Which extended release hydrocodone formulations have lower abuse potential?

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  • Intranasal hydrocodone extended release (ER) has a low abuse potential compared with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER).

Why this matters

  • Prior studies have found that abuse-deterrent formulations reduce the overdoses of those specific formulations, but do not appear to affect illicit drug use.
  • ER opioid formulations are more likely to be manipulated for illicit use, particularly for intranasal use.

Study design

  • A single-dose, randomized, double-blind, quadruple-dummy, active- and placebo-controlled crossover study identified 170 healthy adults to assess the abuse potential of hydrocodone formulations.
  • Funding: Teva Branded Pharmaceutical Products R&D, Inc.

 Key results

  • Mean efficacy of drug liking “at the moment” was significantly lower for intranasal hydrocodone ER (Maximum effect [Emax], 72.8) vs hydrocodone powder (Emax, 80.2; P=.004) and bitartrate ER capsules (Emax, 83.2; P<.001).
  • Overall drug liking, 24 h after administration was significantly lower with intranasal hydrocodone ER (Emax, 68.5) compared with hydrocodone powder (Emax, 77.1; P=.004) and bitartrate ER capsules (Emax, 79.8; P<.001).
  • Overall adverse events with placebo, intranasal hydrocodone powder, intranasal hydrocodone ER tablets and bitartrate ER capsules were 18%, 53%, 52%, and 61%, respectively.
  •  Most adverse events were mild and resolved.


  • Single-center study.

Coauthored with Anand Ramanathan, PharmD