Abuse-deterrent properties, identical efficacy for pain relief, reversal of opioid-induced constipation, and theoretical tolerance mitigation may give Targiniq ER an interesting advantage over other oral opioids.
Do we need another oxycodone product? Is there a real advantage to a product that combines extended-release oxycodone with naloxone, as in the case of the newly FDA-approved Targiniq ER?
According to the FDA’s July 23, 2014, news release about Targiniq ER, it is “an extended-release/long-acting (ER/LA) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.” Additionally, the FDA release notes that “Targiniq ER has properties that are expected to deter, but not totally prevent, abuse of the drug by snorting and injection. When crushed and snorted, or crushed, dissolved and injected, the naloxone in Targiniq ER blocks the euphoric effects of oxycodone, making it less liked by abusers than oxycodone alone.”
The “tempering” of oxycodone with naloxone actually has clinical utility beyond limiting abuse. The main problem with opioid analgesics is their tendency to cause opioid-induced constipation (OIC). Rather than administer laxatives intended to mitigate the constipating effects of opioids by softening bowel contents or driving peristalsis through stimulating mechanisms, the addition of naloxone to any oral opioid analgesic allows for physiological reversal of constipation in the wall of the bowel. Naloxone in the bowel binds to opioid receptors as an antagonist, reversing the constipating effects of opioids. Additionally, with only 3% bioavailability, there is minimal risk of reversal of opioid analgesia in the central nervous system when naloxone is taken orally.
At another level, ultra-low-dose naloxone may mitigate the development of opioid tolerance. While not proven in humans, animal models suggest a potentially valuable role for naloxone. A pair of papers published by Lin and colleagues in 2010 described this.
One paper reported results from a study in which researchers administered naloxone in morphine-tolerant rats to investigate “the possible mechanisms by which ultra-low dose naloxone modulates spinal neuroinflammation, particularly the role of anti-inflammatory cytokine interleukin 10 (IL-10).” The authors concluded that “IL-10 contributes to the attenuation of pro-inflammatory cytokine expression caused by ultra-low dose naloxone/morphine co-infusion and thus the attenuation of morphine tolerance.”
The other paper looked at “the effect of ultra-low dose naloxone on spinal glutamatergic transmission and glial cell activity in rats chronically infused with morphine.” The authors reported that “attenuation of glutamatergic transmission and neuroinflammation by ultra-low dose naloxone co-infusion preserves the lasting antinociceptive effect of morphine in rats chronically infused with morphine.”
Targiniq ER is the US version of the medication Targin, which is sold outside of the US with a 2:1 ratio of oxycodone to naloxone. In Canada, Targin has been available in several strengths, up to 40:20 twice daily, and has not been shown to precipitate opioid withdrawal when taken intact and orally.
Outside of the US, Targin is used to treat moderate to severe pain while correcting OIC. Conversions from another oxycodone product to Targin are based upon oxycodone content, not naloxone, and are done straightforwardly with one subtle “trick.” To lessen potential diarrhea (perhaps just voluminous relief of constipation), some Canadian pain specialists do an initial 50 percent conversion for two days (continue half of the original oxycodone product and introduce half of the equianalgesic amount of Targin), and then complete the conversion after 48 hours.
Branded opioids cost more than generic ones, of course. Conversion from generic immediate-release or forms of controlled-release oxycodone to branded extended-release oxycodone (eg, OxyContin) or oxycodone with naloxone (eg, Targiniq ER) will cost patients more for their therapy. Beyond cost, improved safety if it is misused, identical efficacy for pain relief, reversal of OIC, and theoretical tolerance mitigation may give Targiniq ER an interesting advantage over other oral opioids. Perhaps we do need another oxycodone product.
What do you think? Send your comments to Editors@HCPLive.com.
B. Eliot Cole, MD, MPA, is a member of the Pain Management editorial advisory board. He has served in executive positions for several prominent pain management organizations and societies, including the American Society of Pain Educators and the American Academy of Pain Management. He has been a pain management fellow, clinician, educator, and advocate for nearly 30 years and has practiced in a variety of settings serving a wide range of patients.