From the Guidelines
The recommended first-line treatment for Pneumocystis jirovecii pneumonia (PJP) prophylaxis is trimethoprim-sulfamethoxazole (TMP-SMX). This recommendation is based on the most recent and highest quality study, which found that TMP-SMX prophylaxis significantly reduced PJP-related mortality (RR, 0.17; 95% CI, 0.03–0.94) 1. The standard adult dosing is one double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) daily or three times weekly.
Key Points
- TMP-SMX is preferred because it is highly effective, relatively inexpensive, and provides additional protection against other opportunistic infections such as toxoplasmosis and some bacterial infections.
- For patients who cannot tolerate daily dosing due to side effects, the three-times-weekly regimen is an effective alternative.
- PJP prophylaxis is indicated for immunocompromised patients, including those with HIV infection with CD4 counts below 200 cells/μL, patients on long-term immunosuppressive therapy, and those with hematologic malignancies or organ transplants.
- Alternative options for patients with sulfa allergies or who cannot tolerate TMP-SMX include dapsone, atovaquone, or aerosolized pentamidine, though these are generally considered less effective than the first-line agent 1.
Patient Groups Requiring PJP Prophylaxis
- Allogeneic HCT recipients
- Patients receiving CAR T-cell therapy for at least 6 months and while receiving IST
- Patients with ALL throughout antileukemic therapy
- Patients receiving treatment with select phosphatidylinositol-3-kinase inhibitors + rituximab
- Patients with neoplastic diseases receiving intensive corticosteroid treatment
- Patients receiving temozolomide 1.
Important Considerations
- Patients who are G6PD deficient may have an increased risk for hemolytic adverse reactions when receiving dapsone therapy.
- Methemoglobinemia can also occur with dapsone therapy.
- Atovaquone appears to be equivalent to dapsone in HIV patients who cannot tolerate TMP-SMX 1.
From the FDA Drug Label
For the prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). The recommended dosage for prophylaxis in adults is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet daily Atovaquone oral suspension is indicated for the prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX).
The recommended first-line treatment for Pneumocystis jirovecii pneumonia (PJP) prophylaxis is:
- Sulfamethoxazole and trimethoprim: 1 DS tablet daily for adults 2
- For children: 750 mg/m2/day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week 2
- For patients who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX): Atovaquone oral suspension is an alternative option for PJP prophylaxis 3
From the Research
PJP Prophylaxis
- The recommended first-line treatment for Pneumocystis jirovecii pneumonia (PJP) prophylaxis is trimethoprim-sulfamethoxazole (TMP-SMX) 4, 5, 6.
- TMP-SMX has been shown to offer superior coverage for PJP, toxoplasmosis, and nocardiosis compared to other alternatives such as pentamidine, dapsone, or atovaquone 4.
- However, some patients may have a history of allergy or severe intolerance to TMP-SMX, in which case alternative agents such as pentamidine, dapsone, or atovaquone may be substituted 4, 5, 6.
- Studies have also shown that intravenous pentamidine can be an effective and well-tolerated alternative for PJP prophylaxis in certain situations 7.
- Additionally, optimizing the dose of TMP-SMX has been shown to reduce the mortality rate and PCP-associated adverse events, while also reducing the economic burden of illness and enhancing patient compliance 8.
Alternative Agents
- Pentamidine is an alternative agent for PJP prophylaxis, particularly for patients who are intolerant to TMP-SMX 5, 7.
- Atovaquone is also an alternative agent, and has been shown to be well-tolerated in patients with connective tissue diseases 5.
- Dapsone is another alternative agent, although its use may be limited by adverse effects such as hemolysis and methemoglobinemia 6.