Oxycodone and Hydrocodone both are analgesics (pain killers), belonging to the opioid (narcotic) category of drugs. They are the commonly prescribed drugs for the acute or chronic management of moderate to severe pain. They are also among the commonly abused drugs in the United States.

In this side by side review of both these drugs, we will discuss the structure, mechanism of action, forms and dosing, efficacy, conditions they are used in, side effect, toxicities and contraindications, abuse liability and withdrawal effects ultimately leading us to the conclusion which drug is the best


Both oxycodone and hydrocodone are semisynthetic, opioid-like, derivatives of codeine. As the name indicates, Hydrocodone is a hydrogenated derivative (having a hydrogen group) of Codeine while Oxycodone is a ketone derivative (having an -OH group).


Mechanism of Action

Both drugs are Opioid agonists and act through a similar mechanism. They exert their analgesic activity by binding specifically to the mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids (those formed within the body naturally).

Activation of mu-opioid receptors in the central nervous system (CNS) results in hyperpolarization of neurons and reduction of neuronal excitability.

In addition, these drugs act directly on a number of tissues not related to their analgesic effects. These tissues include the respiratory center in the brain stem, the cough center in the medulla, muscles of the pupils, cardiovascular system, gastrointestinal tract, immune system, and endocrine system. Their effects on these tissues are as follows:

  • Respiratory center: Dose-dependent Respiratory Depression.
  • Cough center: Suppression of the Cough Reflex
  • Pupils: They become constricted and decrease in size.
  • Cardiovascular system: Histamine may be released leading to vasodilation, increased vascular permeability, edema and decreased blood pressure.
  • Gastro-Intestinal Tract: Peristalsis is slowed down along the entire GI tract. Muscle tone in the colon may increase causing constipation.
  • Endocrine effects: These may include increased prolactin, decreased cortisol and decreased testosterone. Histamine released may also lead to pruritis, red eyes, flushing, and sweating.
  • Immune system: It is not yet known if the effects of opioids on the immune system are clinically significant.

They exert these effects not only by binding to mu receptors but also through kappa and delta-opioid receptors.

Metabolism and Excretion

Both these drugs are metabolized by the liver enzymes, specifically by cytochrome P450 enzyme. After metabolism, the metabolites of these drugs are mostly eliminated in urine. A small amount of the drug is also present in the milk of feeding mothers.

Biological Half-life

The apparent elimination half-life of oxycodone is 3.2 hours in case of immediate-release formulations and 4.5 hours for extended-release formulations.

On the other hand, the half-life of hydrocodone is 1.5 to 3 hrs. Thus, oxycodone’s effects last for a prolonged period of time after its consumption by the patient.

Formulations or Preparations

Frequently, both oxycodone and hydrocodone are combined with other painkillers or anti-inflammatory drugs. However, pure formulations of these drugs are also available.

The extended-release form of Hydrocodone is available as hydrocodone bitartrate by the trade name Hysingla ER. They are designed for the delayed release of the drug over a prolonged period of time.

Hydrocodone combined with acetaminophen, an anti-inflammatory drug, is available by the trade name Hydrogesic.

Hydrocodone in combination with ibuprofen, an NSAID, in available by the trade name Vicoprofen.

The oxycodone in immediate-release form oxycodone hydrochloride is available as Roxicodone.

The oxycodone in extended-release form is available as Oxycontin.

Oxycodone in combination with acetaminophen is available as Roxicet.

Oxycodone in combination with aspirin is available as Endodan.

Therapeutic Uses

Both these drugs are used for the acute relief of moderate to severe pain. They are also used to treat moderate to severe pain caused by chronic conditions like malignancy, injury or surgery.

Those people who take oxycodone or hydrocodone, do so on a regular basis. They go on taking the medicine until the doctor ends prescription and tells them to stop taking it. Thus, oxycodone should not be used like over the counter painkillers which are taken when needed and can be stopped any time. It is important because of the risk of addiction.

Research shows that hydrocodone appears more likely to cause dependency than oxycodone. This will be further discussed under the heading of addiction and dependency.

Expanded release forms are used for chronic management of severe pain, requiring continuous opioid analgesics for an extended period.

Combination of hydrocodone with ibuprofen is used for the treatment of pain, fever, and inflammation.

