Important Safety Information:

Avastin

Avastin (bevacizumab) Indications and Important Safety Information

Avastin indication statements

As of 11.15.10

(RCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

(GBM)
Avastin is indicated for the treatment of glioblastoma as a single agent for adult patients with progressive disease following prior therapy. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin.

(NSCLC)
Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

(CRC)
Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy.

Full Pan Tumor Medium Safety [3/9/10]

Boxed WARNINGS and additional important safety information

• Gastrointestinal (GI) perforation:Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls. The incidences of GI perforation ranged from 0.3% to 2.4% across clinical studies. Discontinue Avastin in patients with GI perforation

• Surgery and wound healing complications: The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound dehiscence requiring medical intervention

• Hemorrhage: Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood). Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention) • Additional serious and sometimes fatal adverse events for which the incidence was increased in the Avastin-treated arm vs control included non-GI fistula formation (≤0.3%), arterial thromboembolic events (grade ≥3, 2.4%), and proteinuria including nephrotic syndrome (<1%). Additional serious adverse events for which the incidence was increased in the Avastin-treated arm vs control included hypertension (grade 3–4, 5%–18%) and reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%). Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients • The most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis. Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

• In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10%vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)

• In GBM Study AVF3708g, in patients receiving Avastin alone, the most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%). Of these, the incidence of grade ≥3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%). Two deaths were possibly related to Avastin: 1 retroperitoneal hemorrhage and 1 neutropenic infection

• In GBM patients receiving Avastin alone or Avastin plus irinotecan, the incidences of Avastin-related adverse events (grade 1–4) were bleeding/hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic events (8%), arterial thromboembolic events (6%), wound healing complications (6%), proteinuria (4%), GI perforation (2%), and RPLS (1%). The incidences of grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic events (7%), arterial thromboembolic events (3%), wound healing complications (3%), proteinuria (1%), and GI perforation (2%). Intracranial hemorrhage occurred in 8 of 163 patients; 2 patients had grade 3–4 hemorrhage

• In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thrombus/embolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)

• In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)

• In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)

Avastin® is a registered trademark and the Access Solutions logo and the Access Solutions Treatment made possible logo are trademarks of Genentech USA, Inc.

ERIVEDGE

Indication
Erivedge is a prescription medicine used to treat adults with a type of skin cancer, called basal cell carcinoma, that has spread to other parts of the body or that has come back after surgery or that your healthcare provider decides cannot be treated with surgery or radiation.

Serious Side Effects
Erivedge can cause your baby to die before it is born (be stillborn) or cause your baby to have severe birth defects.

Erivedge Patient Important Safety Information

Possible Serious Side Effects and Additional Important Safety Information

What is the most important information I should know about Erivedge?

• Erivedge can cause your baby to die before it is born (be stillborn) or cause your baby to have severe birth defects
• For females who can become pregnant:
• You should talk with your healthcare provider about the risks of Erivedge to your unborn child
• Your healthcare provider should do a pregnancy test within 7 days before you start taking Erivedge to find out if you are pregnant
• In order to avoid pregnancy, you should start using highly effective birth control before you start Erivedge, and continue during treatment and for 7 months after your last dose. Talk with your healthcare provider about what birth control method is right for you during this time
• Talk to your healthcare provider right away if you have unprotected sex or if you think that your birth control has failed
• Tell your healthcare provider right away if you become pregnant or think that you may be pregnant
• For males:
• You should always use a condom with a spermicide, even if you have had a vasectomy, during sex with female partners while you are taking Erivedge and for 2 months after your last dose to protect your female partner from being exposed to Erivedge
• Tell your healthcare provider right away if your partner becomes pregnant or thinks she is pregnant while you are taking Erivedge

Exposure to Erivedge during pregnancy:

• If you think that you or your female partner may have been exposed to Erivedge during pregnancy, talk to your healthcare provider right away. Pregnant women are encouraged to participate in a program that collects information about exposure to Erivedge during pregnancy, and the effects on the mother and her unborn child. This program is called the Erivedge pregnancy pharmacovigilance program. You may participate in this program by calling the Genentech Adverse Event Line at (888) 835-2555

What should I tell my healthcare provider before taking Erivedge?

• If you are pregnant or plan to become pregnant
• If you are breast-feeding or plan to breast-feed. It is not known if Erivedge passes into your breast milk. You and your healthcare provider should decide if you will take Erivedge or breast-feed. You should not do both

What should I avoid while taking Erivedge?

