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Pharmacovigilance / Other

Poster Session A

(A-258) Trimethoprim-Sulfamethoxazole (TMP-SMX) and Risk of Hemophagocytic Lymphohistiocytosis (HLH): A Literature Review and Disproportionality Analysis Using Individual Safety Case Reports from FAERS

Sunday, August 24, 2025
12:00 PM - 1:30 PM ET

    Co-Author(s)

  • RL

    Rinko Lau

    Department of Physiology and Pharmacology, Western University, London, Ontario, Canada, Canada

  • HS

    Hasti Sadeghi

    Department of Biology, Western University, London, Ontario, Canada, Canada

  • FA

    Fatemeh Ahmadi

    Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London ON, Canada, Canada

  • NC

    Niaz Chalabianloo

    Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
    London, Ontario, Canada

  • MA

    Mohammad Ali Omrani

    Department of Physiology and Pharmacology, Western University, London, Ontario, Canada, Canada

    • Presenting Author(s)

  • FT

    Flory T Muanda

    Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, Ontario, Canada

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) has been linked to hematologic adverse events, but its association with hemophagocytic lymphohistiocytosis (HLH) remains unclear.

Objectives: To review the literature on TMP-SMX and HLH and assess its risk using the FDA Adverse Event Reporting System (FAERS).

Methods: A Medline/Embase search (up to September 6, 2024) identified studies on TMP-SMX and HLH. The Naranjo scale assessed causality in case reports. FAERS data (2004Q1–2023Q4) were analyzed, comparing HLH reports for TMP-SMX versus amoxicillin/clavulanic acid and azithromycin. Disproportionality analyses used Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), and Information Components (IC025), with logistic regression adjusting for confounders. The study follows READUSPV guidelines.

Results: Five case reports (median age: 34 years, 80% male) described TMP-SMX-associated HLH, with symptom onset 2–12 days post-initiation. The Naranjo scale suggested a possible to probable association. In FAERS, HLH was reported in 0.09% of TMP-SMX cases, compared to 0.03% for amoxicillin/clavulanic acid and 0.01% for azithromycin. TMP-SMX-associated HLH was more common in males (75.7%) and in patients ≤18 years (69.2%). Disproportionality analysis showed that HLH reports were significantly higher for TMP-SMX compared to amoxicillin/clavulanic acid (ROR: 3.08; 95% CI 1.67–5.68) and compared to azithromycin (ROR: 13.89; 95% CI 5.88–32.82). These findings remained consistent across frequentist and Bayesian methods and adjusted analyses.

Conclusions: TMP-SMX may be linked to an increased risk of HLH. Clinicians should remain vigilant for this rare but serious adverse event. Further pharmacoepidemiologic studies are needed to confirm these findings to ensure safe use.