Does atovaquone need to be held pre-operatively in patients taking it for malaria prophylaxis or Pneumocystis jirovecii pneumonia treatment?

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Last updated: February 3, 2026View editorial policy

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Atovaquone Does Not Need to Be Held Pre-Operatively

Atovaquone can be safely continued through the perioperative period without interruption, as there are no documented drug interactions with anesthetic agents, no effects on coagulation, and no specific perioperative risks associated with this medication.

Rationale for Continuation

  • No anesthetic interactions: Atovaquone has no known interactions with general or regional anesthetic agents, neuromuscular blocking drugs, or other perioperative medications commonly used in surgery 1.

  • No coagulation effects: Unlike anticoagulants or antiplatelet agents, atovaquone does not affect hemostasis or increase surgical bleeding risk 1.

  • Maintains prophylaxis: Interrupting atovaquone prophylaxis creates a gap in protection against Pneumocystis jirovecii pneumonia (PCP), which is particularly dangerous in immunocompromised patients who require this medication 1.

Key Clinical Context

When Atovaquone Is Used

Atovaquone is prescribed as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) for PCP prophylaxis in patients who cannot tolerate sulfa drugs, including:

  • Allogeneic hematopoietic stem cell transplant recipients 1
  • Patients with acute lymphoblastic leukemia during chemotherapy 1
  • HIV-infected patients with CD4+ counts <200 cells/μL 2
  • Patients receiving high-dose corticosteroids (≥20 mg prednisone daily for ≥4 weeks) 1
  • Patients on T-cell depleting agents like alemtuzumab 1

Absorption Considerations

  • Food requirement: Atovaquone bioavailability increases 1.4-fold when taken with food; patients should continue taking it with meals perioperatively to maintain therapeutic levels 3.

  • NPO status: If the patient must be NPO for extended periods, consider administering atovaquone with a small amount of permitted clear liquid or resuming immediately when oral intake is allowed, as even brief interruptions can lead to subtherapeutic levels 4.

Critical Pitfalls to Avoid

  • Do not discontinue prophylaxis: Stopping atovaquone perioperatively exposes immunocompromised patients to life-threatening PCP infection, which has mortality rates of 30-50% in non-HIV immunocompromised patients 2.

  • Beware of rifamycin interactions: If the patient is also receiving rifampin or rifabutin for tuberculosis or other infections, consider alternative PCP prophylaxis, as rifamycins substantially decrease atovaquone concentrations and may lead to prophylaxis failure 1.

  • Monitor absorption: Approximately 58% of immunocompromised patients have subtherapeutic atovaquone levels even with standard dosing; ensure the patient resumes oral intake with food as soon as possible postoperatively 4.

Special Surgical Considerations

  • Gastrointestinal surgery: For patients undergoing GI procedures that may affect absorption, discuss with the surgical and infectious disease teams whether temporary conversion to IV pentamidine or resumption of TMP-SMX (if tolerated) is warranted during the immediate postoperative period 1.

  • Prolonged NPO status: If extended NPO status is anticipated (>48 hours), consider alternative prophylaxis strategies such as aerosolized pentamidine or IV pentamidine during the perioperative period 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

First-Line Treatment for Pneumocystis jirovecii Pneumonia (PJP)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Atovaquone for PJP Prophylaxis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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