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Clinically Relevant Interactions Between Ritonavir-Boosted Nirmatrelvir and Concomitant Antiseizure Medications: Implications for the Management of COVID-19 in Patients with Epilepsy
Clinical Pharmacokinetics ( IF 4.6 ) Pub Date : 2022-07-27 , DOI: 10.1007/s40262-022-01152-z
Maor Wanounou 1, 2 , Yoseph Caraco 1 , René H Levy 3 , Meir Bialer 2, 4 , Emilio Perucca 5, 6
Affiliation  

Ritonavir-boosted nirmatrelvir (RBN) has been authorized recently in several countries as an orally active anti-SARS-CoV-2 treatment for patients at high risk of progressing to severe COVID-19 disease. Nirmatrelvir is the active component against the SARS-CoV-2 virus, whereas ritonavir, a potent CYP3A inhibitor, is intended to boost the activity of nirmatrelvir by increasing its concentration in plasma to ensure persistence of antiviral concentrations during the 12-hour dosing interval. RBN is involved in many clinically important drug–drug interactions both as perpetrator and as victim, which can complicate its use in patients treated with antiseizure medications (ASMs). Interactions between RBN and ASMs are bidirectional. As perpetrator, RBN may increase the plasma concentration of a number of ASMs that are CYP3A4 substrates, possibly leading to toxicity. As victims, both nirmatrelvir and ritonavir are subject to metabolic induction by concomitant treatment with potent enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital and primidone). According to US and European prescribing information, treatment with these ASMs is a contraindication to the use of RBN. Although remdesivir is a valuable alternative to RBN, it may not be readily accessible in some settings due to cost and/or need for intravenous administration. If remdesivir is not an appropriate option, either bebtelovimab or molnupiravir may be considered. However, evidence about the clinical efficacy of bebtelovimab is still limited, and molnupiravir, the only orally active alternative, is deemed to have appreciably lower efficacy than RBN and remdesivir.



中文翻译:

利托那韦增强的 Nirmatrelvir 与伴随的抗癫痫药物之间的临床相关相互作用:对癫痫患者 COVID-19 管理的意义

Ritonavir-boosted nirmatrelvir (RBN) 最近已在多个国家获得批准,作为一种口服活性抗 SARS-CoV-2 治疗药物,用于治疗进展为严重 COVID-19 疾病的高风险患者。Nirmatrelvir 是抗 SARS-CoV-2 病毒的活性成分,而 ritonavir 是一种有效的 CYP3A 抑制剂,旨在通过增加其在血浆中的浓度来增强 nirmatrelvir 的活性,以确保在 12 小时的给药间隔内保持抗病毒浓度。RBN 作为肇事者和受害者都参与了许多临床上重要的药物-药物相互作用,这可能使其在接受抗癫痫药物 (ASM) 治疗的患者中的使用变得复杂。RBN 和 ASM 之间的交互是双向的。作为肇事者,RBN 可能会增加许多作为 CYP3A4 底物的 ASM 的血浆浓度,可能导致中毒。作为受害者,nirmatrelvir 和利托那韦都受到代谢诱导,同时使用有效的酶诱导 ASM(卡马西平、苯妥英、苯巴比妥和扑米酮)进行治疗。根据美国和欧洲的处方信息,使用这些 ASM 进行治疗是使用 RBN 的禁忌症。尽管瑞德西韦是 RBN 的一种有价值的替代品,但由于成本和/或需要静脉内给药,在某些情况下可能不容易获得。如果瑞德西韦不是一个合适的选择,可以考虑使用 bebtelovimab 或 molnupiravir。然而,关于 bebtelovimab 临床疗效的证据仍然有限,并且认为唯一的口服活性替代品 molnupiravir 的疗效明显低于 RBN 和 remdesivir。nirmatrelvir 和 ritonavir 都受到代谢诱导,同时使用有效的酶诱导 ASM(卡马西平、苯妥英、苯巴比妥和扑米酮)进行治疗。根据美国和欧洲的处方信息,使用这些 ASM 进行治疗是使用 RBN 的禁忌症。尽管瑞德西韦是 RBN 的一种有价值的替代品,但由于成本和/或需要静脉内给药,在某些情况下可能不容易获得。如果瑞德西韦不是一个合适的选择,可以考虑使用 bebtelovimab 或 molnupiravir。然而,关于 bebtelovimab 临床疗效的证据仍然有限,并且认为唯一的口服活性替代品 molnupiravir 的疗效明显低于 RBN 和 remdesivir。nirmatrelvir 和 ritonavir 都受到代谢诱导,同时使用有效的酶诱导 ASM(卡马西平、苯妥英、苯巴比妥和扑米酮)进行治疗。根据美国和欧洲的处方信息,使用这些 ASM 进行治疗是使用 RBN 的禁忌症。尽管瑞德西韦是 RBN 的一种有价值的替代品,但由于成本和/或需要静脉内给药,在某些情况下可能不容易获得。如果瑞德西韦不是一个合适的选择,可以考虑使用 bebtelovimab 或 molnupiravir。然而,关于 bebtelovimab 临床疗效的证据仍然有限,并且认为唯一的口服活性替代品 molnupiravir 的疗效明显低于 RBN 和 remdesivir。

更新日期:2022-07-28
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