Service de pharmacologie-toxicologie, CHU Nantes, Nantes, France.
Inserm UMRS1144, University of Paris, Paris, France.
Clin Toxicol (Phila). 2021 Sep;59(9):786-793. doi: 10.1080/15563650.2021.1878206. Epub 2021 Feb 8.
Paliperidone palmitate (PP), a long-acting intramuscular formulation of paliperidone, has been marketed in Europe within the last 10 years and provides an important treatment option for patients with schizophrenia.Our aim was to describe PP-related adverse drug reactions (ADRs) leading to death or life-threatening events, specifying their main clinical and pharmacological characteristics.
This observational study was a retrospective review of PP-related ADRs in the French pharmacovigilance database between January 1, 2013, and December 31, 2019.
Out of 473 PP-related ADRs, we identified 13 deaths and 14 life-threatening events. ADRs were primarily cardiorespiratory ( = 17; 63%). Other symptoms observed were mainly metabolic ( = 4), digestive ( = 4), and neurological ( = 4). Cardiorespiratory symptoms were generally observed within first 6 months after initiation of treatment (11 out of 17 cases), unlike metabolic disorders (all 4 cases 12-21 months after initiation). Cardiac arrests and sudden unexpected deaths occurred 10-14 days after the last PP once-monthly injection (23 cases) or 11-24 days after the last PP three-monthly injection (remaining 4 cases). No PP blood concentration assays were performed for these patients.
In this study, PP-related ADRs leading to death or life-threatening events mainly presented with cardiorespiratory symptoms and tended to occur in the first 6 months after the initiation of treatment and within postadministration periods aligned with peak plasma PP concentrations. The hypothesis of supratherapeutic drug concentrations following intramuscular PP injection must be raised.
PP-related ADRs leading to death or life-threatening events mainly presented with cardiorespiratory symptoms. Cardiac arrests and sudden unexpected deaths following initiation of PP treatment could be due to supratherapeutic drug concentrations. This study highlights the need to monitor blood concentrations of PP.Key pointsAdverse reactions to paliperidone palmitate can lead to death or life-threatening events.It is hypothesized that cardiac arrests and sudden unexpected deaths following initiation of paliperidone palmitate treatment could be due to supratherapeutic drug concentrations.This paper proposes the need to monitor blood concentrations of paliperidone palmitate in future studies.
棕榈酸帕利哌酮（PP）是一种长效肌内注射制剂，在过去 10 年中已在欧洲上市，为精神分裂症患者提供了重要的治疗选择。我们的目的是描述与棕榈酸帕利哌酮相关的导致死亡或危及生命的药物不良反应（ADR），并详细说明其主要的临床和药理学特征。
这是一项回顾性研究，对 2013 年 1 月 1 日至 2019 年 12 月 31 日期间法国药物警戒数据库中与棕榈酸帕利哌酮相关的 ADR 进行了分析。
在 473 例与棕榈酸帕利哌酮相关的 ADR 中，我们确定了 13 例死亡和 14 例危及生命的事件。ADR 主要为心肺症状（ = 17；63%）。其他观察到的症状主要为代谢异常（ = 4）、消化异常（ = 4）和神经异常（ = 4）。心肺症状通常在治疗开始后 6 个月内（17 例中的 11 例）观察到，而代谢紊乱则不然（所有 4 例均在治疗开始后 12-21 个月）。心脏骤停和突发性意外死亡发生在最后一次每月注射棕榈酸帕利哌酮后 10-14 天（23 例）或最后一次每三个月注射棕榈酸帕利哌酮后 11-24 天（其余 4 例）。未对这些患者进行棕榈酸帕利哌酮的血药浓度检测。
在这项研究中，与棕榈酸帕利哌酮相关的导致死亡或危及生命的 ADR 主要表现为心肺症状，且倾向于在治疗开始后 6 个月内和给药后与血浆棕榈酸帕利哌酮浓度峰值相一致的时间段内发生。因此，需要提出在肌肉注射棕榈酸帕利哌酮后药物浓度超治疗范围的假设。
与棕榈酸帕利哌酮相关的导致死亡或危及生命的 ADR 主要表现为心肺症状。棕榈酸帕利哌酮治疗开始后出现的心脏骤停和突发性意外死亡可能与药物浓度超治疗范围有关。这项研究强调了在未来的研究中监测棕榈酸帕利哌酮血药浓度的必要性。
棕榈酸帕利哌酮的不良反应可导致死亡或危及生命事件。假设棕榈酸帕利哌酮治疗开始后出现的心脏骤停和突发性意外死亡可能与药物浓度超治疗范围有关。本文提出需要在未来的研究中监测棕榈酸帕利哌酮的血药浓度。