Hydrocodone is also used for the symptomatic relief of nonproductive cough, either alone or in combination with other expectorants or antitussive agents.


Both oxycodone and hydrocodone have been shown to be highly effective at treating pain.

Studies have shown that both these drugs are equally effective when used for the relief of acute pain after 30 to 60 minutes of consumption.

Oxycodone has a prolonged analgesic effect due to greater half-life and thus is more effective in the management of chronic pain.

Formulations that contain acetaminophen are equally effective in case of both drugs.

Side Effects

Being opioid agonists acting directly on various tissues within the brain, these drugs can cause severe side effects even when used in therapeutic doses recommended by the doctor. For better understating, we will be discussing each of the possible side effects with the underlying mechanism involved.

Common side effects with therapeutic doses:

  • Respiratory depression: Decrease in respiratory rate.
  • Cyanosis: Bluish discoloration of the skin due to decreased oxygen in the blood.
  • Sleepiness: Due to decreased neuronal activity.
  • Skeletal muscle flaccidity: Due to decreased neuronal activity.
  • Constricted pupils: Due to the contraction of radial muscles of the eye.
  • Bradycardia and Hypotension: Due to histamine-induced vasodilation and decreased sympathetic outflow to the heart.
  • Constipation: Due to decreased peristalsis along the GI tract.

More severe side effects due to toxic doses:

  • Respiratory depression: Decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration (alternating rapid and shallow breathing pattern) due to severe depression of respiratory center in the brain.
  • Coma and Death: Severe CNS and respiratory depression can cause coma and ultimately death of the person.

Studies have shown that oxycodone causes more of CNS and respiratory effects. On the other hand, hydrocodone causes more severe constipation or other GI effects.


Oxycodone is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma or suspected gastrointestinal obstruction, including paralytic ileus. Oxycodone may cause spasm of the sphincter of Oddi. It may cause an increase in serum amylase. Patients with biliary tract disease, including acute pancreatitis, should be monitored for worsening symptoms. It is also contraindicated in patients hypersensitive to oxycodone.

Hydrocodone is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation.

Both these drugs are contraindicated in patients using drugs that inhibit hepatic cytochrome P450 enzymes such as barbiturates and clonazepam. P450 inhibitors result in increased plasma levels of these drugs which can cause a number of side effects as mentioned earlier.

Hepatic Toxicity:

As both these drugs are metabolized by the liver, they can cause hepatic toxicity when used in large dosages. When used in therapeutic dosages, both hydrocodone and oxycodone are safe for the liver and do not cause any clinically apparent or life-threatening injury to the liver.

However, when used in combination with acetaminophen in high doses, they can cause subsequent liver injury. The liver injury is not due to these drugs, but due to acetaminophen. Studies show that oxycodone and hydrocodone, both induce hepatic cytochrome P450 enzyme. Increased levels of cytochrome P450 convert acetaminophen into a hepato-toxic metabolite which causes centrilobular necrosis of the liver.

Use in Pregnancy and Breastfeeding

According to recent studies, the use of opioids such as oxycodone and hydrocodone is safe in the first trimester of pregnancy. However, they should be used with caution, especially in higher doses in late pregnancy.

In earlier publications, authors recommended against oxycodone use in breastfeeding due to lack of studies on safety considerations such as excretion and repeated dosing.

However, now the studies have confirmed that though oxycodone accumulates in breast milk, the benefits of maternal comfort outweigh the minimal risks to infants. However, careful monitoring of infants is recommended to look for the signs of opioid exposure, such as sedation, poor attachment, gastrointestinal symptoms, and respiratory depression.

So, both oxycodone and hydrocodone have similar risk factors in case of pregnant and lactating ladies.

Abuse liability

The rates of prescription opioid abuse including oxycodone and hydrocodone have been on the rise in the United States for the past several years. One of the reviews suggests that the relative prevalence of opioid prescription abuse is comparable to the prevalence of heroin and cocaine abuse.

In the case of the individuals initiating illicit drug use for the first time, the most recent data shows that the prescription opioids have now surpassed marijuana as the most common drugs of initiation.

Hydrocodone, a full mu-opioid agonist, is metabolized by cytochrome P450 and transformed into another mu agonist, hydromorphone; however, this conversion does not appear to be critical to the abuse potential of hydrocodone.

