Ombitasvir/paritaprevir/ritonavir + dasabuvir +/-ribavirin in real world hepatitis C patients

BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following treatment.

Ombitasvir, paritaprevir, ritonavir, dasabuvir and ribavirin in cirrhosis after complete destruction of hepatocellular carcinoma

We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.

Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis

A fast,reliable,and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019,namely,Lianhua Qingwen granules,Huoxiang Zhengqi capsules,Jinhua Qinggan granules,Shufeng Jiedu capsules,and Angong Niuhuang pills,on the pharmacokinetics of lopinavir/ritonavir in rats.Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard(IS).Separation was performed on an Agilent ZORBAX eclipse plus C18(2.1 mm×50 mm,1.8 μm)column using acetonitrile and water containing 0.1%formic acid as the mobile phase for gradient elution.The flow rate was 0.4 mL/min and the injection volume was 2 μL.Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir,m/z 721.3→296.1 for ritonavir,and m/z 705.4→168.1 for the IS.The method showed good linearity in the concentration range of 25→2500 ng/mL(r=0.9981)for lopinavir and 5e500 ng/mL(r=0.9984)for ritonavir.The intra-day and inter-day precision and accuracy were both within±15%.Items,such as dilution reliability and residual effect,were also within the acceptable limits.The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats.The pharmacokinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approximately 1.5-to 2-fold relative to that in the control group.Similarly,the pharmacokinetic parameters of lopinavir were altered.Overall,the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

Thermal stability and hydration behavior of ritonavir sulfate:A vibrational spectroscopic approach

Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was investigated under forced thermal and hydration stress conditions as recommended by the Inter- national Conference on Harmonization guidelines. In addition, competency of vibrational （infrared and Raman） spectroscopy was assessed to identify structural changes of the drug symbolizing its stress degradation. High performance liquid chromatography was used as a confirmatory technique for both thermal and hydration stress study, while thermogravimetric analysis]differential thermal analysis and atomic force microscopy substantiated the implementation of vibrational spectroscopy in this frame- work. The results exhibited high thermal stability of the drug as significant variations were observed in the diffuse reflectance infrared Fourier transform spectra only after the drug exposure to thermal radiations at 100 ℃. Hydration behavior of ritonavir sulfate was evaluated using Raman spectroscopy and the value of critical relative humidity was found to be 〉 67%. An important aspect of this study was to utilize vibrational spectroscopic technique to address stability issues of pharmacological molecules, not only for their processing in pharmaceutical industry, but also for predicting their shelf lives and suitable storage conditions.

Danoprevir/ritonavir联合聚乙二醇化干扰素a-2a/利巴韦林治疗丙型肝炎的疗效、安全性、药代动力学研究

Danoprevir（RG7227；ITMN-191）能够有效抑制HcVNS3／4A丝氨酸蛋白酶的活性。为了解在应用低剂量ritonavir的情况下，Danoprevir联合聚乙二醇化干扰素a-2a（40KD）／利巴韦林治疗初治的基因1型的HCV患者的安全性、耐受性、效果、耐药性、药代动力学（每日1次和每日2次），新西兰奥克兰临床研究中心进行了一项双盲、安慰剂对照、多重剂量的1b研究。

Dose prediction of lopinavir/ritonavir for 2019-novel coronavirus (2019-nCoV) infection based on mathematic modeling

Wuhan novel coronavirus or 2019-novel coronavirus(2019-nCoV)infection is a rapidly emerging respiratory viral disease[1].2019-nCoV infection is characterized as febrile illness with possible severe lung complication[1].The disease was firstly reported in China in December 2019 and then spread to many countries(such as Thailand,Japan and Singapore)[2,3].As a new disease,there is a limited knowledge of treatment for the infection.Lu recently proposed that some drug might be useful in treatment of 2019-nCoV infection[3].

