Safety and Tolerability of Biphasic Immediate‐Release/Extended‐Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials

Objectives To characterize the safety of immediate‐release (IR)/extended‐release (ER) oxycodone (OC)/acetaminophen (APAP). Methods Data were assessed from 9 phase 1 trials in healthy volunteers and recreational users of prescription opioids ( N  = 405), including 5 single‐dose and 3 multidose open‐label pharmacokinetic studies of IR/ER OC/APAP and active comparators; and 1 randomized, controlled, single‐dose human abuse potential (HAP) study comparing IR/ER OC/APAP, IR OC/APAP, and placebo in recreational users of opioids; and 2 phase 3 trials ( N  = 701) including a 48‐hour placebo‐controlled safety and efficacy study in patients with moderate to severe postbunionectomy pain with a 14‐day open‐label safety extension and a long‐term (≤ 35 days) open‐label safety study in patients with chronic osteoarthritis pain or chronic low back pain. Results Adverse events (AEs) experienced by ≥ 10% of participants receiving IR/ER OC/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache, and somnolence; these AEs occurred with similar frequency for equianalgesic doses of IR OC/APAP and IR OC but less frequently for IR tramadol HCl/APAP. In the HAP study, crushing IR/ER or IR OC/APAP tablets did not increase frequency of AEs. Constipation was experienced by < 10% of participants receiving IR/ER OC/APAP. No serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of 8 reported SAEs, only 1 treatment‐related SAE (hypersensitivity to placebo) required treatment discontinuation. No clinically meaningful changes in vital signs, oxygen saturation, electrocardiograms, or laboratory values were reported. Conclusions Safety and tolerability of IR/ER OC/APAP are similar to other low‐dose opioid/APAP analgesics.