Last week (April 26, 2016), the US Food and Drug Administration (FDA) approved Xtampza (oxycodone extended-release), a twice-daily abuse deterrent formulation (ADF).1 Xtampza indications follow the same updated FDA template indications we see for all extended release opioids and is “indicated for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate”.1
Xtampza is the sixth officially FDA approved abuse-deterrent opioid formulation, which include OxyContin (oxycodone), Embeda (morphine sulfate and naltrexone ER), MorphaBond (morphine sulfate ER), Targiniq (oxycodone and naloxone ER tablets), and Hysingla ER (hydrocodone ER tablets).2 There are others that are arguably abuse deterrent but do not meet the FDA specifications for such labeling.
Here to school us all on the new oxycodone ER formulation is “Dr.” Mena Raouf who will be an official PharmD after one more week of experiential learning at the Albany College of Pharmacy and Health Sciences.
Oxycodone Where Are We?
Prescriptions for extended-release oxycodone have declined from 7.3 million in 2010 to 4.7 million in 2014 while prescriptions for immediate release oxycodone have increased from 10.4 million in 2010 to 15.8 million. 3
OxyContin (oxycodone extended-release) was first approved in 1995.2 However, its original extended-release formulation was manipulated to allow more rapid release of the drug, leading to increased risk of overdose and deaths. In 2010, the FDA approved a reformulated OxyContin with abuse-deterrent properties and the original OxyContin was withdrawn from the market.4 The reformulated OxyContin was more difficult to inject or snort but as all opioids, it was still vulnerable to misuse by oral route. Drug abuse “chefs” found methods to marinate, microwave, and microwave the tablets to bypass the extended-release profile allowing for more rapid release.5
The introduction of Purdue’s “new and improved” OxyContin 2.0 started a new era of abuse-deterrent formulations (ADF). Of note, soon after in 2011, Endo Pharmaceuticals reformulated Opana (oxymorphone extended-release) to a crush resistant preparation and pulled the original Opana from the market.2
Xtampza; New Kid on the Block
Xtampza is formulated using DETERx® technology where the agent is combined with fatty acids and waxes and incorporated into microspheres designed to resist physical and chemical manipulations to reduce particle size (chewing, crushing, breaking, and dissolving).6
How Does Xtampza Differ From The Reformulated OxyContin?
OxyContin is a tablet while Xtampza is a capsule. OxyContin’s extended-release profile relies on the overall tablet integrity that could be vulnerable to misuse by oral route. On the contrary, Xtampza’s extended-release profile relies on the individual microsphere rather than the capsule6, rendering it likely more difficult to manipulate from a chemical and pharmacological standpoint, but without a doubt will not be affected by crushing, or blending. Click on image to the left to see a clearer view.
Can The Xtampza Capsule Be Opened and Sprinkled? Would This Affect its Extended-release Profile?
The answers are Yes and No respectively. Since each microsphere has its own extended-release profile, Xtampza’s can be opened and sprinkled on food/drink or administered through feeding tubes without affecting its extended-release profile.6 This could be a promising option for chronic pain patients with swallowing difficulties and cancer patients with radiation-induced dysphagia. It is also important to note that in cases where an unsuspecting elderly patient might otherwise crush or break their medications for ease of ingestion, the Xtampza formulation will maintain its extended release properties whereas another one could inadvertently result in opioid toxicity.
Are Abuse-deterrent Formulations The Only Solution?
ADF are more difficult to abuse (hence the word ‘deter’) but are not abuse proof. For more details on ADF, refer to Abuse-Deterrent Opioid Formulations: Purpose, Practicality, and Paradigms. ADF is a step towards combating drug abuse but it is not the only solution. For instance, currently available ADFs do not address overconsumption by oral ingestion of doses higher than prescribed, which is the most common form of prescription opioid abuse.7
As previously mentioned by Drs. Fudin and Ahmed, “As health care professionals, we must seek a comprehensive method that involves not only ADFs, but also collaborative drug therapy management between providers, utilization of prescription drug monitoring programs (PDMP), and prescriber/patient education tools. While it is incumbent upon all of us (clinicians and patients alike) to prevent opioids from getting into the wrong hands, we shouldn’t deny legitimate patients from receiving the medications they need”.
A more comprehensive follow up article on Xtampza will be forthcoming soon in Pharmacy Times. Stay tuned!!
Mena Raouf is a 2016 PharmD Candidate at the Albany College of Pharmacy and Health Sciences with a concentration in Nephrology. He has been involved developing an automated software platform to assess pre-validated risk for opioid-induced respiratory depression to qualify patients for in-home naloxone. Following graduation, Mena will be pursuing PGY-1 Pharmacy Practice Residency at the VA Tennessee Valley Healthcare System. He is under the mentorship of Dr. Jeffrey Fudin subsequent to completion of an advanced practice rotation in pain management.
- FDA Gives Final Approval to Abuse-Deterrent Xtampza ER. Medscape. Apr 29, 2016.
- US Food and Drug Administration. Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse. Available from: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm338566.htm. Accessed April 29,2016
- MacLaren E. Oxycodone History and Statistics. 2015. Available from: http://drugabuse.com/library/oxycodone-history-and-statistics/#the-oxycodone-market Accessed April 30, 2016.
- US Food and Drug Administration. FDA approves abuse-deterrent labeling for reformulated OxyContin. 2013 April. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm348252.htm. Accessed April 29, 2016.
- Fudin J, Ahmed N. Abuse-Deterrent Opioid Formulations: Purpose, Practicality, and Paradigms. 2015 January. Available from: http://www.pharmacytimes.com/contributor/jeffrey-fudin/2015/01/abuse-deterrent-opioid-formulations-purpose-practicality-and-paradigms. Accessed April 29, 2016.
- US Food and Drug Administration. Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling[draft guidance]. Silver Spring, MD: FDA; 2013.