What medication is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis (PPX) in patients who cannot take Bactrim (trimethoprim/sulfamethoxazole)?

From the Guidelines

For PJP prophylaxis in patients who cannot take Bactrim (trimethoprim-sulfamethoxazole), atovaquone is a recommended alternative, typically given as 1500mg daily with food, as it appears to be equivalent to dapsone in HIV patients who cannot tolerate TMP/SMX 1. When considering alternatives to Bactrim for PJP prophylaxis, it's essential to weigh the benefits and risks of each option.

• Atovaquone is a viable choice, with a dosage of 1500mg daily, taken with food to enhance absorption.
• Dapsone is another option, typically given as 100mg daily or 50mg twice daily, but it requires measurement of G6PD levels before initiation to avoid hemolytic adverse reactions.
• Aerosolized pentamidine (300mg monthly via nebulizer) can be used in patients who cannot tolerate atovaquone or dapsone, although it may be less convenient and potentially less effective.
• Intravenous pentamidine (4mg/kg monthly) is a less common alternative, usually reserved for cases where other options are not feasible. The choice between these alternatives depends on the specific reason for Bactrim intolerance, patient comorbidities, and potential drug interactions, as noted in recent guidelines 1. These medications work through different mechanisms: atovaquone disrupts electron transport in the parasite, dapsone inhibits folate synthesis, and pentamidine interferes with the organism's DNA and RNA synthesis. Prophylaxis should be continued as long as immunosuppression persists, particularly when CD4 counts remain below 200 cells/μL in HIV patients or during periods of significant immunosuppression in other conditions, emphasizing the importance of ongoing monitoring and adjustment of prophylactic strategies as needed 1.

From the FDA Drug Label

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 medication used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis (PPX) in patients who cannot take Bactrim (trimethoprim/sulfamethoxazole) is atovaquone (PO), with a recommended oral dosage of 1,500 mg (10 mL) once daily administered with food 2.

• The dosage is specifically for the prevention of P. jirovecii Pneumonia.
• Atovaquone should be administered with food to avoid lower plasma concentrations that may limit response to therapy.

From the Research

Pneumocystis jirovecii Pneumonia Prophylaxis Alternatives

In patients who cannot take Bactrim (trimethoprim/sulfamethoxazole) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, alternative medications can be used. These alternatives include:

• Pentamidine: Intravenous pentamidine has been shown to be a safe and effective alternative for PJP prophylaxis in adult patients undergoing hematopoietic stem cell transplantation or intensive chemotherapy 3, 4.
• Dapsone: Dapsone is another alternative for PJP prophylaxis, although it may not be suitable for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of hemolysis 5, 6.
• Atovaquone: Atovaquone is also used as an alternative for PJP prophylaxis, particularly in patients who are intolerant to trimethoprim-sulfamethoxazole or pentamidine 5, 7.

Considerations for Alternative Prophylaxis

When considering alternative prophylaxis for PJP, it is essential to evaluate the patient's medical history, laboratory values, and potential allergies to ensure the chosen alternative is suitable. For example:

• Patients with G6PD deficiency may require careful monitoring when using certain alternative medications, such as dapsone or trimethoprim-sulfamethoxazole 6.
• Patients with a history of sulfonamide allergy may be at risk of adverse reactions to certain alternative medications, such as dapsone or pentamidine 7.

Efficacy and Safety of Alternative Prophylaxis

Studies have demonstrated the efficacy and safety of alternative prophylaxis for PJP, including:

• Intravenous pentamidine: Shown to be effective in preventing PJP in adult patients undergoing hematopoietic stem cell transplantation or intensive chemotherapy, with minimal side effects 3, 4.
• Atovaquone: Demonstrated to be effective in preventing PJP in patients who are intolerant to trimethoprim-sulfamethoxazole or pentamidine, although the risk of breakthrough infections may be higher 5, 7.