Prevalence of drug-drug interactions with pangenotypic direct-acting antivirals for hepatitis C and real-world care management in the United States: a retrospective observational study

Curry, Michael P.; Flamm, Steven L.; Milligan, Scott; Tsai, Naoky; Wick, Nicole; Younossi, Zobair M.; Afdhal, Nezam H.

doi:10.18553/jmcp.2021.20550

Cited by 7 publications

(11 citation statements)

References 18 publications

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“…On the other hand, the choice of prescribing a DAA despite a potentially significant drug interaction cannot be recommended; negative consequences of drug interactions with DAAs may include decreased concentration resulting in loss of efficacy, or, on the contrary, increased levels associated with drug toxicity. For example, drugs used for HCV patients with cardiovascular disease, such as statins, are substrates of various drug transporters and drug-metabolizing enzymes that are inhibited by specific DAAs, resulting in a clinically relevant increase in statin plasma concentrations and, consequently, potential safety issues [ 3 , 5 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…As previously stated, since almost all HCV patients can now be treated, it results in the prevalence of more comorbidities and multiple concomitant medications, putting a significant proportion of patients at risk of clinically significant drug–drug interactions (DDIs). Real-world studies have shown that more than 50–70% of patients were taking concomitant medications, and the prevalence of potentially significant DDIs was present in as high as 40% of patients [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Borghi

Ciancio

Gentile

et al. 2022

JCM

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Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Borghi

Ciancio

Gentile

et al. 2022

JCM

View full text Add to dashboard Cite

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“…In patients with chronic hepatitis, particularly chronic hepatitis C, drug-drug interactions are present and influence the sustained virological response (SVR) due to the use of a direct-acting antiviral (DAA) regimen along with a frequent use of other drugs. 134 An underlying mechanism for this lies in the fact that PPIs reduce gastric acid secretion, resulted in a decrease in the solubility of some antiviral drugs such as ledipasvir and velpatasvir in the stomach, thus potentially reducing SVR. 135 The frequency of PPI use among patients infected with HCV was about 15% in a pooled dataset, 136 and was higher in some studies.…”

Section: Ppi and Other Chronic Liver Diseasesmentioning

confidence: 99%

The impact of proton pump inhibitors in liver diseases and the effects on the liver

Liu

Chen

2022

J of Digest Diseases

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In this systematic and comprehensive overview, we aimed to evaluate the impact of proton pump inhibitors (PPIs) on chronic liver diseases, especially on cirrhosis. A manual and comprehensive search of the PubMed database was conducted to obtain relevant literatures. PPIs altered the composition and function of the intestinal microflora and might lead to small intestinal bacterial overgrowth and bacterial translocation, which were associated with adverse effects in liver diseases. They might increase the risk of hepatic encephalopathy, spontaneous bacterial peritonitis, infections, and are related to an increased mortality in cirrhosis. PPIs might lead to an increased risk of hepatocellular carcinoma, although the mechanism is unknown, and the results are controversial. PPIs also had an impact on the direct‐acting antiviral regimen in patients with chronic hepatitis C. They were associated with an increased risk of liver abscess and increased mortality. Additionally, PPIs might lead to metabolic risk events, such as liver steatosis and weight gain. PPIs are associated with several adverse outcomes in liver diseases. Cautious use of PPIs is recommended and clinicians should be aware of the indications for their use in patients with liver diseases.

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“…In the United States, chronic PPI use is very common, especially in the aging population. Furthermore, in a recent study, the most common DDI for patients receiving SOF/VEL was with a PPI 13 . As such, it is essential that we fully understand the impact of this medication combination on HCV treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in a recent study, the most common DDI for patients receiving SOF/VEL was with a PPI. 13 As such, it is essential that we fully understand the impact of this medication combination on HCV treatment outcomes. Although pharmacokinetic evidence is available, little is known regarding the clinical outcomes of concomitant PPI and SOF/VEL use at this time.…”

Section: Introductionmentioning

confidence: 99%

Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study

et al. 2022

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Study Objective The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection. Design This was a multicenter retrospective cohort study. Setting Data was collected on patients from 128 Veterans Affairs Medical Centers throughout the United States. Patients This study included veterans aged 18‐89 years with viremic HCV who received a full course of SOF/VEL treatment from June 2016 – July 2017. Intervention Sustained viral response was compared in patients taking SOF/VEL with or without concurrent PPI prescriptions. Measurements and Main Results Analysis of the primary outcome was completed utilizing logistic regression. The relationship between SVR and PPI use was adjusted for African‐American race, presence of cirrhosis, prior treatment, BMI greater than 30 kg/m2, and HCV genotype. The final analysis included 4,008 veterans, 830 with concomitant PPI use and 3,178 without PPI use. After adjustment for other variables in the logistic model, there was no statistically significant association between PPI use and lower SVR (odds ratio 0.67; 95%CI: 0.42, 1.06; p = 0.087). Conclusion Concomitant PPI treatment adjusted for other variables did not significantly impact success or failure of SOF/VEL treatment of chronic HCV. Despite the lack of significant association identified in this study, in efforts to provide the best care possible, it remains prudent to proceed with caution in patients desiring to use PPI therapy while receiving SOF/VEL, and ensure prescribing instructions are closely followed in regard to concomitant PPI use, especially in patients with other risk factors for decreased SVR.

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Prevalence of drug-drug interactions with pangenotypic direct-acting antivirals for hepatitis C and real-world care management in the United States: a retrospective observational study

Cited by 7 publications

References 18 publications

Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

The impact of proton pump inhibitors in liver diseases and the effects on the liver

Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study

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