Practical management of opioid rotation and equianalgesia

Figures & data

Figure 1 Flow diagram for the selection of studies.

Table 1 Equianalgesic dose ratios for morphine vs other opioids and routes in cancer pain

Lead author and year	Opioids and routesa	Study design	Number of patients	Mean follow-up	Ratio calculated	Ratio applied	Bidirectionality	Dose dependency
Babul et al (1998)^Citation46	Mpo to Msu and Msu to Mpo	Crossover, DB, RCT	27	7 days	NA	1:1	Yes	Not investigated
Bruera et al (1995)^Citation47	Msc to Msu and Msu to Msc	Crossover, DB, RCT	23	4 days	1:2.4 2.4:1	1:2.5 2.5:1	Yes	Not investigated
Kalso and Vainio (1990)^Citation48	OXiv to OXpo and Miv to Mpo	Crossover, DB, RCT	20	4 days	0.70:1 0.31:1		Not investigated	No
Watanabe et al (1998)^Citation50	Mpo to Fsc	Retrospective	4	7.4 days (range 2–32)	85.4:1 (range 65–112.5)	50-100:1	Not investigated	Not investigated
Kato et al (2004)^Citation49	Mpo to Ftd	Retrospective	144	≥9 days	78:1	150:1	Not investigated	Not investigated
Donner et al (1996)^Citation51	Mpo to Ftd	Prospective	38	15 days	70:1	100:1	Not investigated	Not investigated
Hunt et al (1999)^Citation36	Msc to Fsc and Fsc to Msc	Crossover, DB, RCT	13 10	6 days	66:1 1:66	66:1 1:66	Not investigated	Not investigated
Kawano et al (2011)^Citation52	Miv to Fsc	Retrospective	45	10 days	28:1 (lower dose Miv) to 48:1 (higher dose Miv)	50:1	Not investigated	Yes
Bruera et al (1998)^Citation38	Mpo to OXpo and OXpo to Mpo	Crossover, DB, RCT	23	7 days	1.5:1 1:1.5	1.5:1 1:1.5	Yes	No
Heiskanen and Kalso (1997)^Citation53	Mpo to OXpo and OXpo to Mpo	Crossover, DB, RCT	27	3–6 days	1.33:1 1:1.5	1.5:1 1:1.5	No	No
Gagnon et al (1999)^Citation32	Msc to OXsc	Prospective	8	15 (±9) days	1.2(±0.4):1	1.5:1	Not investigated	Not investigated
Bruera et al (1996)^Citation34	Mpo or Msc to HMpo or HMsc and HMpo or HMsc to Mpo or Msc	Retrospective	36	2 days	5.33:1 (range 1.33–16.67) 1:3.57 (range 1.4–5)	5:1 1:5	No	No
Inoue et al (2018)^Citation54	Mpo to HMpo	Prospective	30 40	5 days	NA	5:1 8:1	Not investigated	Not investigated
Reddy et al (2017)^Citation55	HMiv to Mpo	Retrospective	163	7 days	1:11	NA	Not investigated	Yes

Notes:

a The word “to” denotes the direction of the switch.

Abbreviations: DB, double-blind; F, fentanyl; HM, hydromorphone; iv, intravenous; M, morphine sulfate; NA, not available or not applicable; OX, oxycodone; po, oral; RCT, randomized controlled trial; sc, subcutaneous; su, suppository; td, transdermal.

Figure 2 Conversion ratios of morphine to and from other opioids.

Abbreviations: iv, intravenous; po, oral; sc, subcutaneous; su, suppository; td, transdermal.

