Comprehensive Guide to Bortezomib: Uses, Dosage, Side Effects, and More
What is Bortezomib?
Overview of Bortezomib
Generic Name: Bortezomib
Brand Name: Velcade, generics
Drug Group: Proteasome inhibitor
Commonly Used For
- Treat multiple myeloma.
- Manage mantle cell lymphoma.
- Improve progression-free survival in blood cancers.
Key Characteristics
Form: Intravenous (IV) injection (3.5 mg vial), subcutaneous (SC) injection (3.5 mg vial) (detailed in Dosage section).
Mechanism: Inhibits proteasome activity to induce cancer cell death.
Approval: FDA-approved (2003) and EMA-approved for multiple myeloma and lymphoma.
Indications and Uses of Bortezomib
Bortezomib is indicated for various hematologic malignancies and related conditions, leveraging its proteasome inhibition:
Multiple Myeloma: Treats newly diagnosed or relapsed/refractory multiple myeloma, often with dexamethasone or lenalidomide, improving overall survival.
Mantle Cell Lymphoma: Manages relapsed or refractory mantle cell lymphoma in patients who have received at least one prior therapy, extending remission.
Previously Untreated Multiple Myeloma: Used in combination with melphalan and prednisone for elderly patients ineligible for stem cell transplant.
Waldenström Macroglobulinemia: Off-label use to reduce IgM levels and tumor burden, under hematologist supervision.
Off-Label Uses: Includes treatment of amyloid light-chain (AL) amyloidosis to reduce amyloid deposits, management of chronic lymphocytic leukemia (CLL) in refractory cases, and adjunctive therapy in follicular lymphoma, supported by clinical trials and case reports.
Post-Transplant Maintenance: Maintains remission post-autologous stem cell transplant in multiple myeloma, delaying relapse, based on oncology guidelines.
Light Chain Deposition Disease: Off-label management to stabilize kidney function, under specialist care.
Dosage of Bortezomib
Dosage for Adults
Multiple Myeloma (Initial Therapy):
- IV/SC: 1.3 mg/m² twice weekly (days 1, 4, 8, 11) for 2 weeks, followed by a 10-day rest (21-day cycle), for 4–6 cycles, often with dexamethasone (20 mg).
- Maintenance: 1.0 mg/m² once weekly after ASCT, continued for 2 years.
Relapsed/Refractory Multiple Myeloma (RRMM): IV/SC: 1.3 mg/m² twice weekly for 2 weeks (days 1, 4, 8, 11), 10-day rest, for up to 8 cycles, with or without lenalidomide.
Mantle Cell Lymphoma (MCL): IV/SC: 1.3 mg/m² twice weekly for 2 weeks, 10-day rest, for 3–6 cycles, adjusted based on response.
Combination Therapy: 1.3 mg/m² with cyclophosphamide and prednisone for MCL, reducing to 1.0 mg/m² if neuropathy occurs.
Off-Label (AL Amyloidosis): 1.3 mg/m² twice weekly for 2 weeks, with dexamethasone, for 4–6 cycles, under hematologist supervision.
Dosage for Children
Not Recommended: Safety not established under 18 years; use only in adolescents (12–18) with relapsed ALL or lymphoma, starting at 0.7 mg/m² twice weekly, under pediatric oncology care.
Special Consideration: Adjust for low body weight, monitoring liver and kidney function.
Dosage for Pregnant Women
Dosage Adjustments
Renal Impairment: No adjustment for mild-moderate (CrCl 20–80 mL/min); reduce to 0.7 mg/m² if CrCl <20 mL/min or on dialysis.
Hepatic Impairment: Reduce to 0.7 mg/m² in mild impairment (bilirubin 1–1.5x ULN); avoid in moderate-severe impairment.
Neuropathy: Decrease to 1.0 mg/m² or switch to once weekly if grade 2+ neuropathy develops.
Elderly: Start with 1.0 mg/m²; increase to 1.3 mg/m² if tolerated, with frequent neurological checks.
Additional Considerations
- Administer this active ingredient on a fixed schedule, with IV given over 3–5 seconds and SC injected into the thigh or abdomen.
