High‐dose Cholecalciferol Supplementation in Adults with Cystic Fibrosis

Introduction Despite the availability of consensus guidelines for the treatment of vitamin D deficiency, prospective trials are lacking to examine alternative dosing strategies for adult patients with cystic fibrosis (CF) who do not meet therapeutic goals with standard regimens. Objectives The primary objective of this study was to determine the efficacy of high‐dose cholecalciferol supplementation in increasing serum vitamin D (25‐OHD) levels in adult patients with CF. Methods Patients were eligible for inclusion if they were 18 years or older, had baseline 25‐OHD levels lower than 30 ng/ml, and were diagnosed with CF and pancreatic insufficiency. Patients were given a single dose of cholecalciferol 300,000 or 500,000 IU based on baseline 25‐OHD levels. Response was defined by 25‐OHD and ionized calcium levels at 3 months. At 6 months, responders received a second dose of the same strength, and nonresponders were given a weekly supplement of cholecalciferol 50,000 IU in addition to cholecalciferol 500,000 IU. A second 25‐OHD level was obtained at 9 months. Results Of the 46 patients enrolled, 32 patients (70%) completed the study. Baseline levels of 25‐OHD significantly increased over time in the per protocol population at 3 and 9 months. A total of 16 patients (50%) were considered nonresponders and required weekly supplementation. Conclusion A protocol using high‐dose cholecalciferol or high‐dose plus weekly cholecalciferol is safe and effective in treating adult patients with CF and pancreatic insufficiency

Comparison of Vancomycin Pharmacokinetics in Cystic Fibrosis Patients Pre and Post-lung Transplant:

Background: Vancomycin is commonly used to treat acute cystic fibrosis (CF) exacerbations associated with methicillin-resistant Staphylococcus aureus (MRSA). Multiple studies have demonstrated pharmacokinetic differences of antimicrobials in the CF population. Very little data exist regarding pharmacokinetics postlung transplant, but 2 studies have noted changes in tobramycin pharmacokinetics. No such studies exist evaluating vancomycin in CF patients postlung transplant. Methods: A retrospective cohort review of CF patients who underwent lung transplantation and received vancomycin pre- and posttransplant was conducted. CF patients who underwent transplant between 2007 and 2016 at 4 medical centers throughout the United States were included. The primary endpoint was the change in elimination rate constant. The secondary endpoints were subgroup analyses of patients grouped by age, time posttransplant, and number of nephrotoxic medications. Results: A total of 25 patients were included, of which just under half were pediatric. Patients were significantly older and heavier posttransplant and had higher serum creatinine and number of nephrotoxic medications. The change in elimination rate constant from pre- to posttransplant was −0.50 hr−1 which was statistically significant (P < .001). This significant decrease was consistent among all subgroups of patients evaluated with the exception of pediatric patients. Conclusion: Vancomycin pharmacokinetics are significantly altered in CF patients in the posttransplant setting as evidenced by a decrease in elimination rate constant. This decrease may be related to a decrease in renal clearance and higher numbers of nephrotoxic medications posttransplant. Regardless, pretransplant vancomycin regimens may not predict appropriate posttransplant regimens

Opportunity for pharmacogenomic testing in patients with cystic fibrosis

Background Patients with cystic fibrosis (CF) are exposed to many drugs in their lifetime and many of these drugs have Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines that are available to guide dosing. Contemporary CF treatments are targeted to specific mutations in the CF transmembrane conductance regulator (CFTR) gene, and thus, require patients to have genetic testing before initiation of modulator therapy. However, aside from CFTR genetic testing, pharmacogenomic testing is not standard of care for CF patients. Aim The aim of this study is to determine the number of non-CFTR modulator medications with CPIC guidelines that are prescribed to patients with CF. Materials & Methods We identified all patients with a diagnosis of CF and queried our hospital electronic medical records (EMR) for all orders, including inpatient and prescriptions, for all drugs or drug classes that have CPIC actionable guidelines for drug–gene pairs that can be used to guide therapy. Results We identified 576 patients with a diagnosis of CF that were treated at our institution during this 16-year period between June 2005 and May 2021. Of these patients, 504 patients (87.5%) received at least one drug that could have been dosed according to CPIC guidelines if pharmacogenomic results would have been available. Conclusions Patients with CF have high utilization of drugs with CPIC guidelines, therefore preemptive pharmacogenomic testing should be considered in CF patients at the time of CFTR genetic testing