BORTEZOMIB
Clinical safety rating: avoid
Contraindicated (not allowed)
Reversible inhibition of the 26S proteasome, disrupting protein homeostasis and leading to apoptosis in cancer cells.
| Metabolism | Primarily metabolized by CYP3A4, CYP2C19, and CYP1A2. Minor contributions from CYP2D6 and CYP2C9. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2C19; <10% excreted unchanged in urine; fecal elimination accounts for ~40% of total clearance. |
| Half-life | Terminal half-life 40-100 hours (mean ~76 hours); supports twice-weekly dosing schedule. |
| Protein binding | ~83% bound to human plasma proteins (primarily albumin). |
| Volume of Distribution | Vd approximately 498-1884 L/m² (large, indicating extensive tissue distribution). |
| Bioavailability | SubQ: 82% relative to IV; oral: not applicable (administered IV or SubQ). |
| Onset of Action | IV: 1-2 weeks for antineoplastic effect; SubQ: similar to IV. |
| Duration of Action | Proteasome inhibition persists for 72-96 hours post-dose; clinical effects last throughout treatment cycle. |
1.3 mg/m2 intravenously or subcutaneously twice weekly for 2 weeks (days 1, 4, 8, 11) followed by a 10-day rest period (days 12-21) for cycles 1-8; for cycles 9-16, administer once weekly on days 1, 8, 15, 22 followed by a 13-day rest period.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for creatinine clearance >30 mL/min. For CCr <30 mL/min, no specific dosing recommendation; use with caution and monitor for toxicity. Patients requiring hemodialysis should receive bortezomib after hemodialysis. |
| Liver impairment | Mild (Child-Pugh A): No adjustment. Moderate (Child-Pugh B): Reduce starting dose to 0.7 mg/m2 per injection. Severe (Child-Pugh C): Not recommended due to lack of data. |
| Pediatric use | Not approved for pediatric use in most indications. In clinical trials for acute lymphoblastic leukemia, dose of 1.3 mg/m2 intravenous push over 3-5 seconds on days 1, 4, 8, 11 of a 21-day cycle has been used, but safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based on age alone. Monitor for neurotoxicity, cardiovascular events, and myelosuppression. Consider dose reductions for comorbidities and decreased organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inducers may decrease efficacy Peripheral neuropathy is a common and sometimes severe toxicity requiring dose adjustment.
| Breastfeeding | Unknown if excreted in human breast milk. No M/P ratio available. Due to potential for serious adverse reactions in breastfeeding infants (e.g., myelosuppression, gastrointestinal toxicity), women should not breastfeed during therapy and for at least 2 months after last dose. |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of embryofetal toxicity including skeletal abnormalities, low birth weight, and increased resorption based on animal studies. Second and third trimesters: Potential for myelosuppression, hypotension, and tumor lysis syndrome in the fetus. Contraindicated in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
BORTEZOMIB can cause severe, potentially fatal, cardiovascular events including heart failure and arrhythmias. It may also cause reversible posterior leukoencephalopathy syndrome (RPLS).
| Common Effects | Peripheral neuropathy |
| Serious Effects |
Hypersensitivity to bortezomib, boron, or mannitol; severe hepatic impairment (total bilirubin >3 × ULN).
| Precautions | Cardiovascular toxicity, pulmonary toxicity, peripheral neuropathy, thrombocytopenia, gastrointestinal toxicity, tumor lysis syndrome, hepatic toxicity, and embryofetal toxicity. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, which may inhibit CYP3A4 metabolism and increase bortezomib exposure. No other specific dietary restrictions are required, but maintain adequate hydration to reduce risk of renal toxicity and tumor lysis syndrome. Limit alcohol intake as it may exacerbate gastrointestinal and hepatic side effects. |
Loading safety data…
| Fetal Monitoring | Baseline and serial CBC with differential (risk of neutropenia and thrombocytopenia), liver function tests, renal function, and tumor lysis syndrome monitoring (urate, electrolytes, calcium, phosphate). Fetal ultrasound for growth and anatomy if continued pregnancy. Monitor for hypotension, cardiac arrhythmias, and peripheral neuropathy. |
| Fertility Effects | Bortezomib may impair fertility in males and females. In animal studies, testicular degeneration and reduced sperm count were observed. In females, ovarian effects including reduced corpora lutea and fertility. Preclinical data suggest potential for temporary or permanent infertility. |
| Clinical Pearls | Bortezomib is a proteasome inhibitor used primarily for multiple myeloma and mantle cell lymphoma. Monitor for peripheral neuropathy, which can be dose-limiting. Administer as a 3-5 second IV bolus or subcutaneous injection; subcutaneous route reduces neuropathy risk. Premedicate with antiemetics due to high emetic potential. Assess for cardiac complications including heart failure and QT prolongation. Check for tumor lysis syndrome in patients with high tumor burden. Reconstitute only with normal saline, not dextrose, as bortezomib degrades in dextrose. |
| Patient Advice | You may experience numbness, tingling, or burning in your hands or feet; report these symptoms immediately. · Take anti-nausea medication as prescribed before each dose to prevent vomiting. · Drink plenty of fluids to help prevent kidney problems and tumor lysis syndrome. · Avoid driving if you feel dizzy or fatigued after treatment. · Report any signs of infection (fever, cough) or unusual bleeding/bruising. · Do not take any new medications or supplements without consulting your doctor due to potential interactions. · Women of childbearing age should use effective contraception during treatment and for 3 months after. |