- Avoid missed doses; delay cycles if platelet count <30,000/µL or ANC <500/µL.
How to Use Bortezomib
Administration:
- Intravenous (IV): Inject 1.3 mg/m² into a peripheral or central vein over 3–5 seconds, followed by a saline flush; use a 22–25 gauge needle.
- Subcutaneous (SC): Inject 1.3 mg/m² into the thigh or abdomen, rotating sites to avoid irritation; pinch skin and insert at a 45–90° angle.
- For combination therapy, administer before other agents (e.g., dexamethasone) on the same day.
Timing: Use twice weekly (e.g., Monday/Thursday) for 2 weeks, followed by a 10-day rest, maintaining a 21-day cycle.
Monitoring: Watch for numbness, tingling, or bruising at injection sites; check for signs of infection (e.g., fever).
Additional Tips:
- Store vials at 2–8°C (36–46°F), protecting from light; reconstitute with 3.5 mL saline for IV/SC use.
- Use gloves and avoid contact with skin or eyes during preparation; dispose of needles in a sharps container.
- Stay hydrated to reduce kidney strain; report severe fatigue or vision changes immediately.
Contraindications for Bortezomib
Hypersensitivity: Patients with a known allergy to Bortezomib, boron, or mannitol (excipient).
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C liver disease due to toxicity risk.
Pregnancy: Category D due to teratogenic effects; mandatory contraception required.
Active Peripheral Neuropathy: Avoid in grade 2+ neuropathy due to exacerbation risk.
Concurrent Use with Strong CYP3A4 Inhibitors: Contraindicated with ketoconazole or ritonavir due to increased toxicity.
Warnings & Precautions for Bortezomib
General Warnings
Peripheral Neuropathy: Grade 2–3 incidence (20–30%); monitor with neurological exams every cycle.
Thrombocytopenia: Platelet count <50,000/µL in 25%; check counts before each dose.
Hepatotoxicity: Elevated liver enzymes (>3x ULN in 5–10%); monitor monthly.
Cardiac Toxicity: Heart failure or arrhythmias (5% in prior cardiac history); perform ECG if symptomatic.
Use in Specific Populations
Pregnancy: Category D; contraindicated unless life-saving with contraception.
Breastfeeding: Excreted in milk; avoid or discontinue breastfeeding.
Elderly: Higher risk of neuropathy and fatigue; use lowest effective dose.
Children: Limited to 12+ years under supervision; monitor growth.
Renal/Hepatic Impairment: Adjust dose in severe cases; avoid in advanced liver disease.
Additional Precautions
- Inform your doctor about liver disease, neuropathy, or prior cardiac issues before starting this medication.
- Avoid abrupt cessation; delay doses if severe toxicity occurs.
Overdose and Management of Bortezomib
Overdose Symptoms
- Severe peripheral neuropathy (e.g., paralysis, burning pain).
- Profound thrombocytopenia (bleeding, petechiae) or neutropenia (fever, sepsis).
- Hypotension, syncope, or cardiac arrest in extreme cases.
- Rare: Hepatic failure (jaundice, coagulopathy) or respiratory distress.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids for hypotension, transfuse platelets if <20,000/µL, and provide oxygen if needed.
Specific Treatment: Use granulocyte colony-stimulating factor (G-CSF) for neutropenia, N-acetylcysteine for liver support, and discontinue the drug.
Monitor: Check CBC, liver enzymes, and neurological status for 48–72 hours; assess cardiac function if symptomatic.
Additional Notes
- Overdose risk increases with renal impairment or polypharmacy; store in a secure, refrigerated location.
- Report persistent symptoms (e.g., severe numbness, uncontrolled bleeding) promptly.
Side Effects of Bortezomib
Common Side Effects
- Peripheral Neuropathy (20–30%, dose-limiting, often reversible)
- Fatigue (30–40%, managed with rest)
- Nausea (20–30%, reduced with antiemetics)
- Diarrhea (15–25%, controlled with loperamide)
- Anorexia (10–20%, improved with nutritional support)
These effects may persist but can be mitigated with supportive care.
