Should cyclophosphamide (an immunosuppressive agent) be withheld during plasmapheresis (plasma exchange therapy)?

Cyclophosphamide Administration During Plasmapheresis

Cyclophosphamide should be administered after plasmapheresis sessions rather than before or during them to prevent removal of the drug and maximize therapeutic efficacy. 1, 2

Rationale for Timing Cyclophosphamide After Plasmapheresis

Plasmapheresis removes circulating antibodies and other plasma components, including medications present in the bloodstream. When cyclophosphamide is administered before or during plasmapheresis, a significant portion of the drug may be removed, reducing its therapeutic effect 3.

The KDOQI guidelines specifically address this timing issue:

• With intravenous cyclophosphamide, the infusion should be given after a plasma exchange session 1
• This prevents premature removal of the medication before it can exert its therapeutic effect

Recommended Protocol for Combined Therapy

1. Complete the scheduled plasmapheresis session
2. Wait 1-2 hours after plasmapheresis completion
3. Administer cyclophosphamide at the prescribed dose (typically 0.5-1 g/m² every 3-4 weeks) 2
4. Continue with subsequent plasmapheresis sessions as scheduled

Evidence Supporting This Approach

Several studies have demonstrated the benefits of synchronizing plasmapheresis with subsequent cyclophosphamide administration:

• This approach maximizes the immunosuppressive effect by targeting antibody-producing cells during their vulnerable proliferative phase 4
• Studies have shown improved remission rates when cyclophosphamide is administered after plasmapheresis rather than before 5, 6

Special Considerations

For ANCA-Associated Vasculitis and Anti-GBM Disease

• Plasmapheresis is recommended for patients requiring dialysis or with rapidly increasing serum creatinine 1
• Plasmapheresis should be continued until antibody titers are no longer detectable 1
• Cyclophosphamide is typically administered for 2-3 months in these conditions 1

For Rituximab Therapy

• If rituximab is used instead of cyclophosphamide, plasmapheresis should be held for 48-72 hours after rituximab infusion 1
• This is because plasmapheresis can remove rituximab from circulation, reducing its effectiveness 1

Potential Pitfalls to Avoid

1. Do not administer cyclophosphamide immediately before plasmapheresis - this will result in significant drug removal and reduced efficacy
2. Do not adjust cyclophosphamide dosing based solely on plasmapheresis schedule - maintain appropriate dosing based on body surface area and renal function
3. Do not forget to monitor for increased infection risk - combined therapy with plasmapheresis and immunosuppression increases infection susceptibility
4. Do not overlook anticoagulation management - patients receiving anticoagulation require careful monitoring during plasmapheresis 7

By following these recommendations, you can optimize the therapeutic effect of cyclophosphamide while ensuring the benefits of plasmapheresis in removing pathogenic antibodies.