title: Oxycodone/naloxone preparation can cause acute withdrawal symptoms when misused parenterally or taken orally.
abstract: BACKGROUND
  Oral oxycodone/naloxone preparations are designed to reduce the incidence of constipation associated with oxycodone use. The low oral bioavailability (< 2%) of naloxone makes the precipitation of the acute opioid withdrawal symptoms unlikely following oral oxycodone/naloxone exposure. The incidence of acute opioid withdrawal symptoms following both oral and intravenous administration of oxycodone/naloxone preparations has not been described.
  
  
  OBJECTIVE
  The aim of the study was to investigate the incidence and circumstances associated with oxycodone/naloxone-induced acute opioid withdrawal.
  
  
  METHODS
  An observational case series of acute opioid withdrawal following oxycodone/naloxone administration were selected from all calls received by the Victoria Poisons Information Centre from January 2012 to December 2014. Data collected included patient demographics, reported symptoms, type of caller, intentional or accidental exposure and advice given.
  
  
  RESULTS
  There were 107 reported exposures to oxycodone/naloxone preparations. Route of exposure was oral in 92 (86%) and intravenous injection of crushed tablets in 14 (14%) of cases, respectively. Nine callers had a history of long-standing opioid treatment and developed withdrawal symptoms with oral oxycodone/naloxone. Temporal relationship between first dose, increased dose and chewing tablets was described. There were 14 exposures to crushed oxycodone/naloxone tablets injected intravenously; all precipitated an acute withdrawal state.
  
  
  CONCLUSIONS
  The development of opioid withdrawal symptoms with intravenous injection of oxycodone/naloxone is likely a result of bypassing first-pass metabolism. Withdrawal symptoms after ingesting increased dose, first dose or chewing oxycodone/naloxone suggests that there is a systemic absorption of naloxone in opioid-dependent callers.
  
  
  CONCLUSIONS
  Oxycodone with naloxone tablets can lead to acute opioid withdrawal symptoms if crushed and injected parentally. First dose, increased dose and chewing of these opioid-naloxone combination tablets in opioid-dependent people can also result in acute opioid withdrawal symptoms or diminished pain relief.
authors.affiliation: Victorian Poisons Information Centre and Austin Toxicology Service, Austin Health , Heidelberg, Victoria , Australia.
authors.forename: Anselm
authors.initials: A
authors.lastname: Wong
authors.forename: Dawson
authors.initials: D
authors.lastname: Macleod
authors.forename: Jeff
authors.initials: J
authors.lastname: Robinson
authors.forename: Zeff
authors.initials: Z
authors.lastname: Koutsogiannis
authors.forename: Andis
authors.initials: A
authors.lastname: Graudins
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Greene
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D011039:Poison Control Centers; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D013607:Tablets; D014739:Victoria / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations; D009292:Narcotic Antagonists; D013607:Tablets; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
keywords: Antidote; Opioid; Therapeutic; poisoning