Table 2 Equianalgesic dose ratios for fentanyl vs other opioids or routes in cancer pain

Lead author and year	Opioids and routesa	Study design	Number of patients	Mean follow-up	Ratio calculated	Ratio applied	Bidirectionality	Dose dependency
Kato et al (2004)^Citation49	Mpo to Ftd	Retrospective	144	≥9 days	78:1	150:1	Not investigated	Not investigated
Donner et al (1996)^Citation51	Mpo to Ftd	Prospective	38	15 days	70:1	100:1	Not investigated	Not investigated
Watanabe et al (1998)^Citation50	Mpo to Fsc	Retrospective	4	7.4 days (range 2–32)	85.4:1 (range 65–112.5)	50–100:1	Not investigated	Not investigated
Hunt et al (1999)^Citation36	Msc to Fsc and Fsc to Msc	Crossover, DB, RCT	13 10	6 days	66:1 1:66	66:1 1:66	Not investigated	Not investigated
Kawano et al (2011)^Citation52	Miv to Ftd	Retrospective	45	10 days	28:1 (lower dose Miv) to 48:1 (higher dose Miv)	50:1	Not investigated	Yes
Kornick et al (2001)^Citation59	Fiv to Ftd	Prospective, open- label	15	24 hours	NA	1:1	Not investigated	Not investigated
Samala et al (2014)^Citation60	Fiv to Ftd	Prospective, observational	17	24 hours	NA	1:1	Not investigated	Not investigated

Notes:

a The word “to” denotes the direction of the switch.

Abbreviations: DB, double-blind; F, fentanyl; HM, hydromorphone; iv, intravenous; M, morphine sulfate; NA, not available or not applicable; po, oral; RCT, randomized controlled trial; sc, subcutaneous; td, transdermal.

Figure 3 Conversion ratios of fentanyl to and from other opioids.

Abbreviations: iv, intravenous; po, oral; sc, subcutaneous; td, transdermal.

Table 3 Equianalgesic dose ratios for oxycodone vs other opioids or routes in cancer pain

Lead author and year	Opioids and routesa	Study design	Number of patients	Mean follow-up	Ratio calculated	Ratio applied	Bidirectionality	Dose dependency
Heiskanen and Kalso (1997)^Citation53	Mpo to OXpo and OXpo to Mpo	Crossover, DB, RCT	27	3–6 days	1.33:1 1:1.5	1.5:1 1:1.5	No	No
Bruera et al (1998)^Citation38	Mpo to OXpo and OXpo to Mpo	Crossover, DB, RCT	23	7 days	1.5:1 1:1.5	1.5:1 1:1.5	Yes	No
Beaver et al (1978)^Citation62	OXpo to OXim and OXim to OXpo	Crossover, DB, RCT	13	6 hours (single-dose study)	2:1 1:2	2:1 1:2	Yes	No
Kalso and Vainio (1990)^Citation48	OXiv to OXpo and Miv to Mpo	Crossover, DB, RCT	20	4 days	0.70:1 0.31:1	NA	Not investigated	No
Hagen and Babul (1997)^Citation37	OXpo to HMpo and HMpo to OXpo	Crossover, DB, RCT	31	7 days	4.13:1 1:4.13	5:1 1:5	Yes	Not investigated
Gagnon et al (1999)^Citation32	HMsc to OXsc and Msc to OXsc	Prospective, observational	11 8	15 (±9) days	0.5(±0.4):1 1.2(±0.4):1	NA 1.5:1	Not investigated	Not investigated

Notes:

a The word “to” denotes the direction of the switch.

Abbreviations: DB, double blind; HM, hydromorphone; im, intramuscular; iv, intravenous; M, morphine sulfate; NA, not available or not applicable; OX, oxycodone; po, oral; RCT, randomized controlled trial; sc, subcutaneous.

Figure 4 Conversion ratios of oxycodone to and from other opioids.

Abbreviations: iv, intravenous; im, intramuscular; po, oral; sc, subcutaneous; td, transdermal.

