Two of the most potent pain relievers that are prescribed to patients with moderate to severe pain are oxycodone and fentanyl. Both of these medications are members of the class of drugs known as opioid analgesics, meaning that they are painkillers derived from compounds found in the poppy plant, and work by activating brain cells that play a role in blocking pain-related signals in the central nervous system. Despite their similarities in function, oxycodone and fentanyl actually have several differences that make them appropriate for different medical conditions.

Perhaps the most important difference between oxycodone and fentanyl is their half-life, or the length of time it takes to break down and remove half the substance from the body. Oxycodone has a half-life of around three to four hours, which means it can only control pain for a few hours before redosing is required, unless it is given in a time-release format. Fentanyl has a rapid half life of just a few minutes when given intravenously (IV), which is why this drug is popular as a surgical anesthetic. Shortly after the IV is removed, this medication no longer affects a patient, and it becomes safe to give post-operative pain relief. The half-life of this drug is longer when it is used through the mouth or through the skin, making it suitable for chronic pain relief as well.

Onset times differ for oxycodone and fentanyl, in addition to their half-lives. Usually, oxycodone is only administered orally, and it takes around an hour to absorb through the stomach into the blood. This means that it is usually best administered for chronic pain that occurs on a predictable basis. Fentanyl, when administered in the form of a lollipop or a lozenge, has an onset time of just a few minutes. The quickness of its onset means that this drug can be used to control acute pain that arises unexpectedly, as a patient can receive pain relief almost as quickly as it occurs.

The risks and side effects of oxycodone and fentanyl are similar, as they belong to the same class of drugs. Fentanyl tends to cause less sedation and has a lower chance of histamine release, a reaction similar to allergies that can cause itching. Oxycodone, on the other hand, may be more sedating, but less likely to cause respiratory depression, a drop in the rate of breathing that can be hazardous if this drug is taken in high doses.