Drug Interactions With Direct-Acting Antivirals for Hepatitis C

Burgess, Sarah; Partovi, Nilufar; Yoshida, Eric M.; Erb, Siegfried R.; Azalgara, Vladimir Marquez; Hussaini, Trana

doi:10.1177/1060028015576180

Cited by 80 publications

(57 citation statements)

References 37 publications

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“…This retrospective study builds on a number of smaller studies suggesting that SOF‐based regimens can be used safely and effectively in patients with severe renal dysfunction, including those receiving hemodialysis, those with decompensated cirrhosis, and those who have undergone liver and/or kidney transplant 14, 15…”

Section: Discussionmentioning

confidence: 99%

“…Renal insufficiency is common in recipients of liver transplantation and complicates the decision to treat. Although there are HCV regimens in evaluation27 and approved28 for use in patients with an eGFR <30 mL/minute/1.73 m 2 , SOF‐based regimens are often preferred in patients who have undergone liver transplantation due to high efficacy and less potential for drug–drug interactions 15. The study findings are also of particular interest in those with CTP class B or C cirrhosis as only SOF‐based treatment regimens are currently approved by the U.S. Food and Drug Administration in this population.…”

Section: Discussionmentioning

confidence: 99%

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Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Cox-North

Hawkins

Rossiter

et al. 2017

Hepatology Communications

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Sofosbuvir (SOF) is a nonstructural 5B polymerase inhibitor with activity in all hepatitis C virus (HCV) genotypes and is the backbone of many anti‐HCV drug regimens. SOF is converted into inactive metabolites that undergo renal excretion. Patients with an estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 may experience increased drug exposure and thus potential toxicities along with decreased efficacy due to dose reduction or drug discontinuation. This is a single‐center study evaluating safety and effectiveness of SOF‐based regimens in patients with severe renal dysfunction, defined as eGFR <30 mL/minute/1.73 m2, including those receiving concurrent hemodialysis. Data were collected from patients with HCV and severe renal dysfunction who started full‐dose (400 mg) SOF‐based antiviral therapy ± ribavirin between April 2014 and February 2016. Medical records were reviewed for demographics, medical history, laboratory, radiologic imaging, echocardiography, transplant status, and liver pathologic findings. Twenty‐nine patients were identified; 12 had cirrhosis and 4 of those had decompensated cirrhosis. Fourteen patients had undergone transplantation of liver and/or kidney and were on calcineurin inhibitors, with 42% requiring dose increases or decreases while on therapy. All patients attained viral suppression on treatment, and 97% had a sustained viral response at 12 weeks posttreatment. There were no early treatment discontinuations. One death occurred posttreatment from a non‐ST elevation myocardial infarction in a patient with a history of coronary artery disease and ischemic cardiomyopathy. Conclusion: SOF‐based regimens appear safe in a broad range of patients with severe renal dysfunction, including those with decompensated cirrhosis and liver transplant. To confirm these retrospective findings, prospective studies that include SOF and SOF metabolite measurements coupled with prospective serial monitoring of electrocardiograms and echocardiograms are needed. (Hepatology Communications 2017;1:248‐255)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Cox-North

Hawkins

Rossiter

et al. 2017

Hepatology Communications

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“…[9][10] In contrast, primary route of elimination of simeprevir is feces (>90%) and only a negligible proportion (<1%) takes the Renal route. [11][12] Currently, the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) guidelines recommend a standard dose (150 mg) of Simeprevir in patients with CKD stage 4; however, there is lack of evidence for regime containing sofosbuvir and simeprevir in CKD stage 5. 13 Though a combination of sofosbuvir and simeprevir (SOF+SMV) has been recommended for treatment of genotype-1 HCV infected patients by AASLD and EASL, 14 the safety and efficacy of this regimen in patients with severe Renal impairment or with GFR<30 ml/min/1.73m 2 is unknown.…”

Section: Efficacy and Safety Of Sofosbuvir With Simeprevir In Hepatitmentioning

confidence: 99%

Efficacy and Safety of Sofosbuvir with Simeprevir in Hepatitis C Infected Patients with Severe Chronic Kidney Disease: A Systematic Review and Meta-Analysis

et al. 2016

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Background & Aims:Conventional treatment (interferon or ribavirin) for Hepatitis C viral (HCV) infection in patients with severe chronic kidney disease (CKD) has limitations of high dropout and less response rate. Directly acting antivirals raise hopes for HCV treatment in these patients. This meta-analysis was performed to evaluate the evidence for efficacy and safety of sofosbuvir and simeprevir, with or without ribavirin, in HCV-infected patients with severe CKD. Methods: Data was collected from Medline database, clinical-trial registry sites, and conference proceedings. This meta-analysis screened 78 studies. Quality of studies was assessed by New-Castle Ottawa scale. Heterogeneity and publication bias was checked by chi-square Q test and Eggers' test, respectively. Summary estimate of SVR12 and dropout rate was calculated at 95% confidence interval (CI). Results: Seven relevant clinical studies were identified. Two case-series and one case-report were excluded; only four studies were eligible for analysis. Three studies were cohort and one was retrospective-cohort in nature. Data was analyzed for 56 subjects. 33/56 subjects had cirrhosis. 39/56 subjects were on hemodialysis. 37/56 subjects were male. 30/56 subjects were treatment-naive. Pooled estimate of SVR12 was found 0.897 (CI 95%=0.957-0.772; p<0.01) and dropout estimate was 0.040 (CI 95%=0.011-0.137; p<0.01). Only one subject discontinued the treatment due to worsening Renal function regardless of ribavirin. Conclusion: This study concluded that combination of sofosbuvir and simeprevir, with or without ribavirin, was significantly effective and safe in HCV patients with severe CKD. For conclusive results, more data is required as this study involved only limited number of subjects.

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“…Furthermore, in patients with severe renal insufficiency, sofosbuvir (which is renally eliminated) has not been studied and safety data has not been established. 14 In contrast, ritonavir, ombitasvir, dasabuvir and paritaprevir are all hepatically eliminated. In the RUBY-1 study, these drugs were shown to be safe in 20 patients with an estimated glomerular filtration rate below 30 mL/min and may thus be preferentially prescribed in those with severe renal insufficiency instead of sofosbuvir containing regimens.…”

Section: Discussionmentioning

confidence: 99%

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

Yeoh

2016

Journal of Clinical and Experimental Hepatology

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Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism. We herein report a novel scenario of CS due to interaction between ritonavir for hepatitis C treatment and oral budesonide for autoimmune hepatitis. ( J CLIN EXP HEPATOL 2016;6:246-249)

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Drug Interactions With Direct-Acting Antivirals for Hepatitis C

Abstract: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.

Cited by 80 publications

References 37 publications

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

Efficacy and Safety of Sofosbuvir with Simeprevir in Hepatitis C Infected Patients with Severe Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy

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