• Do not donate blood or blood products while you are taking Erivedge and for 7 months after your last dose

What are the possible side effects of Erivedge?

The most common side effects of Erivedge are:

• Muscle spasms
• Hair loss
• Change in how things taste or loss of taste
• Weight loss
• Tiredness
• Nausea
• Diarrhea
• Decreased appetite
• Constipation
• Vomiting
• Joint aches

Because everyone is different, it is not possible to predict what side effects any one person will have. If you have questions or concerns about side effects, you should talk to your doctor.

Please see the accompanying full Prescribing Information, including serious side effects, and the Medication Guide.

Herceptin

Herceptin (trastuzumab) Indications and Important Safety Information

Adjuvant Indications
Who is Herceptin for?

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. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high risk feature.*

Herceptin can be used in several different ways:

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

*High risk is defined as ER/PR-positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

Metastatic Indications
Who is Herceptin for?
Herceptin has 2 approved uses in metastatic breast cancer:

• Herceptin in combination with the chemotherapy drug 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

Who is Herceptin for?

• Herceptin is approved, in combination with chemotherapy (cisplatin and either capecitabine or 5-fluorouracil), for the treatment of HER2+ metastatic cancer of the stomach or gastroesophageal junction (where the esophagus meets the stomach) in patients who have not received prior treatment for their metastatic disease

What possible Serious Side Effects and Additional Important Safety Information should I know about Herceptin?

• Herceptin treatment can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as 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). One patient died in an adjuvant (early) breast cancer trial of significantly weakened heart muscle.
• Your doctor will evaluate your heart function before and during treatment. For adjuvant breast cancer therapy, your doctor will also evaluate heart function after the end of treatment. Your doctor will stop Herceptin therapy if you have serious weakening of the heart muscle or changes in the heart muscle structure.
• Some patients have had serious infusion reactions and lung problems; infusion reactions leading to death have been reported. Your doctor may have you completely stop Herceptin treatment if you have a severe allergic reaction, swelling, lung problems, swelling of the lungs, or severe shortness of breath.
• Herceptin can cause harm to the fetus (unborn baby), in some cases death to the fetus, when taken by a pregnant woman.
• Worsening of low white blood cell counts associated with chemotherapy has also occurred.
• You must have a HER2 test to determine if your cancer is HER2-positive before taking Herceptin.
• The most common side effects associated with Herceptin in patients with stomach cancer are low white and red blood cell counts, diarrhea, fatigue, swelling of the mouth lining, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of the mucous membranes, swelling of the nose and throat, and a change in taste.
• The most common side effects associated with Herceptin in patients with stomach cancer are low white and red blood cell counts, diarrhea, fatigue, swelling of the mouth lining, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of the mucous membranes, swelling of the nose and throat, and a change in taste.

Because everyone is different, it is not possible to predict what side effects any one person will have. If you have questions or concerns about side effects, you should talk to your doctor.

Please see the full Prescribing Information for Serious Side Effects and additional important safety information.

Rituxan

INDICATIONS

RITUXAN® (Rituximab) is indicated for the treatment of patients with:

• Relapsed or refractory, low-grade or follicular CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as a single-agent maintenance therapy
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line CVP chemotherapy
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
• Previously untreated CD20-positive CLL in combination with FC chemotherapy
• Previously treated CD20-positive CLL in combination with FC chemotherapy

People with serious infections should not receive RITUXAN.

IMPORTANT SAFETY INFORMATION
RITUXAN can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (TLS; kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (PML; a rare, serious brain infection).

RITUXAN has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel that can sometimes lead to death.

The most common side effects of RITUXAN seen in patients with non-Hodgkin's lymphoma were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common side effects of RITUXAN in patients with chronic lymphocytic leukemia were infusion reactions and low white blood cells. Before starting treatment with RITUXAN it is important to talk to your doctor about your medical history.

Tell your doctor about any side effect that bothers you or that does not go away. These are not all of the possible side effects with RITUXAN. For more information, ask your doctor.

Please see full Prescribing Information, including the Medication Guide.

Rituxan® and its logo are trademarks of Biogen Idec, Inc.
The Access Solutions logo and the Access Solutions Treatment made possible logo are trademarks of Genentech USA, Inc.

