Tacrolimus response

Tacrolimus is an immunosuppressive agent administered to transplant recipients to prevent and treat allograft rejection. Clinical use of tacrolimus is complicated by a narrow therapeutic index and high inter-patient pharmacokinetic variability, partly due to variations within the CYP3A5 gene. Patients who are CYP3A5 extensive or intermediate metabolizers may require increased starting doses of tacrolimus. Adjustment of dose based on CYP3A5 phenotype may allow for a more rapid achievement of therapeutic drug concentrations. This particular dosing recommendation is unusual in that it is those with the extensive metabolizer phenotype (typically referred to as the "normal" metabolizer phenotype) who may require a dosage modification (here, an increase in normal starting dose), while those with the poor metabolizer phenotype often do not require a change to the starting dose. This is because, in the case of CYP3A5, extensive metabolizers are actually the minority in most worldwide populations (excluding those of African descent), while those with the poor metabolizer phenotype are the majority. Therapeutic guidelines for tacrolimus based on CYP3A5 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]