From the Guidelines
Tacrolimus dosage is adjusted based on trough levels, with typical targets ranging from 5-15 ng/mL initially and 5 ng/mL after a year.
Key Considerations
- The dosage is highly individualized and based on trough levels of the drug 1
- Higher trough levels are sought initially after transplant when the risk of rejection is high, and lower levels are sought later when concerns about adverse effects start to predominate 1
- Trough levels should be below the range recommended for tacrolimus monotherapy to preserve renal function, such as 4-7 ng/ml during the first month, followed by 3-5 ng/ml when using combination regimens 1
- Monitoring of tacrolimus levels is crucial, with daily monitoring until a steady level is attained, and subsequent monitoring every 1-2 weeks in the first 1-2 months post-transplant, and every 1-2 months once stable levels are attained 1
- Drug interactions should be considered, as certain medications can increase or decrease tacrolimus concentrations, and target trough levels may need to be adjusted accordingly 1
- Renal function and potential adverse effects should be closely monitored, with intermittent measurement of serum potassium and glucose levels, renal function, and hepatic function, at least every 4-6 weeks 1
From the FDA Drug Label
Due to intersubject variability in tacrolimus pharmacokinetics, individualization of the dosing regimen is necessary for optimal therapy [see Dosage and Administration (2. 6)].
Table 15 displays the effects of other drugs on tacrolimus. * Tacrolimus dosage adjustment recommendation based on observed effect of co-administered drug on tacrolimus exposures [see Clinical Pharmacology (12. 3)], literature reports of altered tacrolimus exposures, or the other drug’s known CYP3A inhibitor/inducer status.
The tacrolimus dosage is adjusted based on the following factors:
- Whole blood trough concentrations: The dose is adjusted to maintain optimal trough concentrations.
- Concomitant medications: The dose is adjusted based on the effect of concomitant medications on tacrolimus exposures, such as:
- CYP3A inhibitors: Reduce tacrolimus dose to avoid increased risk of serious adverse reactions.
- CYP3A inducers: Increase tacrolimus dose to avoid decreased efficacy.
- Individual patient factors: The dose is individualized based on the patient's pharmacokinetic profile and clinical response. The dosage adjustment is guided by therapeutic drug monitoring, which involves measuring the whole blood trough concentrations of tacrolimus to ensure that the patient is receiving an effective and safe dose 2.
From the Research
Tacrolimus Dosage Adjustment
The dosage of tacrolimus is typically adjusted based on the trough concentration (C0) and the area under the curve (AUC) [ 3 ]. However, the relationship between TAC C0 and clinical outcomes has seldom been reported.
Factors Influencing Dosage Adjustment
Several factors influence the dosage adjustment of tacrolimus, including:
- Genetic polymorphisms, such as CYP3A5 genotype [ 4, 5,6 ]
- Clinical factors, such as hemoglobin levels [ 4 ]
- Pharmacokinetic considerations, such as the C/D ratio [ 7 ]
Methods of Dosage Adjustment
Different methods can be used to adjust the dosage of tacrolimus, including:
- Bayesian estimation of AUC [ 3 ]
- Machine learning approaches [ 3 ]
- Microsampling devices for blood sample collection [ 3 ]
- Classification and regression tree analysis to predict the starting dose [ 4 ]
- Genotype-based dosing equations to calculate the required starting daily dose [ 6 ]
Monitoring and Adjustment
Tacrolimus dosage can be adjusted based on the results of therapeutic drug monitoring, which includes: