Rebecca S. Pettit

Background: The clinical impact of pharmacists and pharmacy technicians on the care of people with cystic fibrosis (pwCF) has been well documented within the literature, including medication access, reduction of hospitalizations, and consolidation of pharmaceutical delivery for pwCF with complex medication regimens. However, challenges related to access and affordability have become increasingly complex, increasing the administrative burden placed upon these members of the multidisciplinary CF care team. The goal of this study was to quantify the time pharmacists and pharmacy technicians at CF Foundation‐accredited care centers (CFACC) spent triaging and resolving errors, categorize the types of interventions required, and tabulate the financial burden for pwCF averted through these interventions. Methods: This study was a retrospective review of pharmacy team members' interactions following a change in limited distribution network of cystic fibrosis transmembrane conductance regulator modulators (CFTRm) over a 4‐month period of time. Each site received institutional review board exemption. Measures were characterized using descriptive statistics and were analyzed in SAS v9.4 (Cary, NC). Collected data were extrapolated to be nationally representative based on the 2023 CFF Patient Registry report. Results: Six CFACC and 1781 pwCF were included in this review. Of these pwCF, 216 required additional interventions following a required change in the dispensing pharmacy for their CFTRm. Collectively, 201.5 h were spent on resolution of issues during the study period with interventions successfully averting a financial burden to pwCF of $226,094.73. Extrapolations of time and financial burden were estimated to be 3700 h and over $4.2 million, respectively. Conclusions: Medication access and affordability continue to present significant barriers for pwCF. We aim to highlight the critical services provided by clinical pharmacy teams at CFACC as well as their integrated health‐system specialty pharmacies, and the vital role they play in improving outcomes and providing cost‐effective care for pwCF.

Background: Many people with cystic fibrosis (PwCF) are colonized with Pseudomonas aeruginosa . Some studies have found that PwCF who use both tobramycin (TOB) and azithromycin during PEx treatment, have worse clinical outcomes, including a greater decline in percent predicted forced expiratory volume (ppFEV1) and lower odds of returning to baseline ppFEV1. The objective of this study was to compare the IV TOB elimination rate constant (Ke) between pediatric PwCF on maintenance azithromycin (mtAZM) versus those not on mtAZM. Methods: This IRB‐approved retrospective cohort study included pediatric PwCF who received IV TOB for PEx treatment from January 1, 2019–June 1, 2024. Results: A total of 83 PwCF were included, 35 in mtAZM group and 48 in no mtAZM. Baseline characteristics were similar between both groups. The percentage of females was significantly higher in the mtAZM group (60%) versus the no mtAZM group (38%, p = 0.04). The mean TOB Ke was 0.39 h ⁻¹ (0.1) in the mtAZM group versus 0.42 h ⁻¹ (0.1) in the no mtAZM group ( p = 0.07). There were no significant differences between mtAZM versus no mtAZM for other PK parameters. Median TOB daily dose was not significantly different between the two groups (11.2 mg/kg/day (9‐12) vs. 10.9 mg/kg/day (9.3–12); p = 0.56). The duration of TOB use, re‐admission rate and time to next admission were similar between the two groups. No participants in either group experienced acute kidney injury. Conclusions: This study demonstrated that mtAZM did not affect the Ke or other PK parameters of IV TOB. Despite previous reports of interactions between the two medications, our study suggests that similar TOB dosing and monitoring strategies can be used in those PwCF regardless of mtAZM use.

The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modulator therapy (HEMT) availability for the majority of PwCF has led to changes in pharmacotherapy regimens and clinical outcomes but has also been associated with adverse effects and drug interactions. The role of CFTR modulator therapy perinatally continues to be of great interest, related to both the mother with CF as well as the infant in utero and after birth. As the median life expectancy for PwCF continues to increase, consideration must also be given for treatment of cardiovascular disease and other comorbidities as well as cancer screening and other preventative care measures.

