title: Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials.
abstract: BACKGROUND
  Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.
  
  
  METHODS
  Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412).
  
  
  RESULTS
  At the data cutoff, median exposure to levodopa-carbidopa intestinal gel was 911 days (range, 1-1980 days) with 963 total patient-years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non-procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non-procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment-emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered "possibly related" to the treatment system.
  
  
  CONCLUSIONS
  In the largest collection of levodopa-carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non-procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients.
authors.affiliation: Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and Division of Neurology, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Ramon L
authors.initials: RL
authors.lastname: Rodriguez
authors.affiliation: University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Boyd
authors.affiliation: University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chouinard
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Zadikoff
authors.affiliation: University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Espay
authors.affiliation: University of Kentucky Medical Center, Lexington, Kentucky, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Slevin
authors.affiliation: Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.affiliation: Keck/University of Southern California School of Medicine, Los Angeles, California, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lew
authors.affiliation: Quintiles, San Diego, California, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Stein
authors.affiliation: Klinikim-Bremerhaven, Germany and Skane University Hospital, Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Odin
authors.affiliation: Westmead Hospital and Sydney Medical School, Sydney, Australia.
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
authors.affiliation: Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Klostermann
authors.affiliation: Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and Division of Neurology, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fasano
authors.affiliation: University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Draganov
authors.affiliation: University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Schmulewitz
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Eaton
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Benesh
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Dubow
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002230:Carbidopa / Q000008:administration & dosage / Q000009:adverse effects*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D004338:Drug Combinations; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects*; D005782:Gels; D006801:Humans; D007263:Infusions, Parenteral / Q000009:adverse effects*; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D010300:Parkinson Disease / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa
keywords: Levodopa-carbidopa intestinal gel; Parkinson's disease; infusion; percutaneous endoscopic gastrojejunostomy; safety