LAUSR

Sir, We would like to report a case of high opioids tolerance due to abuse of transmucosal fentanyl in a patient without history of drug abuse. A 59-year-old man (75 kg) without history of drug abuse was admitted to the Emergency Department in May 2016 because of a withdrawal syndrome (lacrimation, rhinorrhea, hot/ cold sensations, no muscular or articular pain). The patient explained that he attempted a self-withdrawal of his fentanyl consumption. He reported the use of transmucosal fentanyl (TMF) medication (Pecfent©, fentanyl pectin nasal spray) since October 2015. He consumed the TMF prescribed to his wife for terminal colorectal cancer. The first reason for use was the curiosity and the search of anxiolytic effect in this particular context. Such as fentanyl relieved the patient’s pain with a feeling of well-being, the patient gradually increased the dosages and asked his doctor to obtain prescriptions. The patient was addressed by his physician to the addictology center because of behavior change. Hospitalization for fentanyl withdrawal was decided, and in June 2016, he was hospitalized in an addictology unit. At that time, he smoked 5 to 15 cigarettes/day, was treated by zolpidem (10 mg/night), and took up to eight daily doses of fentanyl (400 μg by dose) for maximal recommended doses of four per day. Bromazepam 6mg/day and paroxetine 20mg/day were introduced few days before the withdrawal. During the hospitalization, methadone syrup 10 mg daily was introduced with titration. Methadone interdoses were taken by the patient due to signs of opiate withdrawal. The withdrawal symptoms disappeared with a maintenance dosage of methadone of 20 mg/day. This case was notified to the regional addictovigilance center as recommended by the French health authorities [1]. At the beginning of the hospitalization, toxicological urine drug screening by immune-enzymology assay was negative for barbiturate, benzodiazepines, methadone, buprenorphine, amphetamines, cocaine, opiates, cannabis, and alcohol. Chromatographic screening (LC-MS/MS) revealed the presence of fentanyl and norfentanyl (plasma fentanyl concentration 21.4 ng/ml, norfentanyl 1.5 ng/ml). Fentanyl and norfentanyl plasma levels measured at day 1, day 3, and day 5 of hospitalization are reported in the Table 1. The fentanyl pectin nasal spray is available at doses of 100 and 400 μg/spray. It was approved for breakthrough pain (BTP) in adults with chronic cancer pain, also treated with long-acting opioids. The level of fentanyl consumption has increased during the past decade in the USA, Canada, and European countries [2]. Cases of TMF misuse reported in the literature occurred both in patients in the setting of BTP and in off-label use (non-cancer chronic pain) [3, 4]. In our case, the context of the TMF abuse is somewhat peculiar because the patient started to use TMF without a medical prescription by the diversion of his wife’ medication. The rapid onset of effects (15–20 min), the ease of use, and the efficacy of this strong opioid make this form of intranasal fentanyl a drug with a high risk of misuse, and addiction, even in nonaddict subjects. The therapeutic plasma concentrations of fentanyl are varying according to the dose and the delivery formulation. Transdermal formulations lead to therapeutic concentrations between 0.3 and 1.5 ng/ml [5]. Intravenous administrations Electronic supplementary material The online version of this article (doi:10.1007/s00228-017-2272-9) contains supplementary material, which is available to authorized users.