Thursday, April 5, 2012

New Perspectives on Safer Opioid Rotation

Opioids Accidental opioid overdose deaths can occur when rotating (switching) patients from one opioid analgesic to another. Now, a pair of new papers from well-respected experts in pain management challenge the use of equianalgesic tables to determine opioid dosing and, instead, provide more practical guidance on opioid safety during rotation. This is “must-read” advice for all prescribers.

Writing in an early online edition of the journal Pain Medicine, Lynn R. Webster, MD, and Perry G. Fine, MD, observe that common practices for changing from one opioid to another, including the use of published dose-conversion ratios, may be contributing to the growing number of opioid-related fatalities [Webster and Fine 2012-A, 2012-B, refs below]. Webster, who is Medical Director of Lifetree Clinical Research in Salt Lake City, Utah, is president elect of the American Academy of Pain Medicine (AAPM); Fine is the immediate past president of AAPM and Professor of Anesthesiology at the University of Utah School of Medicine.

Opioids serve an essential role in the management of many chronic pain syndromes and patients may be rotated from one opioid to another for various reasons, the authors note, such as inadequate pain relief, intolerable side effects, or lack of insurance coverage for the original opioid. Rotating or switching to a different opioid can be helpful in up to 80% of patients who are not experiencing adequate pain relief.

Yet, according to recent reports from the U.S. Centers for Disease Control and Prevention (CDC), nearly 15,000 people die every year as a result of overdoses involving prescription opioids. While many decedents are persons who abuse the drugs without being prescribed them, a significant proportion of deaths are in patients with pain who are taking opioids as prescribed by healthcare providers.

According to Webster in a press release [here], “Our goal is to reverse the national trend of unintentional overdose deaths while advocating for appropriate therapy for the one in three Americans who experience chronic pain.” Indeed, according to a recently-revised estimate from the U.S. Institute of Medicine, 100 million adult Americans suffer some degree of chronic pain and many would benefit from opioid therapy.

In their papers, Webster and Fine discuss flaws uncovered in current methods of rotating opioids, such as prescriber errors due to inadequate training and the use of inaccurate dose-conversion ratios found in published protocols, including in product package inserts. Most protocols call for the use of an equianalgesic dosing table to convert the daily dose of the current opioid to an expectedly comparable dose of morphine; then, using the table again, this dose of morphine is converted to the new opioid dose — adding a margin of safety by reducing the calculated equianalgesic dose of the new opioid.

The math itself is relatively straightforward, but it is a multistep process fraught with a potential for error. Moreover, Webster and Fine point out that there are multiple conversion tables to choose among, with each being somewhat different and none of them adequately validated by research relevant for everyday patients. Plus, a particularly pesky problem is that there can be individual differences in how patients respond to or metabolize opioids, causing the pharmacokinetics and pharmacodynamics of different opioids to vary unpredictably among patients. As a result, safety can be unexpectedly compromised when switching from one opioid to another.

Concluding from their review of the evidence that most fatal outcomes during opioid rotation are preventable, the authors suggest 3 easy-to-implement steps that could eliminate the need to use conversion tables altogether [Webster and Fine 2012-A]:

  1. Reduce the original opioid dose by 10% to 30% while starting the new opioid at the lowest available dose formulation for the product.

  2. After step 1, further reduce the dose of the original opioid by 10% to 25% per week while increasing the daily dose of the new opioid by 10% to 20%, based on clinical need to relieve pain and maintain safety (such as to control the emergence of adverse effects or opioid withdrawal).

  3. Throughout the rotation period, provide sufficient immediate-release “rescue” opioid to prevent withdrawal and help keep pain levels down so the patient is not tempted to take too much of the original or new opioid medication.

In most instances, the authors suggest that the complete switch can occur within 3 to 4 weeks, but some patients may need more time. This is a longer but safer rotation process than for most current methods.

NOTE: In e-mail correspondence (March 30, 2012), Webster suggested to us that the above approach is meant to primarily address rotation between long-acting or extended-release opioids for chronic pain, but it also could apply to large doses of immediate-release opioids. Furthermore, he recommends giving enough immediate-release “rescue” opioid for only one week at a time, using the same basic opioid molecule as the original opioid primarily to prevent withdrawal symptoms. As for the amount, he says the “rescue” dose should be about 20% to 50% of the decreased opioid. For example, if 240 mg/day OxyContin is decreased to 160 mg/day, he would prescribe 28 oxycodone tablets, 15 mg each, to be taken up to 1 every 6 hours as needed (PRN), but not to exceed 4 tabs per day. This might be in addition to any fast-acting “rescue” medication the patient had been periodically using previously for breakthrough pain.