Virologic and Lipoprotein Changes after Halving Ritonavir Boosting in HIV-Infected Patients Stabilized on Once-Daily Fosamprenavir plus Abacavir/Lamivudine

Background: The effect of reducing ritonavir boosting doses on the efficacy and safety of fosamprenavir-based regimens has not been well studied. Methods: In a 52-week, phase 4, open-label, single-center pilot study, 26 antiretroviral-naive, HIV-infected patients with viral loads >1000 copies/mL received induction with fosamprenavir/ritonavir 1400 mg/200mg plus abacavir/lamivudine 600 mg/300mg once daily for 28 weeks. Patients achieving a viral load 10 copies/mL and CD4+ count 110/mm3. Of 12 induction/maintenance completers, 10 (83%) achieved viral loads 3 at baseline to 292/mm3 at induction-week 28 and to 296/mm3 at maintenance-week 24. The incidence of adverse events at maintenance-week 24 did not differ from that at induction-week 28 (P > 0.05). Median fasting total-cholesterol, LDL-cholesterol, and triglycerides remained below NCEP cut-off levels. Baseline/induction-week 28/maintenance-week 24 median total-cholesterol was 130/177/183 mg/dL, LDL-cholesterol 78/107/114 mg/dL, HDL-cholesterol 33/41/43 mg/dL, total-cholesterol: HDL-cholesterol ratio 3.9/4.3/4.3, and triglycerides 93/145/119 mg/dL. During induction, total VLDL/chylomicron, LDL, and HDL particles increased;during maintenance, VLDL/chylomicron particles decreased, but LDL and HDL particle concentrations did not notably change. Conclusions: Reducing ritonavir boosting from 200 mg to 100 mg once daily in HIV-infected patients stabilized on once-daily fosamprenavir/abacavir/lamivudine resulted in maintenance of virologic suppression, enhanced CD4+ count, and improved triglycerides.

Trizivir (Abacavir/Lamivudine/Zidovudine) plus Lopinavir/Ritonavir Induction Therapy Followed by Trizivir-Alone Maintenance for HIV-1-Infected Patients: A 96-Week Pilot Treatment Simplification Study

Objective: The purpose of this study was to investigate whether switching HIV-infected patients stabilized on Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg) plus lopinavir/ritonavir 400 mg/100mg twice daily to Trizivir alone affects clinical efficacy and tolerability. Methods: This phase 4, open-label, pilot study was conducted over 96 weeks in 23 antiretroviral-na?ve, HIV-infected patients. Initially, these patients received induction therapy with Trizivir plus lopinavir/ritonavir 400 mg/100mg twice daily. Patients who achieved a viral load 3. Nineteen patients completed induction;of the four who did not, three were lost to follow-up and one withdrew due to gastrointestinal adverse events. In 14 induction completers who had viral load measurements taken at week 48, intent-to-treat: observed analysis showed a week 48 viral load 3 higher than the baseline count. Twelve patients completed the subsequent 48-week Trizivir-alone maintenance phase, of whom 11 (92%) achieved viral loads of both 3 above baseline. Trizivir-only maintenance was associated with fewer adverse events than the Trizivir-lopinavir/ritonavir induction phase and with improvement in total cholesterol, LDL-cholesterol, and triglycerides. Conclusions: Trizivir-alone maintenance after Trizivir-lopinavir/ritonavir induction maintained virologic and CD4+ cell response, and was associated with an improved adverse event and lipid profile.

Optimized Antiretroviral Therapy with Darunavir/Ritonavir, Etravirine and/or Raltegarvir: A Salvage Therapy Option in HIV-1 Infected Patients with Long-Term Therapeutic Failures, about 23 Cases

Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.

Lopinavir/Ritonavir in the Treatment of COVID-19:A Systematic Review and Meta-Analysis

Objective:To systematically evaluate the efficacy and safety of lopinavir/ritonavir(LPV/r)in the treatment of COVID-19.Methods:PubMed,Embase,Ovid,CNKI,CBM,Wanfang,and VIP databases were searched to obtain the clinical studies of LPV/r in the treatment of COVID-19 from December 2019 to July 2020.The literatures were screened according to the inclusion and exclusion criteria.Their qualities were evaluated according to the Newcastle-Ottawa Scale(NOS)and RevMan 5.3 software was used for meta-analysis.Results:A total of 688 patients were included in five studies,involving China and France.Compared with patients in the control group,who was only treated with routine treatment,there were no significant differences of the 7-day nucleic acid negative conversion rate and 14-day nucleic acid negative conversion rate in the treatment group.However,the use of LPV/r increased the incidence of adverse reactions in the treatment group compared to the control group.Conclusion:There is no available evidence to support the use of Lopinavir/ritonavir in the treatment of COVID-19.

