Opana ER Pulled From Market Due to Abuse-Related Disorders

At the request of the Food and Drug Administration (FDA) the manufacturer of Opana ER, an opioid analgesic with a troubling history of abuse and public health crises, announced earlier this month that it was removing the drug from the market.

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Opana ER is not the only opioid drug with a potential for misuse and abuse. It is the first drug in this class, however, to be removed for dangers associated with abuse, even if not explicitly for its addictive properties.

While other opioids such as morphine and oxycodone are also abused, Opana ER tablet is somewhat unusual: contributing to some of its deadly consequences are the inactive ingredients, rather than the active ingredient.

The active ingredient in Opana ER is oxymorphone, one of several morphine-like molecules that effectively suppress pain but can lead to addiction in some individuals. Oxymorphone is approximately three times as potent as morphine when taken orally and up to 10 times as potent when injected directly intravenously. Oxymorphone, which was first marketed in 1959, is available as an injectable solution, rectal suppository, and immediate-release oral tablets. These formulations are not affected by the FDA’s decision and will remain available. Only the extended-release (ER) tablet, manufactured by Endo Pharmaceuticals, is the target of the removal.

Ironically, the current Opana ER tablet was designed to improve on an older formulation to prevent abuse. The older version of Opana ER tablet, which had been on the market from 2006 to 2011, was a simple formulation that released a small and steady amount of oxymorphone over 12 hours to maintain continuous pain relief. There were reports of abuse by crushing the tablet and snorting the powder.

In February 2012, Endo replaced the original Opana ER tablet with a new formulation. The new tablet contains a polymer known as polyethylene oxide (PEO) to make the tablet difficult to crush. If mixed with water, the tablet turns into a gel-like substance. The company had hoped to win the FDA’s “abuse deterrent” label for this formulation, but the agency rejected the request, noting that it did not reach the standard for abuse deterrence.

Unfortunately, the uncrushable new Opana ER did not stop its abuse. While snorting had decreased, more users found that it was easier to “melt” and dissolve the tablet with heat. The liquid could be injected intravenously to produce the desired effect. This practice caused complications more dangerous than snorting crushed tablets.

In 2012, 15 cases that looked like thrombotic thrombocytopenic purpura (TTP), a rare but serious blood disorder that can lead to tissue and organ damage, were reported in northern Tennessee within a span of just six months. An investigation by the state health department concluded that the illness was associated with injected Opana ER tablets. In animal experiments, the inactive ingredients, in Opana ER, including PEO, were found to be the likely cause of thrombotic microangiopathy (TMA).

Since then, cases of the same kind of blood disease have been reported to the FDA’s voluntary reporting system from around the country. Patients with TMA are often hospitalized and at least one has died. Treatment for TMA is limited to supportive care and, in some cases, plasma exchange and platelet transfusion.

In 2015, an outbreak of HIV infection involving 135 people was reported in a small rural community in Indiana. This outbreak was traced back to sharing needles while injecting Opana ER. In addition, 114 people were co-infected with hepatitis C. After interviewing some of these patients, the CDC concluded that the pharmacological properties of oxymorphone and the formulation of Opana ER both contributed to behaviors that led to the rapid spread of blood-borne infections.

In light of these health crises, the FDA held an advisory committee meeting in March. A panel of outside experts reviewed data presented by the agency and the CDC and voted 18-8, with one abstention, to agree with the position that the benefit of Opana ER no longer outweighed its risk, even though the risk comes from the misuse—not the intended use—of the drug.

The recommendation of the advisory committee led to the agency’s formal request for the voluntary removal of Opana ER three months later.

In an interview with Psychiatric News, the FDA said that a company in Endo’s position “can choose to comply and take steps for removing the product from the market, or can deny the request, and the FDA will issue a notification for an opportunity for hearing on a proposal to withdraw approval of the application.” ■