Possible side effects of treatment with VELCADE^® (bortezomib)

Peripheral neuropathy (tingling or numbness in the hands, arms, feet, or legs), which may be caused by your treatment, can progress to discomfort, pain, muscle weakness, or a burning sensation. In some cases, it can be severe.

• These symptoms should be immediately reported to your doctor or nurse, who may be able to help you manage them.
• Your doctor may lower your dose of VELCADE (bortezomib), interrupt your treatment until your symptoms get better, or stop your treatment with VELCADE.
• Should your symptoms improve, your doctor may decide to continue VELCADE at a lower dose.
• Your doctor may also suggest medicines or therapies to relieve or lessen these symptoms.
• If you already have peripheral neuropathy before treatment or if you believe you may be at high risk for peripheral neuropathy, your doctor may prescribe subcutaneous VELCADE (VELCADE given as a shot). Consider asking your doctor about this option.

A clinical trial showed differences in occurrence of peripheral neuropathy between patients treated with intravenous VELCADE and those treated with subcutaneous VELCADE. This trial included 222 relapsed patients who had been previously treated for multiple myeloma.

In this study:

• The rates of peripheral neuropathy were 37% with subcutaneous VELCADE compared to 50% with VELCADE given intravenously for all levels of severity.
• For more severe cases, the rates were 6% with subcutaneous VELCADE compared to 15% of patients who received intravenous VELCADE.

If you have pre-existing or are at high risk for peripheral neuropathy:

• Ask your healthcare team about the possibility of taking VELCADE subcutaneously.
• Apply cream or lotion to soothe your hands and feet.
• Avoid tight, uncomfortable shoes.
• Wear gloves when washing dishes.
• Use insulated potholders.

VELCADE (bortezomib) can cause a drop in blood pressure. Tell your doctor if you have low blood pressure. Also mention if you feel dizzy, feel as though you might faint, or feel light-headed upon rising. If you are taking drugs that lower blood pressure, your medications might need to be adjusted. If you are not drinking enough liquids, your healthcare team may need to give you fluids by IV. If you have dizziness or fainting, don’t drive or operate machinery.

Treatment with VELCADE (bortezomib) can cause heart rhythm problems and heart failure, or make them worse. Your healthcare team may closely monitor you if you have heart disease or are at risk for it. Tell your healthcare team if you have chest pressure or pain; palpitations (rapid heartbeat); swelling in your hands, ankles, or feet; or shortness of breath.

There have been reports of lung disorders in patients receiving VELCADE (bortezomib). Some of these events have been fatal. Tell your healthcare team if you have any cough, shortness of breath, wheezing, or difficulty breathing.

If you have liver problems, it can be harder for your body to process VELCADE (bortezomib). VELCADE has caused sudden liver failure in patients who were taking many medications or who had other serious medical conditions. Symptoms of liver problems include a yellow color to eyes and skin (jaundice) and changes in liver enzymes (measured with blood tests).

Your healthcare team will closely monitor you if you have liver disease. In patients who have moderate or severe liver disease, VELCADE should be started at a lower dose. More dose adjustments may be made based on tolerance to the drug.

There have been reports of a rare condition (called PRES) involving the brain in patients treated with VELCADE (bortezomib). It has, however, been reversible. Patients with PRES can have seizures, high blood pressure, headaches, tiredness, confusion, blindness, or other vision problems. If PRES occurs, treatment with VELCADE should be stopped.

Gastrointestinal problems (nausea, diarrhea, constipation, and vomiting) are generally mild to moderate. Most symptoms may be managed with medications, although some may be more serious. If you have these symptoms, ask your healthcare team about medications that you can take to help prevent these side effects.

Some ways to cope with nausea and vomiting:

• Avoid big meals. Instead, eat small meals and snacks throughout the day.
• Eat and drink slowly.
• Wear loose-fitting clothing.
• Drink cool, clear liquids.
• Avoid greasy, spicy, or heavily flavored foods.
• Try eating food with ginger, such as ginger snaps and ginger ale, which might help with nausea.

Some ways to cope with diarrhea:

• Eat frequent, small meals.
• Avoid caffeine and alcohol.
• Avoid fiber, sweets, and greasy, spicy foods.
• Drink plenty of water so that your body will have enough fluids.
• Eat foods high in potassium, like bananas, potatoes, and oranges.

VELCADE (bortezomib) can cause low levels of white blood cells (cells that fight infection) and/or platelets (cells that form clots).

• You will have regular blood tests to check your cell counts during your treatment with VELCADE.
• During your treatment cycle, there is a period (usually 10 days) when no VELCADE, melphalan, or prednisone is received. During that time, both platelets and neutrophils generally return to their original levels.
• If the number of these platelets and neutrophils is very low, your doctor may change the dose and/or the schedule of VELCADE.
• If your white blood cells become low, you can be at higher risk for infections. Tell your doctor if you develop a fever or believe you have an infection.
• If platelets become very low, there is an increased risk of bleeding. Your doctor may recommend a platelet transfusion.

TLS is a condition that can occur after cancer treatment. As tumor cells die, they break apart and cause changes in certain chemicals in the blood. This could cause damage to your kidneys and heart. Your healthcare team will routinely monitor your blood and urine for signs of TLS. If you develop TLS, your doctor will take steps to treat it.

Asthenia (fatigue, malaise, and weakness) may occur during treatment.

Some ways to cope with asthenia:

• Get plenty of rest.
• Eat nutritious food.
• Drink enough water so that your body will have enough fluids.
• Maintain some daily activity.

Your doctor or nurse can suggest ways to help you manage fatigue and tell you how much activity is right for you.

Anemia (a low level of red blood cells) may occur temporarily during treatment with VELCADE (bortezomib). Red blood cells carry oxygen. A low number of red blood cells may lead to symptoms such as fatigue (tiredness) and shortness of breath. Your doctor may decide to treat anemia with medication or a blood transfusion.

Herpes Zoster (a painful, itchy rash usually located in an area on 1 side of the body) may develop during treatment with VELCADE (bortezomib). Patients with multiple myeloma have a higher risk for developing it because their immune system is weakened. Your doctor might suggest taking an antiviral medication to help decrease your risk for this condition.

Pyrexia (fever) may occur after VELCADE (bortezomib) is administered. A cause of fever may be infections.

Some ways to avoid infections and fever:

• Wash your hands often.
• Avoid crowds.
• Clean cuts and scrapes immediately with warm water and soap.
• Take a shower or bathe daily.

If you experience a fever or infection, contact your healthcare team.

Anorexia (decreased appetite) is a condition that may result from taking VELCADE (bortezomib) (described above, including nausea, diarrhea, constipation, and vomiting). Drinking more fluids can help prevent dehydration (too much loss of body fluids). Eating frequent small meals may also help.