The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs-disulfiram and ritonavir

Based on reporting in the last several years,an impressive but dismal list of cytotoxic chemotherapies that fail to prolong the median overall survival of patients with glioblastoma has prompted the development of treatment protocols designed to interfere with growth-facilitating signaling systems by using non-cytotoxic,non-oncology drugs.Recent recognition of the pro-mobility stimulus,interleukin-18,as a driver of centrifugal glioblastoma cell migration allows potential treatment adjuncts with disulfiram and ritonavir.Disulfiram and ritonavir are well-tolerated,non-cytotoxic,non-oncology chemotherapeutic drugs that are marketed for the treatment of alcoholism and human immunodeficiency virus(HIV) infection,respectively.Both drugs exhibit an interleukin-18—inhibiting function.Given the favorable tolerability profile of disulfiram and ritonavir,the unlikely drug-drug interaction with temozolomide,and the poor prognosis of glioblastoma,trials of addition of disulfiram and ritonavir to current standard initial treatment of glioblastoma would be warranted.

Viral rebound and safety of nirmatrelvir/ritonavir for lung-transplant recipients infected with SARS-CoV-2

Data on the viral rebound and safety of nirmatrelvir/ritonavir in lung transplant(LTx)recipients are limited.The study prospectively followed four LTx recipients.Clinical characteristics,viral RNA dynamic in throat swabs,and tacrolimus blood concentration were monitored regularly.All four LTx recipients,aged 35–74 years,were not vaccinated against severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2).They got coronavirus disease 2019(COVID‐19)after more than one week of admission during the era of Omicron.All cases received nirmatrelvir/ritonavir(NM/r)within two days of infection,and the relative viral RNA copies dropped quickly.Viral load rebound was observed in all four cases after discontinuation of the first five days of NM/r treatment.Three of them received another 5‐days antiviral therapy with NM/r.The duration of positive viral PCR testing was 25‐28 days.None of them progressed into severe or critical COVID‐19.Tacrolimus was stopped 12 h before NM/r and held during the 5‐day course of antiviral therapy.Blood concentration of tacrolimus were maintained at a baseline level during these five days.Tacrolimus was re‐initiated at its baseline daily dose 3‐4 days after NM/r therapy.However,during the second round of antiviral therapy with NM/r,the concentration of tacrolimus fluctuated wildly.In conclusion,the 5‐day course of NM/r treatment was not sufficient for LTx recipients and the viral rebound was common.More data are needed to clarify whether LTx recipients with SARS‐CoV‐2 viral rebound could benefit from additional treatment with NM/r.

重症患者新型冠状病毒感染应用奈玛特韦/利托那韦的药学监护实践

目的总结临床药师对治疗新型冠状病毒感染(COVID-19)的口服新药——奈玛特韦片/利托那韦片组合包装(Paxlovid)的药学监护要点。方法收集2022年12月~2023年1月奥密克戎毒株暴发期间,山东大学附属威海市立医院住院重症患者应用Paxlovid的病例10例,临床药师从适应证、启用时机、用法用量、不良反应、药物间相互作用等方面评价药物应用的合理性,并参与临床实施药学监护。结果10例患者中,男性4例,女性6例,平均年龄(73.8±12.3)岁。临床药师会诊确定这10例患者的COVID-19的分型为中型,符合Paxlovid的适应证,除1例患者启用时间较晚,其余患者均在核酸阳性5 d内应用Paxlovid,服药后核酸转阴时间平均为(7.9±4.7)d。临床药师通过计算患者的肾小球滤过率来调整剂量,并查阅文献资料对其中3例无法口服的重症患者采取鼻饲给药方式。通过不良反应评估量表,判断2例患者出现的消化道不良反应与Paxlovid的使用很可能相关。对患者进行药物重整,发现3例患者应用的药物与Paxlovid有潜在相互作用风险,临床药师与主治医师进行沟通,对有相互作用风险的药物进行停药、更换品种或严密监测指标等处理。结论Paxlovid作为口服治疗COVID-19的新药,在临床中表现出较好的优势,但因适用人群、药物相互作用等问题,存在应用上的局限性。临床药师通过总结Paxlovid应用时的注意事项,可在查房时运用思维导图一对一地对患者进行个体化药学监护,以保障药物治疗的安全性和合理性。

