What precautions are necessary when using Cyclophosphamide (an alkylating agent) in patients with active viral infections?

From the Guidelines

Cyclophosphamide should be avoided in patients with active viral infections due to its potent immunosuppressive effects, as recommended in the 2023 evidence-based guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis 1. When considering the use of cyclophosphamide, it is crucial to weigh the potential benefits against the risks, particularly in patients with active viral infections. The guideline emphasizes the importance of screening for major chronic infections, such as hepatitis B virus and HIV, before initiating treatment with cyclophosphamide or rituximab 1. Some key points to consider when using cyclophosphamide in patients with active viral infections include:

• The risk of viral reactivation and severe, potentially life-threatening complications, particularly with infections like hepatitis B, hepatitis C, HIV, herpes zoster, and cytomegalovirus 1
• The need for comprehensive viral screening, including hepatitis panels and HIV testing, before initiating therapy 1
• The potential use of prophylactic antiviral medications for patients with a history of viral infections 1
• The importance of close collaboration between rheumatologists, infectious disease specialists, and other relevant providers to balance the benefits of cyclophosphamide against the risks of worsening viral infection 1
• The recommendation for prophylaxis against Pneumocystis jirovecii infection with sulfamethoxazole–trimethoprim in all patients treated with cyclophosphamide and/or rituximab 1. Overall, the use of cyclophosphamide in patients with active viral infections requires careful consideration and close monitoring to minimize the risks of worsening infection and other complications.

From the FDA Drug Label

Myelosuppression, Immunosuppression, and Infections Inform patients of the possibility of myelosuppression, immunosuppression, and infections. Explain the need for routine blood cell counts Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever [see Warnings and Precautions ( 5.1)] .

The use of cyclophosphamide in patients with active viral infections may increase the risk of severe infections due to immunosuppression. Patients should be advised to monitor their temperature frequently and immediately report any occurrence of fever. However, the label does not provide specific precautions for patients with active viral infections.

• Key considerations:
  • Immunosuppression
  • Increased risk of severe infections
  • Monitor temperature frequently
  • Report any occurrence of fever immediately 2 2

From the Research

Cyclophosphamide Precautions in Active Viral Infection

• There are no direct studies on cyclophosphamide precautions in active viral infection among the provided evidence 3, 4, 5, 6, 7.
• However, the studies suggest that cyclophosphamide can be used in combination with other treatments for various conditions, such as ANCA-associated vasculitis 3, 4, 5, 7 and connective tissue disease-associated interstitial lung disease 6.
• The risk of infection is a consideration when using cyclophosphamide, as it can suppress the immune system 4, 5.
• One study found that the serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment with cyclophosphamide is not associated with an enduring risk of infection 3.
• Another study found that the rate of infections did not differ between patients treated with rituximab and cyclophosphamide or rituximab only 4.
• A network meta-analysis found that mycophenolate mofetil showed a lower risk of serious infection than methotrexate, and that rituximab had a higher risk of serious infection than mycophenolate mofetil, but the difference was only significant between mycophenolate mofetil and methotrexate 5.