestly increased in subjects with moderate hepatic impairment due to cirrhosis. The dose of letrozole tablets in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50% [see Warnings and Precautions (5.3) ]. The recommended dose of letrozole tablets for such patients is 2.5 mg administered every other day.
The effect of hepatic impairment on Letrozole exposure in noncirrhotic cancer patients with elevated bilirubin levels has not been determined.
2.6Use in Renal Impairment No dosage adjustment is required for patients with renal impairment if creatinine clearance is ≥10 mL/min. [see Clinical Pharmacology (12.3 ) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Letrozole tablets USP, 2.5 mg are dark yellow coloured, round, biconvex, film coated tablets with ‘LET’ debossed on one side and ‘2.5’ on other side. 2.5 milligram tablets (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Letrozole tablets may cause fetal harm when administered to a pregnant woman and the clinicl benefit to premenopausal women with breast cancer has not been demonstrated. Letrozole tablets are contraindicated in women who are or may become pregnant. If 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. [see Use in Specific Populations (8.1) ] Women of premenopausal endocrine status, including pregnant women (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Decreases in bone mineral density may occur. Consider bone mineral density monitoring (5.1) Increases in total cholesterol may occur. Consider cholesterol monitoring. (5.2) Fatigue, dizziness and somnolence may occur. Exercise caution when operating machinery (5.4)
5.1Bone Effects Use of 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-L4) bone mineral density (BMD) of adjuvant treatment with letrozole to that with tamoxifen showed at 24 months a median decrease in lumbar spine BMD of 4.1% in the letrozole arm compared to a median increase of 0.3% in the tamoxifen arm (difference = 4.4%) (P<0.0001) [See Adverse reactions (6.1) ].
Updated results from the BMD sub-study in the extended adjuvant setting demonstrated that at 2 years patients receiving letrozole had a median decrease from baseline of 3.8% in hip BMD compared to a median decrease of 2.0% in the placebo group. The changes from baseline in lumbar spine BMD in letrozole and placebo treated groups were not significantly different [see Adverse Reactions (6.2 ) ] . In the adjuvant trial the incidence of bone fractures at any time after randomization was 13.8% for letrozole and 10.5% for tamoxifen.
The incidence of osteoporosis was 5.1% for letrozole and 2.7% for tamoxifen [See Adverse Reactions (6.1) ] . In the extended adjuvant trial the incidence of bone fractures at any time after randomization was 13.3% for letrozole and 7.8% for placebo. The incidence of new osteoporosis was 14.5% for letrozole and 7.8% for placebo [See Adverse Reactions (6.3) ] .
5.2Cholesterol Consideration should be given to monitoring serum cholesterol. In the adjuvant 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., <=1.5 X ULN) in 151/1843 (8.2%) on letrozole vs 57/1840 (3.2%). Lipid lowering medications were required for 25% of patients on letrozole and 16% on tamoxifen [See Adverse Reactions (6.1) ].
5.3Hepatic Impairment Subjects with cirrhosis and severe hepatic impairment who were dosed with 2.5 mg of letrozole experienced approximately twice the exposure to letrozole as healthy volunteers with normal liver function. Therefore, a dose reduction is recommended for this patient population. The effect of hepatic impairment on letrozole exposure in cancer patients with elevated bilirubin levels has not been determined. [see Dosage and Administration (2.5) ].
5.4Fatigue and Dizziness Because fatigue, dizziness, and somnolence have been reported with the use of letrozole, caution is advised when driving or using machinery until it is known how the patient reacts to letrozole use.
5.5Laboratory Test Abnormalities No dose-related effect of letrozole on any hematologic or clinical chemistry parameter was evident. Moderate decreases in lymphocyte counts, of uncertain clinical significance, were observed in some patients receiving letrozole 2.5 mg. This depression was transient in about half of those affected.
Two patients on letrozole developed thrombocytopenia; relationship to the study drug was unclear. Patient withdrawal due to laboratory abnormalities, whether related to study treatment or not, was infrequent.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most serious adverse reactions from the use of letrozole are: Bone effects [see Warnings and Precautions (5.1) ] Increases in cholesterol [see Warnings and Precautions (5.2) ] 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. The most common adverse reactions (>20%) were hot flashes, arthralgia (6.1) ; flushing, asthenia, edema, arthralgia, headache, dizziness, hypercholesterolemia, sweating increased, bone pain ( 6.2 , 6.3 ); and musculoskeletal (6.4) .
To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Limited Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Adjuvant Treatment of Early Breast Cancer The median treatment duration of adjuvant treatment was 60 months and the median duration of follow-up for safety was 73 months for patients receiving letrozole and tamoxifen. Certain adverse reactions were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs. Adverse reactions were analyzed irrespective of whether a symptom was present or absent at baseline.
