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10 Articles in Volume 16, Issue #5
A Review of Skeletal Muscle Relaxants for Pain Management
Applying Kinesiology as a Multi-Prong Approach to Pain Management
Arachnoiditis: Diagnosis and Treatment
Bench to Bedside: Clinical Tips from APS Poster Presentations
Conversation With David Williams, PhD, President of the American Pain Society
Letters to the Editor: Prince Fentanyl Overdose, High-Dose Opioids, Mystery Care
Los Angeles Times Versus Purdue Pharma: Is 12-Hour Dosing of OxyContin Appropriate?
My Experience With OxyContin 12-Hour Dosing
Technology: Changing the Delivery of Healthcare
The Neuroscience of Pain

My Experience With OxyContin 12-Hour Dosing

Purdue has known for decades that some patients need more frequent dosing of extended-release OxyContin (see LA TImes Versus Purdue Pharma). As a pain specialist, I too have known this for decades. I have certainly observed it in my practice, as have other pain medicine physicians. Many years ago, I learned from other specialists that at least 25% of patients require 8-hour dosing of OxyContin, and at least 25% of those prescribed a Duragesic patch (which contains fentanyl, an opioid that is almost 100 times as powerful as oxycodone) require every-48-hour dosing, rather than the FDA-approved 72-hour dosing interval.1

A retrospective chart review presented as a poster at the 2002 annual meeting of the American Pain Society described the dosing intervals at pain clinics for OxyContin, MS Contin, Duragesic, and other opioids. It showed that MS Contin was dosed 3 times a day in 68% of patients, and Duragesic patches were dosed every 48 hours in 23.4% of patients.2

The current Purdue package insert for OxyContin demonstrates clearly that the company is aware that OxyContin works in some patients for less than 12 hours and requires additional dosing. It says, “Patients who experience breakthrough pain may require a dosage increase of OxyContin or may need rescue medication with an appropriate dose of an immediate-release analgesic….There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours.”3

What this means is that this subgroup of patients either needs to be prescribed an additional immediate-release version of the drug to get them through until the next 12-hour dose is due; an increased dose of OxyContin, which often does last for the longer time frame; or the drug at a shorter interval. None of this is news! The biggest problem for physicians and patients is when insurance plans won’t cover every-8-hour dosing of OxyContin or every-48-hour dosing of the Duragesic patch.

Blood Levels

Regarding the cycle of addiction diagram in the LA Times article, the variation in blood levels can be prevented if the drug is given at appropriate intervals, which, as stated above, can vary. In fact, providing smoother blood levels rather than the ups and downs shown in that diagram is precisely the benefit of the extended-release formulations of various opioids.

What causes euphoria in the brain is not the quantity of opioid in the bloodstream, but rather how quickly the concentration in the brain’s blood vessels increases. It’s the rapid increase that causes a high, and in turn makes it more likely that the patient will want more. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, states, “Routes of administration that produce more rapid and efficient absorption into the bloodstream (for example, intravenous injections, smoking, and snorting) tend to result in a more intense intoxication and an increased likelihood of an escalating pattern of substance use leading to withdrawal.”4

Everyone knows this about marijuana, for example. People using marijuana for its brain effects prefer to smoke it rather than eat marijuana brownies because the active chemical THC (tetrahydrocannabinol) gets into the lungs’ blood vessels faster with smoking, and thence into the brain much faster, and produces more psychological effects. The same is true of immediate-release versus extended-release opioids: immediate-release oxycodone has a much higher street value than does OxyContin (same chemical, but released more slowly into the blood stream, and thus gets into the brain more slowly).

In 2010, when the formulation of OxyContin was changed to a formula that can’t be crushed, inhaled, or injected, its street value dropped enormously.5 In addition, declines in abuse and therapeutic error exposures decreased by 39% and 25%, respectively.

In a 2009 paper on this topic, Charles Argoff, MD, and Daniel I. Silvershein, MD, wrote that there are no high-
quality studies showing that at the same total daily dose, extended-release opioids are more effective in reducing pain compared with immediate-release opioids.6 However, extended-release agents have better adherence, less dose-watching, and result in improved  sleep.6 Immediate-release opioids and extended-release opioids that can be crushed to produce immediate release have greater appeal to abusers.6

This is exactly why the extended-release formulations are preferred for around-the-clock dosing for chronic pain. Other experts have concurred with this. For example, Richard L. Rauck, MD, stated, “The body of data that supports the role of LAOs [long-acting opioids] in chronic pain management and their beneficial effects on function, as well as quality of life and sleep, is more robust than that for SAO [short-acting opioids]. Whenever possible, it is this author’s opinion that LAOs should be considered because less frequent dosing and more consistent pain relief may be associated with better functional outcomes.”7

It is absolutely not true that the shorter dosing schedule is safer, nor that the 12-hour dosing “fosters” addiction. If a patient reports that efficacy wears off at 8 hours, the next step would be to try an 8-hour dosing regimen. One can start by prescribing the same total daily dose split into 3 doses per day (every 8 hours) rather than 2 per day (every 12 hours). On the contrary, the relatively greater street value of immediate-release formulations than extended-release versions makes the immediate-release drugs much more attractive to abuse and divert.

Too many articles on opioids assume that it’s all about addiction and diversion. Health care providers have to do appropriate risk assessment for every chronic pain patient. This should include performing urine drug screens when the patient doesn’t expect them; checking each state’s online Prescription Drug Monitoring Program, which lists every controlled drug (such as an opioid) that the patient has been prescribed; and checking for “red flags,” such as when the patient reports the prescription was lost or stolen or the patient needs an early refill.

Don’t Confuse Addiction With Dependence

It’s very common, as it was in the LA Times article, to confuse 2 separate concepts: addiction and physical dependence. It’s important to note that withdrawal symptoms do not mean the person is addicted; rather, they mean his body has adapted to the drug so that he is physically dependent.

Almost everyone who is on a more than minimal opioid dose for more than a few weeks becomes physically dependent, meaning they will experience withdrawal symptoms. The same thing happens for other drugs that are used a lot in medicine (including corticosteroids such as prednisone, and antidepressants such as paroxetine [Paxil]), and no one thinks that patients on those drugs are addicts if they stop the prednisone or paroxetine suddenly and experience withdrawal symptoms.

Last updated on: July 12, 2016
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Conversation With David Williams, PhD, President of the American Pain Society

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