Letoval

Letoval (INN, trade name Letoval®) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letoval blocks production of estrogens in this way by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and Letoval does not reduce production of mineralo- or corticosteroids. In contrast, the antiestrogenic action of tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, is due to its interfering with the estrogen receptor, rather than inhibiting estrogen production. Letoval is approved by the United States Food and Drug Administration (FDA) for the treatment of local or metastatic breast cancer that is hormone receptor positive or has an unknown receptor status in postmenopausal women. Side effects include signs and symptoms of hypoestrogenism. There is concern that long term use may lead to osteoporosis, which is why prescriptions of Letoval are often accompanied by prescriptions of osteoporosis-fighting medication such as Fosamax. Letoval has shown to reduce estrogen levels by 98 percent while raising testosterone levels. The anti-estrogen action of Letoval is preferred by athletes and bodybuilders for use during a steroid cycle to reduce bloating due to excess water retention and prevent the formation of gynecomastia related breast tissue that is a side effect of some anabolic steroids. Usage above 2.5 mg/day is known to potentially temporarily kill sex drive. Above 5mg/day for extended periods may cause kidney problems. Letoval has also been shown to delay the fusing of the growth plates in adolescents. This may boost the effectiveness of growth hormone, and thus Letoval is used to treat adolescents and children with short stature.

Adjuvant Treatment of Early Breast Cancer

Letoval (Letoval) is indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.

Extended Adjuvant Treatment of Early Breast Cancer

Letoval is 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 Letoval in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival in patients treated with Letoval for a median of 60 months.

First and Second-Line Treatment of Advanced Breast Cancer

Letoval is indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. Letoval is also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Letoval is used to treat certain types of breast cancer in women who have already stopped menstruating (postmenopausal). It is also used for women who have already had other cancer treatments (e.g., tamoxifen).

Female hormones that occur naturally in the body can increase the growth of some breast cancers. Letoval works by decreasing the amounts of these hormones in the body.

Letoval is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Letoval is used in certain patients with the following medical conditions:

• Breast cancer that is hormone receptor-positive in women who have already gone through menopause (treatment before surgery).

Recommended Dose

The recommended dose of Letoval is one 2.5 mg tablet administered once a day, without regard to meals.

Use In Adjuvant Treatment Of Early Breast Cancer

In the adjuvant setting, the optimal duration of treatment with Letoval 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.

Use In Extended Adjuvant Treatment Of Early Breast Cancer

In the extended adjuvant setting, the optimal treatment duration with Letoval 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.

Use In First And Second-Line Treatment Of Advanced Breast Cancer

In patients with advanced disease, treatment with Letoval should continue until tumor progression is evident.

Use In Hepatic Impairment

No dosage adjustment is recommended for patients with mild to moderate hepatic impairment, although Letoval blood concentrations were modestly increased in subjects with moderate hepatic impairment due to cirrhosis. The dose of Letoval in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50%. The recommended dose of Letoval for such patients is 2.5 mg administered every other day. The effect of hepatic impairment on Letoval exposure in noncirrhotic cancer patients with elevated bilirubin levels has not been determined.

Use In Renal Impairment

No dosage adjustment is required for patients with renal impairment if creatinine clearance is ≥ 10 mL/min..

How supplied

Dosage Forms And Strengths

2.5 mg tablets: dark yellow, film-coated, round, slightly biconvex, with beveled edges (imprinted with the letters FV on one side and CG on the other side).

Storage And Handling

Packaged in HDPE bottles with a safety screw cap.

2.5 milligram tablets Bottles of 30 tablets..............................................NDC 0078-0249-15

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F).

Novartis Pharmaceuticals Corporation East Hanover, New Jersey, 07936. Revised: Jan 2014

See also:
What is the most important information I should know about Letoval?

Letoval can harm an unborn baby or cause birth defects. Do not use if you are pregnant.

You should not use this medication if you are allergic to Letoval, or if you have not gone completely through menopause.

Before taking Letoval, tell your doctor if you have osteoporosis, high cholesterol, or liver disease (especially cirrhosis).

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

To be sure Letoval is helping your condition, your blood may need to be tested often. Your bone mineral density may also need to be checked. Visit your doctor regularly.