Most adverse reactions reported (approximately 75% of patients reporting 1 or more AE) were Grade 1 or Grade 2 applying the Common Toxicity Criteria Version 2.0/ Common Terminology Criteria for Adverse Events, version 3.0. Table 1 describes adverse reactions (Grades 1-4) irrespective of relationship to study treatment in the adjuvant trial for the monotherapy arms analysis (safety population). Table 1: Patients with Adverse Reactions (CTC Grades 1-4, Irrespective of Relationship to Study Drug) in the Adjuvant Study- Monotherapy Arms Analysis (Median follow-up 73 Months; Median Treatment 60 Months) Grades 1-4 Grades 3-4 Adverse Reaction Letrozole N=2448 n (%) tamoxifen N=2447 n (%) Letrozole N=2448 n (%) tamoxifen N=2447 n (%) Pts with any adverse event 2310 (94.4) 2214 (90.5) 635 (25.9) 604 (24.7) Hypercholesterolemia 1280 (52.3) 700 (28.6) 11 (0.4) 6 ( 0.2) Hot Flashes/Flushes 821 (33.5) 929 (38.0) 0 - 0 - Arthralgia/Arthritis 618 (25.2) 501 (20.4) 85 (3.5) 50 ( 2.0) Night Sweats 357 (14.6) 426 (17.4) 0 - 0 - Bone Fractures 2 338 (13.8) 257 (10.5) -- -- Weight Increase 317 (12.9) 378 (15.4) 27 (1.1) 39 ( 1.6) Nausea 283 (11.6) 277 (11.3) 6 (0.2) 9 ( 0.4) Bone Fractures 1 247 (10.1) 174 (7.1) -- -- Fatigue (Lethargy, Malaise, Asthenia) 235 (9.6) 250 (10.2) 6 (0.2) 7 ( 0.3) Myalgia 217 (8.9) 212 (8.7) 18 (0.7) 14 ( 0.6) Edema 164 (6.7) 160 (6.5) 3 (0.1) 1 (<0.1) Weight Decrease 140 (5.7) 129 (5.3) 8 (0.3) 5 ( 0.2) Vaginal Bleeding 128 (5.2) 320 (13.1) 1 (<0.1) 8 ( 0.3) Back Pain 125 (5.1) 136 (5.6) 7 (0.3) 11 ( 0.4) Osteoporosis NOS 124 (5.1) 66 (2.7) 10 (0.4) 5 ( 0.2) Bone pain 123 (5.0) 109 (4.5) 6 (0.2) 4 ( 0.2) Depression 119 (4.9) 114 (4.7) 16 (0.7) 14 ( 0.6) Vaginal Irritation 111 (4.5) 77 (3.1) 2 (<0.1) 2 (<0.1) Headache 105 (4.3) 94 (3.8) 9 (0.4) 5 ( 0.2) Pain in extremity 103 (4.2) 79 (3.2) 6 (0.2) 4 ( 0.2) Osteopenia 87 (3.6) 74 (3.0) 0 - 2 (<0.1) Dizziness/Light-Headedness 84 (3.4) 84 (3.4) 1 (<0.1) 6 (0.2) Alopecia 83 (3.4) 84 (3.4) 0 - 0 - Vomiting 80 (3.3) 80 (3.3) 3 (0.1) 5 (0.2) Cataract 49 (2.0) 54 (2.2) 16 (0.7) 17 ( 0.7) Constipation 49 (2.0) 71 (2.9) 3 (0.1) 1 (<0.1) Breast pain 37 (1.5) 43 (1.8) 1 (<0.1) 0 - Anorexia 20 (0.8) 20 (0.8) 1 (<0.1) 1 (<0.1) Endometrial Hyperplasia/ Cancer 2, 3 11/1909 (0.6) 70/1943 (3.6) -- -- Endometrial Proliferation Disorders 10 (0.3) 71 (1.8) 0 - 14 (0.6) Endometrial Hyperplasia/ Cancer 1, 3 6/1909 (0.3) 57/1943 (2.9) -- -- Other endometrial disorders 2 (<0.1) 3 (0.1) 0 - 0 - Myocardial Infarction 1 24 (1.0) 12 (0.5) -- -- Myocardial Infarction 2 37 (1.5) 25 (1.0) -- -- Myocardial ischemia 6 (0.2) 9 (0.4) -- -- Cerebrovascular accident 1 52 (2.1) 46 (1.9) -- -- Cerebrova…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Tamoxifen 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 trials indicates that the therapeutic effect of letrozole therapy is not impaired if letrozole is administered immediately after tamoxifen. Cimetidine A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on letrozole pharmacokinetics.
