Side effects of VELCADE^® (bortezomib)

Fatigue is the feeling of physical, emotional, or mental exhaustion. It is commonly associated with symptoms of multiple myeloma and treatment side effects.

If you experience fatigue, talk with your doctor or healthcare team.

• Your doctor may be able to identify and treat the underlying cause of fatigue, such as anemia or malnourishment
• Your doctor can prescribe medications to make you feel less tired or more awake
• Behavioral modification and exercise can help improve mood and sleeping difficulties, resulting in more energy

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

• Report these symptoms immediately to your doctor or nurse, who may be able to help you manage them
• Your doctor may give you medications to relieve symptoms or lower your dose of VELCADE
• Your doctor may also interrupt your treatment until your symptoms get better, or may stop treatment with VELCADE

If you already have peripheral neuropathy or are at high risk, ask your doctor about subcutaneous VELCADE (VELCADE given as a shot).

Subcutaneous VELCADE is associated with fewer and less severe peripheral neuropathy symptoms than intravenous VELCADE.

• In a study of 222 people, peripheral neuropathy rates were 37% with subcutaneous VELCADE versus 50% with intravenous VELCADE for all levels of severity
• For more severe cases, peripheral neuropathy rates were 6% with subcutaneous VELCADE and 15% with intravenous VELCADE

Ask your doctor for everyday strategies for relieving peripheral neuropathy symptoms.

VELCADE 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 intravenously. If you have dizziness or fainting, don’t drive or operate machinery.

Treatment with VELCADE 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. 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 get rid of VELCADE. VELCADE has caused sudden liver failure in people who were taking many medications or had other serious medical conditions. Symptoms of liver problems include a yellow discoloration of the eyes and skin (jaundice) and changes in liver enzymes measured in blood tests.

Your doctor will closely monitor you if you have liver disease. It is not known whether restarting VELCADE therapy in patients previously experiencing this complication is safe.

VELCADE can lead to the formation of blood clots in small blood vessels. These clots can result in low platelets, kidney damage, confusion, and an increased risk of bleeding. Tell your doctor if you develop pinpoint-sized purple dots (petechiae), larger bruises, or you see blood in your urine. Your doctor may stop treatment with VELCADE. It is not known whether restarting VELCADE therapy in patients previously experiencing this complication is safe.

There have been reports of a rare condition (called PRES) involving the brain in patients treated with VELCADE. 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, vomiting, constipation, and diarrhea) 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.

Nausea and vomiting

• Make sure you let your healthcare team know the first time you experience nausea or vomiting so they can help you best manage your symptoms
• There are many ways to manage nausea/vomiting, including lifestyle changes such as changing some things you eat or drink. Ask your healthcare team for recommendations
• Your healthcare provider may also give you a medication to prevent or treat nausea
• Let your healthcare team know if the medicines for nausea/vomiting aren’t working. You may have to try a few different medicines to find the one that works best for you

Constipation

• After talking with your healthcare provider, you may be asked to modify your diet to include more liquids or change to certain foods to reduce constipation
• Exercise may also be recommended. Always consult with your healthcare team if a certain exercise regimen is appropriate for you
• Your healthcare provider may prescribe a laxative or other medicine

Diarrhea

• Ask your healthcare team for specific recommendations for coping with diarrhea
• You may be asked to eat certain foods and make changes to your overall diet
• You may be advised to drink fluids to stay hydrated
• Your healthcare provider may give you medicines to reduce the diarrhea

VELCADE 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.

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

• It is important to immediately report rash or any skin changes to your healthcare team
• Do not diagnose or treat yourself to avoid making the rash worse

Fever (pyrexia) may occur after VELCADE 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 bath daily

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

Decreased appetite (anorexia) is a condition that may result from taking VELCADE. Drinking more fluids can help prevent dehydration (too much loss of body fluids). Eating frequent small meals may also help.