How is the tacrolimus level affected when drawing a blood sample 20 minutes after the 24-hour trough for Envarsus (tacrolimus)?

Impact of Delayed Tacrolimus Trough Level Measurement for Envarsus

Drawing a tacrolimus level 20 minutes after the 24-hour trough for Envarsus (extended-release tacrolimus) will result in a significantly lower measured concentration that does not accurately reflect the true trough level.

Understanding Tacrolimus Monitoring Requirements

Tacrolimus is a calcineurin inhibitor with a narrow therapeutic window that requires careful therapeutic drug monitoring. For Envarsus, which is a once-daily extended-release formulation:

• Trough levels should ideally be drawn 24 hours after the last dose, immediately before the next scheduled dose 1
• The recommended trough levels for tacrolimus typically range between 5-15 ng/mL 2
• For most patients, more specific targets are 6-10 ng/mL during the first month post-transplant and 4-8 ng/mL thereafter 1

Effect of Delayed Sampling on Tacrolimus Levels

Research specifically examining delayed trough level measurements with extended-release tacrolimus has shown:

• A 20-minute delay after the 24-hour trough will result in measurably lower tacrolimus concentrations
• In a study examining delayed measurements up to 32 hours post-dose, the mean concentrations at 24 hours versus 32 hours were 8.3 μg/L and 6.7 μg/L respectively, representing a significant decrease (p<0.0001) 3
• Even this small delay can impact clinical decision-making, as tacrolimus has a narrow therapeutic window

Clinical Implications

The impact of drawing levels 20 minutes after the scheduled trough time includes:

1. Underestimation of true trough level: This could lead to inappropriate dose increases
2. Risk of toxicity: If doses are increased based on falsely low levels, patients may experience adverse effects including nephrotoxicity, neurotoxicity, and metabolic complications 2
3. Monitoring challenges: The correlation between delayed measurements and 24-hour exposure remains strong, but requires adjustment of target ranges 3

Recommendations for Practice

To ensure accurate monitoring of Envarsus (tacrolimus) levels:

• Always draw blood samples at the true trough (24 hours after last dose, immediately before next dose)
• If a 20-minute delay is unavoidable, document this timing discrepancy when interpreting results
• Consider that the measured level will be lower than the true trough level
• If consistent delayed sampling is necessary due to clinic scheduling, establish adjusted target ranges based on the specific delay time 3

Monitoring Parameters

In addition to tacrolimus levels, regular monitoring should include:

• Complete blood count to detect bone marrow suppression
• Renal function (creatinine, BUN) to detect nephrotoxicity
• Electrolytes, particularly potassium and magnesium
• Blood glucose and lipid profiles
• Liver function tests 2, 1

Tacrolimus monitoring is critical for balancing efficacy and safety, making the timing of blood draws an important consideration in therapeutic drug monitoring.