Warfarin An interaction study with warfarin showed no clinically significant effect of letrozole on warfarin pharmacokinetics. Other Anticancer Agents There is no clinical experience to date on the use of letrozole in combination with other anticancer agents.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Pregnancy Category X [see Contraindications (4) ]. Letrozole 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 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. Letrozole caused adverse pregnancy outcomes, including congenital malformations, in rats and rabbits at doses much smaller than the daily maximum recommended human dose (MRHD) on a mg/m 2 basis. Effects included increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems.
Animal data and letrozole’s mechanism of action raise concerns that letrozole could be a human teratogen as well. Reproduction studies in rats showed embryo and fetal toxicity at letrozole doses during organogenesis equal to or greater than 1/100 the daily maximum recommended human dose (MHRD) (mg/m 2 basis). Adverse effects included: intrauterine mortality; increased resorptions and postimplantation loss; decreased numbers of live fetuses; and fetal anomalies including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals.
Letrozole doses 1/10 the daily MHRD (mg/m 2 basis) caused fetal domed head and cervical/centrum vertebral fusion. In rabbits, letrozole caused embryo and fetal toxicity at doses about 1/100,000 and 1/10,000 the daily MHRD respectively (mg/m 2 basis). Fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs. [see Nonclinical Toxicology (13.2) ].
Physicians should discuss the need for adequate contraception with women who are recently menopausal. Contraception should be used until postmenopausal status is clinically well established.
8.3Nursing Mothers It is not known if letrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from letrozole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4Pediatric Use The safety and effectiveness in pediatric patients have not been established.
8.5Geriatric Use The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 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 <70.
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.
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category X [see Contraindications (4) ]. Letrozole 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 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. Letrozole caused adverse pregnancy outcomes, including congenital malformations, in rats and rabbits at doses much smaller than the daily maximum recommended human dose (MRHD) on a mg/m 2 basis. Effects included increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems.
Animal data and letrozole’s mechanism of action raise concerns that letrozole could be a human teratogen as well. Reproduction studies in rats showed embryo and fetal toxicity at letrozole doses during organogenesis equal to or greater than 1/100 the daily maximum recommended human dose (MHRD) (mg/m 2 basis). Adverse effects included: intrauterine mortality; increased resorptions and postimplantation loss; decreased numbers of live fetuses; and fetal anomalies including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals.
Letrozole doses 1/10 the daily MHRD (mg/m 2 basis) caused fetal domed head and cervical/centrum vertebral fusion. In rabbits, letrozole caused embryo and fetal toxicity at doses about 1/100,000 and 1/10,000 the daily MHRD respectively (mg/m 2 basis). Fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs. [see Nonclinical Toxicology (13.2) ].
Physicians should discuss the need for adequate contraception with women who are recently menopausal. Contraception should be used until postmenopausal status is clinically well established.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use The median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 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 <70.
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.
🆘 Overdosage ▾
10 OVERDOSAGE Isolated cases of 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/m 2 basis); 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/m 2 basis); death was preceded by depressed blood pressure and arrhythmias.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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 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 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 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 adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones.
12.2Pharmacodynamics In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg letrozole suppress plasma concentrations of estradiol, estrone, and estrone sulfate by 75%-95% from baseline with maximal suppression achieved within two-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 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 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 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 in patients, nor was thyroid function as evaluated by TSH levels, T3 uptake, and T4 levels.
12.3Pharmacokinetics Absorption and Distribution: Letrozole is rapidly and completely absorbed from the gastrointestinal tract and absorption is not affected by food. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway. About 90%…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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 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 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 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 adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Letrozole tablets USP, 2.5 mg are dark yellow coloured, round, biconvex, film coated tablets with ‘LET’ debossed on one side and ‘2.5’ on other side and is supplied in Bottles of 30’s count and Unit dose package of 100 (10 x 10). Bottles of 30 NDC 55111-646-30 Unit dose Package of 100 (10 x 10) NDC 55111-646-78
📋 Description ▾
11 DESCRIPTION Letrozole tablets USP for oral administration contains 2.5 mg of letrozole, a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis). It is chemically described as 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile, and its structural formula is Letrozole is a white to yellowish crystalline powder, freely soluble in dichloromethane, slightly soluble in alcohol and practically insoluble in water. It has a molecular weight of 285.31, molecular formula C 17 H 11 N 5 , and a melting range of 184°C-185°C.
Letrozole tablets USP are available as 2.5 mg tablets for oral administration. Inactive Ingredients. Colloidal Silicon Dioxide, Croscarmellose Sodium, Hypromellose, Lactose Monohydrate, Magnesium stearate, Polyethylene Glycol, Povidone, Talc, Titanium dioxide, and Yellow iron oxide .
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Information for Patients Pregnancy: Letrozole tablets are 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 and somnolence was uncommonly reported, caution is advised when driving or using machinery.
Bone Effects: Consideration should be given to monitoring bone mineral density. Rx Only Manufactured by: Dr. Reddy’s Laboratories Limited Visakhapatnam - INDIA Issued: 0710