A case of extrapyramidal side effects due to possible paliperidone: voriconazole interaction

IF 1 Q4 PHARMACOLOGY & PHARMACY

Journal of Pharmacy Practice and Research Pub Date : 2023-11-10 DOI:10.1002/jppr.1892

Louise Beilby BPharm, GradCertPharmPrac, Lucy Arno BPharm (Hons), MHA

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引用次数: 0

Abstract

Background

It is thought that paliperidone, an active metabolite of risperidone, has limited potential for pharmacokinetic drug–drug interactions (DDIs) due to minimal metabolism by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6). However, DDIs have been reported and include a theoretical interaction between paliperidone and voriconazole based on interactions between risperidone and strong CYP3A4 inhibitor azoles.

Aim

To describe the first recorded DDI between paliperidone and voriconazole leading to extrapyramidal side effects (EPSEs).

Clinical details

A 34-year-old male presented with febrile neutropenia presumed due to clozapine. Clozapine was ceased and paliperidone commenced with voriconazole added to the patient's empiric piperacillin/tazobactam therapy due to a suspected fungal infection. Two days after starting voriconazole, the patient developed hypertonia and hyperreflexia in all limbs, thought most likely to be antipsychotic induced EPSEs. Paliperidone was withheld and EPSEs resolved.

Outcomes

The patient had previously tolerated long-term paliperidone at higher doses, prior to transitioning to clozapine. The development of EPSEs occurred two days post azole initiation, indicating a probable paliperidone adverse drug reaction (ADR) due to strong CYP3A4 inhibition by voriconazole. This case appears to be the first documented report of this previous theoretical DDI in practice. Further studies, including therapeutic drug monitoring, are required to confirm findings.

Conclusion

Paliperidone may be affected by pharmacokinetic drug–drug interactions and patients should be monitored for ADRs when CYP3A4 inhibitors are concomitantly administered.

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帕潘立酮：伏立康唑可能相互作用导致的锥体外系副作用病例

背景据认为，由于细胞色素 P450 3A4 (CYP3A4) 和细胞色素 P450 2D6 (CYP2D6) 的代谢作用极小，利培酮的活性代谢产物帕利哌酮发生药代动力学药物相互作用 (DDI) 的可能性有限。然而，DDIs 已有报道，其中包括根据利培酮与强 CYP3A4 抑制剂唑类之间的相互作用而得出的帕利哌酮与伏立康唑之间的理论相互作用。目的描述帕利哌酮与伏立康唑之间导致锥体外系副作用（EPSE）的首次DDI记录。临床详情一名34岁的男性因发热性中性粒细胞减少症就诊，推测是氯氮平所致。由于怀疑是真菌感染，患者停用了氯氮平，开始服用帕利哌酮，并在哌拉西林/他唑巴坦的经验性治疗基础上加用了伏立康唑。开始服用伏立康唑两天后，患者出现四肢肌张力亢进和反射亢进，被认为很可能是抗精神病药物诱发的EPSE。患者停用帕潘立酮后，EPSE症状消失。结果患者在转用氯氮平之前曾长期耐受较高剂量的帕潘立酮。EPSE发生在开始使用唑类药物两天后，这表明帕利哌酮可能是由于伏立康唑对CYP3A4的强烈抑制而引起的药物不良反应（ADR）。本病例似乎是以前理论上的 DDI 在实践中的首次有据可查的报告。需要进一步研究，包括治疗药物监测，以确认研究结果。结论帕潘立酮可能会受到药代动力学药物相互作用的影响，当同时服用 CYP3A4 抑制剂时，应监测患者的 ADR。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmacy Practice and Research Health Professions-Pharmacy

CiteScore

1.60

自引率

9.50%

发文量

期刊介绍： The purpose of this document is to describe the structure, function and operations of the Journal of Pharmacy Practice and Research, the official journal of the Society of Hospital Pharmacists of Australia (SHPA). It is owned, published by and copyrighted to SHPA. However, the Journal is to some extent unique within SHPA in that it ‘…has complete editorial freedom in terms of content and is not under the direction of the Society or its Council in such matters…’. This statement, originally based on a Role Statement for the Editor-in-Chief 1993, is also based on the definition of ‘editorial independence’ from the World Association of Medical Editors and adopted by the International Committee of Medical Journal Editors.