Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

Loreta A Kondili, Giovanni Battista Gaeta, Donatella Ieluzzi, Anna Linda Zignego, Monica Monti, Andrea Gori, Alessandro Soria, Giovanni Raimondo, Roberto Filomia, Alfredo Di Leo, Andrea Iannone, Marco Massari, Romina Corsini, Roberto Gulminetti, Alberto Gatti Comini, Pierluigi Toniutto, Denis Dissegna, Francesco Paolo Russo, Alberto Zanetto, Maria Grazia RumiGiuseppina Brancaccio, Elena Danieli, Maurizia Rossana Brunetto, Liliana Elena Weimer, Maria Giovanna Quaranta, Stefano Vella, Massimo Puoti

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.

AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.

METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).

RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.

CONCLUSIONS: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.

Original languageEnglish
Pages (from-to)e0172159
JournalPLoS One
Volume12
Issue number2
DOIs
Publication statusPublished - 2017

Fingerprint

Drug interactions
chronic hepatitis C
drug interactions
Chronic Hepatitis C
Virus Diseases
interferons
cohort studies
Drug Interactions
Interferons
liver diseases
Antiviral Agents
Cohort Studies
Liver
Liver Diseases
drugs
therapeutics
infection
Pharmaceutical Preparations
Therapeutics
monitoring

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents/adverse effects
  • Drug Administration Schedule
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic/drug therapy
  • Humans
  • Interferons
  • Italy
  • Liver Cirrhosis/chemically induced
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk

Cite this

Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study. / Kondili, Loreta A; Gaeta, Giovanni Battista; Ieluzzi, Donatella; Zignego, Anna Linda; Monti, Monica; Gori, Andrea; Soria, Alessandro; Raimondo, Giovanni; Filomia, Roberto; Di Leo, Alfredo; Iannone, Andrea; Massari, Marco; Corsini, Romina; Gulminetti, Roberto; Gatti Comini, Alberto; Toniutto, Pierluigi; Dissegna, Denis; Russo, Francesco Paolo; Zanetto, Alberto; Rumi, Maria Grazia; Brancaccio, Giuseppina; Danieli, Elena; Brunetto, Maurizia Rossana; Weimer, Liliana Elena; Quaranta, Maria Giovanna; Vella, Stefano; Puoti, Massimo.

In: PLoS One, Vol. 12, No. 2, 2017, p. e0172159.

Research output: Contribution to journalArticle

Kondili, LA, Gaeta, GB, Ieluzzi, D, Zignego, AL, Monti, M, Gori, A, Soria, A, Raimondo, G, Filomia, R, Di Leo, A, Iannone, A, Massari, M, Corsini, R, Gulminetti, R, Gatti Comini, A, Toniutto, P, Dissegna, D, Russo, FP, Zanetto, A, Rumi, MG, Brancaccio, G, Danieli, E, Brunetto, MR, Weimer, LE, Quaranta, MG, Vella, S & Puoti, M 2017, 'Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study', PLoS One, vol. 12, no. 2, pp. e0172159. https://doi.org/10.1371/journal.pone.0172159
Kondili, Loreta A ; Gaeta, Giovanni Battista ; Ieluzzi, Donatella ; Zignego, Anna Linda ; Monti, Monica ; Gori, Andrea ; Soria, Alessandro ; Raimondo, Giovanni ; Filomia, Roberto ; Di Leo, Alfredo ; Iannone, Andrea ; Massari, Marco ; Corsini, Romina ; Gulminetti, Roberto ; Gatti Comini, Alberto ; Toniutto, Pierluigi ; Dissegna, Denis ; Russo, Francesco Paolo ; Zanetto, Alberto ; Rumi, Maria Grazia ; Brancaccio, Giuseppina ; Danieli, Elena ; Brunetto, Maurizia Rossana ; Weimer, Liliana Elena ; Quaranta, Maria Giovanna ; Vella, Stefano ; Puoti, Massimo. / Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study. In: PLoS One. 2017 ; Vol. 12, No. 2. pp. e0172159.
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title = "Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study",
abstract = "BACKGROUND: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20{\%}) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25{\%}) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3{\%}) were contraindicated in severe liver disease. In patients with mild liver disease 30{\%} (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44{\%}) were at risk for one or more DDI.CONCLUSIONS: Based on these results, we can estimate that 30-44{\%} of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from {"}dose adjustment/closer monitoring{"}, in mild to moderate liver disease, to {"}the use is contraindicated{"} in severe liver disease.",
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author = "Kondili, {Loreta A} and Gaeta, {Giovanni Battista} and Donatella Ieluzzi and Zignego, {Anna Linda} and Monica Monti and Andrea Gori and Alessandro Soria and Giovanni Raimondo and Roberto Filomia and {Di Leo}, Alfredo and Andrea Iannone and Marco Massari and Romina Corsini and Roberto Gulminetti and {Gatti Comini}, Alberto and Pierluigi Toniutto and Denis Dissegna and Russo, {Francesco Paolo} and Alberto Zanetto and Rumi, {Maria Grazia} and Giuseppina Brancaccio and Elena Danieli and Brunetto, {Maurizia Rossana} and Weimer, {Liliana Elena} and Quaranta, {Maria Giovanna} and Stefano Vella and Massimo Puoti",
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TY - JOUR

T1 - Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

AU - Kondili, Loreta A

AU - Gaeta, Giovanni Battista

AU - Ieluzzi, Donatella

AU - Zignego, Anna Linda

AU - Monti, Monica

AU - Gori, Andrea

AU - Soria, Alessandro

AU - Raimondo, Giovanni

AU - Filomia, Roberto

AU - Di Leo, Alfredo

AU - Iannone, Andrea

AU - Massari, Marco

AU - Corsini, Romina

AU - Gulminetti, Roberto

AU - Gatti Comini, Alberto

AU - Toniutto, Pierluigi

AU - Dissegna, Denis

AU - Russo, Francesco Paolo

AU - Zanetto, Alberto

AU - Rumi, Maria Grazia

AU - Brancaccio, Giuseppina

AU - Danieli, Elena

AU - Brunetto, Maurizia Rossana

AU - Weimer, Liliana Elena

AU - Quaranta, Maria Giovanna

AU - Vella, Stefano

AU - Puoti, Massimo

PY - 2017

Y1 - 2017

N2 - BACKGROUND: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.CONCLUSIONS: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.

AB - BACKGROUND: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.CONCLUSIONS: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antiviral Agents/adverse effects

KW - Drug Administration Schedule

KW - Drug Interactions

KW - Drug Therapy, Combination

KW - Female

KW - Hepacivirus

KW - Hepatitis C, Chronic/drug therapy

KW - Humans

KW - Interferons

KW - Italy

KW - Liver Cirrhosis/chemically induced

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Risk

U2 - 10.1371/journal.pone.0172159

DO - 10.1371/journal.pone.0172159

M3 - Article

C2 - 28245248

VL - 12

SP - e0172159

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

ER -