Switching to Another Opioid or Route of Administration

Chapter outline

WITH few exceptions, analgesia is dose-related rather than opioid-related. Thus unrelieved pain per se is not a sound reason for switching to another opioid. Other options for improving analgesia should be tried, such as increasing the opioid dose, providing a nonsteroidal antiinflammatory drug (NSAID) around the clock (ATC), or adding local anesthetic to epidural opioids. Adverse effects that are intolerable and unmanageable are more likely to be an appropriate reason to switch to another opioid (Knotkova, Fine, Portenoy, 2009). Because of great interindividual variability, even opioids that bind to the same receptor site can produce adverse effects of different intensities in patients. The development of toxic effects from metabolite accumulation is a common reason for opioid rotation during long-term opioid therapy, and some recommend multiple switches if the first change in drug does not relieve symptoms (Hanks, Cherny, Fallon, 2004; Knotkova, Fine, Portenoy, 2009) (see Table 18-1 for options when analgesia from opioids is limited by adverse effects). Although switching to another opioid is common and recommended under these circumstances, a Cochrane Collaboration Review concluded that randomized controlled research is lacking and the practice is based largely on anecdotal or observational and uncontrolled studies (Quigley, 2004).

Table 18-1

Options When Analgesia from Opioids Is Limited by Adverse Effects

TENS, Transcutaneous electrical nerve stimulation.

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, p. 474, St. Louis, Mosby. Modified from Portenoy, R. K. (1998). Adjuvant analgesics in pain management. In D. Doyle, G. Hanks, & N. MacDonald (Eds.), Oxford textbook of palliative medicine, ed 2, New York, Oxford University Press. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

Patient difficulty in adhering to an analgesic regimen may be a sound reason to switch to another opioid. Sometimes another opioid allows a reduction in pills or liquid volume needed for pain relief. Fewer or smaller doses may be possible, making it easier for some patients to comply with the pain treatment regimen.

There is no good evidence that analgesic efficacy is dependent on route of administration; morphine is equally efficacious when given in appropriate doses by the oral, parenteral, or intraspinal routes (Hanks, Cherny, Fallon, 2004). However, occasionally switching from one opioid or route to another opioid or route is done to reduce the cost of long-term opioid treatment (Knotkova, Fine, Portenoy, 2009). For example, in one case the cost of opioid treatment was reduced from $1000 per day to less than $25 per day when a patient was switched from parenteral hydromorphone to oral methadone (Thomas, Bruera, 1995). The cost of the 10-day hospital stay required during the conversion process was not included in the cost analysis. Thus several factors must be considered when switching opioids to reduce costs.

When switching an opioid-tolerant patient to an alternative opioid drug, it is wise to assume that cross-tolerance will be incomplete (Knotkova, Fine, Portenoy, 2009). This means that a patient who has developed tolerance to one opioid analgesic may not be equally tolerant to another. In such cases, the starting dose of the new opioid must be reduced by at least 25% to 50% of the calculated equianalgesic dose to prevent overdosing (see Chapter 13, pp. 339-350, for the recommended approach when converting to methadone); otherwise, the full calculated equianalgesic dose of the new opioid could lead to effects such as sedation that would be greater than expected (Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009; Knotkova, Fine, Portenoy, 2009; Indelicato, Portenoy, 2002; Vadalouca, Moka, Argyra, et al., 2008). Even with this approach, some patients will experience underdosing and some will experience overdosing because of individual sensitivities.

It is also best not to abruptly discontinue the present opioid and convert to the new opioid in one step. This could cause a significant overdose that precipitates undesirable adverse effects or an underdose that precipitates severe pain. Instead, it is best to make the transition with 50% of the current opioid dose combined with 50% of the projected dose for the new opioid for several days. From this starting point, gradual increases in the new opioid drug and decreases in the old drug can be made until the switch is complete. The higher the dose of the current opioid, the more important it is to make the transition using 50/50 dosing (see Box 18-1 for guidelines when switching from one opioid to another).

Box 18-1 Switching from One Opioid to Another ¹

NOTE: See Chapter 14 and Box 14-6 (p. 393) for switching to transdermal fentanyl; see Chapter 13 and Box 13-3 (p. 345) and Table 13-8 (pp. 346-347) for switching to methadone. For all other opioid analgesics, use the equianalgesic dose chart in Table 16-1 on pp. 444-446 and follow the steps listed below, which provide direction for switching from one oral opioid to another oral opioid, using the example of oral short-acting morphine to oral short-acting oxycodone:

1. Determine the total daily dose of the current opioid (e.g., morphine, 30 mg, taken q 4 h PO: 30 mg × 6 doses/day = 180 mg/24 h).

2. Locate the dose of the current opioid by the current route listed in the equianalgesic dose chart (e.g., 30 mg).

3. Determine the number of equianalgesic dose units in the 24-hour dose by dividing the 24-hour dose by the equianalgesic dose (e.g., 180 mg ÷ 30 mg = 6 units).

4. Locate the dose of the new opioid by the route of the new opioid listed on the equianalgesic dose chart (e.g., oxycodone 20 mg).

5. Determine the 24-hour dose of the new opioid by multiplying the equianalgesic dose of the new opioid by the equianalgesic dose units of the current opioid (e.g., 20 mg × 6 units = 120 mg/24 h of oxycodone).

6. Divide the 24-hour dose of the new drug by the number of doses to be given each 24 hours (e.g., 120 mg/24 h of oxycodone ÷ 6 doses = 20 mg of oxycodone q 4 h).