Tell your doctor about all other medicines you use, especially tamoxifen (Soltamox).

Use Letoval as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Letoval by mouth with or without food.
• Take Letoval on a regular schedule to get the most benefit from it.
• If you miss a dose of Letoval, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Letoval.

Use: Labeled Indications

Breast cancer in postmenopausal women: Adjuvant treatment of hormone receptor-positive early breast cancer, extended adjuvant treatment of early breast cancer after 5 years of tamoxifen; treatment of advanced breast cancer with disease progression following antiestrogen therapy; first-line treatment of hormone receptor-positive or hormone receptor-unknown, locally-advanced, or metastatic breast cancer

Off Label Uses

Infertility/Ovulation stimulation in anovulatory females with polycystic ovary syndrome

Two meta-analyses of randomized, placebo-controlled studies suggest Letoval is superior to clomiphene for ovulation induction in subfertile females with polycystic ovary syndrome (PCOS). A greater increase in ovulation rate, clinical pregnancy rate, and live birth rate was observed with Letoval compared to clomiphene; complications were not found to differ between treatments. Additional trials may be necessary to further define the role of Letoval in this condition.

See also:
What other drugs will affect Letoval?

Tamoxifen: Co-administration of Letoval and tamoxifen 20 mg daily resulted in a reduction of Letoval plasma levels of 38% on average. Clinical experience in the second-line breast cancer trials indicates that the therapeutic effect of Letoval therapy is not impaired if Letoval is administered immediately after tamoxifen.

Cimetidine: A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on Letoval pharmacokinetics.

Warfarin: An interaction study with warfarin showed no clinically significant effect of Letoval on warfarin pharmacokinetics.

Other Anticancer Agents: There is no clinical experience to date on the use of Letoval in combination with other anticancer agents.

See also:
What are the possible side effects of Letoval?

Letoval tablets was generally well-tolerated in 2 controlled clinical trials.

Study discontinuations in the megestrol acetate comparison study for adverse events other than progression of tumor occurred in 5/188 (2.7%) of patients on Letoval tablets 0.5 mg, in 4/174 (2.3%) of the patients on Letoval tablets 2.5 mg and in 15/190 (7.9%) of patients on megestrol acetate. There were fewer thromboembolic events at both Letoval tablet doses than on the megestrol acetate arm (2 of 362 patients or 0.6% vs 9 of 190 patients or 4.7%). There was also less vaginal bleeding (1 of 362 patients or 0.3% vs 6 of 190 patients or 3.2%) on Letoval than on megestrol acetate. In the aminoglutethimide comparison study, discontinuations for reasons other than progression occurred in 6/193 (3.1%) of patients on Letoval 0.5 mg, 7/185 (3.8%) of patients on Letoval 2.5 mg and 7/178 (3.9%) of patients on aminoglutethimide.

Other less frequent (<5%) adverse experiences considered consequential and reported in at least 3 patients treated with Letoval included hypercalcemia, fracture, depression, anxiety, pleural effusion, alopecia, increased sweating and vertigo.

Laboratory Tests: No dose-related effect of Letoval on any hematologic or clinical chemistry parameter was evident. Moderate decreases in lymphocyte counts, of uncertain clinical significance, were observed in some patients receiving Letoval 2.5 mg. This depression was transient in about ½ of those affected. Two (2) patients on Letoval developed thrombocytopenia; relationship to the study drug was unclear. Patient withdrawal due to laboratory abnormalities, whether related to study treatment or not, was infrequent. Increases in SGOT, SGPT, and γGT ≥5 times the upper limit of normal (ULN) and of bilirubin ≥1.5 times the ULN were most often associated with metastatic disease in the liver. About 3% study participants receiving Letoval had abnormalities in liver chemistries not associated with documented metastases; these abnormalities may have been related to study drug therapy. In the megestrol acetate comparative study about 8% of patients treated with megestrol acetate had abnormalities in liver chemistries that were not associated with documented liver metastases; in the amino glutethimide study about 10% of aminoglutethimide-treated patients had abnormalities in liver chemistries not associated with hepatic metastases.