PMID- 26787287
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20220410
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Linking)
VI  - 43
IP  - 6
DP  - 2016 Mar
TI  - Review article: safety and tolerability of direct-acting anti-viral agents in the 
      new era of hepatitis C therapy.
PG  - 674-96
LID - 10.1111/apt.13514 [doi]
AB  - BACKGROUND: Direct-acting anti-virals (DAAs) licensed to treat chronic HCV 
      infection have revolutionised treatment algorithms by drastically mitigating side 
      effects while enhancing efficacy relative to interferon-based therapy. AIM: To 
      review adverse events (AEs) uniquely associated with DAA therapy across a broad 
      spectrum of patient populations. METHODS: Searches of PubMed and FDA surveillance 
      studies were undertaken to complete an exhaustive review. Search terms included 
      'DAAs', 'safety', and 'tolerability'. RESULTS: While DAAs are remarkably well 
      tolerated, they are accompanied by unique AEs. Simeprevir, an NS3/4A protease 
      inhibitor, has been known, albeit infrequently, to cause mild hyperbilirubinemia 
      and photosensitivity reactions; and paritaprevir boosted with ritonavir causes 
      bilirubin and ALT elevations. Asunaprevir, another protease inhibitor, 
      infrequently causes elevated transaminase levels. NS5A and NS5B inhibitors are 
      well tolerated, although sofosbuvir is contraindicated in patients with severe 
      renal impairment. Ribavirin co-administered in certain treatment regimens has 
      been associated with cough, rash and haemolytic anaemia. CONCLUSIONS: With the 
      impending reality of a more tolerable interferon-sparing regimen, the future of 
      DAA therapy offers shorter treatment duration, simplified disease management, and 
      a patient-centred regimen. With advantages come drawbacks, including development 
      of resistance to therapy and accessibility to this expensive treatment. DAA 
      therapy continues to advance at a brisk pace with a promising trend for higher 
      tolerability, even in difficult-to-treat subgroups such as those with cirrhosis, 
      nonresponders to prior therapy, and transplant recipients. Subgroup-specific 
      contraindications and safety-related limitations are active areas of research. 
      Concerted research efforts and continuing advances lend hope to the goal of 
      rendering HCV a routinely curable disease.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Banerjee, D
AU  - Banerjee D
AD  - Hospital of the University of Pennsylvania, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Reddy, K R
AU  - Reddy KR
AD  - Hospital of the University of Pennsylvania, University of Pennsylvania, 
      Philadelphia, PA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160120
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Antiviral Agents)
RN  - 0 (Cyclopropanes)
RN  - 0 (Isoquinolines)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 9DLQ4CIU6V (Proline)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - O3J8G9O825 (Ritonavir)
RN  - OU2YM37K86 (paritaprevir)
RN  - S9X0KRJ00S (asunaprevir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
CIN - Aliment Pharmacol Ther. 2016 May;43(9):1021-2. PMID: 27040170
CIN - Aliment Pharmacol Ther. 2016 May;43(9):1022-3. PMID: 27040171
MH  - Aged
MH  - Antiviral Agents/*adverse effects/therapeutic use
MH  - Cyclopropanes
MH  - Drug Therapy, Combination
MH  - Female
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Humans
MH  - Isoquinolines/adverse effects
MH  - Lactams, Macrocyclic
MH  - Macrocyclic Compounds/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Proline/analogs & derivatives
MH  - Protease Inhibitors/*adverse effects/therapeutic use
MH  - Ritonavir/adverse effects
MH  - Simeprevir/adverse effects
MH  - Sofosbuvir/adverse effects
MH  - Sulfonamides/adverse effects
EDAT- 2016/01/21 06:00
MHDA- 2016/09/22 06:00
CRDT- 2016/01/21 06:00
PHST- 2015/09/24 00:00 [received]
PHST- 2015/10/25 00:00 [revised]
PHST- 2015/11/20 00:00 [revised]
PHST- 2015/12/13 00:00 [accepted]
PHST- 2016/01/21 06:00 [entrez]
PHST- 2016/01/21 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
AID - 10.1111/apt.13514 [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2016 Mar;43(6):674-96. doi: 10.1111/apt.13514. Epub 2016 
      Jan 20.