Pneumocystis Jirovecii Pneumonia Prophylaxis for Patients on Rituximab Therapy
Patients receiving rituximab induction (two doses) followed by maintenance therapy every 6 months for 3 years should receive Bactrim (trimethoprim-sulfamethoxazole) prophylaxis for at least 6 months following induction, with consideration for extended prophylaxis throughout the maintenance period for those with additional risk factors. 1
Prophylaxis Recommendations
First-line Prophylaxis Regimen:
- Low-dose trimethoprim-sulfamethoxazole (TMP-SMX/Bactrim) at 80/400 mg three times weekly or single-strength tablet three times weekly 1
- This regimen has been shown to be effective with fewer adverse events compared to higher doses (160/800 mg twice weekly) 2
Duration of Prophylaxis:
- Minimum duration: 6 months following rituximab induction 1
- Extended prophylaxis: Consider throughout the 3-year maintenance period for patients with risk factors 1
Risk Stratification for Extended Prophylaxis
Patients should be assessed for the following risk factors that warrant extended prophylaxis beyond the initial 6 months:
- Concomitant use of high-dose glucocorticoids (≥30 mg/day prednisone or equivalent) 1, 3
- Pre-existing structural lung disease 1
- Low IgG levels 1
- Previous history of PJP infection 1
The risk-benefit analysis strongly favors prophylaxis in patients receiving concomitant high-dose glucocorticoids, with a number needed to treat of only 20 to prevent one PJP case 3.
Monitoring During Rituximab Therapy
- Measure IgG levels at baseline and every 6 months 1
- Monitor for adverse events related to TMP-SMX, particularly leukopenia, rash, and nephropathy 4
- Consider immunoglobulin supplementation for patients with hypogammaglobulinemia (IgG <3 g/L) and recurrent infections 1
Alternative Prophylaxis Options
For patients who cannot tolerate TMP-SMX, consider:
- Atovaquone
- Dapsone
- Pentamidine (inhaled) 1
Clinical Considerations
Efficacy of Prophylaxis
Recent evidence shows that TMP-SMX prophylaxis significantly reduces PJP incidence in patients receiving rituximab treatment, with an adjusted subdistribution hazard ratio of 0.20 (95% CI, 0.10-0.42) 5.
Adverse Events
While prophylaxis is associated with some adverse events (leukopenia, rash, nephropathy) 4, most are mild to moderate in severity 5. The number needed to harm due to severe adverse events (101) is higher than the number needed to treat to prevent one PJP infection (32) in the general rituximab population 5.
Caution
Be aware of potential drug interactions between methotrexate and TMP-SMX at higher doses, though prophylactic doses are generally well tolerated 1.
PJP Incidence and Mortality
Without prophylaxis, PJP can occur during both induction and maintenance therapy with rituximab, with mortality rates reported as high as 27.2% 5 to 63.6% 3 in different patient populations.