Introduction: Medication adherence in cystic fibrosis (CF) has been shown to slow disease progression. Integrated pharmacy services can help increase medication access. The objective of this study was to compare the medication possession ratio (MPR) of dornase alfa between people with cystic fibrosis (PwCF) filling maintenance CF medications at one integrated health system specialty pharmacy (IHSSP) to those filling at multiple pharmacies. Methods: This retrospective study included PwCF < 18 years of age who were prescribed dornase alfa from January 1 to December 31, 2019. The primary endpoint was the MPR for dornase alfa. Subgroup analyses were performed for those with Medicaid and those with private insurance. Results: A total of 85 patients were included, with 29 (34.1%) filling all medications at IHSSP and 56 (65.9%) filling at multiple pharmacies. The median MPR of dornase alfa was 0.98 (IQR: 0.76–1) and 0.64 (IQR: 0.34–0.85), ( p < 0.001), and ppFEV1 changed by −1% (IQR: −7% to 5%) compared to −5% (IQR: −10% to −1%), ( p = 0.03) for the IHSSP group and multiple pharmacies groups, respectively. There was no difference in the number of hospitalizations or length of stay. Improved MPR for PwCF in the IHSSP group was sustained in the Medicaid and private insurance subgroups. Conclusions: The MPR of dornase alfa was higher, and pulmonary function was maintained in PwCF who were able to use the IHSSP for CF medications. Some insurance policies require specific pharmacies for specialty medications, requiring PwCF to fill prescriptions at multiple pharmacies and potentially worsening adherence and clinical outcomes.

Background: Inhaled tobramycin solution is recommended for eradication treatment of Pseudomonas aeruginosa (PA) infections in people with cystic fibrosis (PwCF). However, there is limited information on the safety of inhaled tobramycin in PwCF less than 1 year old and no studies primarily analyzing the safety of the 300 mg inhaled solution. The objective of this study was to compare the incidence of adverse drug events (ADE) of inhaled tobramycin in PwCF less than 1 year old to PwCF ages 1 year to 18 years old. Methods: This retrospective analysis evaluated the incidence of inhaled tobramycin ADEs in PwCF ages 14 days to 18 years with CF between January 01, 2008 to January 01, 2022. PwCF less than 1 year of age (infant group) were matched based on genotype in a 1:3 ratio with a PwCF at least a year old to 18 year‐old (children group). Results: Forty‐eight patients were included (infant group: 12, children group: 36). Median (IQR) age was 0.48 years (0.2–0.7) and 4.7 years (2.3–10) in infant group and children group respectively ( p < 0.05). There were 5 (41.7%) ADE in the infant group and 3 (8.3%) in the children group ( p = 0.016). When cough was removed there was no significant difference between the two groups [2 (16.7%) vs. 1 (2.7%), p = 0.15]. There was no difference in treatment failure [3 (25%) vs. 7 (19.4%), p = 0.68]. Conclusions: This study found a higher incidence of inhaled tobramycin ADE in infants compared to children. These results show a low risk of ADE outside of cough, indicating that inhaled tobramycin may be safely used in this age group.

Background: Patients with primary ciliary dyskinesia (PCD) are commonly treated for pulmonary exacerbations with intravenous tobramycin, but data on tobramycin pharmacokinetics in PCD is lacking. The objective of this study was to compare tobramycin pharmacokinetics in pediatric patients with PCD to those with cystic fibrosis (CF). Methods: This retrospective study included pediatric patients hospitalized for a pulmonary exacerbation between January 2018 and June 2023. Included patients were treated with systemic tobramycin and had two concentrations usable to calculate patient‐specific pharmacokinetics. Each patient with PCD was matched 1:2 to patients with CF based on age. The primary outcome was tobramycin elimination rate constant. Results: Seven patients with PCD were matched to 14 patients with CF. Baseline characteristics were similar between groups. The final tobramycin dose was not significantly different between groups (9.3 vs. 11.8 mg/kg, p = 0.192). All doses were infused over 30 min every 24 h. Tobramycin elimination rate constant (0.510 vs. 0.493 h ⁻¹ , p = 0.433) and volume of distribution (0.31 vs. 0.23 L/kg, p = 0.640) were not different between groups. No patient experienced acute kidney injury. Additionally, both groups experienced similar duration of tobramycin therapy (12.3 vs. 9.6 days, p = 0.184) and length of stay (12.0 vs. 12.6 days, p = 0.801). Conclusions: No difference in tobramycin elimination rate constant was found between patients with PCD and those with CF. Clinical outcomes were not significantly different between groups. Although not statistically significant, a lower tobramycin dose was observed in patients with PCD.

Following the approval of elexacaftor/tezacaftor/ivacaftor (ETI), there have been post‐marketing reports and published cases of papilledema and intracranial hypertension in children with cystic fibrosis (CF) taking ETI. In those reports, the patients often presented with marked symptoms and concomitant hypervitaminosis A. In this multicenter case series, we report eight cases of papilledema in children with CF taking ETI that were diagnosed via routine eye exam, the majority of whom presented with minimal to no symptoms and all had normal serum Vitamin A levels.