Full Prescribing Information, including Boxed WARNINGS
Herceptin Dear Healthcare Provider Letter (198K/PDF)
Herceptin Vial Dear Healthcare Provider Letter (35K/PDF)

Herceptin® (Trastuzumab) is the first humanized antibody approved for the treatment of HER2-positive metastatic breast cancer. Herceptin is designed to target and block the function of HER2 protein overexpression.

Research has shown that HER2-positive breast cancer is a more aggressive disease with a greater likelihood of recurrence, a poorer prognosis, and a decreased chance of survival compared with HER2-negative breast cancer.

WARNINGS

• Herceptin treatment can result in heart problems, including those without symptoms (reduced heart function) and those with symptoms (congestive heart failure). The risk and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline).
• Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. In most cases, these reactions occurred during or within 24 hours of receiving Herceptin. Patients receiving their first dose of Herceptin may have chills and fever as well as nausea, vomiting, pain, headache, dizziness, shortness of breath, low blood pressure, rash, and weakness.

Adjuvant indications Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2+ and has not spread into the lymph nodes, but has one high risk feature.* Herceptin can be used in several different ways:

• As part of a treatment course including the chemotherapy drugs Adriamycin® (doxorubicin), Cytoxan® (cyclophosphamide), and either Taxol® (paclitaxel) or Taxotere® docetaxel). This treatment course is known as "AC→TH"
• With Taxotere and Paraplatin® (carboplatin). This treatment course is known as "TCH"
• Alone after treatment with multiple other therapies, including an anthracycline (Adriamycin)-based therapy (a type of chemotherapy)

*High risk can be defined as ER/PR-negative, tumor size >2 cm, age <35 years, or histological and/or nuclear grade 2 or 3.

Metastatic indications Herceptin has 2 approved uses in metastatic breast cancer:

• Herceptin in combination with the chemotherapy drug Taxol® (paclitaxel) is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer
• Herceptin alone is approved for the treatment of HER2+ breast cancer in patients who have received one or more chemotherapy courses for metastatic disease

Status The U.S. Food and Drug Administration (FDA) approved Herceptin in September 1998. In November 2006, the FDA approved Herceptin as part of a treatment regimen containing doxorubicin, cyclophosphamide and paclitaxel, for the adjuvant treatment of patients with HER2-positive, node-positive breast cancer.

In January 2008, the FDA approved Herceptin as a single agent for the adjuvant treatment of HER2-overexpressing node-negative (ER/PR-negative or with one high-risk feature) or node-positive breast cancer, following multi-modality anthracycline-based therapy.

Important Safety Information, including Boxed WARNINGS

• Herceptin treatment can result in heart problems, including those without symptoms (reduced heart function) and those with symptoms (congestive heart failure). The risk and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). The doctor will stop or strongly consider stopping Herceptin if the patient has a significant drop in their heart function. Patients should be monitored for decreased heart function before their first dose of Herceptin, and frequently during the time they are receiving Herceptin and after their last dose of Herceptin. If patients must permanently or temporarily stop Herceptin due to heart problems, they should be monitored more frequently. In one study with Herceptin and certain types of chemotherapy, an inadequate blood supply to the heart occurred. Before taking the first dose of Herceptin, a patient's doctor should check to see if there are any health conditions that may increase the patient's chance of having serious heart problems. This includes a review of their health history and tests to see how well their heart muscle is working. These tests may include an echocardiogram or a MUGA scan.
  • Echocardiogram (ECHO) is an ultrasound image of the heart
  • MUGA scan takes a moving picture of your heart pumping blood following an injection of a radioactive substance
• Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. In most cases, these reactions occurred during or within 24 hours of receiving Herceptin. The patient's Herceptin infusion should be temporarily stopped if they have shortness of breath or very low blood pressure. The doctor will monitor the patient until these symptoms go away. If patients have a severe allergic reaction, swelling, lung problems, inflammation of the lung, or severe shortness of breath, their doctor may need to completely stop their Herceptin treatment.
• Worsening of low white blood cell counts associated with chemotherapy has also occurred. In advanced breast cancer clinical trials, the risk of low white blood cell counts was higher in patients who received both Herceptin and chemotherapy, compared with patients who received chemotherapy alone.
• Taking Herceptin can result in serious and potentially fatal lung problems, including severe shortness of breath, inflammation of the lung, fluid in or around the lungs, weakening of the valve between the heart and lungs, too little oxygen in the body, swelling of the lungs, scarring of the lungs.
• Herceptin can cause harm to the fetus when taken by a pregnant woman. This may be related to a lowering of amniotic fluid levels in the second and third trimesters. Patients should use effective birth control methods while receiving Herceptin and for at least 6 months after they finish Herceptin. Patients should talk to their doctor if they are pregnant or become pregnant while taking Herceptin. Patients who are pregnant and receiving Herceptin should consider joining MotHER — the Pregnancy Registry by calling 1-800-690-6720.
• Patients receiving their first dose of Herceptin may have chills and fever as well as nausea, vomiting, pain, headache, dizziness, shortness of breath, low blood pressure, rash, and weakness.
• Patients should call their doctor immediately if they have any of the following: new or worsening shortness of breath; cough; swelling of the ankles or legs; swelling of the face; heartbeats that are unusually strong, fast, slow, or irregular in rhythm; weight gain of more than 5 pounds in 24 hours; dizziness; or loss of consciousness.
• The most common side effects associated with Herceptin were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain.
  
  Because everyone is different, it is not possible to predict what side effects any one person will have. Patients with questions or concerns about side effects should talk to their doctor.

Please visit www.herceptin.com for the Herceptin full prescribing information, including Boxed WARNINGS and additional important safety information.