Saturday, November 21, 2009

Opioid Rotation: Benefits, Challenges, Hazards

There are many reasons why switching from one opioid analgesic to another may be necessary and helpful, yet safely doing so appears to involve as much clinical art as science. This can make healthcare providers and their patients justifiably nervous, and may be a prime reason why opioids are not prescribed appropriately. What can practitioners do?

In an earlier blogpost [10/23/09] we noted that many healthcare providers avoid prescribing opioid analgesics due to concerns about patient compliance with treatment, the possibility of opioid abuse, and perceived scrutiny by regulatory authorities. However, there is another reason: once having started a patient on opioids there is a well-founded fear of how to manage switching or rotating from one opioid to another if it becomes necessary. Recent APS/AAPMed guidelines on opioid-analgesic therapy have recommended opioid rotation as a strategy for patients who experience intolerable adverse effects or inadequate benefit despite increased opioid doses [Chou et al. 2009]. Patients often may respond better to a different opioid that overcomes individual genetic variations, interactions with comedications, effects of coexisting disease, or a nonresponsive pain condition. However, well-designed studies evaluating the benefits versus harms of opioid rotation are lacking, and available studies in patients with various types of pain show inconsistent results.

The APS/AAPMed opioid guidelines warn that there is insufficient evidence to guide specific recommendations for performing opioid rotation [Chou et al. 2009]. Current opioid rotation protocols generally call for using Equianalgesic Dosing Tables to mathematically convert daily dosing of the current opioid(s) to equivalent doses of morphine, then using the Tables again to convert from morphine to the new opioid and, finally, reducing the calculated equianalgesic dose of the new opioid by a safety margin to avoid overmedication. In theory, this is straightforward; however, conversions become more complex when patients are rotated to or from such drugs as methadone or fentanyl, and calculations that normally involve only basic algebra become almost mind-boggling when simultaneously changing opioid molecules, routes of administration (eg, oral vs parenteral), and/or type of formulation (eg, long- vs short-acting). The outcomes, at least short-term, can be unfavorable: patients may be undermedicated and uncomfortable, possibly experiencing opioid withdrawal syndrome; or, they may be overmedicated to the point of life-threatening overdose.

In September 2009, a pair of discussion articles [Knotkova et al. 2009; Shaheen et al. 2009] and a “best practice” guidelines document [Fine et al. 2009] addressing opioid rotation appeared in the Journal of Pain and Symptom Management. Additionally, a first-ever textbook solely dedicated to the subject was recently published [McPherson 2010]. Here are some brief highlights from those publications:
  • Some authors candidly acknowledge that, “Current information in equianalgesic tables is confusing for physicians, and dangerous to the public” [Shaheen et al. 2009]. Some of the increases in opioid-related deaths reported in recent years may be due to improper dosing during rotation from one opioid and/or route of administration to another.

  • Current Equianalgesic Dosing Tables, of which there are a number of variations, have been used for more than 40 years with little modification [Fine et al. 2009; Knotkova et al. 2009] Data incorporated in these tables are often anecdotal or based on average responses in single-dose studies, without regard for patient-response variables, and they also are deficient in other ways [McPherson 2010; Shaheen et al. 2009]. Comparisons of different commonly used tables show that they often provide inconsistent and variable equianalgesic ratios for calculating conversions — there is no current consensus on a standard set of ratios (for example, different recommended conversion ratios of oral oxycodone to oral morphine remarkably range from 1:1 to 1:3, a 300% variance) [Knotkova et al. 2009; Shaheen et al. 2009].

  • “Best practice” recommendations are that, after calculating the equianalgesic dose of the new opioid it should be reduced by 25% to 50% [Fine et al. 2009; Shaheen et al. 2009] to account for incomplete analgesic cross-tolerance (that is, physiologic tolerance established to the first opioid does not carry over completely to the new one, so the patient is more sensitive to the new opioid). Doing this allows for a safety margin to help prevent overmedication; although, initial undermedication with the new agent is highly likely.

