Atovaquone Prophylaxis for Pneumocystis jirovecii Pneumonia (PJP) – NCCN Guideline Recommendations

Dosing and Administration

The NCCN recommends atovaquone 1500 mg oral suspension once daily taken with a high‑fat meal as the standard prophylactic regimen for patients who cannot tolerate trimethoprim‑sulfamethoxazole** 1.
For immunocompromised adults intolerant to TMP‑SMX, the established prophylactic dose is 1500 mg per day divided into 750 mg twice daily (oral suspension) 2.

Prophylaxis should be continued for the entire period of immunosuppression, including at least 6 months after an allogeneic stem‑cell transplant and while the patient remains on immunosuppressive therapy 1.
Patients with acute lymphoblastic leukemia should remain on atovaquone throughout the course of anti‑leukemic therapy 1.
When T‑cell‑depleting agents such as alemtuzumab are used, prophylaxis is continued until the CD4⁺ count exceeds 200 cells/µL 1.
For individuals receiving ≥20 mg prednisone daily (or equivalent) for ≥4 weeks, atovaquone prophylaxis is maintained 1.

Clinical assessment should be performed to detect breakthrough PCP infection while the patient is on atovaquone prophylaxis 1.

Dapsone 100 mg daily is an alternative, but G6PD testing is required before initiation 1.
Aerosolized pentamidine 300 mg monthly (delivered via a Respirgard II nebulizer) is another recommended option 1.
For patients who also need toxoplasmosis prophylaxis, a dapsone‑pyrimethamine combination may be used 2.

The CDC/NIH/IDSA guidelines recommend atovaquone as an alternative therapeutic regimen for mild-to-moderate PCP when patients are TMP-SMX intolerant or when clinical treatment fails after 5-7 days of TMP-SMX 3, 4, 5
Atovaquone is recommended as an alternative prophylactic agent for PCP when TMP-SMX cannot be tolerated 6

For adults, atovaquone carries a BI recommendation strength for PCP treatment 3
For children, dosing is 30-40 mg/kg/day in 2 divided doses with fatty foods; infants aged 3-24 months may require 45 mg/kg/day 3, 4, 5
Atovaquone may be considered to complete a 21-day course after 7-10 days of IV pentamidine in patients showing clinical improvement 3, 4, 5

Atovaquone MUST be administered with food, particularly fatty foods, as bioavailability increases 1.4-fold compared to fasting state 3, 4, 5
Failure to administer with food may result in suboptimal plasma concentrations and treatment failure
Patients with gastrointestinal disorders may have limited absorption resulting in suboptimal atovaquone concentrations 4

Most common adverse reactions include rash (10-15%), nausea, diarrhea, and elevated liver enzymes 3, 4, 5
Atovaquone concentrations are increased by fluconazole and prednisone 3, 4, 5
Atovaquone concentrations are decreased by rifampin, rifabutin, acyclovir, opiates, cephalosporins, tetracycline, metoclopramide, and benzodiazepines 3, 4, 5