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Oxycodone: Drug Whys

This medication is notorious as a street drug and with good reason


OxyContin tablets

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Updated October 17, 2016

Generic Name: oxycodone (multiple generics available)
Common U.S. Brand Names: OxyContin® (Perdue Pharma)
Popularity: 25th most commonly prescribed drug between 2014-2015 (U.S.)
Class: analgesic, opioid

Treatment Uses — Treatment of moderate to severe pain. Common uses include cancer pain, back pain, arthritis, neuropathic pain and other chronic pain conditions. Oxycodone has also been used to treat restless leg syndrome.

Oxycodone comes in controlled-release and immediate-release forms. Controlled-release tablets are intended for round the clock pain management when pain is expected to continue for an extended period of time.

Immediate-release capsules, tablets, solutions and concentrate are intended for use on an as needed basis such as the first 12 to 24 hours post-operatively or for preemptive analgesia. It would be highly inappropriate and dangerous to prescribe controlled-release oxycodone when pain is not chronic.

Caution is also warranted with dosing oxycodone in opioid-naïve patients (i.e., patients without long term exposure to opioid medications). Many adverse events, particularly respiratory depression and respiratory arrest occur in opioid-naive patients compared to opioid-tolerant individuals.

The working definition of an opioid-tolerant patient is someone taking at least 60 milligrams of oral morphine daily, 25 micrograms per hour of transdermal fentanyl, 30 milligrams of oral oxycodone daily, 8 milligrams of oral hydromorphone daily, 25 milligrams of oral oxymorphone daily, or an equivalent (also called equianalgesic) dose of another opioid for one week or longer.

Another pearl sometimes forgotten by patients and clinicians is the added benefit of non-narcotic analgesics such as NSAIDs (non-steroidal anti-inflammatory drugs including aspirin, acetaminophen, and ibuprofen). While narcotics offer greater analgesia than non-narcotic agents, combinations of the two nearly always provide better pain control than either agent alone.

When treating pain with opioid agents, remember to continue non-narcotic analgesics for improved pain control. For chronic pain, round-the-clock dosing with analgesics to prevent pain recurrence is more effective than trying to treat pain after it occurs.

Of particular note in the United States, the Food and Drug Administration is extremely concerned about inappropriate use of opioids; a problem that is now a major public health issue. Oxycodone has long been at the center of this public health problem. Deaths, hospital admissions and emergency department visits related to narcotics continue to climb.

Troubles are not limited to the community. Inside the doors of hospitals, patient advocacy groups and oversight bodies (such as The Joint Commission) have propagated a culture of zero pain, often leading to narcotic over prescribing and over treatment.

As an editorial note, it is interesting that narcotic overuse and abuse is a greater problem in the U.S. than elsewhere. Perhaps our “feel good” culture has given rise to a society intolerant of pain at any level, expecting pharmacologic relief for all that ails us.

Going forward, the FDA intends to strike a balance between treating patients with pain and the risks of abuse, misuse, and addiction from this most dangerous drug class.

Dosing and Administration — Initial dosing recommended for acute pain in opioid-naive adult patients is 5 to 15 milligrams (oxycodone immediate-release tablets, solution, liquid concentrate) orally every 4 to 6 hours as needed for pain with titration based on patient response. Immediate-release capsules are dosed at 5 milligrams orally every 6 hours as needed with dose adjustments based on patient response.

For chronic pain in opioid-naïve patients, initial oxycodone controlled-release tablet dosing is 10 milligrams orally every 12 hours, titrated up to 40 milligrams every 12 hours based on patient response. The maximum daily dose (MDD) of oxycodone is 80 milligrams and maximum single dose, 40 milligrams in opioid-naive patients.

For opioid-tolerant patients (patients already taking other opioids), prescribers should use a dose-conversion reference to calculate the equivalent total daily dose of oxycodone, dividing the calculated daily oxycodone dose in half to approximate a 12-hour dose of controlled-release oxycodone. All other around-the-clock opioid drugs should be discontinued.

If converting from transdermal fentanyl to oxycodone, allow 18 hours after removal of the fentanyl patch before starting oxycodone. Opioid-tolerant patients may require greater than the maximum doses of oxycodone suggested for opioid-naïve patients.

Doses of controlled-release oxycodone tablets can be adjusted every 1 to 2 days. The tablet strength should be adjusted, not the dosing frequency. The total daily dose can usually be increased 25% to 50% at each titration.

