A tapentadol related fatality: Case report with postmortem concentrations

Cantrell, F. Lee; Mallett, Phyllis; Aldridge, Lenore; Verilhac, Kimi; McIntyre, Iain M.

doi:10.1016/j.forsciint.2016.08.020

Cited by 17 publications

(16 citation statements)

References 13 publications

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“…Besides these findings, foam cone was observed in the nose and mouth, and pulmonary congestion was detected in an autopsy context, for which tapentadol might be regarded as a possible lung damage‐triggering factor (Kemp et al., ; Faria 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., ).…”

Section: Toxicitymentioning

confidence: 90%

“…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., ).…”

Section: Toxicitymentioning

confidence: 99%

See 1 more Smart Citation

Comparative pharmacology and toxicology of tramadol and tapentadol

Faria

Barbosa

Moreira

et al. 2018

European Journal of Pain

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Section: Toxicitymentioning

confidence: 90%

Section: Toxicitymentioning

confidence: 99%

Comparative pharmacology and toxicology of tramadol and tapentadol

Faria

Barbosa

Moreira

et al. 2018

European Journal of Pain

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“…Another published case reported by Kemp et al described a patient death following intravenous injection of tapentadol [ 17 ]. Also, Cantrell et al reported a case in which elevated post-mortem blood tapentadol levels were found following a patient death [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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

2017

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Patient: Female, 32Final Diagnosis: Cardiac arrest after intravenous tapentadol abuseSymptoms: HeadacheMedication: —Clinical Procedure: Tapentadol drug levels in serumSpecialty: Forensic MedicineObjective:Rare diseaseBackground:Tapentadol is a centrally acting opioid analgesic, with a dual mode of action, as a norepinephrine reuptake inhibitor and an agonist of the μ-opioid receptor (MOR). Tapentadol is used for the management of musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.Case Report:A 32-year-old woman attended hospital for evaluation of an intractable headache. Computed tomography and magnetic resonance imaging of the brain were negative. She was found unresponsive in the bathroom on the day following hospital admission, and despite resuscitative measures, the patient died following cardiac arrest. Autopsy toxicology revealed significantly elevated levels of tapentadol, and bedside evidence suggested that the patient had self-administered this medication intravenously before her death.Conclusions:We report a rare adverse effect of tapentadol causing respiratory depression leading to cardiac arrest. Medical examiners and forensic toxicologists should be aware of the toxicity of this novel opiate drug.

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“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Tramadol and tapentadol are fully synthetic and extensively used analgesic opioids, presenting enhanced therapeutic and safety profiles as compared with their peers. However, reports of adverse reactions, intoxications and fatalities have been increasing. Information regarding the molecular, biochemical, and histological alterations underlying their toxicological potential is missing, particularly for tapentadol, owing to its more recent market authorization. Considering the paramount importance of liver and kidney for the metabolism and excretion of both opioids, these organs are especially susceptible to toxicological damage. In the present study, we aimed to characterize the putative hepatic and renal deleterious effects of repeated exposure to therapeutic doses of tramadol and tapentadol, using an in vivo animal model. Male Wistar rats were randomly divided into six experimental groups, composed of six animals each, which received daily single intraperitoneal injections of 10, 25 or 50 mg/kg tramadol or tapentadol (a low, standard analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively). An additional control group was injected with normal saline. Following 14 consecutive days of administration, serum, urine and liver and kidney tissue samples were processed for biochemical, metabolic and histological analysis. Repeated administration of therapeutic doses of both opioids led to: (i) increased lipid and protein oxidation in liver and kidney, as well as to decreased total liver antioxidant capacity; (ii) decreased serum albumin, urea, butyrylcholinesterase and complement C3 and C4 levels, denoting liver synthesis impairment; (iii) elevated serum activity of liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase, as well as lipid profile alterations, also reflecting hepatobiliary commitment; (iv) derangement of iron metabolism, as shown through increases in serum iron, ferritin, haptoglobin and heme oxygenase-1 levels. In turn, elevated serum cystatin C, decreased urine creatinine output and increased urine microalbumin levels were detected upon exposure to tapentadol only, while increased serum amylase and urine N-acetyl-β-D-glucosaminidase activities were observed for both opioids. Collectively, these results are compatible with kidney injury. Changes were also found in the expression levels of liver- and kidney-specific toxicity biomarker genes, upon exposure to tramadol and tapentadol, correlating well with alterations in lipid profile, iron metabolism and glomerular and tubular function. Histopathological analysis evidenced sinusoidal dilatation, microsteatosis, mononuclear cell infiltrates, glomerular and tubular disorganization, and increased Bowman’s spaces. Although some findings are more pronounced upon tapentadol exposure, our study shows that, when compared with acute exposure, prolonged administration of both opioids smooths the differences between their toxicological effects, and that these occur at lower doses within the therapeutic range.

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A tapentadol related fatality: Case report with postmortem concentrations

Cited by 17 publications

References 13 publications

Comparative pharmacology and toxicology of tramadol and tapentadol

Comparative pharmacology and toxicology of tramadol and tapentadol

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

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

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