Fact Sheet Apo-Letrozole

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Contact: Bureau of Pharmaceutical Sciences

What is APO-LETROZOLE?

APO-LETROZOLE are tablets that contain 2.5 mg of the active substance letrozole.

Marketing authorization with conditions has been issued for APO-LETROZOLE for the following indication: APO -LETROZOLE is indicated for use in the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer; and the extended adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women who have received approximately 5 years of prior standard adjuvant tamoxifen therapy.

What is APO-LETROZOLE used for?

• Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women.
• Extended adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women who have received approximately 5 years of prior standard adjuvant tamoxifen therapy.

What is Adjuvant Treatment of Early Breast Cancer?

Early breast cancer is confined to the breast, and may or may not have spread to the lymph nodes in the breast or armpit area. Breast cancer that has metastasized (spread) to other parts of the body is considered to be advanced/metastatic breast cancer.

Adjuvant treatment of early breast cancer is used to help reduce the risk of recurrence (cancer coming back or spreading to other parts of the body) after surgery.

What other hormonal treatments have been used to treat Early Breast Cancer?

• Tamoxifen
• Anastrozole

What are the advantages of APO-LETROZOLE over other hormonal therapies?

It has been shown that women taking letrozole as an adjuvant therapy, reduce the risk of breast cancer recurrence by an additional 19% compared to tamoxifen. In addition, letrozole reduced the spread of the cancer to other parts of the body (distant metastasis) by 27 % as compared to the gold standard, tamoxifen. However, women treated with letrozole who did not have cancer in the lymph nodes had not yet shown an efficacy benefit compared to those treated with tamoxifen.

Letrozole has not yet been compared to other Aromatase Inhibitors in a clinical study.

What is extended adjuvant therapy?

The purpose of extended adjuvant therapy is to treat hormone receptor-positive early breast cancer in postmenopausal women who have received approximately 5 years of prior standard adjuvant tamoxifen therapy in order to prevent recurrence. Treating breast cancer with APO-LETROZOLE beyond the standard 5 years of hormone therapy is called “extended adjuvant therapy”.

Letrozole 2.5 milligrams tablet is the only drug approved for this kind of therapy. The long term benefit (whether letrozole prolongs life) of extended adjuvant therapy is unconfirmed as this single, large placebo controlled trial was terminated early, and data from clinical trials with tamoxifen beyond five years did not show benefit.

APO-LETROZOLE as extended adjuvant therapy

Authorization with conditions under the Notice of Compliance with Conditions (NOC/c) policy of Letrozole 2.5 mg tablet was issued for extended adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women who have received approximately 5 years of prior standard adjuvant tamoxifen therapy. This authorization reflects the promising nature of the clinical efficacy and safety of letrozole in patients with this serious disease, and the need for further follow up to verify the clinical benefit. The approval is based on data from a single, double-blind placebo controlled clinical trial with more than 5,100 postmenopausal women, who either received 2.5 mg of letrozole daily or placebo (no active therapy). The planned duration of treatment was 5 years. The first planned analysis, which occurred at 28 months median follow up, gave a statistically significant decrease in recurrence and new breast cancer in women treated with letrozole. The results were communicated to participants, and patients on the placebo arm were offered the choice of starting therapy with letrozole. Although the study continues, due to this optional switch, future data on long term benefits may not be available. Although survival was one of the secondary endpoints of the study, the data are not mature enough to conclude that women treated with letrozole will outlive women treated with placebo.

In node-positive patients, at 28 months follow up, letrozole significantly reduced the risk of death. At an updated safety analysis with median follow-up of 30 months, letrozole continued to reduce deaths but the difference was no longer statistically significant.

In node-negative patients, at 28 months follow up, there was a statistically insignificant numerical increase in deaths due to all causes. Overall, the benefit/risk profile of letrozole was considered superior to that of placebo. At an updated safety analysis with median follow-up of 30 months, overall deaths in node-negative patients were similar.

How does APO-LETROZOLE work?

