Opioid rotation with extended-release opioids: where should we begin?

Figures & data

Patient vignette Opioid Rotation^a

Patient	42-year-old patient
	Primary diagnosis: neuropathic pain from multiple back surgeries for lumbosacral spine disease
Initial opioid treatment	Baseline opioid: 40 mg/8 hours oxycodone ER
	Supplemental analgesic: 5/500 mg hydrocodone IR/APAP, up to 6/day as needed
Rationale for rotation to a new opioid	Inadequate pain control with current medications
	Clinician concern over risks associated with total daily dose of APAP
Selected opioid for rotation	Baseline opioid: hydromorphone ER
	Supplemental analgesic: oxycodone IR
Conversion to hydromorphone ER	Previous total daily dose (baseline opioid):	120 mg/day oxycodone ER
		30 mg/day hydrocodone IR
	ER oxycodone morphine equivalent dose:	240 mg/day
	IR hydrocodone morphine equivalent dose:	60 mg/day
	Total daily morphine equivalent dose:	300 mg/day
	Conversion ratio to hydromorphone ER^b:	5:1 morphine equivalent:hydromorphone
	New total daily dose:	60 mg/day hydromorphone ER
	Starting dose (with ∼50% additional reduction of equianalgesic dose):	32 mg/day (2 × 16 mg tablets) hydromorphone ER^c
	Stable opioid dose:	48 mg/day hydromorphone ER titrated over next 2 weeks^d
Outcome	Well tolerated with adequate around-the-clock pain control

Notes:

a This example is taken from the author’s experience with one patient during a clinical trial;

b clinical trials of patients with chronic pain support the efficacy and safety of 5:1 morphine equivalent:hydromorphone ER conversion ratio^23,24;

c an alternative conversion strategy would be to administer 36 mg/day (3 × 12 mg tablets) hydromorphone ER and titrate to 48 mg/day over the next 2 weeks;

d provided 5 mg/day oxycodone IR, up to 3/day as needed for supplemental analgesia.

Abbreviations: ER, extended-release; IR, immediate-release; APAP, acetaminophen.

Figure 1 Cumulative percentage of patients achieving an effective opioid dose with opioid rotation.²⁷

Adapted with permission from Quang-Cantagrel et al. Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review. Anesth Analg. 2000;90(4):933–937.

Table 1 Major reasons for opioid rotation³

Major reasons for opioid rotation
Development of intolerable AEs with current opioid	Patient displays drug-aberrant behavior(s)
Lack of analgesia following dose escalation	Patient prefers alternative route of administration
Occurrence of drug–drug interactions	Financial limitations or access barriers to certain medications

Reprinted from J Pain Symptom Manage, vol 38, issue 3, Fine et al, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing “best practices” for opioid rotation: conclusions of an expert panel, p418–425, Copyright (2009), with permission from Elsevier.

Abbreviation: AEs, adverse events.

Table 2 Original equianalgesic dose table²⁸

Medication	Equianalgesic (mg) doses, route of administration
	Intramuscular/intravenous/subcutaneous	Oral
Morphine^a	10 mg	60 mg
Hydromorphone^b	1.5 mg	7.5 mg
Oxycodone		20–30 mg
Oxymorphone^c	1 mg	15 mg
Levorphanol	2 mg	4 mg
Methadone^d	10 mg	20 mg
Fentanyl	50–100 μg^e

Notes:

a Potency estimates relative to the original dose table have undergone little change; however, the oral morphine dose is often revised to 20 to 30 mg, as the original acute dosing data do not apply to chronic opioid therapy;

b although the morphine:hydromorphone equianalgesic potency ratio is as high as 8:1 for hydromorphone IR, the equianalgesic potency ratio for hydromorphone ER is 5:1^23,24,29;

c oxymorphone equianalgesic dose for rectal administration: 10 mg;

d in clinical practice, methadone appears to be more potent than originally estimated, warranting caution during rotation (see text: Rotation to Methadone);

e dose ratio only applicable to intravenous and subcutaneous administration.

Reprinted from J Pain Symptom Manage, vol 38, issue 3, Knotkova et al, Opioid rotation: the science and the limitations of the equianalgesic dose table, p426–439, Copyright (2009), with permission from Elsevier.

Table 3 Expert consensus for a two-step approach to opioid rotation³

Step 1

Calculate the equianalgesic starting dose of the new opioid using an equianalgesic dosing table Apply an additional dose reduction of 25% to 50% to the equianalgesic starting dose^a ○ Reduction closer to 50% if the patient was previously receiving a relatively high opioid dose, is not Caucasian, or is elderly, or medically frail ○ Reduction closer to 25% in patients without the aforementioned characteristics or in patients changing only the route of administration

Step 2

Assess the patient’s current pain severity, occurrence of adverse events, medical status, and other medical or psychosocial factors influencing therapeutic efficacy ○Initiate opioid therapy with the starting dose determined using step 1 or apply an additional 15% to 30% dose increase or decrease based on the likelihood of achieving adequate analgesia with tolerable adverse events and without inducing withdrawal Consider providing supplemental opioid analgesia during the titration process of 5% to 15% of the total daily opioid dose^b Frequently monitor for patient response and individual dose titration

Notes:

a Great caution is needed when initiating treatment with methadone.² A 75% to 90% additional dose reduction or inpatient monitoring is recommended with an equianalgesic starting dose of ≥100 mg/day of methadone³;

b no additional dose reduction is recommended when rotating to transdermal fentanyl when using the conversion tables provided in the drug’s prescribing information.

Reprinted from J Pain Symptom Manage, vol 38, issue 3, Fine et al, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing “best practices” for opioid rotation: conclusions of an expert panel, p418–425, Copyright (2009), with permission from Elsevier.

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