bortezomib
Brand: Velcade
ISMP High Alert Prototype Drug
Drug Class: proteasome inhibitor antineoplastic
Drug Family: antineoplastic
Subclass: first-in-class proteasome inhibitor
Organ Systems: hematology-oncology
Mechanism of Action
Reversibly inhibits the chymotryptic activity of the 26S proteasome, blocking ubiquitin-mediated protein degradation; accumulates misfolded proteins, induces endoplasmic reticulum stress, activates unfolded protein response, and triggers apoptosis; myeloma cells are particularly dependent on proteasomal clearance.
26S proteasome (20S catalytic core — chymotryptic activity)
Indications
- multiple myeloma (front-line and relapsed/refractory)
- mantle cell lymphoma
Contraindications
- bortezomib hypersensitivity
- hypersensitivity to boron or mannitol
Adverse Effects
Common
- peripheral neuropathy (dose-limiting — sensorimotor)
- nausea/vomiting
- fatigue
- diarrhea/constipation
- thrombocytopenia
Serious
- severe peripheral neuropathy (often irreversible)
- thrombocytopenia
- herpes zoster reactivation
- pulmonary toxicity (interstitial pneumonitis)
- posterior reversible encephalopathy syndrome (PRES)
- hepatotoxicity
Pharmacokinetics (ADME)
| Absorption | IV or SC (SC preferred to reduce peripheral neuropathy); SC and IV have equivalent AUC but SC has lower Cmax |
| Distribution | large Vd; distributes extensively into tissues and organs |
| Metabolism | hepatic CYP3A4/2C19/1A2 via oxidative deboronation |
| Excretion | primarily biliary/fecal; metabolites excreted in urine and feces |
| Half-life | 9–15 hours |
| Onset | rapid |
| Peak | 30 min (IV); 1–2 hours (SC) |
| Duration | twice-weekly dosing per cycle |
| Protein Binding | 83% |
| Vd | very large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP3A4 inhibitors/inducers | alter bortezomib metabolism; clinical significance moderate | moderate |
| antidiabetic drugs | bortezomib can cause both hypoglycemia and hyperglycemia; monitor glucose closely | moderate |
Nursing Considerations
- SC administration is preferred over IV to significantly reduce peripheral neuropathy risk while maintaining equivalent efficacy.
- Antiviral prophylaxis against herpes zoster (acyclovir or valacyclovir) is mandatory throughout therapy and for 3 months after completion.
- Baseline neurological assessment before each cycle; dose reduction or discontinuation required for grade ≥3 peripheral neuropathy.
- Monitor platelet counts before each dose; dose adjustments based on platelet nadir are standard.
Clinical Pearls
- Bortezomib's proteasome inhibition specifically exploits the fact that plasma cells (from which myeloma derives) are among the most proteasome-dependent cells in the body due to their massive immunoglobulin synthesis demands.
- Switching from IV to SC bortezomib significantly reduces the incidence and severity of peripheral neuropathy (38% vs 53% in clinical trials) without sacrificing efficacy — a major clinical advance in myeloma care.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.