Drug users who inject the new "abuse-deterrent" version of Opana ER (oxymorphone) may be at risk of developing a serious blood disease, according to Tennessee health officials.
A total of 15 cases of thrombotic thrombocytopenic purpura (TTP) have been reported among injection-drug users in the state since the new formulation of the opioid painkiller was launched in February 2012, David Kirschke, MD, of the Tennessee Department of Health, and colleagues reported in the Jan. 10 issue of the Morbidity & Mortality Weekly Report.
"Healthcare providers who prescribe Opana and pharmacists who dispense it should inform patients of the risks from the drug when used other than as prescribed," they wrote.
Both the and the recently issued warnings about the link between Opana abuse and TTP -- a condition characterized by blood clots in small vessels throughout the body that can lead to organ damage.
Last August, a nephrologist reported three cases of TTP to Tennessee health officials, all of which had occurred in injection-drug users who lived in a rural county in the northeastern part of the state.
Health officials launched a statewide investigation and found a total of 15 cases of TTP among injection-drug users; 14 occurred in patients who reported dissolving and injecting reformulated Opana. There were no deaths.
Most of the cases (13) were women, who are generally at higher risk for TTP than men, and the overall sample ranged in age from 22 to 49.
Patients had reported symptoms characteristic of TTP, including nausea, abdominal pain, fatigue, and fever, officials said.
Investigators also conducted a case-control study, recruiting 28 controls from a state methadone clinic who'd injected drugs within the last 6 months. Seven had injected reformulated Opana.
Overall, they found a strong link between TTP and shooting up the reformulated version of the drug (OR 35.0, 95% CI 3.9 to 312.1).
It's not clear what aspect of reformulation could be causing the blood disorder. Another opioid painkiller subject to wide injection abuse, OxyContin, launched an abuse-deterrent formulation in 2010 but has not been linked to TTP, according to Tennessee health officials.
The inactive ingredients not found in the original version of Opana ER include polyethylene oxide (PEO) and polyethylene glycol (PEG) -- but officials noted that reformulated OxyContin also contains PEO and has not been tied to the same problems.
The condition could also have something to do with the methods of preparing the drug for injection, the researchers added.
They largely ruled out the possibility of adulterated product because at least two of the patients got their drugs directly from a pharmacy and all of the communities involved are far enough apart to make a single, nonmedical source unlikely.
"I would speculate that it relates to endothelial damage from a component of the new formulation," David Juurlink, MD, PhD, a drug safety researcher at the University of Toronto who was not involved in the study, told 鶹ý. "It's not likely the drug itself."
Indeed, no other opioids have been associated with TTP, though other agents, including platelet aggregation inhibitors, quinine, and cocaine, are known to increase the risk of the condition.
There are few data on occurrences of TTP in Opana abusers in other states. Health officials in Kentucky told 鶹ý that their state is also investigating "a couple of cases" of TTP that may be tied to Opana abuse but could not disclose more details of the investigation.
Opana drugmaker Endo Pharmaceuticals has been trying to block generic versions of its drug that do not contain abuse-resistance technology.
One such generic, made by Impax Labs, started shipping last week.
The FDA also recently launched guidance for industry on developing abuse-deterrent opioids -- an area in which the science is "relatively new," officials said.
Disclosures
The researchers reported no conflicts of interest.
Primary Source
Morbidity & Mortality Weekly Report
Marder E, et al "Thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse -- Tennessee 2012" MMWR 2013; 62(1): 1-4.