Characteristics of fatal tapentadol-related toxicity in Australia

Tapentadol is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe pain. The study aimed to determine the characteristics of Australian toxicity deaths related to tapentadol.

All cases in which tapentadol use was coded contributory to death (n = 159) were retrieved from the National Coronial Information System (1 July 2000-31 December 2020).

The mean age was 48.5 (18-81) and 56% were female. Documented histories of problems with chronic pain (66%), mental health (60.4%), substance use (44%) and injecting drug use (23.3%) were common. The majority of deaths were deemed unintentional (76.1%) and in 18.9% pre-existing disease was co-contributory. The median peripheral blood tapentadol concentration was 1.00 mg L^-1 (0.02-47.00), and the median aortic concentration was 2.05 mg L^-1 (0.10-30.00). In all cases, psychoactive drugs other than tapentadol were also detected, most commonly antidepressants (72.3%), opioids (66.7%), hypnosedatives (64.2%) and gabapentinoids (43.4%). Of cases where autopsies were conducted, 27.7% were diagnosed with cardiomegaly and 18.5% with severe coronary artery stenosis. Pulmonary oedema (68.1%), aspiration of vomitus (39.5%) and acute pneumonia (26.9%) were common.

The typical tapentadol-related toxicity death involved unintentional death in the presence of multiple drugs, although a notable minority were intentional self-harm. Multiple morbidities were common. The identification and characteristics of these cases indicate that the adverse event profile of tapentadol needs to be considered in the setting of polypharmacy.