Webster and Fine caution that safe rotation to/from methadone can be particularly troublesome due to its unique pharmacokinetic and pharmacodynamic profile, with a long and highly variable half-life but much shorter duration of analgesic effects. A reliance on published equianalgesic conversion tables, particularly when converting to methadone from another opioid, can be especially hazardous. Presumably the above 3-step approach might be useful with methadone, but the authors do not specifically discuss that.

The authors stress that more research is needed to establish that their new paradigm for opioid rotation is safe and effective in a broad population of patients. “It is time for professional societies, government agencies and industry to work together and correct the important flaws in current opioid rotation practices," Webster and Fine conclude. “All patients who have indications for opioid therapy must be assured that routine clinical practices are safe and have an evidentiary basis.”

COMMENTARY: Several years ago we discussed difficulties of safe opioid rotation in an UPDATE titled, “Opioid Rotation: Benefits, Challenges, Hazards” [here]. Even then, some authors candidly acknowledged that conversion methods and information in the various equianalgesic tables were confusing for healthcare providers and dangerous to the public. Most of the principles that we discussed at that time are in accord with the paradigm suggested in these two new papers.

Webster and Fine propose that their 3-step approach is consistent with sound clinical practice and experience, but it still needs to be more extensively tested and validated, using a variety of opioids and in diverse patient populations. To that, we would add several often overlooked aspects that might be included in further development of their approach:

  1. Assuredly, more and better education for prescribers would be appropriate. Webster and Fine mention a number of studies finding that many healthcare providers — eg, physicians, pharmacists, nurses — have surprisingly low competency when it comes to an understanding of opioid rotation and they find the necessary dose-conversion calculations difficult to perform.

  2. Setting up and following a schedule of incrementally decreasing one opioid while increasing the other over a period of weeks could pose difficulties in tracking and record-keeping. Plus, this protocol may need adjusting from week to week, depending on individual patient response. Therefore, prescribers may need tools to help them in this process; perhaps, a specialized charting approach or even a computerized program that will help them to track and adjust the shifting dosing percentages and daily-dose amounts over time.

  3. Successful opioid rotation seems highly dependent on patient compliance with the prescribed regimen, with the need for them to keep track of at least 3 different analgesics; the original opioid, the new one, and “rescue” medication. Certainly, extensive patient education and clear instructions would be a critical factor.

    Along with that, for added safety, patients and their personal caregivers (family, friends, etc.) need education on identifying signs/symptoms of opioid overmedication and overdose, and what to do in emergencies. This could be critical at any stage of the rotation process and our online program, Opioids911-Safety [here], was specifically and extensively designed to fulfill this educational need.

  4. In their papers, Webster and Fine discuss a number of case examples of serious overmedication during opioid rotation, with life-threatening respiratory depression that was reversed by the timely administration by medical personnel of the opioid antagonist naloxone. We have previously advocated at length for making this effective, safe, and inexpensive antidote more widely and readily available directly to patients and their caregivers for at-home overdose rescue [see UPDATEs here and here], and the U.S. FDA will soon be convening a meeting to discuss this topic [discussed in UPDATE here]. Having naloxone close at hand during opioid rotation (and thereafter) would be an added safety measure, providing peace of mind for both patients and their opioid prescribers while potentially saving many lives.

In sum, opioids are often a necessary component for the effective management of moderate to severe chronic pain, but there have been concerns about safety due to opioid-related mortality. Rather than considering ways in which these medications can be limited, replaced, or eliminated from the therapeutic milieu in pain management, the focus should be on helping to ensure their safe prescribing and proper use.

> Webster LR, Fine PG. Overdose Deaths Demand a New Paradigm for Opioid Rotation. Pain Med. 2012-A(Mar); online ahead of print [
abstract here].
> Webster LR, Fine PG. Review and Critique of Opioid Rotation Practices and Associated Risks of Toxicity. Pain Med. 2012-B(Mar); online ahead of print [
abstract here].

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