What is the acceptable timing to measure trough levels for Envarsus (tacrolimus)?

Timing for Envarsus (Tacrolimus) Trough Level Measurement

For Envarsus (extended-release tacrolimus), trough levels should be measured at 24 hours after the last dose, immediately before the next scheduled dose. 1

Understanding Tacrolimus Monitoring

Tacrolimus is a calcineurin inhibitor (CNI) with a narrow therapeutic window that requires careful monitoring to ensure efficacy while avoiding toxicity. Proper timing of trough level measurement is critical for accurate therapeutic drug monitoring.

Standard Monitoring Protocol for Tacrolimus

• The KDIGO guidelines recommend measuring CNI blood levels (1B evidence level) 2
• For tacrolimus specifically, monitoring should use the 12-hour trough (C0) for standard twice-daily formulations (2C evidence level) 2
• For Envarsus, which is a once-daily extended-release formulation, the trough level should be measured at 24 hours post-dose 1, 3

Frequency of Monitoring

Monitoring frequency should follow this schedule:

• Every other day during immediate post-transplant period until target levels are reached 2
• Whenever there is a medication change or patient status change that may affect blood levels 2
• Whenever kidney function declines, which may indicate nephrotoxicity or rejection 2

For stable patients:

• Weekly for months 2-3 post-transplant
• Every 2 weeks for months 4-6
• Monthly for months 7-12
• Every 2-3 months thereafter 2, 1

Special Considerations for Envarsus

Envarsus has different pharmacokinetic properties compared to immediate-release tacrolimus:

• Envarsus demonstrates approximately 30% greater bioavailability compared to other prolonged-release tacrolimus formulations 4
• It requires approximately 40% lower daily dose to achieve similar trough concentrations 4
• It has lower peak-to-trough fluctuation (approximately 30% less) 4

Delayed Trough Measurement

If the standard 24-hour trough measurement is not possible:

• Trough levels can be measured up to 32 hours after ingestion but will provide lower values (mean 6.7 μg/L at 32 hours vs. 8.3 μg/L at 24 hours) 3
• Delayed measurements still correlate strongly with 24-hour exposure (correlation coefficient 0.82) 3
• If using delayed measurements, the target range must be adjusted downward accordingly 3

Target Trough Levels

For Envarsus, target trough levels generally follow these guidelines:

• 6-11 ng/mL during the first 30 days post-transplant
• 4-11 ng/mL thereafter 5

Pitfalls to Avoid

• Failure to adjust dosing when adding/removing interacting medications can lead to toxicity or underexposure 1
• Relying solely on trough levels may not fully capture drug exposure in all patients, especially those with unusual pharmacokinetics 6
• Not accounting for the extended-release properties of Envarsus when timing blood draws can lead to inaccurate dosing decisions

By following these guidelines for trough level measurement timing, clinicians can optimize tacrolimus therapy to improve graft survival and minimize adverse effects.