Table 4 Equianalgesic dose ratios for hydromorphone vs other opioids or routes in cancer pain

Lead author and year	Opioids and routesa	Study design	Number of patients	Mean follow- up	Ratio calculated	Ratio applied	Bidirectionality	Dose dependency
Bruera et al (1996)^Citation34	Mpo or Msc to HMpo or HMsc and HMpo or HMsc to Mpo or Msc	Retrospective	36 12	2 days	5.33:1 (range 1.33–16.67) 1:3.57 (range 1.4–5)	5:1 1:5	No	No
Lawlor et al (1997)^Citation27	Msc to HMsc Mpo to HMpov HMsc to Msc HMpo to Mpo	Retrospective	34 10 35 12	3 days (range 2–11)	5:1 1:3.7	NR	No	No
Inoue et al (2018)^Citation54	Mpo to HMpo	Prospective	30 40	5 days	NA	5:1 8:1	Not investigated	Not investigated
Wallace et al (2008)^Citation40	Opioids to HMpo (using MEDD)	Prospective, open-label	148	21 days	(5:1 confirmed)	Mpo:HMpo 5:1 (MEDD)	Not investigated	Not investigated
Gagnon et al (1999)^Citation32	HMsc to OXsc	Prospective	11	15 (±9) days	0.5(±0.4):1	NA	Not investigated	Not investigated
Hagen and Babul (1997)^Citation37	OXpo to HMpo and HMpo to OXpo	Crossover, DB, RCT	31	7 days	4.13:1 1:4.13	5:1 1:5	Yes	Not investigated
Reddy et al (2017)^Citation55	HMiv to HMpo HMiv to Mpo HMiv to OXpo	Retrospective	147 163 84	7 days	1:2.5 (range 2.14–2.75) 1:11 1:8.06	NA	Not investigated	Yes Yes Yes

Notes:

a The word “to” denotes the direction of the switch.

Abbreviations: DB, double blind; HM, hydromorphone; iv, intravenous; M, morphine sulfate; MEDD, morphine equivalent daily dose; NA, not available or not applicable; NR, not reported; OX, oxycodone; po, oral; PCA, patient controlled analgesia; RCT, randomized controlled trial; sc, subcutaneous.

Figure 5 Conversion ratios of hydromorphone to and from other opioids.

Abbreviations: po, oral; sc, subcutaneous.

Table 5 Ratios for use in routine clinical practice

To: From:	Mpo	Msc	Miv	Msu	HMpo	HMsc	HMiv	OXpo	OXsc	OXiv	Ftd	Fsc	Fiv
Mpo		2:1*	1:0.31	1:1	5:1 (range 1.33–16.67:1)			1.3 to 1.5:1a			70:1 to 78:1a	85.4:1 (range 65– 112.5)	100:1*
Msc	1:2*			1:2.4		5:1 (range 1.33–16.67:1)			1.2:1 (±0.4)			66:1
Miv	1:3*										28:1 (lower dose Miv) to 48:1 (higher dose Miv)
Msu	1:1	2.4:1
HMpo	1:3.7 (range 1.35–5)							1:4.13
HMsc		1:3.7 (range 1.35–5)							0.5(±0.4):1
HMiv	1:11				1:2.5 (range 2.14–2.75)			1:8.06
OXpo	1:1.5				4.13:1					1:0.70
OXsc		1:1.2 (±0.4)				1:0.5 (±0.4)
OXiv								0.70:1
Ftd	1:70 to 1:78a												1:1
Fsc	1:85.4 (range 65– 112.5)	1:66
Fiv	1:100*										1:1

Notes: Data are expressed in accordance with published results; that is why both ranges and standard errors are presented in this table, depending on the source.

* (Shaded box) pharmaceutical industry data.

a When two or more published data are available, we present the range of results (ie, lowest and highest published ratios).

Abbreviations: F, fentanyl; HM, hydromorphone; iv, intravenous; M, morphine sulfate; NA, not available or not applicable; Msu, morphine; OX, oxycodone; po, oral; RCT, randomized controlled trial; sc, subcutaneous; td, transdermal.