Paxlovid对肺移植患者他克莫司血药浓度影响的研究

目的探索奈玛特韦片/利托那韦片组合包装(Paxlovid)对肺移植患者他克莫司(Tacrolimus,TAC)血药浓度的影响,为肺移植术后的新型冠状病毒感染患者服用Paxlovid与TAC时的用药安全提供合理参考。方法回顾性分析2022年11月1日至2023年1月31日中日友好医院收治的5例肺移植术后服用Paxlovid的患者(服用Paxlovid之前,5例患者的TAC血药浓度均已达稳态),测定服用Paxlovid期间及之后的TAC谷浓度,记录Paxlovid停药后重新启用TAC的时间和剂量,同时收集用药期间患者的肝肾功能指标数据。结果在Paxlovid使用期间,3例患者的TAC血药浓度分别下降19.4%、8.4%、14.7%,另外2例分别升高了21.6%、80.6%。重新启用TAC之后,3例患者TAC谷浓度出现了先上升(平均上升59.5%)后下降(平均下降33.3%)的趋势,而另外2例患者TAC谷浓度则一直持续下降。4例患者分别是在TAC血药浓度为基线水平的47.2%、72.6%、83.8%、60.3%时开始恢复使用TAC,1例则是在基线水平的171.2%开始启用TAC。2例患者以基线剂量开始启用TAC,另外3例患者分别以85.7%、44.4%、90.9%的基线剂量开始重新使用。结论Paxlovid会对TAC血药浓度产生影响,不仅是在Paxlovid治疗期间,甚至持续至停药后第6天,存在显著的个体差异,建议在患者治疗期间严密监测TAC血药浓度,根据血药浓度实行个体化TAC给药方案。

奈玛特韦/利托那韦潜在药物相互作用对新型冠状病毒感染治疗的影响:基于倾向评分匹配的回顾性研究

目的探讨奈玛特韦/利托那韦潜在药物相互作用(pDDI)对新型冠状病毒感染患者治疗有效性和安全性的影响。方法回顾性分析2022年12月1日至2023年2月28日期间某院使用奈玛特韦/利托那韦治疗新型冠状病毒感染患者264例,根据是否存在奈玛特韦/利托那韦pDDI分为DDI组(n=163例)和N-DDI(n=101例)。通过倾向评分匹配均衡两组队列的基线特征后,比较两组病情进展的复合终点(包括ICU入住率、机械通气率和死亡率)、住院时长和不良反应发生率的结局指标。结果奈玛特韦/利托那韦总体的pDDI发生率为61.74%,药物不良反应发生率为7.95%,未发生严重不良反应事件。匹配后DDI组(n=91例)和N-DDI组(n=101例)在人口统计、并发症以及治疗前后实验室检查之间的差异无统计学意义,结局指标病情进展的复合终点(P=0.632)、住院时长(P=0.459)和药物不良反应发生率(P=0.459)之间的差异没有统计学意义。结论奈玛特韦/利托那韦pDDI对新型冠状病毒感染患者病情进展未见显著影响,因纳入样本量限制,结论有待进一步确认,临床仍需警惕严重或发生率较高的DDI,确保患者用药安全。

某医联体内奈玛特韦片/利托那韦片药学监护实践效果

目的促进临床新型冠状病毒感染小分子药物(简称新冠小分子药物)的合理使用。方法以上海交通大学医学院附属第六人民医院及上海市徐汇区康健街道、凌云街道、田林街道社区卫生服务中心组建医疗联合体(简称医联体),构建新冠小分子药物药学监护模式,包括社区药师培训、开展药学监护及三级医院药师指导评价等环节。收集3个社区卫生服务中心2023年1月至2月使用奈玛特韦片/利托那韦片(NMV/RTV)新冠病毒感染门诊患者的资料,分析患者的用药情况,以及药物相关问题(DRP)的发生情况。结果共纳入79例患者,其中78例(98.73%)年龄≥60岁;合并疾病(3.04±1.71)种,主要为心血管疾病(64例次、81.01%),糖尿病(35例次、44.30%),高脂血症(16例次、20.25%);使用药品(6.00±3.66)种;使用中成药36例(45.57%)。社区药师共完成150次随访,发现并干预87件DRP,其中NMV/RTV 77件,主要为药物相互作用(70件),涉及药物类型排前3的分别为钙离子通道阻滞剂(31件、44.29%),抗焦虑药(12件、17.14%),羟甲基戊二酰辅酶A还原酶抑制剂(11件、15.71%)。根据出现的DRP,医联体药师提出了减量服用、暂停给药、密切监测相关指标(如疗效、药品不良反应、血压、血栓风险)等用药建议。结论社区新冠病毒感染老年患者占比较高,用药复杂,NMV/RTV使用过程中存在较多DRP。基于医联体的新冠小分子药物药学监护模式可帮助社区药师规范化开展药学监护工作,及时发现并干预DRP,有利于促进医联体内药学服务同质化,为后续新冠小分子药物的用药管理提供依据。