Tarceva

Tarceva (erlotinib) tablets INDICATIONS AND USAGE

Maintenance NSCLC: Tarceva is prescribed for patients with advance-stage non-small cell lung cancer (NSCLC) whose cancer has not spread or grown after initial treatment with certain types of chemotherapy

Second/Third-line NSCLC: Tarceva is prescribed for patients with advanced-stage non-small cell lung cancer (NSCLC) whose cancer has spread or grown after receiving at least 1 chemotherapy regimen.

Tarceva is not meant to be used at the same time as certain types of chemotherapy for NSCLC.

Pancreatic Cancer: Tarceva in combination is prescribed for patients with advanced-stage pancreatic cancer whose cancer has spread, grown or cannot be surgically removed, and who have not received previous chemotherapy.

Important Safety Information
There have been reports of serious adverse events involving the lungs in a small number of patients taking Tarceva (including deaths). The medical name for these events is interstitial (in-tur-STISH-ul) lung disease-like events (or ILD-like events).

Liver and/or kidney problems (including deaths) have been reported in some patients taking Tarceva. Let your healthcare provider (HCP) know if you have a history of liver or kidney disease.

Some patients taking Tarceva have developed a hole in the lining of their stomach or intestines.

Some patients taking Tarceva have developed serious skin conditions. Some patients have died from these conditions.

Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke.

Some patients taking Tarceva have developed eye irritation and damage to the cornea.

Women should not become pregnant while on treatment with Tarceva. DO NOT breast-feed while receiving treatment with Tarceva.

Call your HCP right away if you have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting, or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation.

Some patients taking Tarceva have experienced difficulty with blood clotting, and bleeding events, including gastrointestinal and non-gastrointestinal bleeding. Patients taking blood thinners (Coumadin®, warfarin or other coumarin-derivatives) should be monitored regularly.

It is important that you tell your HCP about all of the medicines and herbal supplements you are taking. DO NOT start taking any new medicines or herbal supplements before talking with your HCP. Tarceva may also affect other medications you are taking. DO NOT eat grapefruit or drink grapefruit juice while on treatment with Tarceva, except under the care of your HCP.

Smoking may affect how well Tarceva works for you. If you smoke, you should stop smoking before starting treatment with Tarceva. If you continue to smoke, you should talk to your HCP before taking Tarceva.

The most common side effects in patients who took Tarceva for non-small cell lung cancer (NSCLC) were mild to moderate rash and diarrhea.

The most common side effects in patients who took Tarceva plus gemcitabine for pancreatic cancer were fatigue [feeling tired], rash, nausea, loss of appetite and diarrhea.

Always let your HCP know if you have any side effects, and ask about the best way to handle them.

Tarceva is not right for everyone. Ask your HCP if once-daily Tarceva is right for you.

For additional important safety information, please see full prescribing information.

Tarceva® and its logo are trademarks of OSI Pharmaceuticals, Inc.
The Access Solutions logo and the Access Solutions Treatment made possible logo are trademarks of Genentech USA, Inc.

XELODA

XELODA (Capecitabine) Indications and Important Safety Information

Who is XELODA for?

XELODA is used to treat:

• Cancer of the colon or rectum (colorectal cancer) that has spread to other parts of the body. This is called metastatic colorectal cancer (mCRC). XELODA is used as a single medicine to treat mCRC. In medical studies, people lived longer when they took other cancer medicines at the same time that they took 5-fluorouracil (5-FU) and leucovorin. In medical studies, XELODA used as a single medicine was no worse than 5-FU and leucovorin taken together. XELODA did not improve survival compared with these 2 medicines
• Cancer of the colon after surgery
• Breast cancer that has spread to other parts of the body. This is called metastatic breast cancer (mBC). For this kind of breast cancer, XELODA is taken together with another medicine called docetaxel
• Breast cancer that has spread to other parts of the body and has not improved after treatment with other medicines. These medicines include paclitaxel and anthracycline-containing medicine such as doxorubicin

What is the most important safety information I should know about XELODA?

XELODA may increase the effect of medicines used to thin your blood. These medicines include warfarin. It is very important for you to tell your doctor if you are taking a blood thinner. This is because you could have serious side effects. The effect of the blood thinner could be increased. If you are taking blood thinners and XELODA, your doctor needs to do simple blood tests to find out how fast your blood clots. He or she can change the dose of the blood thinner, if needed. These blood tests should be done more often when you are taking XELODA.

