Generic
Bortezomib
2 brands available in the market
At a glance
Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma and mantle cell lymphoma. It stops or slows down the growth of cancer cells by blocking protein breakdown, leading to cell death.
Description
Bortezomib is a proteasome inhibitor indicated for the treatment of multiple myeloma and mantle cell lymphoma. It is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells.
Bortezomib prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that Bortezomib is cytotoxic to a variety of cancer cell types in vitro.
The medicine is administered as an IV or SC injection by a healthcare professional.
Indications
- Multiple myeloma
- Mantle cell lymphoma
Therapeutic class
Targeted Cancer Therapy
Pharmacological class
Proteasome Inhibitor
Pharmacology
Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. The 26S proteasome degrades ubiquitinated proteins. The ubiquitin-proteasome pathway regulates intracellular protein concentrations, maintaining cellular homeostasis. Proteasome inhibition prevents targeted proteolysis, affecting multiple signaling cascades and disrupting normal homeostatic mechanisms, leading to cell death. Bortezomib is 83% bound to human plasma proteins and is primarily metabolized by CYP3A4, CYP2C19, and CYP1A2. Half-life is 9-15 hours.
Mechanism of action
Bortezomib inhibits the chymotrypsin-like activity of the 26S proteasome, preventing targeted proteolysis of ubiquitinated proteins. This leads to accumulation of proteins within the cell, affecting multiple signaling pathways and ultimately inducing apoptosis (programmed cell death) of cancer cells.
Dosage
Adults:
Mantle Cell Lymphoma (previously untreated): 1.3 mg/m² IV/SC twice weekly (Days 1, 4, 8, 11), 10-day rest (Days 12-21), for 6 cycles (3-week each). Given with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Prednisone).
Mantle Cell Lymphoma (relapsed): 1.3 mg/m² IV/SC twice weekly (Days 1, 4, 8, 11), 10-day rest (Days 12-21).
Multiple Myeloma (previously untreated, with Melphalan+Prednisone):
Cycles 1-4 (twice weekly): 1.3 mg/m² IV/SC on Days 1, 4, 8, 11, 22, 25, 29, 32
Cycles 5-9 (once weekly): 1.3 mg/m² IV/SC on Days 1, 8, 22, 29
Multiple Myeloma (relapsed): 1.3 mg/m² IV/SC twice weekly (Days 1, 4, 8, 11), 10-day rest (Days 12-21). Beyond 8 cycles: once weekly (Days 1, 8, 15, 22), 13-day rest (Days 23-35).
Re-treatment (Multiple Myeloma): Start at last tolerated dose. Twice weekly (Days 1, 4, 8, 11), 10-day rest (Days 12-21).
Hepatic impairment (Moderate-severe, bilirubin >1.5x ULN): Reduce to 0.7 mg/m² in first cycle; may escalate to 1 mg/m² or reduce to 0.5 mg/m² in subsequent cycles based on tolerability.
Renal impairment: No dose adjustment needed. Administer after dialysis.
Administration
For IV or SC injection only. Administered by doctor or nurse as a 3-5 second bolus injection. Patient should not self-administer. Intrathecal administration is contraindicated (fatal events have occurred).
Missed dose
Hospital-only medicine. Administered by doctor or nurse. Patient should not self-administer. If you miss a dose, consult your doctor. Do not double the dose.
Side effects
Common side effects:
Fatigue, nausea, vomiting, loss of appetite (anorexia), diarrhea, constipation, fever, anemia (low red blood cells), thrombocytopenia (low platelets), neutropenia (low white blood cells), peripheral neuropathy (tingling and numbness of hands and feet), psychiatric disturbances.
Serious: Hypotension, cardiac toxicity (heart failure), pulmonary toxicity (ARDS, pneumonitis), Posterior Reversible Encephalopathy Syndrome (PRES), tumor lysis syndrome, hepatic toxicity (liver toxicity), gastrointestinal hemorrhage.
Precautions & warnings
- Monitor for peripheral neuropathy (burning sensation, hyperesthesia, paresthesia, neuropathic pain). Dose/schedule adjustment needed if pre-existing or worsening neuropathy.
- Caution in patients with history of syncope, receiving antihypertensives, or dehydrated patients.
- Monitor closely for heart failure in patients with cardiac risk factors or existing heart disease.
- Gastrointestinal symptoms (nausea, diarrhea, constipation, vomiting) may require antiemetics and antidiarrheals; fluid and electrolyte replacement to prevent dehydration.
- If new or worsening cardiopulmonary symptoms occur, interrupt Bortezomib for diagnostic evaluation.
- Monitor CBC frequently; measure platelet count before each dose.
- Monitor closely for tumor lysis syndrome in patients with high tumor burden.
- If hepatic toxicity occurs, interrupt therapy to assess reversibility.
- Do not use during pregnancy and lactation (Category D).
- Avoid driving or operating machinery (fatigue, dizziness, fainting, blurred vision).
- Drink plenty of fluids during treatment.
Contraindications
- Hypersensitivity to bortezomib, boron, or mannitol (including anaphylactic reactions)
- Intrathecal administration (fatal events have occurred)
- Pregnancy and lactation
- Use in children
Drug interactions
- Amiodarone, antivirals, isoniazid, nitrofurantoin, statins: May increase the chance of peripheral neuropathy.
- Antihypertensives: May increase the chance of hypotension.
- CYP3A4, CYP2C19, CYP1A2 substrates: Bortezomib is metabolized by these enzymes; caution with co-administration.
- Oral antidiabetic agents: Close monitoring of blood glucose levels required.
Food interactions
Excessive drowsiness may occur with alcohol. Avoid alcohol consumption.
Use in pregnancy
Unsafe during pregnancy (Category D). Definite evidence of risk to the developing baby. May be prescribed rarely in life-threatening situations if benefits outweigh risks. Women of childbearing potential should avoid becoming pregnant.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Unsafe during breastfeeding. Data suggests the drug may cause toxicity to the baby.
Pediatric use
Safety and effectiveness in children have not been established.
Geriatric use
No specific dose adjustment required for elderly, but caution advised.
Renal / hepatic impairment
Hepatic impairment: Moderate-severe hepatic impairment (bilirubin >1.5x ULN): Reduce to 0.7 mg/m²; dose adjust based on tolerability.
Overdose effects
Overdose more than twice the recommended dose may cause acute symptomatic hypotension and thrombocytopenia with fatal outcomes. No specific antidote. Monitor vital signs and provide supportive care (fluids, pressors, inotropic agents).
Storage conditions
Unopened vial: Do not store above 25°C. Keep in outer box to protect from light. Reconstituted solution: Store at 2-8°C; use within 8 hours. Do not use if particulate matter is observed or if solution is discolored.
Chemical structure
Bortezomib (Proteasome Inhibitor)