PMID- 30049994
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 11
IP  - 3
DP  - 2018 Jul 26
TI  - Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated 
      (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric 
      Population: History and Safety.
LID - 10.3390/ph11030075 [doi]
LID - 75
AB  - Polyethylene glycol (PEG) is an inert, water soluble polymer, used for decades in 
      pharmaceuticals. Although PEG is considered safe, concerns persist about the 
      potential adverse effects of long-term exposure to PEG-containing therapies, 
      specifically in children, following the introduction of PEGylated recombinant 
      factor products used for the treatment of hemophilia. Given the absence of 
      long-term surveillance data, and to evaluate the potential risk, we estimated PEG 
      exposure in the pediatric population receiving PEGylated therapies with pediatric 
      indications administered intravenously or intramuscularly. We used a range of 
      pediatric weights and doses based on prescribing information (PI) or treatment 
      guidelines. PIs and reporting websites were searched for information about 
      adverse events (AEs). For a child weighing 50 kg on the highest prophylactic dose 
      of a FVIII product, the range of total PEG exposure was 40(-)21,840 mg/year; for 
      factor IX (FIX) products, the range was 13(-)1342 mg/year; and for other products, 
      the range was 383(-)26,743 mg/year, primarily as a derivative excipient. No AE 
      patterns attributable to PEG were found for any of these products, including 
      potential renal, neurological, or hepatic AEs. Our analyses suggest the pediatric 
      population has had substantial exposure to PEG for several decades, with no 
      evidence of adverse consequences.
FAU - Stidl, Reinhard
AU  - Stidl R
AD  - Baxalta Innovations GmbH, Shire, Industriestrasse 67, 1220 Vienna, Austria. 
      reinhard.stidl@shire.com.
FAU - Denne, Michael
AU  - Denne M
AD  - Shire, Bank of America Plaza, 540 W Madison St, Chicago, IL 60661, USA. 
      michael.denne@shire.com.
FAU - Goldstine, Jimena
AU  - Goldstine J
AD  - Shire, Bank of America Plaza, 540 W Madison St, Chicago, IL 60661, USA. 
      jimenag@gmail.com.
FAU - Kadish, Bill
AU  - Kadish B
AD  - PAREXEL International, 433 Hackensack Avenue, 10th Floor, Hackensack, NJ 07601, 
      USA. Bill.Kadish@ppsigroup.com.
FAU - Korakas, Katherine I
AU  - Korakas KI
AD  - PAREXEL International, 433 Hackensack Avenue, 10th Floor, Hackensack, NJ 07601, 
      USA. Kate.Korakas@PAREXEL.com.
FAU - Turecek, Peter L
AU  - Turecek PL
AUID- ORCID: 0000-0002-6161-1556
AD  - Baxalta Innovations GmbH, Shire, Industriestrasse 67, 1220 Vienna, Austria. 
      peter.turecek@shire.com.
LA  - eng
PT  - Journal Article
DEP - 20180726
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC6160981
OTO - NOTNLM
OT  - PEGylation
OT  - biologics
OT  - conjugation
OT  - excipient
OT  - hemophilia
OT  - pediatric
OT  - polyethylene glycol
OT  - polysorbate
OT  - rurioctocog alfa pegol
OT  - safety
COIS- M.D. and P.L.T. are full-time employees of Shire; R.S. and J.G. were full-time 
      employees of Shire at the time of the present study. M.D., P.L.T. and R.S. are 
      Shire shareholders. B.K. and K.I.K. are full-time employees of PAREXEL 
      International.
EDAT- 2018/07/28 06:00
MHDA- 2018/07/28 06:01
PMCR- 2018/09/01
CRDT- 2018/07/28 06:00
PHST- 2018/06/25 00:00 [received]
PHST- 2018/07/21 00:00 [revised]
PHST- 2018/07/23 00:00 [accepted]
PHST- 2018/07/28 06:00 [entrez]
PHST- 2018/07/28 06:00 [pubmed]
PHST- 2018/07/28 06:01 [medline]
PHST- 2018/09/01 00:00 [pmc-release]
AID - ph11030075 [pii]
AID - pharmaceuticals-11-00075 [pii]
AID - 10.3390/ph11030075 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2018 Jul 26;11(3):75. doi: 10.3390/ph11030075.