What are the implications of using Bactrim (Trimethoprim/Sulfamethoxazole) with Janus kinase (JAK) inhibitors?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

Combining Bactrim with JAK inhibitors requires careful monitoring due to potential increased infection risk, and prophylactic Bactrim at a lower dose should be considered when co-administration is necessary. While there is no absolute contraindication to using these medications together, caution is warranted as both can affect immune function. JAK inhibitors like tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq) already carry an increased risk of infections, and Bactrim may compound this risk 1. If co-administration is necessary, patients should be closely monitored for signs of infection. Consider prophylactic Bactrim at a lower dose (typically one single-strength tablet three times weekly) rather than daily dosing when possible. Laboratory monitoring should include complete blood counts and renal function tests, as both medication classes can affect these parameters. The concern stems from JAK inhibitors' mechanism of inhibiting cytokine signaling pathways crucial for immune function, while Bactrim can occasionally cause bone marrow suppression. In immunocompromised patients requiring both medications, the benefit of preventing opportunistic infections with Bactrim may outweigh the risks, but individualized assessment is essential.

Some key points to consider when using JAK inhibitors include:

  • Pre-treatment screening for infections, including TB and opportunistic infections 1
  • Monitoring for adverse events, such as serious infections, malignancies, and venous thromboembolism (VTE) 1
  • Consideration of dose adjustments in patients with higher age, significantly impaired renal or hepatic function, or risk of drug interactions 1
  • Evaluation of response using validated, disease-specific measures of disease activity 1

It is also important to note that the safety of JAK inhibitors in certain populations, such as pregnant or lactating women, and patients with prior or current malignancies, is not well established 1. Additionally, the long-term safety of JAK inhibitors is still being studied, and further research is needed to fully understand their risks and benefits 1.

In terms of specific guidance on the use of Bactrim with JAK inhibitors, there is limited evidence available. However, based on the potential increased risk of infection, it is recommended to use prophylactic Bactrim at a lower dose when co-administration is necessary, and to closely monitor patients for signs of infection 1.

Overall, the use of Bactrim with JAK inhibitors requires careful consideration of the potential risks and benefits, and individualized assessment of each patient's needs. By following the recommended guidelines and monitoring patients closely, healthcare providers can help minimize the risks associated with these medications and optimize their benefits.

From the Research

Use of Bactrim with JAK Inhibitors

There is no direct evidence in the provided studies regarding the use of Bactrim with JAK inhibitors.

Infection Risks Associated with JAK Inhibitors

  • JAK inhibitors have shown an increased risk of infection across the class compared to placebo, most commonly affecting respiratory and urinary tracts, nasopharynx, and skin 2.
  • The risk of infection is dose-dependent and similar to that seen with biologic therapies at licensed JAK inhibitor doses 2.
  • Herpes zoster reactivation is more common with JAK inhibitors compared to other targeted immune modulation, making screening for varicella exposure and vaccination in appropriate cohorts an advisable strategy 2.
  • The rates of serious infections were 0.4-4.8% compared with no events to 0.5-1.3% in the placebo in dermatology-specific phase 3 clinical trials 3.

Safety and Monitoring of JAK Inhibitors

  • JAK inhibitors have a black box warning due to safety concerns based on data from studies investigating tofacitinib in patients with rheumatoid arthritis 3.
  • Dermatologists should consider patients' baseline risk factors for developing serious complications when prescribing oral JAK inhibitors 3.
  • The most common adverse events of oral JAK inhibitors included upper respiratory infections, nasopharyngitis, nausea, headache, and acne 3.

Comparative Safety of JAK Inhibitors

  • The risk of infections seems to be similar among the currently approved JAK inhibitor drugs 4.
  • Compared with filgotinib, adalimumab, etanercept, peficitinib, tofacitinib, and upadacitinib have an increased risk of herpes zoster infection 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The infection risks of JAK inhibition.

Expert review of clinical immunology, 2022

Research

The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis: A Systematic Review and Network Meta-analysis.

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2022

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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