These recommendations include the use of tacrolimus in kidney, heart, lung, and hematopoietic stem cell transplant patients, and liver transplant patients in which the donor and recipient genotypes are identical.
Normal Metabolizer (CYP3A5 Expresser)
Clinical Implication
- Functional CYP3A5 enzyme activity present (“Abnormal result”; inconsistent with the majority of the population).
- Increased risk of treatment failure with standard doses.
Therapeutic Recommendation
- Increase starting dose by 1.5–2 times the recommended starting dose without exceeding 0.3 mg/kg/day. Adjust as clinically appropriate per therapeutic drug monitoring.
Intermediate Metabolizer (CYP3A5 Expresser)
Clinical Implication
- Functional CYP3A5 enzyme activity present (“Abnormal result”; inconsistent with the majority of the population).
- Increased risk of treatment failure with standard doses.
Therapeutic Recommendation
- Increase starting dose by 1.5–2 times the recommended starting dose without exceeding 0.3 mg/kg/day. Adjust as clinically appropriate per therapeutic drug monitoring
Poor Metabolizer (CYP3A5 Non-Expresser)
Clinical Implication
- No CYP3A5 enzyme activity (“Normal result”; consistent with the majority of the population).
- Normal response expected.
Therapeutic Recommendation
- Initiate standard dosing and adjust as clinically appropriate per therapeutic drug monitoring.
Unable to Genotype or Assay Failure
- The analysis failed to yield an informative result and thus no genotype is reported.
Reference
- Birdwell KA et al. Clin Pharmacol Ther. 2015 Jul;98(1):19-24. PMID: 25801146.