BOROFAIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BOROFAIR (BOROFAIR).
BOROFAIR (bortezomib) is a reversible inhibitor of the 26S proteasome, a large protease complex that degrades ubiquitinated proteins. By blocking proteasomal degradation, it disrupts intracellular protein homeostasis, leading to cell cycle arrest and apoptosis, particularly in malignant cells.
| Metabolism | Primarily metabolized by cytochrome P450 enzymes, specifically CYP3A4, CYP2C19, and CYP1A2, with minor contributions from CYP2D6 and CYP2C9. |
| Excretion | BOROFAIR is primarily excreted unchanged in urine via glomerular filtration and active tubular secretion. Approximately 85% of the administered dose is recovered in urine within 24 hours, with less than 1% in feces. |
| Half-life | The terminal elimination half-life is approximately 10 hours in patients with normal renal function. This half-life supports twice-daily dosing for continuous beta-lactamase inhibition. |
| Protein binding | Protein binding is approximately 30%, primarily to albumin. |
| Volume of Distribution | The volume of distribution is approximately 0.3 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Bioavailability is 100% via intravenous administration. Oral bioavailability is negligible due to poor gastrointestinal absorption, and no other routes are clinically used. |
| Onset of Action | Intravenous administration: Onset of action occurs within 30 minutes post-infusion, corresponding to the time to reach effective plasma concentrations. |
| Duration of Action | Duration of action is approximately 12 hours, allowing twice-daily dosing. Clinical effect correlates with plasma levels above the inhibitory concentration for beta-lactamases. |
1.5 mg/m2 intravenously over 10-20 seconds on Days 1, 8, 15 of a 28-day cycle.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 30-50 mL/min: reduce dose to 1.2 mg/m2; CrCl 15-29 mL/min: reduce dose to 0.9 mg/m2; CrCl <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 1.2 mg/m2; Child-Pugh C: not recommended. |
| Pediatric use | 1.5 mg/m2 intravenously on Days 1, 8, 15 of a 28-day cycle for patients aged 12-18 years; safety and efficacy not established for <12 years. |
| Geriatric use | No specific dose adjustment, but monitor for renal function and myelosuppression; use same dosing as for younger adults with normal renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BOROFAIR (BOROFAIR).
| Breastfeeding | No data on bortezomib in human milk. Due to potential for serious adverse reactions in breastfed infants (e.g., myelosuppression, neurotoxicity), breastfeeding is not recommended during therapy and for 2 months after last dose. M/P ratio unknown. |
| Teratogenic Risk | Borofair (bortezomib) is contraindicated in pregnancy. Animal studies show embryofetal lethality and teratogenicity (skeletal and visceral malformations) at doses below clinical exposure. First trimester exposure carries high risk of major congenital anomalies. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. Effective contraception is mandatory. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to bortezomib, boron, or any component of the formulation","Intrathecal administration (fatal outcomes reported)"]
| Precautions | ["Peripheral neuropathy (may be severe; monitor and dose adjust)","Hepatic toxicity (monitor liver function; dose reduction for moderate to severe impairment)","Cardiac toxicity (congestive heart failure, arrhythmias; caution in patients with risk factors)","Hematologic toxicity (neutropenia, thrombocytopenia, anemia; monitor blood counts)","Tumor lysis syndrome (especially in patients with high tumor burden)","Pregnancy (fetal harm; advise effective contraception)"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase bortezomib levels. No other specific food restrictions; maintain adequate hydration. |
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| Fetal Monitoring | Monitor complete blood count with differential weekly, hepatic and renal function tests every 2-4 weeks. Assess for peripheral neuropathy at each visit. Fetal ultrasound for growth and amniotic fluid volume monthly if exposure occurs after 20 weeks. Monitor for hypotension and cardiac toxicity. |
| Fertility Effects | Bortezomib may impair fertility in males and females based on animal studies (reduced spermatogenesis, ovarian follicle depletion). Effects may be reversible. Preclinical data show no direct effect on estrous cycle or mating; but embryofetal toxicity may indirectly affect reproductive outcomes. |
| Clinical Pearls | BOROFAIR (bortezomib) is a proteasome inhibitor used in multiple myeloma and mantle cell lymphoma. Key pearl: Administer as a 3- to 5-second bolus via IV or subcutaneously; SC route reduces peripheral neuropathy risk. Monitor for thrombocytopenia, especially nadir around day 11. Premedicate with antiemetics. Not interchangeable with other bortezomib formulations. |
| Patient Advice | Take exactly as prescribed; do not stop or change dose without consulting your doctor. · Report any new or worsening numbness, tingling, or burning in hands/feet immediately. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during and for 3 months after treatment. · Do not drive or operate heavy machinery if you experience dizziness, fatigue, or visual changes. |