BabulNProvencherLLabergeFHarsanyiZMoulinDComparative efficacy and safety of controlled-release morphine suppositories and tablets in cancer painJ Clin Pharmacol199838174819597563

 PubMed Web of Science ®Google Scholar

BrueraEFainsingerRSpachynskiKBabulNHarsanyiZDarkeACClinical efficacy and safety of a novel controlled-release morphine suppository and subcutaneous morphine in cancer pain: a randomized evaluationJ Clin Oncol1995136152015277751901

 PubMed Web of Science ®Google Scholar

KalsoEVainioAMorphine and oxycodone hydrochloride in the management of cancer painClin Pharmacol Ther19904756396462188774

 PubMed Web of Science ®Google Scholar

WatanabeSPereiraJHansonJBrueraEFentanyl by continuous subcutaneous infusion for the management of cancer pain: a retrospective studyJ Pain Symptom Manage19981653233269846027

 PubMed Web of Science ®Google Scholar

KatoKMizakiTYamazakiSA study of transdermal fentanyl in cancer pain at Aichi-Cancer CenterYakugaku Zasshi2004124528729115118241

 PubMed Web of Science ®Google Scholar

DonnerBZenzMTrybaMStrumpfMDirect conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer painPain19966435275348783318

 PubMed Web of Science ®Google Scholar

HuntRFazekasBThorneDBrooksbankMA comparison of subcutaneous morphine and fentanyl in hospice cancer patientsJ Pain Symptom Manage199918211111910484858

 PubMed Web of Science ®Google Scholar

KawanoCHirayamaTKuroyamaMDose conversion in opioid rotation from continuous intravenous infusion of morphine hydrochloride injection to fentanyl patch in the management of cancer painYakugaku Zasshi2011131346346721372544

 PubMed Web of Science ®Google Scholar

BrueraEBelzileMPituskinERandomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer painJ Clin Oncol19981610322232299779695

 PubMed Web of Science ®Google Scholar

HeiskanenTKalsoEControlled-release oxycodone and morphine in cancer related painPain199773137459414055

 PubMed Web of Science ®Google Scholar

GagnonBBielechMWatanabeSWalkerPHansonJBrueraEThe use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer painSupport Care Cancer19997426527010423053

 PubMed Web of Science ®Google Scholar

BrueraEPereiraJWatanabeSBelzileMKuehnNHansonJOpioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphineCancer19967848528578756381

 PubMed Web of Science ®Google Scholar

InoueSSaitoYTsunetoSArugaEOgataTUemoriMA double-blind, randomized comparative study to investigate the morphine to hydromorphone conversion ratio in Japanese cancer patientsJpn J Clin Oncol201848544244929635632

 PubMed Web of Science ®Google Scholar

ReddyAVidalMStephenSThe conversion ratio from intravenous hydromorphone to oral opioids in cancer patientsJ Pain Symptom Manage201754328028828711751

 PubMed Web of Science ®Google Scholar

KornickCASantiago-PalmaJKhojainovaNPrimaveraLHPayneRManfrediPLA safe and effective method for converting cancer patients from intravenous to transdermal fentanylCancer200192123056306111753984

 PubMed Web of Science ®Google Scholar

SamalaRVBloiseRDavisMPEfficacy and safety of a six-hour continuous overlap method for converting intravenous to transdermal fentanyl in cancer painJ Pain Symptom Manage201448113213624291296

 PubMed Web of Science ®Google Scholar

BeaverWTWallensteinSLRogersAHoudeRWAnalgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodoneJ Pharmacol Exp Ther1978207192100359779

 PubMed Web of Science ®Google Scholar

HagenNABabulNComparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer painCancer1997797142814379083166

 PubMed Web of Science ®Google Scholar

LawlorPTurnerKHansonJBrueraEDose ratio between morphine and hydromorphone in patients with cancer pain: a retrospective studyPain1997721–279859272790

 PubMed Web of Science ®Google Scholar

WallaceMRauckRLMoulinDThipphawongJKhannaSTudorICConversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer painJ Int Med Res200836234335218380946

 PubMed Web of Science ®Google Scholar