Bortezomib

What is Bortezomib?

• Bortezomib (Velcade) is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma.

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What are the uses of this medicine?

Bortezomib (Velcade) is used for the:

• treatment of adult patients with multiple myeloma.
• treatment of adult patients with mantle cell lymphoma.

How does this medicine work?

• Bortezomib (bor tez’ oh mib) is an orally available, small molecule inhibitor of the 26S proteasome, the intracellular complex that degrades proteins involved in cell signaling and cell cycle regulation.
• Blocking proteasome activity prevents activation of factors involved in cell growth and resistance to chemotherapy induced apoptosis, leading to cancer cell death.
• Preclinical studies in vitro and in vivo suggested that bortezomib had activity against several hematologic malignancies.
• Clinical trials of bortezomib in patients with multiple myeloma showed improvements in progression free survival.

Who Should Not Use this medicine ?

This medicine cannot be used:

• in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol.
• for intrathecal administration.

What drug interactions can this medicine cause?

• Avoid coadministration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin).
• Coadministration with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) increases the exposure of bortezomib. Monitor patients for signs of bortezomib toxicity and consider a bortezomib dose reduction if bortezomib must be given in combination with strong CYP3A4 inhibitors.

Is this medicine FDA approved?

• Bortezomib received approval for use in the United States in 2003 for therapy of multiple myeloma and mantle cell lymphoma when given in combination with other chemotherapeutic agents.

How should this medicine be used?

Recommended dosage:

• The recommended starting dose of Velcade is 1.3 mg/m2. Velcade is administered intravenously at a concentration of 1 mg/mL, or subcutaneously at a concentration of 2.5 mg/mL.

• Velcade retreatment may be considered for patients with multiple myeloma who had previously responded to treatment with Velcade and who have relapsed at least six months after completing prior Velcade treatment. Treatment may be started at the last tolerated dose.

• Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment.

Administration:

• For subcutaneous or intravenous use only.
• Each route of administration has a different reconstituted concentration; Exercise caution when calculating the volume to be administered.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: Single-dose vial contains 3.5 mg of bortezomib as lyophilized powder for reconstitution and withdrawal of the appropriate individual patient dose.

This medicine is available in fallowing brand namesː

• Velcade

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• diarrhea
• thrombocytopenia
• neutropenia
• peripheral neuropathy
• fatigue
• neuralgia
• anemia
• leukopenia
• constipation
• vomiting
• lymphopenia
• rash
• pyrexia
• anorexia

What special precautions should I follow?

• Velcade treatment causes a peripheral neuropathy that is predominantly sensory; however, cases of severe sensory and motor peripheral neuropathy have been reported. Manage with dose modification or discontinuation. Patients with preexisting severe neuropathy should be treated with Velcade only after careful risk-benefit assessment.
• The incidence of hypotension (postural, orthostatic, and hypotension NOS) are observed throughout therapy. Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration.
• Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during Velcade therapy. Worsening of and development of cardiac failure has occurred. Closely monitor patients with existing heart disease or risk factors for heart disease.
• Acute Respiratory Distress Syndrome (ARDS) and acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration have occurred in patients receiving Velcade. Acute respiratory syndromes have occurred. Monitor closely for new or worsening symptoms and consider interrupting Velcade therapy.
• Posterior Reversible Encephalopathy Syndrome (PRES; formerly termed Reversible Posterior Leukoencephalopathy Syndrome (RPLS)) has occurred in patients receiving Velcade. Consider MRI imaging for onset of visual or neurological symptoms; discontinue Velcade if suspected.
• Velcade treatment can cause nausea, diarrhea, constipation, and vomiting . Nausea, diarrhea, constipation, and vomiting may require use of antiemetic and antidiarrheal medications or fluid replacement.
• Velcade is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle.Monitor complete blood counts regularly throughout treatment.
• Tumor lysis syndrome has been reported with Velcade therapy. Closely monitor patients with high tumor burden.
• Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Monitor hepatic enzymes during treatment. Interrupt Velcade therapy to assess reversibility.
• Cases, sometimes fatal, of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in the postmarketing setting in patients who received Velcade. Monitor for signs and symptoms. Discontinue Velcade if suspected.
• Based on the mechanism of action and findings in animals, Velcade can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy.

What to do in case of emergency/overdose?

Symptoms of overdosage:

• In humans, fatal outcomes following the administration of more than twice the recommended therapeutic dose have been reported, which were associated with the acute onset of symptomatic hypotension and thrombocytopenia.

Management of overdosage:

• There is no known specific antidote for Velcade overdosage.
• In the event of an overdosage, the patient's vital signs should be monitored and appropriate supportive care given.

Can this medicine be used in pregnancy?

• Based on its mechanism of action and findings in animals, Velcade can cause fetal harm when administered to a pregnant woman.
• There are no studies with the use of Velcade in pregnant women to inform drug-associated risks.

Can this medicine be used in children?

• Safety and effectiveness have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• bortezomib

Inactive ingredients:

• mannitol

Who manufactures and distributes this medicine?

Distributed and Marketed by:

• Millennium Pharmaceuticals, Inc.
• 40 Landsdowne Street
• Cambridge

What should I know about storage and disposal of this medication?

• Unopened vials may be stored at controlled room temperature 25°C (77°F); excursions permitted from 15 to 30°C (59 to 86°F).
• Retain in original package to protect from light.
• Follow guidelines for handling and disposal for cytotoxic drugs, including the use of gloves and other protective clothing to prevent skin contact.

• Dailymed label info on Bortezomib
• FDA Bortezomib

Bortezomib Resources
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