This Is Everything You Need to Know About Bortezomib | AASraw

1. www.aasraw.com This Is Everything You Need to Know About Bortezomib | AASraw Content This Is Everything You Need to Know About Bortezomib | AASraw...........................................................................................1 1. What Is Bortezomib?........................................................................................................................................................................................1 2. What is bortezomib used for?.......................................................................................................................................................................3 3. Bortezomib Dosage..........................................................................................................................................................................................4 4. How to use Bortezomib?................................................................................................................................................................................7 5. Is Bortezomib a chemo?.................................................................................................................................................................................8 6. What are the side effects of bortezomib?.................................................................................................................................................9 7. What special precautions you should follow before using bortezomib?........................................................................................12 8. Bortezomib Warning......................................................................................................................................................................................15 1. What Is Bortezomib? Bortezomib powder cas 179324-69-7, formerly known as PS-341, saled as brand "Velcade" in the market. is an anti-cancer drug and the first therapeutic proteasome inhibitor to be tested in humans. Proteasomes are cellular complexes that break down proteins. In some cancers, the proteins that normally kill cancer cells are broken down too quickly. Bortezomib powder interrupts this process and lets those proteins kill the cancer cells. The boron atom within bortezomib powder catalytically binds the active site of the 26S proteasome with high affinity and specificity, thereby resulting in cell cycle arrest and apoptosis. In normal cells, the proteasome is involved in degradation of ubiquitylated proteins that have been tagged for destruction because they are damaged or unneeded by the cell. However, in cancerous cells, proteasome activity degrades 1 aas18@aasraw.com

2. www.aasraw.com pro-apoptotic proteins such as p53 that would normally result in programmed cell death of the dysfunctional cells. Specifically, the agent inhibits nuclear factor (NF)-kappaB, a protein that is constitutively activated in some cancers, thereby interfering with NF-kappaB-mediated cell survival, tumor growth, and angiogenesis. In vivo, bortezomib powder delays tumor growth and enhances the cytotoxic effects of radiation and chemotherapy. Bortezomib powder cas 179324-69-7 is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. Bortezomib powder may also be used to treat other types of cancer as part of a research trial. Product name: Bortezomib powder CAS: 179324-69-7 Molecular Formula: C19H25BN4O4 Molecular Weight: 384.24 Melt Point: 122-124°C Density: 1.214 Storage Temp: -20°C Freezer Color: White to off white Crystalline 2 aas18@aasraw.com

3. www.aasraw.com powder Soluble in chloroform, dimethyl Solubility: sulfoxide,ethanol and methanol. Physical Form: Solid Reports: COA, HPLC, HNMR Bortezomib price: Contact US Velcade Manufacturer: AASraw 2. What is bortezomib used for? Bortezomib raw powder cas 179324-69-7 is a cancer chemotherapy drug used to treat certain types of tumors, It blocks certain proteins which helps to slow the growth and spread of the cancer. Treatment of multiple myeloma(a type of cancer of the bone marrow).  Treatment of mantle cell lymphoma (a fast-growing cancer that begins in  the cells of the immune system) who have already been treated with at least one other medication. It Sometimes can be given after other cancer medications have been tried  without successful treatment, talk with the doctor. 3 aas18@aasraw.com

4. www.aasraw.com Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful. 3. Bortezomib Dosage Bortezomib powder cas 179324-69-7 is injected into a vein through an IV: 3.5mg/vial Adult Dose for the treatment of Lymphoma DOSAGE IN PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA: 1.3 mg/m2 as a bolus IV injection twice weekly in combination with IV rituximab, cyclophosphamide, doxorubicin, and oral prednisone for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21) 4 aas18@aasraw.com

5. www.aasraw.com Comments: -The three week period is considered a treatment cycle. -A minimum of 72 hours should elapse between consecutive doses of bortezomib. -For patients with a response first documented at cycle 6, two additional cycles (for a total of 8 cycles) are recommended. FOR USE IN THE TREATMENT OF RELAPSED MANTLE CELL LYMPHOMA: -Usual dose: 1.3 mg/m2 as a bolus IV injection or subcutaneously twice weekly for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21). Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35). Adult Dose for the treatment of Multiple Myeloma FOR USE IN THE TREATMENT OF PREVIOUSLY UNTREATED MULTIPLE MYELOMA: 5 aas18@aasraw.com

