Drug-drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors.

BACKGROUND: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide. RESEARCH DESIGN AND METHODS: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs. RESULTS: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI. CONCLUSIONS: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

Sulfonylurea monotherapy and emergency room utilization among elderly patients with type 2 diabetes.

AIM: In elderly Americans with type 2 diabetes, use of insulin and oral antidiabetic drugs (OADs) accounts for almost one-fourth of drug adverse event-related hospitalizations. It is not clear, however, if sulfonylureas (SUs), frequently prescribed OADs known to cause hypoglycemia, increase the risk of emergency room (ER) visits compared to other OADs. The aim of this study was to compare the emergency room utilization between US elderly patients with diabetes on SU monotherapy vs. other non-SU monotherapies. METHODS: This retrospective cohort study was conducted using MarketScan(®) database (2009-10) and aimed to evaluate the association between use of SU and ER visits. The analysis included 28,533 patients (aged ≥65 years) receiving SU monotherapy at baseline and 1:1 propensity score (PS)-matched group receiving monotherapy with other OADs. ER utilization was determined during a 1-year follow-up period. RESULTS: The SU and non-SU groups were overall well balanced after PS matching. The mean (SD) number of ER visits during the follow-up was 0.56 among users of SU users compared to 0.49 (P<0.0001) among non-users. In multivariable analysis, the adjusted odds ratios for ≥2 ER visits were 1.21 (95% CI=1.13-1.30) comparing SU users to non-users and 1.31 (95% CI=1.21-1.41) for SU vs. metformin users. CONCLUSION: Elderly patients with type 2 diabetes on SU monotherapy were more likely to use ER than those on other monotherapies. Further studies are needed to confirm our findings and evaluate other factors associated with ER visits.

Sulfonylurea use and risk of hip fractures among elderly men and women with type 2 diabetes.

BACKGROUND: Both increased age and type 2 diabetes mellitus are risk factors for developing bone fractures. While recent data in the elderly suggest a link between hypoglycemia and fall-related fractures, the association between sulfonylureas, commonly used hypoglycemic agents, and fracture risk has not been well investigated. METHODS: We used patient data from a large commercial health insurer from 2002-2005. Individuals aged ≥65 years receiving oral sulfonylurea treatment (n=13,195) were matched 1:1 to non-users based on propensity for sulfonylurea use. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs). RESULTS: During an average 4 years of follow-up, sulfonylurea users experienced 226 incident hip fractures (1.7%) and non-users experienced 157 (1.2%). Sulfonylurea use was associated with increased risk of developing hip fracture (aOR 1.46, 95% CI 1.17-1.82), and this association was apparent for men (120 cases; aOR 1.83, 95% CI 1.25-2.66) and women (263 cases; aOR 1.32, 95% CI 1.03-1.69). Patients with documented hypoglycemia in the follow-up period had increased odds of hip fracture relative to those without such diagnosis (aOR 2.42, 95% CI 1.35-4.34). CONCLUSION: Sulfonylureas are associated with increased risk of hip fracture in elderly men and women with type 2 diabetes.

A comparison of daily average consumption (DACON) of oxycodone and oxymorphone long-acting oral tablets.

BACKGROUND: The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists. OBJECTIVES: To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER. METHODS: The main outcome measure for the analysis was DACON. Pharmacy and medical claims data from a large commercially insured population (i3 InVision Data Mart database) were analyzed to identify patients with at least 1 pharmacy claim for either oxycodone CR or oxymorphone ER from July 1, 2007, to September 30, 2009. After an initial 30-day titration period, all subjects included in the study had 1 or more claims totaling at least a 90-day supply of either study drug during the subsequent 90 days (DACON measurement period). Patients were excluded if there was evidence of a switch from one to the other study opioid during the 90-day measurement period. There were no limitations on the use of other opioids, either short- or long-acting, during either the DACON measurement period or the previous 6 months (baseline period). In addition, patients were excluded if the enrollee was younger than 18 years old, pregnant, did not have continuous insurance coverage for the 6 months before and after the start of the 90-day DACON measurement, or were enrolled in an HMO plan. Bivariate analyses were performed with between-group differences in DACON values assessed using t-tests and Wilcoxon rank sum tests. Patient characteristics including age, sex, geographic location, and baseline Charlson Comorbidity Index (CCI) for each drug group were evaluated descriptively using either the Pearson chi-square test or t-test. Multivariate analyses were conducted using generalized linear models (GLM) to adjust for the observed heterogeneity among patients in the observational database. For the GLMs, the gamma distribution and log link function were chosen to account for non-normal distributions of DACON. Independent variables included study drug, tablet strengths, age, sex, CCI, the maximum days gap between prescription refills during the DACON measurement period, and other opioid medication use. Several sensitivity analyses were conducted to verify all findings. RESULTS: The final analyses were conducted on 6,567 oxycodone CR patients and 796 oxymorphone ER patients. The unadjusted DACON mean value for the highest strength of oxycodone CR 80 milligrams (mg) was 3.9, compared with 2.9 for oxymorphone ER 40 mg (P < 0.001); mean DACON values were 3.0 versus 2.4, respectively, for lower strengths (P < 0.001) and 3.1 versus 2.5 for all strengths (P < 0.001). After adjusting for age, sex, CCI, maximum gap days, and other opioid medication use, a risk-adjusted mean difference in DACON remained, with oxycodone CR patients receiving on average 0.6 tablets more per day than those dispensed oxymorphone ER (P < 0.001). The direction, magnitude, and statistical significance of these differences were essentially unchanged in sensitivity analyses. CONCLUSIONS: On average during a 90-day time period, patients taking oxymorphone ER consumed 0.6 fewer tablets per day than did patients taking oxycodone CR. Further research is necessary to see if this difference amounts to cost savings for health plans that provide prescription reimbursement for patients with chronic pain syndromes.