Oxycodone/naloxone preparation can cause acute withdrawal symptoms when misused parenterally or taken orally

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. DISCUSSION: 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. CONCLUSION: Oxycodone with naloxone tablets can lead to acute opioid withdrawal symptoms if crushed and injected parentally. First dose, increased