6. www.aasraw.com -Usual dose: 1.3 mg/m2 administered as a 3 to 5 second bolus IV injection or subcutaneously in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles: -In cycles 1 through 4, bortezomib is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29, and 32). In cycles 5 through 9, bortezomib is administered once weekly (days 1, 8, 22, and 29). Comments: -At least 72 hours should elapse between consecutive doses of bortezomib. FOR USE IN THE TREATMENT OF RELAPSED MULTIPLE MYELOMA: -Usual dose: 1.3 mg/m2 as a bolus intravenous injection or subcutaneously twice weekly for two weeks (days 1, 4, 8, and 11) followed by a ten day rest period (days 12 through 21). Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35). Comments: -Bortezomib velcade may be administered alone or in combination with dexamethasone. -The three week period is considered a treatment cycle. -A minimum of 72 hours should elapse between consecutive doses of bortezomib. -Patients with multiple myeloma who have previously responded to treatment with 6 aas18@aasraw.com

7. www.aasraw.com bortezomib (either alone or in combination) and who have relapsed at least 6 months after their prior therapy may be started on the last tolerated dose. 4. How to use Bortezomib? Bortezomib velcade cas 179324-69-7 is given by injection into a vein or under the skin by a healthcare professional person. If you are receiving Bortezomib velcade under the skin, make sure that Bortezomib site is changed each time to lessen injury under the skin. The recommended bortezomib injection dosage is varies according to body size. It is injected into a vein (intravenously) or under the skin (subcutaneously), it's usually injected once or twice weekly, for varying periods of time, depending on the condition being treated. There should be a minimum of 72 hours between each dose of Bortezomib velcade cas 179324-69-7.The rotating schedule may be followed for up to eight cycles. It is important to drink plenty of fluids while you are being treated with this drug to prevent becoming dehydrated. After that, your doctor may decide to continue your treatment, but you will receive Bortezomib velcade less often. Be sure to tell your doctor how you are feeling during your treatment. Your doctor may stop your treatment for a while or decrease your dose of Bortezomib velcade if you experience side effects of the medication. and consult your doctor or pharmacist if you have any questions. 7 aas18@aasraw.com

8. www.aasraw.com Bortezomib velcade should be stored at room temperature protected from light, and kept out of the reach of children. After mixing, the solution can be stored for up to 8 hours at room temperature. Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired. 5. Is Bortezomib a chemo? Bortezomib powder cas 179324-69-7 is a type of chemotherapy called a targeted therapy. It is approved by the FDA for the treatment of multiple myeloma and mantle cell lymphoma in a class of medicines called proteasome inhibitors. Bortezomib 8 aas18@aasraw.com

9. www.aasraw.com powder has been studied in several important clinical trials. Since its approval, Bortezomib powder has been used to treat an estimated 550,000 patients* worldwide. It has been studied in a wide range of people, including those with renal impairment and diabetes. 6. What are the side effects of bortezomib? To prevent problematic interactions between bortezomib powder and other drugs, be sure to tell your doctor if you are allergic to any medications, and what other medications and supplements you are currently taking. You should also inform your doctor if you have or ever had a liver tumor, liver disease, or kidney disease, if you are pregnant or planning to become pregnant, or if you are breastfeeding. Bortezomib powder should not be taken during breastfeeding The following side effects are common while taking bortezomib powder cas 179324-69-7: Labored breathing, generalized weakness;  Burning, crawling, itching, numbness, prickling, "pins and needles", or  burning pain in your hands or feet; Muscle pain, bone or joint pain;  Peripheral neuropathy: characterized by decreased sensation and  paresthesia (numbness and tingling of the hands and feet). There may be worsening of 9 aas18@aasraw.com

10. www.aasraw.com preexisting neuropathy. Your doctor may need to change your dose or schedule of bortezomib. Symptoms may improve or return to baseline in some patients once bortezomib is discontinued. Dizziness, headache, lightheadedness when getting up suddenly from a  lying or sitting position, Loss of appetite, Nausea, vomiting;  Diarrhea, constipation, bloating;  Increase in heart rate  Loss of voice  Sunken eyes  Sweating  Swollen glands  Thirst  Fever, chills, cold or flu symptoms;  Painful blisters on the trunk of the body  Poor appetite  Constipation  Blurred vision,  Bleeding gums  Ulcers, sores, or white spots in the mouth  Sleep problems (insomnia),  10 aas18@aasraw.com

