In 2011, there were an estimated 17,000 deaths in the US resulting directly from the use of opioids, according to the US Centers for Disease Control and Prevention. Additionally, drug deaths due to addictive prescription drugs, including opioids, are greater than 3 times what they were 20 years ago. Opioids can be abused through a number of delivery methods, including orally, snorting, or dissolution into liquid form for injection.
The science of abuse deterrence is relatively new and evolving rapidly. Pharmaceutical manufacturing companies are responding to a call to action for creating abuse-deterrent formulations that target anticipated abuse strategies. However, whereas abuse-deterrent properties may help the cause, they do not make an opioid impossible to abuse, and do not prevent all cases of overdose or death.
Suboxone and Subutex: The Opioid Substitutes
In 2002, the FDA approved Suboxone and Subutex for opiate dependence treatment. These drugs are used to prevent the often deadly symptoms related to withdrawal from opiates. In order to ingest these substitutes, you cannot inject, crush, or snort them, which prevents the triggers for abusive behaviors for addicts dealing with opioid abuse. Historically, methadone has been used for opioid addiction recovery. However, methadone must be dispensed in methadone clinics, which greatly limits the application of this treatment method. Suboxone and Subutex are prescribed in a doctor’s office, under far fewer restrictions, thus increasing access to this life-altering treatment.
These new options for the treatment of opioid addicts are encouraging for those who are struggling with opioid dependency, which can often occur following the legal use of opioids, such as Zohydro. However, the introduction of more powerful, and more addictive, opioid prescription drugs is contradictory to these new treatment methods for opioid addiction.
Dr. Hamburg Hanging up Her Hat?
One of the most influential names in the prescription drug business is Dr. Margaret Hamburg, the FDA commissioner. According to recent reports by Politico, Dr. Hamburg may soon have to step down from her position. The main reason? Zohydro, a pure form of the opioid hydrocodone, was approved by the FDA nearly a year ago. This prescription pain medicine is the first extended-release hydrocodone to be approved in the US market.
Unlike previously available immediate-release hydrocodone, this more powerful extended-release version is much more dangerous for addicts. The National Center for Biotechnology Information addresses the differences between extended-release and immediate-release opioids:
“Extended-release (ER) formulations hold a greater attraction for abusers than immediate-release (IR) formulations because of their per-dose level of drug. ER opioid formulations provide higher drug concentrations that can be manipulated. When ER formulations are altered, not only is there a more rapid onset of action (a shorter Tmax) than that proposed by the manufacturer; there is also greater euphoria or anxiolysis, an affect that abusers desire.”
For the drug Zohydro, the application of ER properties in the purest form of this opioid is all but a deterrent to the application of non-abusive opioids. That is not always the case, however, given the other available opioids that do deter abuse, often through the use of IR formulations.
FDA Labels Abuse-Deterrent Opioids
In this battle, the FDA drafted a guidance in January 2013 to aid in the evaluation and labeling of opioids to deter the abuse of opioid prescription drugs. Via this guidance, sponsors are given the tools needed to make informed decisions about the formulations of opioid drugs in accordance with their abusive properties. The FDA acknowledges that while opioid drugs are used to manage pain legally, there is the possibility of addiction and abuse. This has created a public epidemic of opioid dependency. According to this drafted guidance, sponsors should look at 6 areas when formulating new opioid-based medications:
- Physical and chemical barriers related to ingestion, ie, chewing, injecting, and solvent extraction
- Agonist and antagonist combinations that change the effect of the opioid depending on the method of ingestion
- Aversive application that encourages unpleasant feelings when the opioid is used incorrectly
- Delivery systems, such as via subcutaneous implant or depot injectable, that deter from using physical or chemical methods for abuse
- Prodrug that ensures opioids are only applicable when in the gastrointestinal track, thus deterring from euphoria associated with snorting or chewing
- Combining more than one of the above application methods for abuse-deterrent opioids
The technology and research prove it. Pharma could be a strong advocate for the reduction of opioid abuse in legally obtained prescriptions, if they applied the guidance suggested by the FDA with regard to deterring opioid abuse.
- Abuse-Deterrent Opioids—Evaluation and Labeling. Draft Guidance. U.S. Food and Drug Administration website. January 2013. http://www.fda.gov/downloads/drugs/guidance complianceregulatoryinformation/guidances/ucm334743.pdf.
- Dr. Margaret Hamburg – the 25 most influential people in biopharma today. Fierce Biotech website. http://www.fiercebiotech.com/special-reports/25-most-influential-people-biopharma-today/dr-margaret-hamburg-25-most-influential-p.
- Drug-poisoning deaths involving opioid analgesics: United States, 1999–2011. Centers for Disease Control and Prevention website. September 2014. http://www.cdc.gov/nchs/ data/databriefs/db166.htm.
- Moorman-Li R, Motycka CA, Inge LD, Myrand Congdon J, Hobson S, Pokropski B. A review of abuse-deterrent opioids for chronic nonmalignant pain. Pharmacy Therapeutics. 2012;37(7):412-418. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411218/.
- Ouster of FDA chief urged. Politico website. Updated September 24, 2014. http://www.politico. com/story/2014/09/ouster-of-fda-chief-urged-111278.html.
- Subutex and Suboxone approved to treat opiate dependence. U.S. Food and Drug Administration website. October 8, 2002. http://www.fda.gov/Drugs/DrugSafety/ ucm191521.htm.