Perioperative Management of Bortezomib, Cyclophosphamide, and Septran Before Major Surgery
For major surgery, stop bortezomib at least 72 hours (approximately 3 days) before the procedure, discontinue cyclophosphamide 5-7 days preoperatively, and hold Septran (co-trimoxazole) 24-48 hours prior to surgery.
Bortezomib (Velcade) Management
Discontinue bortezomib 72 hours (3 days) before major surgery to allow adequate clearance and minimize bleeding risk, as bortezomib can affect platelet function and increase perioperative bleeding complications 1.
- Bortezomib is a proteasome inhibitor with a half-life of approximately 40-80 hours after the first dose 2
- The standard recommendation for biologic agents is to withhold them for at least twice their half-lives before major surgeries 1
- For bortezomib specifically, this translates to approximately 3-5 days (72-120 hours) before major procedures 1
- Resume bortezomib 48-72 hours postoperatively once adequate hemostasis is achieved and wound healing is progressing normally 1
Cyclophosphamide (Cytoxan) Management
Stop cyclophosphamide 5-7 days before major surgery to allow bone marrow recovery and reduce infection risk.
- Cyclophosphamide causes myelosuppression with nadir typically occurring 7-14 days after administration 3
- Discontinuing 5-7 days preoperatively allows partial recovery of white blood cell counts, reducing perioperative infection risk 4
- The immunosuppressive effects necessitate adequate time for immune function recovery before surgical stress 1
- Resume cyclophosphamide only after confirming adequate wound healing and absence of infection, typically 7-14 days postoperatively 1
Septran (Co-trimoxazole) Management
Hold Septran 24-48 hours before major surgery to minimize bleeding risk and drug interactions with anesthesia.
- Co-trimoxazole can potentiate anticoagulant effects and increase bleeding risk through vitamin K antagonism 5
- The medication has a half-life of approximately 10 hours for trimethoprim and 9 hours for sulfamethoxazole, making 24-48 hours adequate for clearance 4
- Resume Septran 24 hours postoperatively once oral intake is established and renal function is stable 4
Critical Timing Algorithm
Use this stepwise approach:
Schedule surgery timing: Ideally, plan surgery during the "off-week" of chemotherapy cycles when possible 3
Preoperative discontinuation sequence:
- Day -7: Stop cyclophosphamide (if last dose was given)
- Day -3: Stop bortezomib (last dose should be at least 72 hours before surgery)
- Day -1 to -2: Stop Septran (24-48 hours before surgery)
Day of surgery: Verify complete blood count shows adequate recovery (WBC >3,000/μL, platelets >100,000/μL) 1
Postoperative resumption:
- Septran: Resume at 24 hours if oral intake tolerated
- Bortezomib: Resume at 48-72 hours if hemostasis adequate
- Cyclophosphamide: Resume at 7-14 days after confirming wound healing and absence of infection
Special Considerations and Pitfalls
Avoid these common errors:
Do not assume prophylactic antibiotics replace Septran - if Septran is being used for Pneumocystis jirovecii prophylaxis in immunocompromised patients, ensure alternative prophylaxis is provided during the perioperative period 4
Check baseline blood counts 48-72 hours before surgery - patients on combination bortezomib-cyclophosphamide regimens may have significant cytopenias requiring delay of surgery 3
Coordinate with oncology regarding the chemotherapy cycle timing - delaying one cycle may be preferable to interrupting mid-cycle 3
Monitor for thrombocytopenia - bortezomib can cause significant platelet dysfunction beyond just low counts, increasing bleeding risk even with "acceptable" platelet numbers 2
Assess infection risk carefully - the combination of these three immunosuppressive agents creates substantial infection vulnerability that persists beyond drug discontinuation 1
Consider bridging prophylaxis - if Septran is being used for infection prophylaxis, discuss alternative coverage (such as pentamidine or atovaquone) with oncology during the perioperative period 4