The present disclosure provides extended release pharmaceutical compositions comprising oxycodone and acetaminophen that produce a quick initial onset of analgesia, yet, maintain analgesia for about 12 hours after administration of the composition to a subject in need thereof. The pharmaceutical compositions disclosed herein also reduce the levels of acetaminophen in a subject's blood near the end of the dosing interval because the acetaminophen released by the pharmaceutical composition is being eliminated by a subject's body faster than it is being absorbed.