Petition calls for FDA to boot ultra-high dose opioids from market

Groups representing public health officials and doctors banded together Thursday to petition the US Food and Drug Administration to take ultra-high-dosage opioid pills, tablets and nasal sprays off the market. When prescribed, these opioids equal more than 90 milligrams of morphine (MME) a day in potency.

The petition is calling for the FDA to pull OxyContin 80mg off the market.

These can include higher dosages of both fast-acting, immediate-release opioids as well as slow-acting, longer-release formulations of oxycodone, hydromorphone, morphine, oxymorphone, hydrocodone, methadone and fentanyl.

The petition specifically requests the removal of OxyContin 80mg, which when taken twice a day equals 240 MME in 24 hours, as well as the removal of oxycodone 30mg, typically taken four times a day for the equivalent of 180 MME daily.

PhRMA, the pharmaceutical industry’s advocacy arm, declined to comment on the petition.

Although the US Centers for Disease Control and Prevention’s 2016 guidelines on opioid prescribing do not prohibit prescribing dosages over 90 milligrams of morphine a day, the agency says clinicians should generally avoid prescribing at such high levels and always start prescribing at the lowest doses. In cases in which they do have to prescribe at high levels, doctors need to use caution and have justified reasons.

Who needs ultra-high dosages?

It’s difficult to say just how many people are using high-dosage opioids because there haven’t been any published data to show what percent of the opioid market they represent or the number of prescriptions for them.

According to the petition, these higher opioid dosage units were an answer to increased patient tolerance as more and more doctors were prescribing opioids in the early 2000s. “Many (ultra-high-dosage unit) opioids entered the market as high dose opioid prescribing became more common,” the petition says.

And that’s in part because of how opioids work. The more a patient takes, the less sensitive their body is to that dosage, meaning a patient needs a higher dose to get the same pain relief.

“The thinking early on was, as patients became tolerant, you respond to tolerance by giving even more,” said Dr. Andrew Kolodny, executive director of Physicians for Responsible Opioid Prescribing, one of the groups filing the petition. However, as opioid overdoses in the United States have increased to epidemic proportions, there has been more scrutiny on how doctors prescribe.

In fact, nearly half of all opioid overdoses in 2015 were from prescription painkillers. Since 1999, according to the CDC, sales of prescription drugs have nearly quadrupled — and so have the number of overdose deaths involving prescription drugs.

High doses increase risk for addiction and overdose

Along with PROP, the petition is being filed by the Association of State and Territorial Health Officials, the National Safety Council and the American College of Medical Toxicology. The groups say that these ultra-high-dosage opioids increase risks for accidental overdoses and addiction.

The petition notes that in 2015, 11.5 million Americans misused a prescription opioid. The most common reason: pain relief. And that includes borrowing a friend’s extra pills and using a family member’s leftover narcotics.

“If you borrow someone’s pills and they are an ultra-high dose, there’s a good chance you’re going to suffer an overdose,” Kolodny said.

According to the CDC, doses at or above 50 MME a day double a person’s risk of overdose compared with someone with a dose of less than 20 MME a day.

Higher dosages also carry an increased risk for addiction. “A person taking a relatively low dose of prescribed opioids is 15 times as likely to develop an opioid use disorder (OUD) as a person who has not been prescribed opioids,” the petition says. At extremely high dosages of more than 120 MME a day, that risk soars to 122 times that of a person who has not taken an opioid.

Who’s using the drugs?

Kolodny believes that taking these high-dosage drugs off the shelves will help reshape opioid prescribing practices and encourage clinicians to prescribe at lower and safer doses. “The thought that (medications) exist in a higher dose gives you a false sense of security,” he said. “Say you are on the 60-milligram oxycodone. The fact that there is 80 milligram makes you think, ‘How high a pill can I be on?’ ”

If the FDA follows through on the petition, it will not be the first time it pulled drugs off of the shelves over public health concerns.

In July, Endo Pharmaceucticals pulled its opioid painkiller Opana ER after the FDA requested that it be taken off of the market because of “the public health consequences of abuse.” It was the first time the FDA had made such a request. The drug was connected to outbreaks of HIV and hepatitis C after injection drug users were crushing up the pill and injecting it.

“We are facing an opioid epidemic — a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Dr. Scott Gottlieb said when the agency made its request. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”

Dr. Jay Butler, president of the Association of State and Territorial Health Officials, explained that the new petition isn’t meant to make it more difficult for patients to get treatment.

It’s “important to recognize, in some instances, a high dosage is appropriate: people receiving palliative care, cancer pain. But there are options to receive these high doses without using the ultra-high dosages,” Butler said. For example, instead of using higher-dose pills fewer times a day, patients may be prescribed lower doses to take more frequently. He added that for patients who have difficulty swallowing pills, other forms of opioids, such as patches and suppositories, would still be available.

Unintended consequences

But Dr. Steven Stanos, president of the American Academy of Pain Medicine, said that focusing on the dosage itself could have some unintended consequences for patient treatment. The academy represents physicians practicing in the field of pain medicine.

Doctors need to consider how the medication overall is impacting a patient’s quality of life, he said. “Assess depression, anxiety, all these other types of social variabilities. How (the opioid is) impacting function,” he said. “If they’re thinking of just the morphine dose, they’re going to forget these other factors that are patient-specific.”

In addition, Stanos said, there is a concern that this could lead to further stigmatization for both patients and doctors. “We want to be helpful as we can as pain physicians … and turn the curve on overdose deaths,” he said. “But we don’t want patients to feel stigmatized. … We don’t want physicians to feel like they can’t use opioids appropriately.”

The new petition comes on the heels of a National Academies of Sciences report in July that says the FDA needs to create a new framework that incorporates evaluating the public health risks that opioids may present when assessing the risks of a narcotic.

The FDA has 180 days to respond to the petition.