[New York Times] The abuse of prescription painkillers has reached epidemic proportions in America.
Nearly half of the nation’s 38,329 drug overdose deaths in 2010 involved painkillers like hydrocodone and oxycodone, according to the Centers for Disease Control and Prevention. These narcotics now kill more adults than heroin and cocaine combined, sending 420,000 Americans to emergency rooms each year.
So many state health officials and advocacy groups were incredulous last fall when the Food and Drug Administration approved an even more powerful prescription painkiller — against the advice of its own expert advisory committee.
The drug is Zohydro ER, a long-acting formulation of the opioid hydrocodone. The short-acting form, sold under brand names like Vicodin and Lortab, is already the most prescribed drug in the country, and the most abused.
In March, Gov. Deval Patrick of Massachusetts sought to ban Zohydro outright, calling it “a potentially lethal narcotic painkiller.” The manufacturer, Zogenix of San Diego, went to court, and last week a federal judge struck down the ban pending further legal action.
But other states in New England are moving to restrict the use of Zohydro, and 29 state attorneys general have asked the F.D.A. to reconsider its approval.
“People are fearful this will be another original OxyContin,” said Sharon Walsh, director of the Center on Drug and Alcohol Research at the University of Kentucky, referring to an early formulation of the painkiller that resulted in a wave of prescription drug deaths in the 1990s and early 2000s. (OxyContin is now available in an abuse-deterrent formulation.)
Zohydro is pure hydrocodone in an extended-release formulation. It is intended for people suffering from chronic pain who now must take short-acting hydrocodone pills every few hours around the clock. Since it does not contain acetaminophen, the new drug will provide steady relief without the risk of liver damage, according to officials at Zogenix. Dr. Bradley Galer, chief medical officer for Zogenix, said the company had fulfilled all of the F.D.A.’s requirements for approval, and there was no reason to treat the medication differently from other extended-release opioids already on the market.
But critics note that Zohydro is being made available in doses of up to 50 milligrams of hydrocodone — or five times greater than the largest doses of immediate-release pills. Moreover, Zohydro is sold in capsules that can be crushed into doses to be snorted, injected or sold.
And it is not available in an abuse-resistant formulation, though company officials say they are doing research to develop one. At the moment, the company is offering pill bottles with combination locks on the caps, as well as lockboxes for storing the drug.
F.D.A. officials say they have an obligation to approve new treatment options for the more than 100 million Americans who live with chronic pain, which can be debilitating and can prevent them from working and living productive lives, though that figure has been questioned.
“To say to people with chronic pain who are taking opiates around the clock that we shouldn’t offer them an extended-release option is unnecessarily penalizing the patient,” Dr. Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, said in an interview. “We need to balance the medical needs of people in severe pain with the risks of these medications, including the risk of abuse and addiction.”
The F.D.A. has instituted a slew of new measures intended to restrict access to opioids and curb abuse. The agency has eliminated automatic refills and strengthened the language on warning labels. Earlier this month, the agency quickly approved a prescription medication that can be used as an injection to treat someone who has overdosed on opioids.
Officials are requiring post-marketing studies of Zohydro to monitor abuse, addiction, overdoses and deaths, as well as a reaction called hyperalgesia, a condition that makes users of painkillers even more sensitive to pain over time.
Members of the F.D.A. committee who voted against approval acknowledged they were influenced by the drug overdoses claiming more and more lives each year. But they were also disturbed by red flags raised during the clinical trials of Zohydro.
Several pointed to what one member called “very modest” reductions in pain scores among trial participants. And some members felt a 12-week trial was not long enough to prove Zohydro was effective for chronic pain, which is defined as lasting more than three months. Many experts do not recommend opioids for chronic pain.
“When you talk to pain specialists in our field, they will all tell you one indisputable fact — opiates are lousy drugs to treat chronic pain,” Dr. Vesna Jevtovic-Todorovic, an anesthesiologist and committee member, told her colleagues, according to a transcript of the Dec. 7, 2012, meeting.
A number of patients had to leave the study because they had serious adverse side effects or didn’t comply with the terms of the trial. Many could not account for all of the pills they had been given.
Fewer than 300 subjects made it through a full year in the long-term safety trial, and there were five deaths. Two were attributed to serious terminal illnesses; one participant committed suicide and another died of a toxic mix of drugs. A third committed suicide 13 months after the study ended; that death also involved drugs.
“You still have a 1 percent, almost, death rate from this drug,” said Dr. Jeanmarie Perrone, a committee member from the University of Pennsylvania. What will happen in the doctor’s office, she wondered, where those receiving the drug will not be as carefully screened?
Among the most vocal opponents of Zohydro are parents who have lost children to drug abuse and addiction. But millions of others live with chronic pain caused by arthritis accidents and other issues. “The right answer would be medication that takes away the pain and isn’t addictive,” said Paul Gileno, president of the U.S. Pain Foundation. “That would be perfect.”