11. www.aasraw.com Wrinkled skin  Weakness in the arms, hands, legs, or feet  Painful or Difficult urination, Decreased urination, Blood in the urine or  stools, Rash or itching, or skin irritation where the medicine was injected.  Pale skin, easy bruising or bleeding; Low platelet count. (This can put you  at Increased risk for bleeding.) (Nadir: 11 days) Low red blood cell count (Anemia).  These side effects are less common side effects when taking bortezomib powder cas 179324-69-7: Shortness of breath  Upper respiratory tract infection  Heartburn  Low blood pressure  Dilated neck veins  general feeling of discomfort or illness  increased sensitivity to touch  increased sensitivity to pain  irregular heartbeat  swelling of the face, fingers, feet, or lower legs  11 aas18@aasraw.com

12. www.aasraw.com thickening of bronchial secretions  tingling in the hands and feet  weight gain  Itching  Swelling of the face, hands, feet or legs (edema).  Low white blood cell count. (This can put you at increased risk for infection.)  Blood test abnormalities: (low sodium, low magnesium, low calcium, low  potassium). Not all side effects are listed above, Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. 7. What special precautions you should follow before usin g bortezomib? Avoid being near people who are sick or have infections. Tell your doctor at once  if you develop signs of infection. tell your doctor and healthcare provider if you are allergic to bortezomib  velcade cas 179324-69-7, mannitol, any other medications, or boron. 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 12 aas18@aasraw.com

13. www.aasraw.com 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 what herbal products you are taking, especially St. John's wort.  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 13 aas18@aasraw.com

14. www.aasraw.com doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you are pregnant or plan to become pregnant. bortezomib  velcade may harm the fetus. Use birth control to prevent pregnancy during your treatment with bortezomib cas 179324-69-7. Ask your doctor if you have questions about types of birth control that will work for you. If you become pregnant while using bortezomib velcade call your doctor immediately. do not breast-feed during your treatment with bortezomib velcade. After your  treatment has finished, talk to your doctor or nurse about when it is safe to restart breast-feeding. 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. Bortezomib velcade may cause blurred vision and may impair your thinking or  reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. if you are having surgery, including dental surgery, tell the doctor or dentist that  you are using bortezomib velcade. Avoid becoming dehydrated if you have any vomiting or diarrhea. Symptoms of  dehydration include dizziness, dry mouth, fainting, or hot and dry skin. Talk with your doctor about how best to keep yourself hydrated. 14 aas18@aasraw.com

15. www.aasraw.com Do not receive any kind of immunization or vaccination without your doctor's  approval while taking bortezomib velcade cas 179324-69-7. Bortezomib velcade can lower blood cells that help your body fight infections  and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. 8. Bortezomib Warning Contact your healthcare provider immediately day or night if you should experience any of the following symptoms as belows: Fever of 100.4° F (38° C) or higher, chills (possible signs of infection)  Shortness of breath, wheezing, difficulty breathing, closing up of the throat,  swelling of facial features, hives (possible allergic reaction). The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following: Vomiting (vomiting more than 4-5 times in a 24 hour period).  Nausea (interferes with ability to eat and unrelieved with prescribed medication).  Signs of infection such as redness or swelling, pain on swallowing, coughing up  mucous, or painful Unusual bleeding or bruising  Diarrhea (4-6 episodes in a 24-hour period).  15 aas18@aasraw.com

16. www.aasraw.com Constipation unrelieved by laxative use.  Blood in the urine.  Black or tarry stools, or blood in your stools.  New or worsening symptoms of peripheral neuropathy.  Swelling, redness and/or pain in one leg or arm and not the other.  Swelling of the feet or ankles. Sudden weight gain.  Extreme fatigue (unable to carry on self-care activities).  urination.Unable to eat or drink for 24 hours or have signs of dehydration:  tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness. Always inform your health care provider if you experience any unusual symptoms. 16 aas18@aasraw.com