奥比帕利联合达塞布韦治疗基因1b型慢性丙型肝炎患者疗效研究

目的探讨应用奥比帕利联合达塞布韦治疗基因1b型慢性丙型肝炎(CHC)患者的疗效。方法2020年1月~2022年1月我院收治的106例基因1b型CHC患者,其中观察组53例接受奥比帕利联合达塞布韦治疗,对照组53例接受达塞布韦单药治疗,两组治疗持续12周。采用实时荧光定量RT-PCR法检测血清HCV RNA载量,考核超快速病毒学应答(SRVR)、快速病毒学应答(RVR)、治疗结束病毒学应答(ETVR)和随访12周时持续病毒学应答(SVR)。结果观察组SRVR、RVR、ETVR和SVR分别为88.7%、94.3%、100.0%和100.0%,显著高于对照组(67.9%、75.4%、83.0%和90.5%,P<0.05);在治疗12周结束时,观察组血清ALT和AST水平分别为(30.8±4.6)U/L和(29.7±2.4)U/L,均显著低于对照组【分别为(52.2±5.1)U/L和(48.1±3.6)U/L,P<0.05】;在治疗期间,观察组不良反应发生率为18.7%,显著高于对照组的9.4%(P<0.05)。结论应用奥比帕利联合达塞布韦治疗基因1b型CHC患者疗效确切,可有效改善肝功能,提高血清HCV RNA转阴率,且安全性尚可。

新型口服小分子抗新型冠状病毒感染药物的快速遴选评价实践

目的:应用《中国医疗机构药品评价与遴选快速指南(第二版)》(以下简称“指南”)对新型口服小分子抗新型冠状病毒感染(COVID-19)药物进行快速遴选评价,为医疗机构合理引进药物提供参考。方法:基于指南制定的百分制评估体系,参照药品说明书、疾病诊治指南,并检索中国知网、万方数据库、PubMed等数据库中的文献,从药学特性、有效性、安全性、经济性、其他属性5个方面对奈玛特韦片/利托那韦片、莫诺拉韦胶囊、阿兹夫定片进行卫生技术评估,并依据评分结果推荐各种药品的引进级别。结果:经量化评分,阿兹夫定片、奈玛特韦片/利托那韦片和莫诺拉韦胶囊的最终得分分别为75.00、71.78和73.36分。上述3药均为早期治疗轻、中型COVID-19患者的一线药物。阿兹夫定片适用人群更广泛,价格便宜,但腹泻、头晕等不良反应发生率略高。奈玛特韦片/利托那韦片、莫诺拉韦胶囊仅限于有发展为重型风险因素的成人患者使用,奈玛特韦片/利托那韦片的疗效优于莫诺拉韦胶囊,但不良药物相互作用较多,且价格昂贵。莫诺拉韦胶囊用于肝肾功异常患者时无需调整剂量,无不良药物相互作用,轻中度不良反应发生率最低。上述3药的总分均>70分,属强推荐范畴,医疗机构可根据用药群体特点酌情选择1~2种引进。结论:本次卫生技术评估可为医疗机构开展药品遴选评价提供实践经验,同时为临床合理使用抗COVID-19药物提供循证依据。

1例肺移植的干燥综合征患者联用奈玛特韦/利托那韦与环孢素、他克莫司导致肾功能损伤

1例76岁右单肺移植的干燥综合征男性患者在新冠病毒感染后使用奈玛特韦/利托那韦治疗,导致合并使用的免疫抑制剂环孢素和他克莫司全血药物谷浓度升高,引起血肌酐升高,后通过停用环孢素、调整他克莫司剂量使他克莫司浓度维持在治疗浓度,血肌酐水平较前改善,患者好转出院。此病例可为临床安全用药实践提供参考。