Oxycodone is not approved for pediatric use, but immediate-release tablets, solution, liquid concentrate are used off-label in children, initially at 0.1 to 0.2 milligrams per kilogram per dose given every 4 to 6 hours as needed or on a regular schedule for chronic pain.

In patients taking other CNS (Central Nervous System) depressants, initial dosing of oxycodone should be one-third to one-half the recommended starting dose.

Oxycodone can be taken without regard to meals. Food does not appear to affect absorption although there is some suggestion that high fat meals may increase oxycodone plasma drug levels at very high oxycodone doses.

As with other drugs that have potentially serious side effects, the FDA requires prescribers to have Risk Evaluation and Mitigation (REMS) in place, including dispensing with a medication guide.

An additional FDA medication guide must be dispensed with OxyContin and also with the oral solution.

Dose adjustments of oxycodone in patients with impaired renal function should be conservative and based on patient response. In patients with hepatic (liver) dysfunction, initial dosing of controlled-release oxycodone should be one-third to one-half the usual recommended doses with cautious and more gradual titration.

Immediate-release oxycodone should also be dosed conservatively. In geriatric patients, initial dosing of oxycodone should start at the lower end of the recommendations.

Overdoses of oxycodone can result in respiratory depression, decreased level of consciousness, constricted pupils, hypotension, and death. Doses greater than 40 milligrams can lead to fatal respiratory depression in opioid-naïve adults.

Pure opioid antagonists such as naloxone are specific antidotes against oxycodone induced respiratory depression but should not be administered in the absence of clinically significant respiratory or cardiovascular compromise.

Administering reversal agents to patients with physical dependence may precipitate an acute abstinence (i.e., withdrawal) syndrome. Given the current trend of placing intranasal naloxone into the hands of civilians and BLS providers, this is an important caveat.

Respiratory depression can be readily managed with ventilation; an acute abstinence syndrome is not so easily managed and can be lethal. Of added note: while constricted pupils are associated with narcotic overdoses, patients may exhibit markedly dilated pupils if profoundly hypoxic due to respiratory depression.

Pharmacology/Pharmacokinetics/Stability — After oral administration of a single dose of oxycodone, analgesic effect is experienced in 1 hour. Peak effect for immediate-release oxycodone occurs in 1.2 to 1.9 hours and in 2.1 to 3.2 hours for controlled-release tablets.

Plasma concentrations vary among groups: they are 15 percent higher in the elderly, 25 percent higher in females, 90 percent to 95 percent higher with hepatic impairment and 60 percent higher with renal insufficiency. Steady state plasma concentrations of oxycodone are usually achieved in 24 to 36 hours following initiation or dose titration.

Oxycodone is extensively metabolized in the liver. Some 7 percent of Caucasians, 3 percent of Blacks, and 1 percent of Asians poorly metabolize oxycodone and will experience little to no pain relief. Most oxycodone is excreted by the kidneys.

The half-life (time to eliminate half of the drug from the body) for immediate release oxycodone is 3.5 to 4 hours and for controlled release, 4.5 to 8 hours. These times are increased by 1 hour for patients with renal impairment and by 2.3 hours in patient with liver disease.

Oxycodone, while similar chemically to codeine, has pharmacologic properties like morphine. It produces analgesia by interacting with opioid receptors in the brain and spinal cord. The exact mechanism by which this occurs is unknown.

Respiratory depression occurs by direct action of oxycodone on the respiratory centers in the brain stem, reducing their responsiveness to increased carbon dioxide levels.

Oxycodone also acts directly on the cough center in the medulla to suppress cough reflex, usually at lower doses than needed for analgesia. Constricted pupils (miosis) also results from drug effects on the CNS.

There are no good human studies of oxycodone use during pregnancy. What limited studies have been done suggest there is little risk of congenital malformations from oxycodone use.

However, opioids do cross the placenta and there is clear evidence that regular use during pregnancy is associated with neonatal respiratory depression, drug dependence and withdrawal and delayed growth and development.

Oxycodone is excreted in breast milk in low concentrations; because of the risk of sedation and respiratory depression in the infant, oxycodone is not recommended for use by nursing mothers.

OxyContin® controlled-release tablets come in 10, 15, 20, 30, 40, 60, 80 and 160 milligram strengths. The 10 milligram tablets are round, white, convex shaped with OC imprinted on one side and 10 on the other. The 20 milligram tablets are round, pink, convex shaped with OC imprinted on one side and 20 on the other.