7. If the patient is opioid tolerant and has been taking a high dose of opioid, it is best to reduce the calculated dose of the new opioid by 25% to 50% (e.g., for 25% reduction: 20 mg oxycodone × 0.25 = 5 mg; 20 − 5 mg = 15 mg; for 50% reduction: 20 mg oxycodone × 0.50 = 10 mg).

8. It is also important not to abruptly discontinue the current opioid and convert to the new in one step. This could lead to an overdose, causing undesirable adverse effects, or an underdose, precipitating severe pain. Instead, in these cases, make the transition starting with 50% of the current opioid dose (e.g., 30 mg of morphine × 0.50 = 15 mg of morphine) combined with 50% of the projected dose for the new opioid (e.g., 15 mg of oxycodone × 0.50 = 7.5 mg of oxycodone, or 10 mg of oxycodone × 0.50 = 5 mg). Gradual increases in the new opioid drug and decreases in the old one can be made until the switch is complete over a period of several days. For example, in the case of a 25% reduction (see step 7), start by giving oxycodone 7.5 mg PO q 4 h and morphine 15 mg PO q 4 h. In the case of a 50% reduction (see step 7), start by giving oxycodone 5 mg PO q 4 h and morphine 15 mg PO q 4 h. It may be necessary to adjust the dose of the new opioid (i.e., maintain the 50% dose of the old opioid and increase the new opioid for insufficient pain relief). Once the combined doses provide good pain control, drop the old opioid dose and double the new one.

9. After all calculations are made, perform a second assessment of pain severity, patient response, and medical and other characteristics to determine whether to apply an additional increase or decrease of 15% to 30% to enhance the likelihood that the initial dose will be effective for pain, or conversely, unlikely to cause withdrawal or opioid-related adverse effects.

10. Have a strategy to frequently assess initial response and titrate the dose of the new opioid regimen to optimize outcomes.

11. If a supplemental dose is used for titration, see Box 16-2 (p. 449) for calculation; if oral transmucosal formulation is used, see Boxes 14-2 (pp. 382-383) and 14-3 (pp. 384-385).

h, Hour; hs, at sleep; PO, oral; q, every.

Occasionally, during opioid treatment it is necessary to switch from one opioid to another. Calculating the equianalgesic dose of the new opioid increases the likelihood that patients will tolerate the switch to a new opioid without loss of pain control or excessive adverse effects. This box provides calculations for equianalgesic dosing.

¹ An expert panel was convened for the purpose of establishing a new guideline for opioid rotation and recently proposed a two-step approach (Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009). The approach presented in the text for calculating the dose of a new opioid can be conceptualized as the panel’s Step One, which directs the clinician to calculate the equianalgesic dose of the new opioid based on the equianalgesic table. Step Two suggests that the clinician perform a second assessment of the patient to evaluate the current pain severity (perhaps suggesting that the calculated dose be increased or decreased) and to develop strategies for assessing and titrating the dose as well as determining the need for a breakthrough dose and calculating that dose (see Box 16-2 on p. 449). The specific steps of patient examples given in the text reflect the panel’s two-step approach (see Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009).

From Pasero, C., & McCaffery, M. (2011). Pain assessment and pharmacologic management, p. 475, St. Louis, Mosby. Data from Fine, P. G., Portenoy, R. K., & Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. (2009). Establishing best practices for opioid rotation: Conclusions of an expert panel. J Pain Symptom Manage, 38(3), 418-425. Pasero C. May be duplicated for use in clinical practice.

The principles described above underscore the importance of careful dose selection and monitoring during opioid rotation (see Chapter 11 for more on cross-tolerance and the use of conversion charts, Box 14-6 on p. 393 for guidelines on switching from oral morphine to transdermal fentanyl, and Box 13-3 on p. 345 for guidelines on switching to methadone). It requires the clinician to have an understanding of opioid pharmacology and a commitment to tailoring the choice of opioid and dose to the patient’s individual characteristics and response (Shaheen, Walsh, Lahsheen, et al., 2009). An expert panel was convened for the purpose of establishing a new guideline for opioid rotation and recently proposed a two-step approach (Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009). The approach presented in this chapter for calculating the dose of a new opioid can be conceptualized as the panel’s Step One, which directs the clinician to calculate the equianalgesic dose of the new opioid based on the equianalgesic table. Step Two suggests that the clinician perform a second assessment of the patient to evaluate the current pain severity (perhaps suggesting that the calculated dose be increased or decreased) and to develop a strategy for assessing and titrating the dose as well as determining the need for a breakthrough dose and calculating that dose (see Box 16-2 on p. 449). The specific steps of patient examples given in this chapter reflect the panel’s two-step approach (see Fine, Portenoy, the Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation, 2009). Following are several patient examples of conversions from one opioid to another, one route of administration to another, and combinations of both. The equianalgesic dose chart in Table 16-1 on pp. 444-446 is used for the necessary conversion calculations.

Patient Example

Switching from One Oral Opioid to Another Oral Opioid

For the last two months, Mrs. N. has been taking 30 mg of PO modified-release oxycodone every 12 hours plus 10 mg of short-acting oxycodone for breakthrough pain about twice daily for severe osteoarthritis pain. Although her pain is well-controlled with pain ratings between 1/10 and 3/10, she has experienced severe nausea that has been unresponsive to all treatment efforts since the oxycodone was started. Her nurse practitioner thinks she will respond more favorably to a different opioid. She will be switched to PO modified-release oxymorphone. The following calculations are necessary (use the equianalgesic dose chart, Table 16-1, on pp. 444-446):