Therapeutic Advances in Drug Safety

The rapid increase in prescribing and use of opioids for noncancer pain has coincided with an increase in opioid-related adverse drug events (ADEs). The objective of our study was to describe ADEs related to tapentadol and oxycodone/naloxone spontaneously reported to the Australian Therapeutic Goods Administration (TGA).

Public case detail reports for tapentadol (September 2013–March 2017) and oxycodone/naloxone (April 2011–March 2017) were sourced from the TGA. The total number of public case detail reports for tapentadol were 104 and 249 for oxycodone/naloxone. Demographic characteristics of patients, concomitant medications, causality assessment and outcome were described for each opioid according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class.

The most prevalent ADEs for tapentadol were nervous system disorders (n = 52, 50%), psychiatric (n = 34, 32.7%), gastrointestinal (n = 18, 17.3%), and general disorders and administration site conditions (n = 21, 20.2%). Sixteen (23.2%) of 69 nervous system disorders reaction terms were consistent with serotonin syndrome of which 14 (87.5%) involved documented coadministration with another serotonergic medication. The most prevalent ADEs for oxycodone/naloxone were psychiatric disorders (n = 78, 31.3%), gastrointestinal (n = 73, 29.3%), general disorders and administration site conditions (n = 87, 35%), and nervous system disorders (n = 62, 24.9%). There were 40 (16%) public case detail reports for oxycodone/naloxone with the MedDRA reaction terms ‘drug withdrawal syndrome’ and ‘withdrawal syndrome’.

The profiles of spontaneous ADE reports for tapentadol and oxycodone/naloxone are largely consistent with their premarketing randomized controlled studies and profiles of opioids in general. Further research into the risk of serotonin syndrome with tapentadol use is warranted. The ADEs suggest clinicians should be cautious when switching patients to oxycodone/naloxone from other opioids.

Medication safety strategies involving trigger alerts have demonstrated potential in identifying drug-related hazardous conditions (DRHCs) and preventing adverse drug events in hospitalized patients. However, trigger alert effectiveness between intensive care unit (ICU) and general ward patients remains unknown. The objective was to investigate trigger alert performance in accurately identifying DRHCs associated with laboratory abnormalities in ICU and non-ICU settings.

This retrospective, observational study was conducted at a university hospital over a 1-year period involving 20 unique trigger alerts aimed at identifying possible drug-induced laboratory abnormalities. The primary outcome was to determine the positive predictive value (PPV) in distinguishing drug-induced abnormal laboratory values using trigger alerts in critically ill and general ward patients. Aberrant lab values attributed to medications without resulting in an actual adverse event ensuing were categorized as a DRHC.

A total of 634 patients involving 870 trigger alerts were included. The distribution of trigger alerts generated occurred more commonly in general ward patients (59.8%) than those in the ICU (40.2%). The overall PPV in detecting a DRHC in all hospitalized patients was 0.29, while the PPV in non-ICU patients (0.31) was significantly higher than the critically ill (0.25) (p = 0.03). However, the rate of DRHCs was significantly higher in the ICU than the general ward (7.49 versus 0.87 events per 1000 patient days, respectively, p < 0.0001). Although most DRHCs were considered mild or moderate in severity, more serious and life-threatening DRHCs occurred in the ICU compared with the general ward (39.8% versus 12.4%, respectively, p < 0.001).

Overall, most trigger alerts performed poorly in detecting DRHCs irrespective of patient care setting. Continuous process improvement practices should be applied to trigger alert performance to improve clinician time efficiency and minimize alert fatigue.