Serious Side Effects
Seek immediate medical attention for:
- Neurological: Severe numbness, weakness, or paralysis.
- Hematologic: Uncontrolled bleeding, bruising, or fever (sepsis).
- Hepatic: Yellow skin, dark urine, or severe abdominal pain.
- Cardiac: Chest pain, shortness of breath, or irregular heartbeat.
- Allergic: Rash, swelling, or anaphylaxis (rare).
Additional Notes
- Regular monitoring for neurological function, blood counts, and liver health is advised.
- Report any unusual symptoms (e.g., persistent tingling, severe fatigue) immediately.
Drug Interactions with Bortezomib
This active ingredient may interact with:
CYP3A4 Inhibitors (e.g., Ketoconazole): Increases Bortezomib levels; monitor for toxicity.
CYP2C19 Substrates (e.g., Omeprazole): May alter metabolism; adjust doses if combined.
Anticoagulants (e.g., Warfarin): Enhances bleeding risk; monitor INR weekly.
Live Vaccines: Reduces efficacy and increases infection risk; avoid during therapy.
Neurotoxic Drugs (e.g., Vincristine): Potentiates neuropathy; use with caution.
Patient Education or Lifestyle
Medication Adherence: Take this proteasome inhibitor as prescribed to manage cancer, following the exact schedule.
Monitoring: Report numbness, bruising, or yellowing skin immediately.
Lifestyle: Avoid alcohol to protect liver health; engage in light activity if tolerated.
Diet: Maintain adequate nutrition; avoid high-fat meals that may worsen nausea.
Emergency Awareness: Know signs of bleeding or neurological decline; seek care if present.
Follow-Up: Schedule regular check-ups every 1–3 months to monitor blood and organ function.
Pharmacokinetics of Bortezomib
Absorption: Rapidly absorbed via SC (peak at 30–60 minutes); IV peak immediate.
Distribution: Volume of distribution ~498–1,884 L/m²; 83% protein-bound.
Metabolism: Hepatic via CYP3A4, CYP2C19, and CYP1A2 to inactive metabolites.
Excretion: Primarily hepatic (50%) and renal (15%) as metabolites; half-life 9–15 hours.
Half-Life: 9–15 hours, with cumulative effects over cycles.
Pharmacodynamics of Bortezomib
Inhibiting the 26S proteasome to prevent protein degradation in cancer cells.
Inducing apoptosis and cell cycle arrest in multiple myeloma and lymphoma cells.
Demonstrating dose-dependent neuropathy and thrombocytopenia, requiring monitoring.
Exhibiting synergy with dexamethasone, enhancing antitumor activity.
Storage of Bortezomib
- Temperature: Store at 2–8°C (36–46°F); do not freeze.
- Protection: Keep in original vial, away from light.
- Safety: Store out of reach of children in a secure location.
- Disposal: Dispose of unused vials and syringes per hazardous waste regulations.
Frequently Asked Questions (FAQs)
Q: What does Bortezomib treat?
A: This medication treats multiple myeloma and mantle cell lymphoma.
Q: Can this active ingredient cause numbness?
A: Yes, peripheral neuropathy is common; report it to a doctor.
Q: Is Bortezomib safe for pregnant women?
A: No, it’s contraindicated; use contraception.
Q: How is this drug administered?
A: Via IV or subcutaneous injection, as directed.
Q: How long is Bortezomib treatment?
A: Variable, from months to years, depending on cancer stage.
Q: Can I stop Bortezomib suddenly?
A: No, taper or delay under medical guidance.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2003 (Velcade) for multiple myeloma and MCL.
European Medicines Agency (EMA): Approved for hematologic malignancies.
Other Agencies: Approved globally for oncology; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Velcade (Bortezomib) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Bortezomib Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Bortezomib: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Bortezomib.
- WHO’s consideration of Bortezomib for multiple myeloma.
- Journal of Clinical Oncology. (2022). Bortezomib in Multiple Myeloma.
- Peer-reviewed article on Bortezomib efficacy (note: access may require a subscription).
