Do you hold tacrolimus (immunosuppressive medication) during an acute infection?

Management of Tacrolimus During Acute Infection

Recommendation

Tacrolimus should be temporarily stopped during active or presumptive infection, pending a negative test result for COVID-19 or after 2 weeks of symptom-free observation. 1

Evidence-Based Rationale

The American College of Rheumatology's 2020 guidance for management of rheumatic disease during the COVID-19 pandemic explicitly recommends that immunosuppressants including tacrolimus should be temporarily discontinued following SARS-CoV-2 exposure or during active infection 1. This recommendation is based on moderate consensus among experts and reflects the increased risk of serious infections in patients taking immunosuppressive medications.

Risk Assessment

Tacrolimus carries significant risks during acute infection:

• The FDA label warns that patients receiving tacrolimus are at increased risk of developing bacterial, viral, fungal, and protozoal infections, which may lead to serious or fatal outcomes 2
• Stronger immunosuppression is associated with severe infectious complications, especially in cirrhotic patients 1
• Tacrolimus inhibits calcineurin, which impairs T-cell function and cytokine production, potentially compromising the immune response to infection

Monitoring During Infection

If tacrolimus must be continued in select circumstances (such as preventing organ rejection):

• Monitor tacrolimus trough levels more frequently during hospitalization for infection 1
• Be aware that infection can affect tacrolimus metabolism, with studies showing up to 35% of kidney transplant recipients admitted for acute infection present with elevated tacrolimus levels 3
• Digestive infections particularly may increase tacrolimus levels, possibly due to disruption of intestinal P-glycoprotein function 4
• Monitor for signs of tacrolimus toxicity including tremors, paresthesias, headache, and changes in mental status 2

Special Considerations

Transplant Recipients

For transplant recipients, the decision to hold tacrolimus must balance infection risk against rejection risk:

• In stable transplant patients with mild infections, tacrolimus may be continued with close monitoring
• In severe infections, especially with hemodynamic instability or respiratory compromise, consider reducing the dose or temporarily discontinuing tacrolimus
• Consult with the transplant team before making any changes to immunosuppressive regimens

COVID-19 Specific Guidance

For patients with COVID-19:

• The American College of Rheumatology recommends stopping tacrolimus regardless of COVID-19 severity 1
• However, case reports suggest that in select circumstances, tacrolimus might be used even in patients with COVID-19 pneumonia when treating severe, steroid-refractory ulcerative colitis 5

Resuming Tacrolimus After Infection

When restarting tacrolimus after an infection:

• Resume the medication after resolution of infection symptoms
• Monitor levels closely as metabolism may still be affected during recovery
• Consider starting at a lower dose and titrating up based on levels
• Resume regular monitoring schedule once stable levels are achieved

Conclusion

While the decision to hold tacrolimus during acute infection must consider the individual clinical scenario, current guidelines recommend temporarily discontinuing tacrolimus during active infection, especially in the context of COVID-19. Close monitoring of drug levels is essential if tacrolimus must be continued, as infections can significantly alter drug metabolism and increase the risk of toxicity.