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Prophylactic Trimethoprim-Sulfamethoxazole Does Not Affect Pharmacokinetics or Pharmacodynamics of Methotrexate

Courtney S Watts1, Joseph N Sciasci, Jennifer L Pauley

  • 1Departments of *Pharmaceutical Sciences §Oncology †Biostatistics, St Jude Children's Research Hospital, Memphis, TN ‡Department of Pediatric Oncology, Skejby Hospital, Aarhus University, Aarhus, Denmark.

Journal of Pediatric Hematology/Oncology
|June 21, 2016
PubMed

Insights

Trimethoprim-sulfamethoxazole (TMP/SMX) does not significantly impact methotrexate clearance or toxicity when used for Pneumocystis jiroveci prophylaxis during chemotherapy. This study found no evidence of a harmful interaction between these commonly used medications.

Area of Science:

  • Oncology
  • Pharmacology
  • Infectious Disease

Background:

  • Trimethoprim-sulfamethoxazole (TMP/SMX) is a standard prophylaxis for Pneumocystis jiroveci pneumonia in chemotherapy patients.
  • Concerns exist that TMP/SMX may interfere with methotrexate clearance, potentially increasing toxicity.

Purpose of the Study:

  • To evaluate the impact of concurrent TMP/SMX use on methotrexate exposure and toxicity during high-dose methotrexate (HDMTX) therapy.
  • To assess the safety of continuing TMP/SMX prophylaxis during HDMTX treatment.

Main Methods:

  • A retrospective analysis of 424 patients receiving HDMTX (NCT00549848), comparing methotrexate clearance and 42-hour concentrations in those concurrently receiving TMP/SMX versus those who did not.
  • Analysis of neutrophil counts and myelosuppression data from HDMTX and low-dose methotrexate studies.

Main Results:

  • No significant difference in methotrexate clearance or 42-hour concentration was observed in the low-risk HDMTX group with concurrent TMP/SMX.
  • In the standard/high-risk HDMTX group, TMP/SMX was associated with slightly higher clearance but no difference in 42-hour concentration.
  • No significant impact on neutrophil counts or myelosuppression was found with concurrent TMP/SMX use during HDMTX or low-dose methotrexate therapy.

Conclusions:

  • Concurrent use of TMP/SMX with HDMTX does not appear to significantly alter methotrexate exposure or increase myelosuppression.
  • TMP/SMX can likely be safely continued for Pneumocystis jiroveci prophylaxis during chemotherapy regimens involving HDMTX.

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