PMID- 29345798
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20210109
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 84
IP  - 5
DP  - 2018 May
TI  - Clinical impact of pharmacokinetic interactions between the HCV protease 
      inhibitor simeprevir and frequently used concomitant medications.
PG  - 961-971
LID - 10.1111/bcp.13519 [doi]
AB  - AIMS: Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C 
      (HCV) can be associated with drug-drug interactions (DDIs) with concomitant 
      medications. The practical clinical implications of such DDIs are poorly 
      understood. We assessed the clinical impact of possible pharmacokinetic (PK) 
      interactions between simeprevir and frequently prescribed concomitant 
      medications. METHODS: This post hoc analysis pooled data from nine studies which 
      evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of 
      frequently used concomitant medications of interest (CMOIs) were analysed 
      [antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs 
      (LLDs)] and categorized as amber or green according to their DDI potential with 
      SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant 
      medications not recommended to be coadministered with SMV were not included. The 
      composite primary endpoint was defined as the frequency of either 
      discontinuation, interruption or dose modification of the CMOI during 12 weeks of 
      SMV treatment. RESULTS: Few patients met the composite endpoint in the various 
      subgroups. Patients on amber CMOIs tended to experience CMOI modification more 
      often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference 
      in the frequency of adverse events between patients taking green and those taking 
      amber CMOIs. CONCLUSIONS: In this large pooled analysis, coadministration of the 
      evaluated commonly prescribed medications with known or potential PK interactions 
      with SMV was manageable and resulted in few adjustments of concomitant 
      medications. Our method could serve as a blueprint for the evaluation of the 
      impact of DDIs.
CI  - (c) 2018 The Authors. British Journal of Clinical Pharmacology published by John 
      Wiley & Sons Ltd on behalf of British Pharmacological Society.
FAU - Marra, Fiona
AU  - Marra F
AD  - Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown 
      Street, Liverpool, L69 3BX, UK.
FAU - Honer Zu Siederdissen, Christoph
AU  - Honer Zu Siederdissen C
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
FAU - Khoo, Saye
AU  - Khoo S
AD  - Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown 
      Street, Liverpool, L69 3BX, UK.
FAU - Back, David
AU  - Back D
AD  - Department of Molecular and Clinical Pharmacology, University of Liverpool, Crown 
      Street, Liverpool, L69 3BX, UK.
FAU - Schlag, Michael
AU  - Schlag M
AD  - Janssen Cilag Pharma GmbH, EMEA Medical Affairs, Vorgartenstrasse 206B, 1020, 
      Vienna, Austria.
FAU - Ouwerkerk-Mahadevan, Sivi
AU  - Ouwerkerk-Mahadevan S
AD  - Janssen Pharmaceutica, Turnhoutseweg 30, 2340, Beerse, Belgium.
FAU - Bicer, Ceyhun
AU  - Bicer C
AD  - BICER Consulting & Research, Oosterveldlaan 12 A, 2610, Antwerp, Belgium.
FAU - Lonjon-Domanec, Isabelle
AU  - Lonjon-Domanec I
AD  - Janssen-Cilag, 1 Rue Camille Desmoulins, 92130, Issy-les-Moulineaux, France.
FAU - Jessner, Wolfgang
AU  - Jessner W
AD  - Janssen Pharmaceutica, Turnhoutseweg 30, 2340, Beerse, Belgium.
FAU - Beumont-Mauviel, Maria
AU  - Beumont-Mauviel M
AD  - Janssen-Cilag, 1 Rue Camille Desmoulins, 92130, Issy-les-Moulineaux, France.
FAU - Kalmeijer, Ronald
AU  - Kalmeijer R
AD  - Janssen Global Services LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, 
      USA.
FAU - Cornberg, Markus
AU  - Cornberg M
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180221
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Protease Inhibitors)
RN  - 9WS5RD66HZ (Simeprevir)
SB  - IM
MH  - Anti-Anxiety Agents/*adverse effects/pharmacology
MH  - Anticholesteremic Agents/*adverse effects/pharmacology
MH  - Antihypertensive Agents/*adverse effects/*pharmacology
MH  - Clinical Trials as Topic/statistics & numerical data
MH  - *Drug Interactions
MH  - Drug Therapy, Combination/*adverse effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Meta-Analysis as Topic
MH  - Protease Inhibitors/pharmacokinetics
MH  - Simeprevir/*pharmacokinetics
PMC - PMC5903235
OTO - NOTNLM
OT  - DDI
OT  - HCV
OT  - SMV
OT  - drug-drug interaction
OT  - hepatitis C virus
OT  - simeprevir
EDAT- 2018/01/19 06:00
MHDA- 2019/06/25 06:00
PMCR- 2018/02/21
CRDT- 2018/01/19 06:00
PHST- 2017/08/30 00:00 [received]
PHST- 2018/01/03 00:00 [revised]
PHST- 2018/01/14 00:00 [accepted]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2018/01/19 06:00 [entrez]
PHST- 2018/02/21 00:00 [pmc-release]
AID - BCP13519 [pii]
AID - 10.1111/bcp.13519 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2018 May;84(5):961-971. doi: 10.1111/bcp.13519. Epub 2018 
      Feb 21.