Hydrocodone itself is listed under Schedule II of drugs. These are the drugs that have a high potential for abuse. has a currently accepted medical use in treatment in the United States. Abuse of these drugs may lead to severe psychological or physical dependence. However, it is only sold in combination formulations (e.g., with acetaminophen) which are regulated under the less restrictive Schedule III category.

Oxycodone is a full mu-opioid agonist, metabolized by the liver enzymes to at least one active metabolite, oxymorphone, which is itself marketed as an analgesic. Historically, oxycodone was considered to be associated with a lower abuse liability because it was initially introduced to the United States in 1981 in combination with over-the-counter non-opioid analgesics.

Oxycontin, a sustained release formulation of oxycodone, has been identified as an especially problematic and dangerous drug of abuse because it is available in higher dosages than other oxycodone formulations, and the sustained release feature can be readily bypassed by crushing the tablets.

However, Oxycontin, immediate-release oxycodone and oxycodone combination products with either acetaminophen or aspirin, all are regulated under Schedule II. They have historically accounted for a smaller portion of prescription opioid sales than those for hydrocodone Moreover, data from recent Drug Enforcement Agency reports suggest that oxycodone mentions are increasing in number, approaching the number of hydrocodone mentions and thus the abuse liability.

Addiction and Dependence

Prescription opioid misuse has recently become a highly prevalent problem in the United States. Opioid addiction is characterized by a powerful, compulsive urge to use the drugs, even when they are no longer required medically. Prescription opioids, such as oxycodone and hydrocodone have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed.

Many prescription opioids are misused or diverted to others. People who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively affecting their professional and personal relationships. Some people are more likely to become addicted than others due to unknown reasons.

Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect.

Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction.

Opioid addiction can cause life-threatening health problems, including the risk of overdose. An overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately.

Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines).

A study conducted in 2013 finds that opioid abusers prefer oxycodone and hydrocodone for different reasons. Those who prefer oxycodone cited the quality of the high as the primary reason behind their choice, while those who prefer hydrocodone were more likely to cite its accessibility.

Patient characteristics also vary between hydrocodone and oxycodone abusers. Hydrocodone users are more likely to be female and to be older than 45 than are oxycodone users. Patients who use hydrocodone are also more likely to take the drug orally and less likely to inject or snort the opioid than are oxycodone users. In addition, hydrocodone users are less likely to obtain their drugs from a dealer and more likely to use or forge a doctor’s prescription to get them.


If a person stops or cuts back on these drugs after heavy use of a few weeks or more, he will have a number of symptoms. This is called withdrawal.

As discussed earlier, these drugs can cause physical dependence. When the person stops taking the drugs, the body needs time to recover. This causes withdrawal symptoms. Withdrawal from oxycodone and hydrocodone can occur any time long-term use is stopped or cut back.

These drugs are CNS depressants, so withdrawal symptoms are due to increased neuronal activity. They are divided into early and late withdrawal symptoms.

Early symptoms of withdrawal include:

  • Agitation
  • Anxiety
  • Muscle aches
  • Insomnia
  • Runny nose
  • Sweating
  • Yawning

Late symptoms of withdrawal include:

  • Abdominal cramping
  • Diarrhea
  • Dilated pupils
  • Goosebumps
  • Nausea
  • Vomiting

These symptoms are common in both oxycodone and hydrocodone withdrawal.


As evident from the above discussion, hydrocodone and oxycodone both are equally effective for the treatment of acute and chronic pain. They both cause similar side effects and have almost similar abuse liability and dependence. There is no significant difference between the two drugs. The best way to pick which drug is best for a person is by having a consultation with a doctor.

A doctor has a better understanding of how a drug works and interacts with the body. He knows the past medical history of the patient, is aware of the drugs he is already taking, his allergies, any drug addiction, and another personal history.

Based on this information, a doctor can better compare the relative efficacy of the two drugs and can decide which one would be a better choice for a particular person. Some researchers and medical professionals find that hydrocodone is less powerful than oxycodone.

In that case, the doctor prefers to start the patient on a smaller dose to see how the body handles the medicine. If the first option the doctor tries doesn’t work or causes adverse side effects, the doctor can think about changing medications or doses to find something that works.