Small increase in dolutegravir trough, but equivalent total dolutegravir exposure with simeprevir in HIV/HCV seronegative volunteers.

BACKGROUND: Dolutegravir, an HIV integrase strand-transfer inhibitor, and simeprevir, an HCV NS3/4A PI, have the potential to interact as dolutegravir is a P-glycoprotein, uridine glucuronosyl transferase 1A1 and cytochrome P4503A substrate and simeprevir has been shown to mildly inhibit these. OBJECTIVES: To compare dolutegravir and simeprevir pharmacokinetics (PK) when given separately versus in combination. METHODS: Healthy volunteers received: (i) 150 mg of simeprevir once daily for 7 days; (ii) 50 mg of dolutegravir once daily for 7 days; and (iii) 150 mg of simeprevir once daily plus 50 mg of dolutegravir once daily for 7 days, with randomization to treatment sequence. Twenty-four hour intensive PK sampling was performed on day 7 of each sequence following observed dosing and a standardized meal. PK parameters were determined using non-compartmental methods and compared using paired t-tests. Bioequivalence for area under the curve (AUCtau) and maximum concentration (Cmax) were also assessed. NCT02404805. RESULTS: Twenty-four subjects completed all three sequences. Dolutegravir trough was increased 24% (P = 0.0003) with simeprevir. Dolutegravir AUCtau was increased 15% (P = 0.002), but was deemed bioequivalent as the 90% CI for the geometric mean ratio was 107%-123%. Dolutegravir Cmax was bioequivalent. Simeprevir PK was unaffected by dolutegravir. There were no discontinuations due to adverse events and all adverse events were mild to moderate in severity. CONCLUSIONS: Dolutegravir trough was increased slightly with simeprevir, but AUCtau was bioequivalent. Despite the increase in trough, dolutegravir concentrations were well within the range with established safety data. Suggesting that simeprevir and dolutegravir can be safely co-administered.

The State of Health, Burnout, Healthy Behaviors, Workplace Wellness Support, and Concerns of Medication Errors in Pharmacists During the COVID-19 Pandemic.

OBJECTIVES: The aims of the study were to describe the well-being and lifestyle behaviors of health-system pharmacists during the COVID-19 pandemic and to determine the relationships among well-being, perceptions of workplace wellness support, and self-reported concern of having made a medication error. METHODS: Pharmacist ( N = 10,445) were randomly sampled for a health and well-being survey. Multiple logistic regression assessed associations with wellness support and concerns of medication error. RESULTS: The response rate was 6.4% ( N = 665). Pharmacists whose workplaces very much supported wellness were 3× more likely to have no depression, anxiety, and stress; 10× more likely to have no burnout; and 15× more likely to have a higher professional quality of life. Those with burnout had double the concern of having made a medication error in the last 3 months. CONCLUSIONS: Healthcare leadership must fix system issues that cause burnout and actualize wellness cultures to improve pharmacist well-being.

Medication utilization in patients in New York hospitals during the COVID-19 pandemic.

PURPOSE: Utilization of hydroxychloroquine, chloroquine, and supportive therapy drugs in hospitals in New York during the early weeks of the coronavirus disease 2019 (COVID-19) pandemic was analyzed. SUMMARY: Drug utilization trends for 7 medications used to treat patients with suspected or confirmed COVID-19 at 47 New York hospitals were identified. The data demonstrated sharp increases in aggregate utilization of hydroxychloroquine and chloroquine and the number of patients receiving either drug beginning on March 15, with a notable 20% median increase per day through March 31. The net quantity of drug charge units per day for midazolam, propofol, ketamine, cisatracurium, and fentanyl also increased during the study period. Following peak utilization, use of all study drugs decreased at different times throughout April 2020. The data were used to provide information to various stakeholders in the drug supply chain during the initial surge of the pandemic. CONCLUSION: This analysis describes the increased use, beginning in mid-March 2020, of hydroxychloroquine, chloroquine, midazolam, propofol, ketamine, cisatracurium, and fentanyl in 47 hospitals in New York State. The increased utilization of supportive therapy drugs was consistent with the surge in patients with presumed or confirmed COVID-19 during the study period. These data and observations can help clinicians, health-system leaders, manufacturers, wholesalers, and policymakers understand the impact of current and future pandemics on the drug supply chain.

Stability of Ribavirin for Inhalation Packaged in Syringes or Glass Vials when Stored Frozen, Refrigerated, and at Room Temperature.

The primary aim of this study was to investigate ribavirin solution for inhalation stability under three different conditions (frozen, refrigerated, room temperature) over a 45-day period. A ribavirin 6000-mg vial was reconstituted with 90 mL of Sterile Water for Injection per the package insert to yield a concentration of approximately 67 mg/mL. The solution was then placed in either syringes or empty glass vials and stored in the freezer (-20°C), in the refrigerator (~0°C to 4°C), or at room temperature (~20°C to 25°C). Original concentrations were measured on day 0 and subsequent concentrations were measured on day 2, 14, and 45 utilizing a validated liquid chromatography with tandem mass spectrometry assay. All analyses were performed in triplicate for each storage condition. Additionally, at each time point the physical stability was evaluated and the pH of solution was measured. The solution was considered stable if =90% of the original concentration was retained over the study period. A validated liquid chromatography with tandem mass spectrometry analysis demonstrated that >95% of the original ribavirin concentration was preserved over the 45-day period for all study conditions. The ribavirin concentration remained within the United States Pharmacopeia (USP)-required range of 95% to 105% of the original labeled product amount throughout the entire study period for all study conditions. Precipitation of ribavirin was noted during the thawing cycle for frozen samples, but the drug went back into solution once the thawing process was completed. No changes in color or turbidity were observed in any of the prepared solutions. Values for pH remained stable over the study period and ranged from 4.1 to 5.3. Ribavirin for inhalation solution is physically and chemically stable for at least 45 days when frozen, refrigerated, or kept at room temperature after reconstitution to a concentration of approximately 67 mg/mL and placed in syringes or glass vials.