Bortezomib

# Bortezomib ## Overview - **Classification**: Proteasome Inhibitor - **Mechanism**: Reversibly inhibits the 26S proteasome, disrupting protein homeostasis. This leads to cell cycle arrest and apoptosis, primarily in cancer cells. ## Primary Indications 1. **Multiple Myeloma (MM)**: Treatment of adult patients. 2. **Mantle Cell Lymphoma (MCL)**: Treatment of adult patients. ## Adult Dosing ### Standard Dosing **Multiple Myeloma (MM) & Mantle Cell Lymphoma (MCL)** - **Dose**: **1.3 mg/m²** - **Frequency**: Twice weekly for 2 weeks (Days 1, 4, 8, 11). Followed by a 10-day rest period (Days 12-21). This completes a 21-day cycle. - **Route**: Subcutaneous (preferred) or Intravenous push. - **Duration**: Up to 8 cycles for monotherapy, or as part of combination regimens. ### Dose Adjustments - **Renal Impairment**: No dose adjustment needed for mild to severe renal impairment. Not studied in dialysis. - **Hepatic Impairment**: - **Moderate to Severe (bilirubin >1.5 x ULN)**: Reduce initial dose to **0.7 mg/m²**. Monitor closely. - **Elderly Patients**: No specific dose adjustment based on age alone. Increased risk of diarrhea and GI events. ## Pediatric Dosing *Bortezomib is not FDA-approved for pediatric use. Dosing below is based on off-label use in clinical trials for certain pediatric malignancies.* ### Neonates (0-28 days) - **Dose**: Not established. - **Frequency**: N/A - **Maximum**: N/A - **Special Notes**: Use with extreme caution. Limited data. ### Infants (1-12 months) - **Dose**: Limited data, typically **0.7-1.3 mg/m²**. - **Frequency**: Often twice weekly for 2 weeks, then rest (similar to adult schedules). - **Maximum**: **1.3 mg/m²** per dose. ### Children (1-12 years) - **Dose**: **0.7-1.3 mg/m²**. - **Frequency**: Often 1-2 times per week for 2-4 weeks, then a rest period. - **Maximum**: **1.3 mg/m²** per dose. ### Adolescents (13-18 years) - **Dose**: Typically follows adult dosing: **1.3 mg/m²**. - **Maximum**: **1.3 mg/m²** per dose. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to bortezomib, boron, or mannitol. - **Absolute**: Intrathecal administration (fatal). - **Relative**: Acute diffuse infiltrative pulmonary and pericardial disease. ### Common Adverse Effects - **Very Common (>10%)**: Peripheral neuropathy, thrombocytopenia, neutropenia, fatigue, nausea, diarrhea, constipation, vomiting, pyrexia, anemia. - **Common (1-10%)**: Rash, dyspnea, hypotension, headache, dizziness, insomnia, anorexia, abdominal pain, asthenia. - **Serious but Rare**: Posterior Reversible Encephalopathy Syndrome (PRES), acute diffuse infiltrative pulmonary disease, severe cardiac events (new or worsening heart failure), tumor lysis syndrome, severe hepatic failure. ### Key Drug Interactions - **Strong CYP3A4 Inducers (e.g., rifampin, phenytoin)**: May decrease bortezomib exposure. Avoid co-administration if possible. - **Strong CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir)**: May increase bortezomib exposure. Monitor closely for toxicity. - **Oral Hypoglycemics**: May exacerbate or cause hypoglycemia/hyperglycemia. Monitor blood glucose closely. ## Monitoring & Follow-up - **Before Treatment**: Complete blood count (CBC) with differential, liver function tests (LFTs), renal function tests, neurological exam. - **During Treatment**: CBC with differential (prior to each dose), LFTs (periodically), neurological exam (at least prior to each cycle), vital signs. - **Clinical Signs**: Monitor for new or worsening peripheral neuropathy, cardiac dysfunction, pulmonary symptoms, abdominal pain, unusual bleeding/bruising. ## Clinical Pearls - 💡 **Subcutaneous Route Preferred**: Associated with lower incidence of peripheral neuropathy compared to IV. - 💡 **Peripheral Neuropathy Management**: Dose modification or interruption often required. Can be debilitating; symptoms may persist. - 💡 **Hydration**: Maintain adequate hydration to prevent tumor lysis syndrome and manage GI side effects. - 💡 **Antiemetics/Laxatives**: Consider prophylactic antiemetics and laxatives/stool softeners due to high incidence of GI effects. - 💡 **Shingles Prophylaxis**: Consider antiviral prophylaxis (e.g., acyclovir) due to increased risk of herpes zoster reactivation. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.