Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

K A Birdwell; B Decker; J M Barbarino; J F Peterson; C M Stein; W Sadee; D Wang; A A Vinks; Y He; J J Swen; J S Leeder; Rhn van Schaik; K E Thummel; T E Klein; K E Caudle; I A M MacPhee

doi:10.1002/cpt.113

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Clin Pharmacol Ther. 2015 Jul;98(1):19-24. doi: 10.1002/cpt.113. Epub 2015 Jun 3.

Authors

K A Birdwell^{1

2}, B Decker³, J M Barbarino⁴, J F Peterson^{2

5}, C M Stein^{2

6}, W Sadee⁷, D Wang⁷, A A Vinks^{8

9}, Y He¹⁰, J J Swen¹¹, J S Leeder¹², Rhn van Schaik¹³, K E Thummel¹⁴, T E Klein⁴, K E Caudle¹⁵, I A M MacPhee¹⁶

Affiliations

¹ Division of Nephrology Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
² Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
³ Division of Nephrology and Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴ Department of Genetics, Stanford University, Stanford, California, USA.
⁵ Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.
⁶ Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
⁷ Center for Pharmacogenomics, School of Medicine, The Ohio State University, Columbus, Ohio, USA.
⁸ Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁹ Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁰ Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, Peoples Republic of China.
¹¹ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
¹² Division of Clinical Pharmacology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
¹³ Department of Clinical Chemistry, Erasmus MC Rotterdam, The Netherlands.
¹⁴ Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
¹⁵ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹⁶ Institute of Medical and Biomedical Education, Renal Medicine, St. George's, University of London, London, UK.

PMID: 25801146
PMCID: PMC4481158
DOI: 10.1002/cpt.113

Abstract

Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).

Publication types

Practice Guideline
Research Support, N.I.H., Extramural

MeSH terms

Cytochrome P-450 CYP3A / genetics*
Genetic Testing
Genotype
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents / administration & dosage*
Organ Transplantation
Tacrolimus / administration & dosage*

Substances

Immunosuppressive Agents
Cytochrome P-450 CYP3A
Tacrolimus

Abstract

Publication types

MeSH terms

Substances

Grants and funding