Bortezomib
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
The first proteasome inhibitor, a cornerstone of multiple myeloma and also used in mantle cell lymphoma. Its main toxicity is peripheral neuropathy.
Quick facts
- Group
- Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
- Target
- 26S proteasome, chymotrypsin-like site (β5 subunit)
- Used for
- Multiple myeloma · Mantle cell lymphoma
- Key effects
- Peripheral neuropathy · Nausea · Thrombocytopenia
- Monitor
- Neuropathy symptoms before each dose · Blood counts
- ATC
- L01XG01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows the human 20S proteasome core with bortezomib in the active sites of its catalytic subunits.
The proteasome destroys proteins tagged with ubiquitin, including misfolded proteins and regulators of cell signalling. Bortezomib, a boronic acid dipeptide, reversibly inhibits its chymotrypsin-like activity. Myeloma cells make huge amounts of antibody protein and are very dependent on this disposal system: when it is blocked, misfolded and regulatory proteins pile up, stress pathways switch on and the cell dies by apoptosis.
- Ubiquitin-tagged proteins go to the proteasome
- Bortezomib blocks its chymotrypsin-like site
- Misfolded and regulatory proteins accumulate
- Protein-loaded myeloma cells die (apoptosis)
Indications
- Multiple myeloma, newly diagnosed or relapsed, usually with other drugs (dexamethasone, lenalidomide, thalidomide). Multiple myeloma →
- Mantle cell lymphoma. Non-Hodgkin lymphoma →
Adverse effects
Common
- Peripheral neuropathy: burning, numbness, pain in hands and feet
- Nausea, diarrhoea, constipation, vomiting
- Thrombocytopenia, neutropenia, anaemia
- Fatigue, fever, loss of appetite
- Rash
Contraindications
- Allergy to bortezomib, boron or mannitol
- Intrathecal administration (never given into the spinal canal)
Key interactions
- Strong CYP3A4 inhibitors (e.g. ketoconazole)
- Raise bortezomib exposure; the patient is watched closely for toxicity.
- Strong CYP3A4 inducers (rifampicin, St John's wort)
- Lower its effect; avoided.
- Oral antidiabetic drugs
- Both low and high glucose have been reported; glucose is followed and treatment adjusted.
- Antihypertensives
- Add to bortezomib's low blood pressure.
What is monitored
- Neuropathy symptoms before each dose
- Blood counts, especially platelets, before each dose
- Blood pressure and hydration
- Liver tests
- Glucose in people with diabetes
- Uric acid and potassium when tumour burden is high
Administration and safety
- Subcutaneous or intravenous only; never intrathecal (wrong-route deaths have occurred with this class of mistakes).
- The reconstituted concentration differs for the subcutaneous and intravenous routes, so the volume is checked carefully for the intended route.
- Subcutaneous injection sites are rotated.
- Hazardous drug: prepared and disposed of following cytotoxic handling procedures.
Pregnancy and breastfeeding
Can harm the fetus; effective contraception is used by women and by men with female partners during treatment.
Nursing care
- Ask about tingling, burning or pain in hands and feet before each dose and report new or worse symptoms.
- Check blood pressure, lying and standing if dizzy; encourage fluids if dehydrated.
- Review platelet count and look for bleeding.
- Confirm antiviral prophylaxis against herpes zoster if ordered.
- Teaching: rise slowly, report fainting, rash with blisters, breathlessness or sudden vision change; avoid driving until the effect is known.
Pharmacokinetics
- Absorption
- Subcutaneous or intravenous injection.
- Distribution
- Large volume of distribution; moderately bound to plasma proteins.
- Metabolism
- Oxidised by liver CYP enzymes (CYP3A4, CYP2C19, CYP1A2) to inactive metabolites.
- Elimination
- The routes of elimination in humans are not well characterised.
Test yourself
Think of the answer, then tap the question to see it.
What does bortezomib inhibit?
The chymotrypsin-like activity of the 26S proteasome.
Why are myeloma cells especially sensitive to proteasome inhibition?
They produce large amounts of immunoglobulin and depend on the proteasome to clear misfolded proteins.
Which route of administration is absolutely contraindicated for bortezomib?
Intrathecal.
Which viral infection prophylaxis is commonly given with bortezomib?
Antiviral prophylaxis against herpes zoster reactivation.
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - BORTEZOMIB injection, powder, lyophilized, for solution (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.