Affiliation:
1. Gregory Fleming James Cystic Fibrosis Research Center University of Alabama at Birmingham (UAB) Birmingham Alabama USA
2. Division of Pulmonary and Sleep Medicine, Department of Pediatrics University of Alabama at Birmingham Birmingham Alabama USA
3. Department of Neurology, School of Medicine University of Alabama at Birmingham Birmingham Alabama USA
4. McWhorter School of Pharmacy Samford University Birmingham Alabama USA
Abstract
AbstractAlthough major advancements have been made in the therapeutics for people with cystic fibrosis (PwCF), many still require the use of multiple medications to manage acute exacerbations of disease and maintain health. Iterative trial and error processes of pharmacotherapeutic management can be optimized by assessing and incorporating pharmacogenetics. For 82 PwCF, we reviewed 2 years of medication use and response history and interrogated metabolizer status for common pharmacogenes, revealing 3336 medication exposure events (MEEs) to 286 unique medications. As expected, the more frequent MEEs were those commonly used to treat cystic fibrosis (CF), such as antibiotics and respiratory medications. Antibiotics also comprised 56.7% of the undesirable drug responses. The impact of gene variants on drug responses was assessed using Pharmacogenomics Knowledgebase (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Thirty‐three (11.5%) medications have strong evidence of genetic influence on response as evidenced by gene‐based dosing guidelines. 110 (38.5%) unique medications had at least one association with a very important pharmacogene, whereas 143 (50%) were associated with at least one clinical or variant annotation. Over 97% of participants had at least one actionable genotype. Eleven (13.4%) patients with an actionable genotype, taking the impacted medication, had an undesirable drug response described in the CPIC guidelines that could potentially have been mitigated with a priori knowledge of the genotype. PwCF take many medications for disease management, with frequent dose changes to elicit a desired clinical effect. As CF care evolves, implementing pharmacogenetics testing can improve efficiency and safety of prescribing practices using precision selection and dosing at medication initiation.
Funder
National Institutes of Health
Cystic Fibrosis Foundation
Subject
General Pharmacology, Toxicology and Pharmaceutics,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience