Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain
Division of Clinical Virology, BiomedicalResearch Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña(CHUAC), SERGAS, Universidade da Coruña (UDC), A Coruña, Spain.
Eur J Hosp Pharm. 2021 Jan;28(1):16-21. doi: 10.1136/ejhpharm-2019-001889. Epub 2019 Jun 13.
Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug-drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug-drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients.
Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug-drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug-drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug-drug interactions related to the effectiveness of direct-acting antivirals.
Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug-drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug-drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug-drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841).
Drug-drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug-drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals.
直接作用抗病毒药物是治疗丙型肝炎感染患者的推荐治疗方法。与伴随治疗的药物相互作用会导致疗效下降和/或安全性问题。本研究的目的是描述直接作用抗病毒药物的药物相互作用，并分析其对丙型肝炎感染患者抗病毒治疗的疗效和整体药物治疗安全性的影响。
在一家综合医院的药学门诊进行了为期 3 年的观察性和前瞻性队列研究，由临床药师和医生共同进行药物相互作用的检测、评估和管理。主要结局指标为第 12 周的持续病毒学应答（SVR）评估疗效，以及严重药物相关不良事件评估安全性。多变量统计分析应用于：（a）与药物相互作用发生相关的患者基础特征；（b）既往抗病毒治疗、病毒基因型、肝硬化、失代偿和与直接作用抗病毒药物疗效相关的药物相互作用。
在总共 1092 例患者中，大多数是男性，年龄在 60 岁左右，HCV 基因型 1 型单感染，病毒载量较高，初治抗病毒治疗，接受 ledipasvir/sofosbuvir 治疗，无肝硬化。24.5%的患者发生药物相互作用。质子泵抑制剂是引起药物相互作用最多的伴随药物。年龄≥65 岁和基于蛋白酶抑制剂的直接作用抗病毒药物是与药物相互作用发生独立相关的因素（p≤0.012）。基于检测到的药物相互作用提出的所有（100%）治疗建议均得到实施；发生药物相互作用的患者中 97.7%与未发生药物相互作用的患者达到持续病毒学失败（p=0.109）。有药物相互作用的患者严重不良事件发生率为 1.5%，无药物相互作用的患者为 1.3%（p=0.841）。
丙型肝炎感染患者接受直接作用抗病毒药物治疗时，药物相互作用很常见。然而，医生和临床药师之间的合作使得能够发现、评估、避免或临床管理这些药物相互作用，以维持整个治疗的治疗安全性和直接作用抗病毒药物的疗效。