Other strengths have different colors and shapes but all have OC imprinted on one side and their strength in milligrams imprinted on the other side.

Immediate-release oxycodone tablets and capsules come in a variety of shapes, colors and sizes with varying imprints. Oxycodone should be dispensed in a tight, light resistant container and stored at room temperature (77 F), with excursions permitted between 59 and 86 F.

Oxycodone tablets must be swallowed whole and not moistened, cut, broken, crushed, chewed or dissolved. Breaking, crushing or chewing controlled-release tablets results in rapid release with absorption that can be fatal.

Controlled-release tablets should not be given rectally as the risk of adverse events increases due to better absorption. Oxycodone tablets and capsules should not be administered through feeding tubes due to potential for obstruction. Oxycodone concentrate should be mixed with 30 milliliters or more of juice or other liquid or added to semi-solid food (applesauce, pudding).

Cautions and Warnings — Like any narcotic, physical and psychological dependence can occur with long term use. Oxycodone is targeted for theft and diversion by criminals. Patients should be counseled about securing opioids to prevent theft or diversion, regardless of their living situation. Additional caution should be directed at keeping this medication away from small children.

Dose adjustments or rescue medications may be needed for patients with breakthrough pain. Good pain control is achieved when no more than 2 doses of supplemental analgesics are required daily (24 hour period). It is important to reassess the need for round-the-clock opioid therapy every 6 to 12 months, particularly in non-cancer patients.

Discontinuing oxycodone following long term use can lead to withdrawal symptoms. Tapering 25 percent to 50 percent of the dose daily is recommended. If withdrawal symptoms appear, it may be necessary to adjust dosing intervals or dosing strengths to facilitate a more gradual taper.

Oxycodone carries a black box warning from the U.S. Food and Drug Administration regarding proper patient selection and potential for abuse. As a controlled substance, oxycodone has an abuse potential similar to morphine. Prescribers and pharmacists should consider this in situations where there is concern for misuse, abuse or diversion.

Important Side Effects and Interactions — Constipation should be anticipated and aggressively treated with a stimulant laxative and/or stool softener. Opioids increase smooth muscle tone in gut, slowing digestion.

Patients do not develop tolerance to the constipating effects of opioids. As a health care provider, you should insist that any person prescribed a narcotic containing medication also take a laxative and/or stool softener. You will prevent immeasurable discomfort with this simple, yet often overlooked advice.

Nausea, although self-limiting, may be treated with antiemetics or other modalities if persistent and intolerable. Reduce the next dose if signs of excessive opioid-related side effects are experienced.

A supplemental dose of immediate-release oxycodone may be administered if this dose adjustment results in breakthrough pain. Alternatively, non-opioid analgesic adjuvants may be used. Adjust dosing to achieve an appropriate balance between pain relief and opioid-related adverse experiences.

The most common side effects of oxycodone are similar to other opioids and include constipation, nausea and vomiting. Skin rash and itching are also reported, as is urinary retention in males. Itching and diaphoresis (sweating) are cardiovascular side effects related to a drug induced histamine release which may also result in vasodilation and orthostatic hypotension.

Lightheadedness and sedation occur in some patients. Patients should be observed for respiratory depression induced by the hydrocodone component of this drug. Confusion and hallucinations have occasionally been reported.

Of note, oxycodone can cross react with urine drug screens for cocaine and tetrahydrocannabinol (THC or cannabinoids). Positive tests should be confirmed with a more specific chemical test.

There are 164 drugs and drug classes specifically reported to interact with oxycodone. The greatest potentially significant interaction is additive or increased CNS or respiratory depression when used in combination with other drugs that have sedating or respiratory depressant effects.

Certain antibiotics, antifungal agents, and protease inhibitors may prolong or increase oxycodone plasma concentrations, leading to adverse effects including potentially fatal respiratory depression. No food-drug interactions involving oxycodone have been reported.

Average Costs – U.S.

OxyContin 10 and 20 milligram tablets:

Patient cost: $2.53 and $4.27 each*

Large Hospital cost: $1.95 and $4.49 each


  1. MICROMEDEX(R) Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed February, 2013).
  2. Albany Medical Center Pharmacy, Albany, New York. columnist Mike McEvoy, is the EMS coordinator for Saratoga County and the EMS director on the Board of the New York State Association of Fire Chiefs. Mike is the Fire-EMS technical editor for Fire Engineering magazine and has authored numerous publications including the book, “Straight Talk About Stress for Emergency Responders.”
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