Drug–Drug Interactions in Italian Patients with Chronic Hepatitis C Treated with Pangenotypic Direct Acting Agents: Insights from a Real-World Study

Mangia, Alessandra; Scaglione, Francesco; Toniutto, Pierluigi; Pirisi, Mario; Coppola, Nicola; Perri, Giovanni Di; Nieto, Gema Alvarez; Calabrese, Stefano; Hernández, Cándido Márquez; Perrone, Valentina; Esposti, Luca Degli; Fagiuoli, S.

doi:10.3390/ijerph18137144

Cited by 12 publications

(13 citation statements)

References 26 publications

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“…Data from real-world studies indicate that the potential for drugdrug interactions is minimal with sofosbuvir-velpatasvir and lower than with regimens containing an HCV NS3/4A protease inhibitor. 23,24 In Japan, the current indication for sofosbuvir-velpatasvir is limited to persons with decompensated cirrhosis or those with or without compensated cirrhosis with prior failure of a DAA regimen. 15 given the risks of developing portal hypertension and variceal bleeds in the setting of asymptomatic compensated cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

Takehara

Izumi

Mochida

et al. 2022

Hepatology Research

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Background & Purpose Protease‐free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir–velpatasvir in participants with HCV and compensated cirrhosis in Japan. Methods This was a Phase 3, multi‐center, open‐label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir–velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment‐naïve or treatment‐experienced with interferon‐based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12). Results Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance‐associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on‐treatment breakthrough or relapse occurred. Sofosbuvir–velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia. Conclusion Sofosbuvir–velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single‐tablet regimen offers a highly effective, protease‐inhibitor free regimen for treating HCV. ClinicalTrials.gov Identifier: NCT04112303.

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Section: Discussionmentioning

confidence: 99%

Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

Takehara

Izumi

Mochida

et al. 2022

Hepatology Research

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“…This statement contrasts with experiences reported in real-world clinical practice, where dose modification, switch, or interruption of concomitant drugs frequently occur at different rates among DAAs, suggesting a different perception regarding the potential severity of DDIs. In addition, many patients may receive contraindicated cotreatment, although most have a dose decrease [ 4 , 5 ]. The clinical relevance of DDI suggests that awareness of comedication administration should be increased.…”

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%

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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“…The data used for the analysis were collected from administrative databases, as previously described. 16 Briefly, the data were extracted from administrative flows from a pool of Italian Healthcare Entities from Piedmont, Veneto, Friuli Venezia Giulia, Umbria, Abruzzo, Lazio and Puglia regions covering a total of 6.9 million individuals (around 11.4% of the Italian population), and specifically on health-assisted subjects with at least one CV risk factor (detected from 2010 to 2018). In a feasibility analysis performed on a sample of the Healthcare Entities included, approximately 99% of the patients responding to the inclusion criteria listed below had at least a cardiovascular record; therefore, the included patients were representative of the overall sample analysed.…”

Section: Methodsmentioning

confidence: 99%

“… 14–16 A previous real-world study by our group conducted in Italy on two cohorts of patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) provided insights on their characteristics and DDI assessment based on the presence of at least one comedication. 16 The present analysis was aimed at an in-depth exploration of the potential impact of polypharmacy regimens and aging on the prevalence of multiple DDIs among patients treated with SOF/VEL or GLE/PIB in settings of daily clinical practice in Italy.…”

Section: Introductionmentioning

confidence: 99%

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug–Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

Fagiuoli

Toniutto

Coppola

et al. 2023

TCRM

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Purpose The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Patients and Methods This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool. Results A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients >50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients). Conclusion This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.

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Drug–Drug Interactions in Italian Patients with Chronic Hepatitis C Treated with Pangenotypic Direct Acting Agents: Insights from a Real-World Study

Cited by 12 publications

References 26 publications

Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

Sofosbuvir–velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan

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

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug–Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

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