Case Report of a Fatal Intoxication by Nucynta

Abstract

Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe acute pain. Its efficacy is believed to be due to μ-opioid receptor agonist activity and inhibition of norepinephrine reuptake resulting in increased norepinephrine concentrations. There is only one other case in the literature relating to the toxicity of this agent or report of a fatality. This case report documents a case in which tapentadol was identified as the cause of death. The tapentadol concentration found in the heart blood submitted in this case was more than 20 times the upper limit of the therapeutic range. Possible mechanisms of death include respiratory depression, central nervous system depression, and serotonin syndrome. Based on the scene investigation and autopsy findings in this case, the medical examiner determined that the cause of death was narcotic (Nucynta) intoxication and the manner of death was undetermined.

Cardiac Arrest Following Drug Abuse with Intravenous Tapentadol: Case Report and Literature Review

“…A study by Dart et al found that rates of drug abuse with intermediate release tapentadol were low during the first 24 months after its launch [ 15 ]. Published reports of lethal tapentadol overdoses include a case report by Franco et al, which describes a patient death attributed to tapentadol intoxication, possibly leading to respiratory depression, central nervous system depression, and serotonin syndrome [ 16 ]. Another published case reported by Kemp et al described a patient death following intravenous injection of tapentadol [ 17 ].…”

Comparative pharmacology and toxicology of tramadol and tapentadol

“…The causes of seizures, after tramadol exposure, are unclear, although some studies, using different models, have associated tramadol antidepressant activity with seizures (Reeves and Cox, ; Reichert et al., ). Besides the adverse reactions discussed so far, more severe toxicological effects, with even more serious implications, have been reported, including respiratory depression, serotonin syndrome (Sansone and Sansone, ; Pilgrim et al., ; Beakley et al., ) and fatal intoxications (Tjaderborn et al., ; Pilgrim et al., ; Larson et al., ; Costa et al., ; Kemp et al., ; Pinho et al., ; Franco et al., ; Cantrell et al., ).…”

“…Pulmonary alterations (namely pulmonary oedema) were also reported in a case of tapentadol and oxycodone intoxication, where tapentadol concentrations reached 1.1 mg/L in peripheral blood, 1.3 mg/L in central blood, 9.9 mg/kg in the liver, 0.94 mg/L in vitreous humour, and 88 mg/L in urine (Cantrell et al., ). Another fatal intoxication by tapentadol was reported by Franco et al., who suggested its acute ingestion; the events responsible for death included respiratory and CNS depression and serotonin syndrome, with tapentadol concentration in cardiac blood being as high as 6600 ng/mL, more than 20 times the higher limit of its therapeutic range (Franco et al., ). These authors also reported autolytic changes in kidney, suggestive of tapentadol nephrotoxicity (Franco et al., ).…”

“…Another fatal intoxication by tapentadol was reported by Franco et al., who suggested its acute ingestion; the events responsible for death included respiratory and CNS depression and serotonin syndrome, with tapentadol concentration in cardiac blood being as high as 6600 ng/mL, more than 20 times the higher limit of its therapeutic range (Franco et al., ). These authors also reported autolytic changes in kidney, suggestive of tapentadol nephrotoxicity (Franco et al., ).…”

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

“…Although tramadol and tapentadol are claimed to have better safety profiles than their opioid peers, several adverse events have been reported, including nausea, vomiting, dizziness, seizures, dyspnea, respiratory depression [ 1 , 2 , 14 , 47 , 48 , 49 , 50 , 51 ], and even fatal cases [ 10 , 42 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. In the VigiBase™ World Health Organization (WHO) Global Database of Individual Case Safety Reports concerning 5-HT toxicity, tramadol ranks 1st and tapentadol ranks 3rd (with 647 and 115 cases out of 1641, respectively) as the only suspected cause or amongst other drugs, and 1st and 2nd (with 62 and 42 cases out of 147, respectively) as the only suspected cause [ 34 , 69 ].…”