Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
I think we all agree that opioids need to be held to a high standard for approval because of their risks, as well as high rate of misuse and abuse. Please consider these questions as you evaluate Hydexor.
1. Should the FDA approve additional conventional opioids?
Commissioner Gottlieb has stated that the FDA’s response to the opioid crisis includes shifting the opioid market from one dominated by conventional opioids to one dominated by opioids with meaningful abuse deterrent properties. Since Hydexor does not have any abuse-deterrent properties, it would NOT fit that goal.
2. Should the FDA approve drugs that combine an opioid that causes unpleasant side effects with a drug to counter those same side effects?
The novelty of Hydexor is that it combines hydrocodone with a drug to prevent the nausea and vomiting caused by hydrocodone. That can encourage patients to take hydrocodone and to continue relying on it.
Commissioner Gottlieb recently warned the public about the abuse of loperamide, a drug that prevents unpleasant opioid withdrawal symptoms. Since Hydexor contains a drug component that prevents unpleasant side effects, it too has a high potential for abuse. Does it make sense to approve Hydexor given this added potential for abuse?
3. What does the human abuse potential study and postmarket data tell us about how this drug would be used?
The human abuse potential study only looked at oral administration. It did not test the abuse potential for other routes such as snorting or IV injection. In addition, it is not clear if there would be a difference in preference for users who experience nausea and vomiting. Hydexor uses a version of promethazine with faster bioavailability which could make it more likely to be abused. But the bottom line is there are reasons to be very concerned about abuse of this drug, and the studies don’t give us enough information to counterbalance those concerns.
It is also difficult to predict how Hydexor would be used in a clinical setting. Not all patients need an anti-nausea drug when they take hydrocodone, however, if heavily promoted, and we know that is likely, Hydexor could be prescribed by doctors to help their patients avoid nausea that they wouldn’t necessarily have experienced. This would expose many patients unnecessarily to adverse events resulting from the addition of promethazine
4. Is this drug safe for older adults?
The safety data indicate that patients in taking Hydexor were more likely to faint and/or fall. However, only a small number of patients 65 and older were included in the clinical trials. Older persons are especially susceptible to drugs that cause sedation or drops in blood pressure. Hydexor has two active ingredients which can potentially cause dangerous cumulative effects. This drug was not studied in enough patients over 65 to determine how risky it might be for them.
5. Are the sponsor’s proposed mechanisms for reducing the risk for misuse adequately address this potential?
The sponsor proposes that the 3-, 5-, and 7-day packaging will help to reduce prescribing large amounts. However, these packages are based on 6 pills a day, while patients took an average of 2-3 pills a day during the “as needed” portion of the trials. If a clinician expected a patient to use 15 pills over the course of 5 days and prescribed the 5-day pack, the patient would have twice as many pills as they were expected to take.
The proposed drug return program could be a great option to remove unneeded opioid pills. However, we do not have data on how well it would work or whether patients and caregivers would use the program. Therefore, we cannot count on it. As you know, many patients keep old prescriptions, especially pain pills, “just in case”, and that contributes to misuse and abuse by patients and their family members.
In conclusion, consider how this drug fits into the context of the drug market and how it is likely to be used or misused. Do the benefits outweigh the risks of putting another conventional opioid on the market, one that is designed to treat its own side effects, and are the attempts to reduce excess pills sufficient? Opioids provide both a benefit and a harm in our society. As Advisory Board members, please advise the FDA to carefully and cautiously consider the potential for abuse of this opioid.
The Anestetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSARM) voted 19-2 against approval of Hydexor; for more information about the Committee members’ views, see https://www.medscape.com/viewarticle/892730.