Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure.

Background: If HIV patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is crushed and dissolved prior to administration. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq®, referred to as TRI); therefore, crushing of TRI is not recommended. Objectives: To investigate whether the TRI fixed-dose combination tablet can be crushed and combined with enteral nutrition without influencing pharmacokinetics (PK). Methods: We carried out an open-label, three-period, randomized, single-dose, crossover trial in 22 healthy adult volunteers. Subjects randomly received whole-tablet TRI with fasting (reference), crushed and suspended TRI with fasting or crushed and suspended TRI with oral intake of enteral nutrition. Bioequivalence criteria (80%-125% acceptance range) of AUC0-∞ and Cmax were used. ClinicalTrials.gov: NCT02569346. Results: Crushing TRI leads to higher dolutegravir exposure (AUC0-∞: +26% and Cmax: +30%) and, if crushed TRI is combined with enteral nutrition, to a decrease in abacavir Cmax (-17%). Lamivudine concentrations were not affected as geometric mean ratios with 90% CIs fell within the 80%-125% range. Conclusions: Bioequivalence could not be demonstrated for a crushed and suspended tablet or a crushed and suspended tablet with oral intake of enteral nutrition compared with whole-tablet TRI with fasting. Both scenarios led to higher dolutegravir exposure, but this did not exceed exposure after intake with food or in twice-daily dosing. In our opinion, TRI can be crushed for patients with swallowing difficulties and can be simultaneously administered with enteral nutrition.

Prolonged oxycodone use and potential risk factors in postoperative patients: a case control study.

BACKGROUND: Prolonged exposure to opioids has a negative influence on the physical and mental health of a person. Currently, little is known about the risk of prolonging opioids after first postoperative use. AIM: A study was conducted to define the proportion of postoperative patients that use oxycodone longer than prescribed to determine risk factors of prolonged use. METHOD: This retrospective single-center nested case-control study was performed in the Elisabeth Tweesteden Hospital. The study population consisted of postoperative adult patients who received an oxycodone prescription at discharge between April 2018 and June 2020. The primary outcome was the proportion of patients with at least one refill of oxycodone during a follow-up period of 30 days. The secondary outcome was the association of potential risk factors with oxycodone refills. Univariate and multivariate logistic regression analyses were performed to determine the association between the variables and outcome. RESULTS: 1203 patients were included of which 280 (23.3%) received one or more refill. Age (adjusted odds ratio 1.01 [95% confidence interval 1.00-1.02]), length of stay (1.10 [1.06-1.14], a Numeric Rating Scale pain score of four or higher (1.52 [1.14-2.01]), use of the continuous release form only (2.15 [1.60-2.89]) and admission to various hospital departments were associated with a refill of oxycodone . CONCLUSION: The proportion of patients with a refill of oxycodone is 23.3%. This could result in chronic oxycodone use and potential misuse. Patients with the determined risk factors may be a suitable population for future interventions to minimize prolonged use.

A multifaceted clinical decision support intervention to improve adherence to thromboprophylaxis guidelines.

Background Venous thromboembolism is a potentially fatal complication of hospitalisation, affecting approximately 3% of non-surgical patients. Administration of low molecular weight heparins to the appropriate patients adequately decreases venous thromboembolism incidence, but guideline adherence is notoriously low. Objective To determine the effect of a multifaceted intervention on thromboprophylaxis guideline adherence. The secondary objective was to study the effect on guideline adherence specifically in patients with a high venous thromboembolism risk. As an exploratory objective, we determined how many venous thromboembolisms may be prevented. Setting A Dutch general teaching hospital. Method A prospective study with a pre- and post-intervention measurement was conducted. A multifaceted intervention, consisting of Clinical Decision Support software, a mobile phone application, monitoring of duplicate anticoagulants and training, was implemented. Guideline adherence was assessed by calculating the Padua prediction and Improve bleeding score for each patient. The number of preventable venous thromboembolisms was calculated using the incidences of venous thromboembolism in patients with and without adequate thromboprophylaxis and extrapolated to the annual number of admitted patients. Main outcome measure Adherence to thromboprophylaxis guidelines in pre- and post-intervention measurements. Results 170 patients were included: 85 in both control and intervention group. The intervention significantly increased guideline adherence from 49.4 to 82.4% (OR 4.78; 95%CI 2.37-9.63). Guideline adherence in the patient group with a high venous thromboembolism risk also increased significantly from 54.5 to 84.3% (OR 2.46; 95%CI 1.31-4.62), resulting in the potential prevention of ± 261 venous thromboembolisms per year. Conclusions Our multifaceted intervention significantly increased thromboprophylaxis guideline adherence.