APO-LETROZOLE is an aromatase inhibitor specifically developed to treat hormone receptor-positive breast cancer in women who have passed menopause. Estrogen is a normally occurring female sex hormone that stimulates normal breast tissue and the growth of some types of breast cancer. APO-LETROZOLE acts by binding to aromatase, a substance needed to make estrogen. As a result, the production of estrogen and the growth of certain types of breast cancer is reduced.

Who can be treated with APO-LETROZOLE?

1. Postmenopausal women with hormone receptor-positive early breast cancer.
2. Postmenopausal women with hormone receptor-positive early breast cancer who have completed about 5 years of prior adjuvant tamoxifen therapy.

What do patients need to know about using APO-LETROZOLE?

APO-LETROZOLE is contraindicated in pre-menopausal women.

The use of some aromatase inhibitors, including APO-LETROZOLE, may increase the risk of cardiovascular events compared to tamoxifen, such as heart attacks and stroke. Women at risk of heart disease should be carefully monitored by their doctor.

The use of aromatase inhibitors, including APO-LETROZOLE, may increase lipid levels.

Your doctor should continue routine checking of your lipid and cholesterol levels on a regular basis.

Long term use of APO-LETROZOLE may result in a reduction in bone mineral density and may increase the risk of osteoporosis and fracture. Your doctor should continue his/her routine clinical practice of monitoring bone mineral density on a regular basis.

Talk to your doctor if you have a personal or family history of high cholesterol, heart disease or osteoporosis or a recent history of fractures.

What are the side effects and how serious are they?

Most side effects are mild to moderate and rarely severe enough to stop treatment with letrozole. The most frequently reported adverse reactions were: hot flushes, pain in the muscles, bones and joints and joint stiffness (arthralgia or arthritis). Other common side effects which may occur are:

• mild headache,
• swelling or puffiness of the feet, ankles or other part of the body due to retained body fluid,
• weight increase,
• fatigue,
• nausea,
• vomiting,
• indigestion,
• increase or loss of appetite,
• constipation,
• diarrhea,
• hair loss,
• rash,
• dizziness,
• increased sweating,
• sad mood (depression),
• vaginal bleeding and irritation,
• breast pain,
• anorexia,
• blurry vision and
• cataracts.

Do not be alarmed by this list of possible side effects. You may not experience any of them. Check with your doctor if the unwanted side effects do not go away during treatment or are bothersome.

How is APO-LETROZOLE taken?

One 2.5 mg tablet once daily by mouth. The tablet should be swallowed with a small glass of water. You can take APO-LETROZOLE with or without food. It is best to take APO-LETROZOLE at about the same time every day. Your doctor will decide for how long you should be treated with APO-LETROZOLE.

What if I forget to take a dose?

If you forget to take a dose of APO-LETROZOLE, don't worry, take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and go back to your regular dosage schedule. Do not double doses.

Can APO-LETROZOLE be taken with other drugs?

Patients should ask their doctor or pharmacist before they start using any other prescription or over-the-counter medicines or natural health products during treatment with APO-LETROZOLE.

What are other uses of APO-LETROZOLE?

APO-LETROZOLE can also be used for:

• the first-line therapy in postmenopausal women with advanced breast cancer; and
• the hormonal treatment of advanced/metastatic breast cancer in women with natural or artificially-induced postmenopausal status, who have disease progression following antiestrogen therapy.

What else patients should know about taking APO-LETROZOLE?

Patients who are hypersensitive to letrozole, or to any ingredient in the tablet formulation, should not take APO-LETROZOLE.

How is APO-LETROZOLE available?

APO-LETROZOLE is available as a tablet containing the medicinal ingredient letrozole (2.5 mg).

APO-LETROZOLE is available in blister packages containing 3x10 tablets and bottles containing 100 tablets.

Where can I learn more about APO-LETROZOLE?

If you have questions concerning APO-LETROZOLE, kindly contact Drug Information Service, DISpedia at 1-800-667-4708.

Please consult your doctor with any questions or concerns you may have regarding your individual condition.