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This is an official
CDC Health Advisory
Distributed via Health Alert Network
October 26, 2012, 18:00 ET (6:00 PM ET)
Cluster of Cases of Thrombotic Thrombocytopenic Purpura (TTP)
Associated with Intravenous Nonmedical Use of Opana ER®
The Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) are working with the Tennessee Department of Health (TDH) on investigating a cluster of at least 12 patients with thrombotic thrombocytopenic purpura (TTP) who have injected the opioid pain reliever, Opana ER® (oxymorphone extended-release), for nonmedical reasons since February, 2012. Investigation is ongoing.
This HAN notice provides information on the following:
Status of the Investigation
On August 13, a nephrologist notified the Tennessee Department of Health (TDH) of a cluster of 3 cases of TTP in a small rural community in northeastern Tennessee. All patients had a history of intravenous use of the prescription opioid pain reliever Opana ER, which is only intended to be taken orally. Initial cases were reported to the Food and Drug Administration by the manufacturer. The FDA contacted the CDC to discuss further investigation on October 5. The FDA issued an alert regarding the issue on October 11.
As of October 22, 2012, case-finding efforts by the TDH had uncovered a total of 12 cases among Tennessee residents. A case was defined as hemolytic anemia combined with thrombocytopenia (platelet count <50,000/microliter) in the absence of any obvious explanation such as advanced cancer or systemic infection. The first case was diagnosed on April 16, the index cluster in mid-July, and the most recent case on October 19. Eleven of 12 case patients were non-pregnant women 20 to 50 years of age. All were hospitalized, and 10 were treated with plasmapheresis. At least 5 patients have had recurrent episodes, but no deaths have occurred. All 12 patients reported IV use of Opana ER® to the TDH or to hospital staff. Case patients all had a history of chronic IV use of Opana ER® for nonmedical purposes until 1-2 days prior to diagnosis. Most patients did not have a prescription for Opana ER® and obtained the drug from other, undisclosed sources. The TDH is conducting a case-control study.
Background on TTP and Opana ER
TTP is an uncommon but serious illness, with an incidence of approximately 1 per 100,000 per year and a high case-fatality rate if not treated. Fewer than 15% of TTP cases can be attributed to specific exposures, with quinine and anti-platelet drugs being the primary substances responsible. Drugs are thought to cause TTP by an immune-mediated mechanism or by direct toxicity. Abnormally low levels of ADAMTS13 are found in some but not all cases. Most cases of drug-associated TTP occur in women.
Opana ER® is an extended-release formulation of oxymorphone, a Schedule II prescription opioid pain reliever manufactured by U.S.-based Endo Pharmaceuticals, Inc. Oxymorphone is roughly three times as potent as oral morphine. Opana ER is approved for the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time. Opana ER® has been available in the United States in pill form for oral use since 2006. In the fourth quarter of 2011, 226,000 prescriptions for Opana ER® were written in the US, compared with 1,279,000 prescriptions for OxyContin.
Although Opana ER® is prescribed less frequently than other extended-release opioid pain relievers such as OxyContin, it is popular among people who abuse prescription drugs. The Drug Enforcement Administration labeled oxymorphone as a drug of concern in 2011 due to reports of increased abuse. People who use Opana ER® nonmedically might refer to the pills as “panda bears,” “stop signs,” or “octagons.”
A new formulation of Opana ER® designed to be more difficult to abuse became available in February, 2012 and has gradually replaced the original formulation. The new formulation was designed to prevent a person from pulverizing the pills or dissolving them for injection; however, some users have developed a way to manipulate the pills to allow their injection. The new formulation contains some inactive ingredients not found in the original formulation, including polyethylene oxide (PEO), polyvinyl alcohol, and talc.
No cases of TTP related to oral use of Opana ER® have been reported, and nothing indicates that use of Opana ER® as prescribed presents a risk of TTP.
Recommendations for Clinicians
The extent of this problem is not clear because there is no requirement to report such cases and because IV drug use might not be suspected or reported among patients with TTP. To provide optimal care and assist in public health surveillance, the CDC recommends that:
CDC Case Definition
The current case definition for IV drug abuse-related TTP is a diagnosis of TTP since February 1, 2012 in a person who had used drugs intravenously for nonmedical reasons.
FDA drug alert: http://www.fda.gov/Drugs/DrugSafety/ucm322432.htm
DEA drug alert: http://www.deadiversion.usdoj.gov/drugs_concern/oxymorphone.pdf
CDC contact for additional information: Len Paulozzi, MD, (770) 365-7616; firstname.lastname@example.org