Bortezomib
VELCADE
Pronunciation: bor-TEZ-oe-mib
What it isReversible 26S proteasome inhibitor; multiple myeloma and mantle cell lymphoma.
Why this oneIt introduced proteasome inhibition and transformed myeloma survival.
What limits itPeripheral neuropathy is dose-limiting and often painful; subcutaneous dosing reduces it substantially. Thrombocytopenia; herpes zoster prophylaxis is required.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Previously untreated multiple myeloma (with melphalan + prednisone; 9 six-week cycles) | Adults | 1.3 mg/m2 IV bolus (3-5 sec) or SC; Cycles 1-4 twice weekly (D1,4,8,11,22,25,29,32); Cycles 5-9 once weekly (D1,8,22,29) | 1.3 mg/m2/dose; >=72 h between consecutive doses | |
| Previously untreated mantle cell lymphoma (VcR-CAP; 6 three-week cycles, up to 8 if response first at Cycle 6) | Adults | 1.3 mg/m2 IV twice weekly x2 wk (D1,4,8,11) then 10-day rest (D12-21); give before rituximab | 1.3 mg/m2/dose; >=72 h between consecutive doses | |
| Relapsed multiple myeloma or relapsed mantle cell lymphoma | Adults | 1.3 mg/m2 IV or SC twice weekly x2 wk (D1,4,8,11) then 10-day rest (21-day cycle); alone or with dexamethasone (MM) | Beyond 8 cycles: standard schedule, or (relapsed MM) maintenance QW x4 wk (D1,8,15,22) then 13-day rest | 1.3 mg/m2/dose; >=72 h between consecutive doses |
| Retreatment of multiple myeloma (relapse >=6 mo after prior bortezomib response) | Adults | Last tolerated dose, twice weekly (D1,4,8,11) q3wk | Max 8 retreatment cycles |
Renal No starting-dose adjustment; in dialysis patients give after the dialysis procedure
Hepatic Mild: no adjustment. Moderate/severe (bilirubin >1.5x ULN): start 0.7 mg/m2 in first cycle; then escalate to 1 mg/m2 or reduce to 0.5 mg/m2 by tolerance
At least 72 h between consecutive doses. Toxicity dose reductions: 1.3 -> 1 -> 0.7 mg/m2 (neuropathy per grade: Gr1+pain/Gr2 -> 1 mg/m2; Gr2+pain/Gr3 -> hold, resume 0.7 mg/m2 QW; Gr4 -> discontinue)
Instructions
- IV or SC ONLY — never intrathecal (fatal); IV concentration 1 mg/mL vs SC 2.5 mg/mL: verify volume calculation
- Reconstitute only with 0.9% sodium chloride
- Rotate SC sites (thigh/abdomen), >=1 inch from prior site; if SC site reactions, use 1 mg/mL SC or switch to IV
- Consider starting SC route in patients with pre-existing or high-risk peripheral neuropathy
- Hazardous drug — special handling/disposal
Available strengths
- inj 3.5 mg
- powder 1, 2.5 mg/vial
- sol 3.5 mg/1.4 mL
Contraindications
- Intrathecal administration — fatal events have occurred
Cautions
- Peripheral neuropathy (mainly sensory; dose-modify per grade)
- Hypotension incl. orthostatic — caution with antihypertensives/dehydration
- Cardiac toxicity: new/worsening heart failure
- Pulmonary toxicity: ARDS, interstitial pneumonia
- Posterior reversible encephalopathy syndrome (PRES)
- GI toxicity: nausea, diarrhea, constipation, vomiting; may need antiemetics/antidiarrheals
- Thrombocytopenia/neutropenia — check counts before each dose (nadir ~day 11)
- Tumor lysis syndrome
- Hepatic toxicity incl. acute liver failure
- Thrombotic microangiopathy (TTP/HUS), sometimes fatal
- Embryo-fetal toxicity — effective contraception required
- Diabetics on oral hypoglycemics: hypo/hyperglycemia reported — monitor glucose
Adverse reactions
- >=20%: nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, anorexia
Pregnancy Can cause fetal harm (embryo-fetal lethality in rabbits below clinical dose); advise of fetal risk
Lactation Advise not to breastfeed during treatment and for 2 months after final dose
Cost
| Strength | #/mo | generic $/unit | CostPlus | |
|---|---|---|---|---|
| 3.5 mg | inj | per unit | not offered |
NO BOXED WARNINGS
Principal riskPeripheral neuropathy, dose-limiting; give subcutaneously