title: Safety and Tolerability of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials.
abstract: To characterize the safety of immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Safety and tolerability of IR/ER OC/APAP are similar to other low-dose opioid/APAP analgesics.
authors: Clinical Research, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A.
authors: Thomas
authors: T
authors: Barrett
authors: Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A.
authors: Kenneth
authors: K
authors: Kostenbader
authors: International Clinical Research Institute, Overland Park, Kansas, U.S.A.
authors: Srinivas
authors: S
authors: Nalamachu
authors: Research and Development, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A.
authors: Michael
authors: M
authors: Giuliani
authors: Clinical Affairs & Program Management, Research and Development, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, U.S.A.
authors: Jim L
authors: JL
authors: Young
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy*; D013607:Tablets / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D013607:Tablets; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D010098:Oxycodone
keywords: acute pain; chronic low back pain; fixed-dose combination; opioid analgesic; osteoarthritis; postoperative pain; tramadol HCl