Brief Report: Pharmacokinetics of Crushed Elvitegravir Combination Tablet Given With or Without Enteral Nutrition.

We investigated whether a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovirDF (Stribild) can be crushed and combined with enteral nutrition without influencing pharmacokinetics. This was an open-label, 3-period, single-dose, randomized, crossover trial in 24 healthy volunteers. Subjects received Stribild whole tablet with breakfast (reference), crushed/suspended Stribild + breakfast, crushed/suspended Stribild + enteral nutrition. Crushed/suspended Stribild + enteral nutrition was bioequivalent (90% confidence interval between 80% and 125%) with a whole Stribild tablet. Crushed/suspended Stribild + breakfast showed bioequivalence for the area under the curve (AUC0-32), but not for maximum concentration (Cmax) (considered not clinically relevant). Patients with swallowing difficulties or an enteral feeding tube can use crushed and suspended Stribild tablets.

Identification of drug-related problems by a clinical pharmacist in addition to computerized alerts.

BACKGROUND: Both clinical pharmacists and computerized physician order entry systems with clinical decision support (CPOE/CDSS) can reduce drug-related problems (DRPs). However, the contribution of a clinical pharmacist in addition to CPOE/CDSS has not been established in a prospective study. OBJECTIVE: To determine which DRPs can be identified by a clinical pharmacist in a setting with routine use of CPOE/CDSS. SETTING: Two surgical and two neurological wards in St. Elisabeth hospital, a 600-bed teaching hospital in the Netherlands. METHODS: In this observational prospective follow-up study a clinical pharmacist reviewed the pharmacotherapy of patients admitted to surgical and neurological wards to identify DRPs (i.e. medication errors and adverse drug events) and discussed the relevance of identified problems and interventions to resolve these with the responsible physician. Acceptance of the proposed interventions and the presence of alerts in CPOE/CDSS were assessed. Primary outcome was the proportion of DRPs identified by the clinical pharmacist that also triggered a CPOE/CDSS alert. Differences between the DRPs that generated an alert and those that did not were expressed as relative risks or analyzed with Chi square statistics or Mann-Whitney U tests. MAIN OUTCOME MEASURE: The proportion of drug-related problems identified by the clinical pharmacist that also generated an alert in the CPOE/CDSS. RESULTS: During 1206 medication reviews, 442 potential DRPs were identified; 286 (65 %) DRPs were considered relevant and 247 (56 %) of the proposed interventions were accepted. A CPOE/CDSS alert was generated for 35 (8 %) of the DRPs the clinical pharmacist identified. The only difference between problems that triggered an alert and those that did not was the class of the DRP (indication 23 vs. 36 %, effectiveness 23 vs. 13 %, safety 23 vs. 10 % and pharmaceutical care issues 31 vs. 42 %, p = 0.02). CPOE/CDSS triggered 623 additional alerts that were handled during routine pharmacy service. CONCLUSIONS: As most DRPs identified by a clinical pharmacist were not detected in daily clinical practice by CPOE/CDSS, a clinical pharmacist contributes to reducing DRPs. The sensitivity of CPOE/CDSS to detect certain classes of problems should be optimized.