Oxycodone in combination with naloxone in managed-release tablets, has been formulated to both deter abuse and reduce "opioid-induced constipation". Dependence and withdrawal
The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and discontinues oxycodone abruptly. Medically, when the drug has been taken regularly over an extended period, it is withdrawn gradually rather than abruptly. People who regularly use oxycodone recreationally or at higher than prescribed doses are at even higher risk of severe withdrawal symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, and other flu-like symptoms".Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy. Hormone levels
As with other opioids, chronic use of oxycodone (particularly with higher doses) often causes concurrent hypogonadism (low sex hormone levels). Overdose
In high doses, overdoses, or in some persons not tolerant to opioids, oxycodone can cause shallow breathing, slowed heart rate, cold/clammy skin, pauses in breathing, low blood pressure, constricted pupils, circulatory collapse, respiratory arrest, and death.In 2011, it was the leading cause of drug-related deaths in the U.S. However, from 2012 onwards, heroin and fentanyl have become more common causes of drug-related deaths.Oxycodone overdose has also been described to cause spinal cord infarction in high doses and ischemic damage to the brain, due to prolonged hypoxia from suppressed breathing. Interactions
Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6.
Doctors in the 1990s often would switch their patients to a dosing schedule of once every eight hours when they complained that the duration of action for OxyContin was too short to be taken only twice a day.Purdue strongly discouraged the practice: Purdues medical director Robert Reder wrote to one doctor in 1995 that "OxyContin has been developed for [12-hour] dosing...I request that you not use a [8-hourly] dosing regimen." Purdue repeatedly released memos to its sales representatives ordering them to remind doctors not to deviate from a 12-hour dosing schedule. One such memo read, "There is no Q8 dosing with OxyContin... [8-hour dosing] needs to be nipped in the bud. NOW!!" The journalists who covered the investigation argued that Purdue Pharma has insisted on a 12-hour duration of action for nearly all patients, despite evidence to the contrary, to protect the reputation of OxyContin as a 12-hour drug and the willingness of health insurance and managed care companies to cover OxyContin despite its high cost relative to generic opiates such as morphine.Purdue sales representatives were instructed to encourage doctors to write prescriptions for larger 12-hour doses instead of more frequent dosing. An August 1996 memo to Purdue sales representatives in Tennessee entitled "$$$$$$$$$$$$$ Its Bonus Time in the Neighborhood!" reminded the representatives that their commissions would dramatically increase if they were successful in convincing doctors to prescribe larger doses.