A sudden and substantial drop in prescription opioid dispensing matched by a similar decrease in opioid overdose has been noted within 2 years of the introduction of abuse-deterrent extended- release formulations of oxycodone (multiple brands) along with the removal of propoxyphene (multiple brands), a weak opioid, from the prescription market, new research shows.
Introduction of abuse-deterrent oxycodone and market withdrawal of propoxyphene occurred in August and November, respectively, of 2010.
Between August 2010 and December 2012, total opioid dispensing decreased by 19% from the expected rate across the United States. This was mirrored by a 20% drop in the estimated prescription opioid overdose rate.
However, the reduction in opioid overdose was accompanied by a 23% increase in heroin overdose during the same 2-year interval.
The study was published April 20 in JAMA Internal Medicine.
Shift to Heroin
Rates of heroin overdose had been increasing prior to the introduction of abuse-deterrent formulations and market changes, as investigators note, but there was a nonsignificant trend toward an acceleration of the previously increasing rates of heroin overdose once these changes had been put into place.
Prescriptions of extended-release oxycodone dropped by 39% in the 2 years following the formulation and market changes.
OxyContin (Purdue Pharma LP) had the greatest market share, at about 40%, prior to the formulation change, but it is not the only extended-release oxycodone product available on prescription.
“This is especially worrisome to me because it means that up to 39% of the use of extended-release oxycodone could have been going to people who were misusing it or diverting it,” Marc Larochelle, MD, MPH, who is a general internal medicine physician and researcher at Boston University School of Medicine, in Massachusetts, said.
“And some of these people may have moved on to heroin as a result.”
From 31.3 million persons between the ages of 18 and 64 years who are enrolled in a commercial health plan, researchers identified 13,816 opioid-overdose episodes during the study interval.
More than 12,000 of these cases of overdose, or 88% overall, involved prescription opioids, and approximately 1800, or 13.2%, were due to heroin overdose.
Prior to the introduction of the formula change in 2010, the dispensing rate for all opioids combined increased from 95.1 to 163 mg of morphine-equivalent dose (MED) per member per quarter.
“Immediately following the interventions, the dispensing rate dropped by 14.8 mg MED per member per quarter,” investigators note.
At the end of 2012, the dispensing rate for all opioids combined was an estimated 139 mg MED per member — or a 19% decrease from the expected rate, as determined on the basis of baseline trends.
The dispensing rate for all extended-release oxycodone products similarly had increased linearly from 22.9 to 27.7 mg MED per member per quarter through 2010, when the market changes occurred.
With regard to opioid subtype, the absolute change in dispensing by milligrams of MED per member per quarter at 2 years was -11.3 for extended-release oxycodone; 3.26 for other long-acting opioids; -8.19 for propoxyphene; and -16.2 for other immediate-release opioids.
“We can’t analyze how much of the [overdose] change was due to how much OxyContin was prescribed and how much was due to the withdrawal of propoxyphene,” Dr. Larochelle observed.
“However, we know that the death rate due to propoxyphene was higher than for other opioids of similar strength, and we also feel that propoxyphene use may be an entry into opioid misuse for individuals because it was so widely available,” he said.
“OxyContin is very strong, but even with its strength advantage, OxyContin was only about twice as strong as propoxyphene, so we took a lot of opioids off the market with the withdrawal of propoxyphene.”
Dr Larochelle also noted that there was a huge pendulum swing from the 1990s, when physicians were averse to dispensing opioids, to the 2000s, when they were much more likely to dispense opioids.
Now the pendulum has begun to swing the other way, as Dr Larochelle suggested, adding: “I think the key thing that we need to do is to try and dispense opioids in the most rational, appropriate, medical way possible.
“So we need to get better assessments in place so physicians can treat pain with confidence but have a way to identify when people move from the therapeutic use of opioids for pain into problem use.”
In an accompanying editorial, Hillary Kunins, MD, MPH, Bureau of Alcohol and Drug Use–Prevention, Care and Treatment, Queens, New York, confirms that rapid increases in the supply of opioid analgesics have largely driven the “nearly unremitting increase” in overdose deaths in the United States, which have grown by more than 150% during the past decade.
Because most overdoses do not occur among patients who are receiving daily prescribed opioids, market supply of opioids is one critical public health factor in stemming the tide of opioid overdose, Dr Kunins notes.
“With fewer opioids prescribed, beneficiaries with prescriptions consumed less, lowering individual risk,” she writes.
Fewer opioid prescriptions also likely led to fewer opioids being available for diversion to both beneficiaries and nonbeneficiaries alike, lowering population risk.
“Making long-acting oxycodone available only in an abuse-deterrent formulation may [also] have prevented diverted medications from being used parenterally or intranasally — both riskier than oral use,” Dr Kunins writes.
“And making long-acting opioids exclusively available in abuse-deterrent formulations, particularly for new medications as they are released to the market, is a structural lever that may minimize adverse public health consequences of long-acting opioids.”
The abuse-deterrent OxyContin formulation is resistant to crushing and dissolving, actions that have been used to bypass the extended-release mechanism to get a quicker and more intense high.
Propoxyphene was approved in 1957 for the treatment of pain. By 1977, it was the second leading agent in prescription drug–induced deaths.