Who should not take XELODA?

Do not take XELODA if:

• You are nursing a baby. Tell your doctor if you are nursing. XELODA may pass on to the baby through your breast milk and harm the baby
• You are allergic to 5-FU, capecitabine, or any of the ingredients in XELODA
• Do not take XELODA if you have been told that you don't have enough of the enzyme DPD (dihydropyrimidine dehydrogenase)

What should I tell my doctor before taking XELODA?

Tell your doctor if you:

• Take a blood thinner such as warfarin (Coumadin)
• Take phenytoin (Dilantin). Your doctor needs to test the levels of phenytoin in your blood more often or change your dose of phenytoin
• Are pregnant or think you may be pregnant. XELODA may harm your unborn child
• Have kidney problems. Your doctor may prescribe a different medicine or lower the XELODA dose
• Have liver problems. You may need to be checked for liver problems while you take XELODA
• Have heart problems because you could have more side effects related to your heart
• Take the vitamin folic acid. It may affect how XELODA works

Stop taking XELODA immediately and contact your doctor right away if you have any of these side effects or any other side effects that worry you:

• Diarrhea- if you have 4 more bowel movements each day than is normal for you or if you have any diarrhea at night
• Throwing up (vomiting)- if you throw up more than once in a 24-hour time period
• Feeling sick to your stomach (nausea)- if you don't feel like eating or if the amount of food you eat each day is much less than usual
• Pain, redness, swelling, or sores in your mouth (stomatitis)
• Hand-and-foot syndrome- if you have pain, swelling, or redness of your hands or feet that prevents normal activity
• Fever or infection- if you have a temperature of 100.5°F or higher or other signs of infection

If you do have any of the side effects listed above, or if you have other side effects that worry you, your doctor can change your dose of XELODA or stop your XELODA treatment for a while. This should help to reduce the side effects and stop them from getting worse.

What are the most common side effects of XELODA?

The most common side effects of XELODA are:

• Diarrhea
• Nausea
• Throwing up (vomiting)
• Sores in the mouth and throat (stomatitis)
• Stomach area pain (abdominal pain)
• Upset stomach
• Constipation
• Loss of appetite
• Too much water loss from the body (dehydration)

The side effects listed above are more common in patients 80 years and older.

Other common side effects are:

• Hand-and-foot syndrome
• Rash
• Dry, itchy, or discolored skin
• Nail problems
• Hair loss
• Tiredness
• Weakness
• Dizziness
• Headache
• Fever
• Pain (including chest, back, joint, and muscle pain)
• Trouble sleeping
• Problems with your sense of taste

If you are concerned about these or any other side effects while taking XELODA, talk with your doctor.

You may have different side effects if you take XELODA with docetaxel. Please talk with your doctor about possible side effects that may be caused by taking XELODA with other medicines.

What should I do if I am pregnant or am thinking about becoming pregnant?

• XELODA may harm your unborn child. Use effective birth control while taking XELODA. Tell your doctor right away if you become pregnant when you are taking XELODA. Men should use birth control while taking XELODA

Please be sure to talk with your doctor if you have any questions about your condition or treatment.

ZELBORAF

Indication and Important Safety Information

This information does not take the place of talking to your doctor about your medical condition or your treatment with ZELBORAF™(vemurafenib).

ZELBORAF is a prescription medicine used to treat a type of skin cancer called melanoma, that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal "BRAF" gene.

ZELBORAF may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC). CuSCC usually does not spread to other parts of the body. Check your skin and tell your doctor about skin changes including a new wart, a sore or bump that bleeds or does not heal, or a mole that changes size or color.

While taking ZELBORAF, you should avoid going out in the sun. When you go outside, wear clothes that protect your skin, including head, face, hands, arms, and legs. Use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.

Possible serious side effects of ZELBORAF include severe allergic reactions, severe skin reactions, changes in the electrical activity of your heart called QT prolongation, which can potentially be life-threatening, abnormal liver function tests, eye problems, or new melanoma lesions.

Common side effects of ZELBORAF include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching, or warts.

These are not all of the possible side effects of ZELBORAF. Tell your doctor if you have any side effect that bothers you or does not go away. For more information about side effects, ask your doctor or pharmacist.

Call your doctor for medical advice about any side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Genentech at 1-888-835-2555.

Please see accompanying full Prescribing Information and Medication Guide for additional important safety information.