An investigational long-acting formulation of the opioid painkiller oxycodone (Troxyca ER, Pfizer) can be manipulated despite its potential to deter abuse, according to a preliminary review by FDA staff. Pfizer is seeking approval of Troxyca ER for the management of chronic pain that may require daily, around-the-clock opioid treatment and for which alternative treatment options are inadequate.
The abuse-deterrent mechanism of Troxyca ER involves the incorporation of naltrexone, a mu-opioid receptor antagonist, in oxycodone-coated pellets, which are housed within a capsule. The product is designed so that that if the pellets are crushed in an attempt to abuse the painkiller, naltrexone is released to counteract the opioid effects of oxycodone. The capsules are manufactured in 10 mg/1.2 mg, 20 mg/2.4 mg, 30 mg/3.6 mg, 40 mg/4.8 mg, 60 mg/7.2mg, and 80 mg/9.6 mg strengths of oxycodone/naltrexone.
According to the staff’s report, studies were conducted to determine the extraction potential of oxycodone and naltrexone when extracted from the pellet formulations with common solvents. The studies used both intact and crushed pellets. When a common solvent was used, 90% of oxycodone could be extracted from intact pellets within three hours or more, and when two other solvents were used, about 60% of oxycodone could be extracted within 15 minutes or less. When crushed pellets were used, a common solvent could extract about 60% of the oxycodone within 15 minutes or less.
Other studies demonstrated, however, that negligible oxycodone is released from heated Troxyca ER vapor, reducing the likelihood of abuse by those seeking to inhale it, the staff added.
On June 8, in a joint meeting of the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee and its Drug Safety and Risk Management Advisory Committee, expert advisors will be asked to decide whether Pfizer should be allowed to claim on the Troxyca ER label that it deters abuse. The panel will vote separately on whether the product is likely to deter abuse when swallowed, snorted, or injected.
Currently, two extended-release analgesic combination drug products containing an opioid agonist and an opioid antagonist are available in the U.S.: morphine/naltrexone (Embeda, Pfizer) and oxycodone/naloxone (Targiniq ER, Purdue Pharma).