  • Proposed new guidelines [Fine et al. 2009] recommend an immediate second assessment with an eye toward further applying either a dose increase or decrease of 15% to 30% to help ensure that the new dose will provide effective analgesia while limiting either opioid side effects or withdrawal.

  • When selecting appropriate dose reduction percentages numerous factors must be taken into account, such as whether rotation is being done because of toxicity (side effects) versus uncontrolled pain; the amount and duration of current dosing; patient age and physical condition; the possibility of interactions with other drugs; and genetic variations in metabolic enzymes or opioid receptor systems [Fine et al. 2009; Shaheen et al. 2009]. While such factors are science-based, determining their relative importance would seem to require some clinical artistry since phenomena of individual variation and cross-tolerance are actually poorly understood [Knotkova et al. 2009].

  • Rotations to/from fentanyl, methadone, or partial opioid agonists are more complex, requiring special conversion tables and knowledge [Shaheen et al. 2009; McPherson 2010]. Such knowledge can be acquired with extra time and effort in studying available literature.

  • Rotating to a different opioid before the first opioid has reached steady state and achieved potential effectiveness is pharmacologically unsound [Shaheen et al. 2009]. After opioid rotation, patients should be monitored for therapeutic response and the new opioid titrated upward (or downward) as necessary to achieve desired analgesia [Fine et al. 2009].

  • Some experts note that successful opioid rotations depend on “common sense” [McPherson 2010], while others say “clinical judgment” or “practitioner discretion” are required [Shaheen et al. 2009]. Nowhere is it described how one acquires such relevant but abstract traits when it comes to this complex subject.
Clearly, opioid rotation is not for prescribers uneducated or inexperienced in its use, and the above highlights should not be viewed as a complete protocol. Perhaps the most comprehensible and comprehensive tutorial at present is McPherson’s textbook [2009]; although, it would be good to also have a companion “quick guide” that one can carry in a lab coat pocket for point-of-care reference. Experts advise that whichever Equianalgesic Dose Table is used it should serve only as a general guide for estimating equivalent opioid doses [Shaheen et al. 2009]; using the same Table consistently, however deficient, will allow the prescriber to learn how to adjust its values for achieving maximum effectiveness and safety. There also are available a number of computerized equianalgesic-conversion calculators for desktop personal computers or handheld PC devices that automate math functions. All of them have their shortcomings and quirks, and some are not recommended [for a review of these, see Quinn 2007]; however, using the same automated program over time, taking its flaws into account, might incur satisfactory results.

A final caveat — all of the papers and discussions on opioid rotation that we have examined overlooked what may be the most critical part of the equation: patient education. There has been a strongly lopsided emphasis in the literature in recent years on minimizing risks of opioid misuse, diversion, or abuse, with relatively little attention paid to educating patients (along with their family or other caregivers who will monitor them) on recognizing opioid dose-related problems (eg, overmedication, side effects) and what to do about them (including responding to overdose crises). While there are currently few patient-education resources addressing these issues for healthcare providers to utilize, this vital aspect of opioid rotation should not be neglected — for safety’s sake.

> Chou R, Fanciullo GJ, Fine PG, et al. APS/AAPM clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009(Feb);10(2):113-130 [
available here].
> Fine PG, Portenoy RH, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing “best practices” for opioid rotation: conclusions of an expert panel. J Pain Symptom Manage. 2009;38(3):418-425.
> Knotkova H, Fine PG, Portenoy RK. Opioid rotation: the science and the limitations of the equianalgesic dose table. J Pain Symptom Manage. 2009;38(3):426-439.
> McPherson ML. Demystifying Opioid Conversion Calculations: A Guide to Effective Dosing. Bethesda, MD: American Society of Health-System Pharmacists; 2010 (softbound, 200 pages, ISBN: 9781585281985 [
click here for info]).
> Quinn TE. Converting opioid analgesics, part II: review of equianalgesic conversion calculators; 3rd revised version. Pain Topics. 2007(Feb) [
PDF available here].
> Shaheen PE, Walsh D, Lasheen W, et al. Opioid equianalgesic tables: are they all equally dangerous? J Pain Symptom Manage. 2009;38(3):409-417.