Effects of intravenous oxycodone alone or in combination with naltrexone on measures of respiratory depression: a randomized placebo-controlled study.

Background: Abuse of prescription opioids, particularly by intravenous (IV) administration, can cause respiratory depression and death. ALO-02, an abuse-deterrent opioid formulation, is designed to release sequestered naltrexone upon manipulation by crushing, thereby antagonizing the pharmacologic effects of oxycodone. This exploratory analysis examined the effects of IV administration of simulated crushed ALO-02 on end-tidal carbon dioxide (EtCO), a surrogate marker of respiratory depression.

Methods: Data were obtained from a randomized, double-blind, placebo-controlled, three-way crossover study in nondependent recreational opioid users that evaluated the abuse potential of IV administered oxycodone 20 mg + naltrexone 2.4 mg (simulating crushed ALO-02) oxycodone 20 mg or placebo. EtCO was measured as a secondary endpoint using noninvasive capnography at baseline and postdose intervals, up to 24 h.

Results: Baseline EtCO (mean ± standard error of the mean (SEM)) values ( = 33) were similar across treatments: 33.5 ± 0.9, 33.5 ± 0.8, and 34.0 ± 0.7 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. After dosing, mean ± SEM of the maximum effect (E) on EtCO was 37.5 ± 0.6, 40.5 ± 0.8, and 36.9 ± 0.6 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. E values were significantly lower for oxycodone 20 mg + naltrexone 2.4 mg oxycodone 20 mg ( = 0.0005), and not different from placebo ( > 0.05).

Conclusions: This abuse-potential study suggests that naltrexone released from ALO-02 tampering by crushing attenuates oxycodone-induced increase of EtCO in nondependent recreational opioid users.