Velcade

Before using bortezomib,

• tell your doctor and healthcare provider if you are allergic to bortezomib, mannitol, any other medications, or boron.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, or nutritional supplements you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone); cimetidine (Tagamet); clarithromycin (Biaxin, Prevpac); diltiazem (Cardizem, Dilacor, Tiazac, others); erythromycin (E.E.S., E-Mycin, Erythrocin); fluvoxamine; certain antifungals such as itraconazole (Sporanox) or ketoconazole (Nizoral); medications to treat diabetes or high blood pressure; certain medications to treat human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as indinavir (Crixivan), nelfinavir (Viracept), or ritonavir (Norvir); certain medications to treat seizures such as carbamazepine (Carbatrol, Tegretol), phenobarbital (Luminal, Solfoton), or phenytoin (Dilantin, Phenytek); mibefradil (no longer available in the U.S.); nefazodone; rifabutin (Mycobutin); rifampin (Rifadin, Rifamate, Rimactane, others); troleandomycin (TAO) (no longer available in the U.S.); or verapamil (Calan, Covera, Isoptin, in Tarka, others). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you or anyone in your family has or has ever had heart disease and if you have or have ever had a herpes infection (cold sores, shingles, or genital sores); diabetes; fainting; high cholesterol (fats in the blood); low or high blood pressure; peripheral neuropathy (numbness, pain, tingling, or burning feeling in the feet or hands) or weakness or loss of feeling or reflexes in a part of your body;or kidney or liver disease. Also tell your doctor if you smoke or drink large amounts of alcohol.
• tell your doctor if you are pregnant or plan to become pregnant. Bortezomib may harm the fetus. Use birth control to prevent pregnancy during your treatment with bortezomib.Ask your doctor if you have questions about types of birth control that will work for you. If you become pregnant while using bortezomib, call your doctor immediately.
• do not breast-feed during your treatment with bortezomib. After your treatment has finished, talk to your doctor or nurse about when it is safe to restart breast-feeding.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using bortezomib.
• you should know that bortezomib may make you drowsy, dizzy, or lightheaded, or cause fainting or blurred vision. Do not drive a car or operate machinery or dangerous tools until you know how this medication affects you.
• you should know that bortezomib may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common in people who have fainted in the past, people who are dehydrated, and people who are taking medications that lower blood pressure. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Bortezomib may cause a serious viral infection of the brain that can lead to disability or death. Call your doctor right away if you have any change in your mental state, decreased vision, or problems with speech or walking. These symptoms may start gradually and get worse quickly.

Also call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• chest pain, dry cough, swelling in your hands or ankles, feeling short of breath, even with mild exertion;
• diarrhea that is severe or ongoing;
• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
• new or worsening cough, shortness of breath;
• new or worsening nerve problems such as numbness, burning, pain, weakness, or tingly feeling;
• pain, redness, bruising, tenderness, or a hard lump where the medicine was injected;
• severe constipation;
• dehydration symptoms--muscle cramps, feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;
• high blood pressure--severe headache, pounding in your neck or ears, anxiety, irregular heartbeats;
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• low white blood cell counts--fever, swollen gums, painful mouth sores, pain when swallowing, skin sores, cold or flu symptoms, cough, trouble breathing; or
• signs of tumor cell breakdown--lower back pain, blood in your urine, little or no urinating; numbness or tingly feeling around your mouth; muscle weakness or tightness; fast or slow heart rate, weak pulse, feeling short of breath; confusion, fainting.

Common side effects may include:

• numbness, tingling, or burning pain in your hands or feet;
• loss of appetite, nausea, vomiting;
• diarrhea, constipation, bloating;
• fever, chills, cold or flu symptoms;
• pale skin, easy bruising or bleeding;
• rash; or
• feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Bortezomib injection is used to treat multiple myeloma (blood plasma cell cancer) in patients with or without a prior history of treatment, and mantle cell lymphoma.

Bortezomib interferes with the growth of cancer cells, which are then eventually destroyed by the body. Since the growth of normal body cells may also be affected by bortezomib, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, such as a skin rash, may not be serious but may cause concern. Some effects may not occur until months or years after the medicine is used.

This medicine is to be given only by or under the supervision of your doctor.

This product is available in the following dosage forms:

• Powder for Solution

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

If Velcade is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Many drugs can interact with bortezomib. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with bortezomib. Give a list of all your medicines to any healthcare provider who treats you.

Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2.

CYP3A4 inhibitors

Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Monitor patients for signs of bortezomib toxicity and consider a bortezomib dose reduction if bortezomib must be given in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir).

CYP2C19 inhibitors

Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients.

CYP3A4 inducers

Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur.

Efficacy may be reduced when Velcade is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving Velcade.

St. John's Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided.

Dexamethasone

Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients.

Melphalan-Prednisone

Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients. However, this increase is unlikely to be clinically relevant.

1. "OSHA Hazardous Drugs" (refer to antineoplastic weblinks including OSHA Technical Manual). OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Many drugs can interact with bortezomib. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Velcade. Give a list of all your medicines to any healthcare provider who treats you.