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Transcript
Medicines Q&As
Q&A 42.6
What are the equivalent doses of oral morphine to other oral opioids
when used as analgesics in adult palliative care?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Date prepared: 20th September 2011
Background
Morphine is generally the strong opioid of choice and a common question is how to convert a dose of
another opioid to morphine or vice versa. Other opioids may be preferred, for example, if a patient obtains
insufficient pain relief with morphine and/or is suffering severe adverse effects. However, switching to an
alternative opioid is only one approach to managing opioid adverse effects (1,2). Other strategies include:



Reducing the dose of opioid (and possibly adding non-opioid or adjuvant analgesics).
Symptomatic management of the adverse effect(s).
Switching the route of administration.
If the strategies above have not worked, or are impractical, then a decision to convert to an alternative
opioid may be taken, preferably with advice from a palliative care or pain team.
Answer
Advice on opioid conversion
NB: Before using Table 1, read the notes below and the Limitations statement at the end of this
document.

Equivalent doses of opioids are given in Table 1. These are an approximate guide only because
comprehensive data are lacking and there is inter-individual variation. There is no widely accepted
algorithm or guideline for equianalgesic conversions (3), borne out by the fact that sources differ in
the equivalent doses they quote.

When converting from one opioid to oral morphine, or vice versa, the initial dose depends on the
relative potency of the two drugs (4) and route of administration (see Table 1). This Q&A deals only
with oral administration.

Some authors have suggested that, in most cases, the calculated dose-equivalent of a new drug
derived from e.g. Table 1 must be reduced to ensure safety. A dose reduction of at least 50% is
recommended when switching at high doses (e.g. morphine or equivalent doses of 1g/24 hours or
more), in elderly or frail patients, or because of intolerable undesirable effects (4). A similar dose
reduction is recommended when there has been a recent rapid escalation of the first opioid. ‘As
required’ doses should be used to make up any deficit while re-titrating to a satisfactory dose of the
new opioid (4).

Based on clinical experience, the starting point for dose reduction from the calculated equianalgesic
dose is 25-50% (3,5). This dose reduction is particularly important when high doses are used.
1
From the National Electronic Library for Medicines. www.nelm.nhs.uk
Medicines Q&As
However, the reduction may not be appropriate if the original opioid failed to control pain (see below).
Reasons for this suggested dose reduction include:
o
Incomplete cross-tolerance between opioid drugs, which would lead to effects (including
adverse effects) that would be greater than expected when a switch to a new drug is made
(2,3,5).
o
There appears to be a large inter-individual variability in the relative potencies among opioids
(2,5).
o
There is a need to adjust for conditions that increase opioid risk (e.g. elderly patients, coexisting medical conditions) (5).
o
Most data are derived from single-dose studies and these values can only approximate to the
clinical situation (5).

When considering opioid conversions, the degree of unrelieved pain should also be taken into
account (5). For example, if pain is not controlled by the current opioid then it may be appropriate to
administer the calculated equianalgesic dose of the new opioid or even increase the calculated dose
by 25-50% (3).

The half-life of the two drugs needs to be considered when converting so that the patient does not
experience breakthrough pain or receive too much opioid during the conversion period.

The time to onset of action needs to be considered, for example, if moving from a non-modified
release to a modified release preparation. The timing of doses will therefore need to be carefully
considered.

The total daily dose of the current opioid(s), including all long-acting and breakthrough doses, must
be determined prior to conversion. If the patient is on multiple opioids, convert all to morphine
equivalents (see Table 1) (3).

Ensure that ‘as required’ doses of an opioid are prescribed for breakthrough pain. These should not
be modified release preparations or transdermal patches.

Once the conversion has occurred, the dose of new opioid should be titrated carefully according to
individual response and the patient monitored closely for the first 7-14 days for side effects and
efficacy especially when switching at high doses (6). Careful monitoring is also particularly necessary
when there has been a recent rapid escalation of the first opioid (4). It is common for upwards or
downwards dosage adjustment of a new long-acting opioid to be necessary during the initial 24-48
hours after conversion (3).

Ensure naloxone is available.
2
From the National Electronic Library for Medicines. www.nelm.nhs.uk
Medicines Q&As
Table 1. Approximate equivalent potencies of oral opioids to oral morphine (see advice above).
Converting from another oral opioid to oral morphine:
Multiply the total daily dose of oral opioid by its potency equivalence to determine the equivalent total daily
dose of oral morphine.
Converting from oral morphine to another oral opioid:
Divide the total daily dose of oral morphine by the potency equivalence for the oral opioid which you are
converting to.
Oral Drug
(refs)
Duration of
action
(hours)
(standard
release
preparations)
Potency
equivalence to
morphine
(oral to oral)
Notes
Buprenorphine (4)
6-8
80 (sublingual)
Only one literature source suggests a
conversion (4) but this potency equivalence has
been cited for a number of years. No published
dose equivalence studies in analgesia have
been undertaken, but one study in opioid
dependence suggests a potency equivalence of
30 (10). The relevance of this to analgesic
equivalents is uncertain.
Codeine (4,7,8,9,19)
3–6
0.08 - 0.15
Dihydrocodeine (4,9)
3-6
0.1
Hydromorphone
(2,4,6,7,8,9,11,12,16,18,
19,23)
4-5
3.5 - 10
Morphine (4)
3-6
1
Oxycodone
(2,4,6,7,8,9,12,13,19,23)
3-6
1.3 - 2
Note high oral bioavailability compared to
morphine (13). Manufacturer advises a potency
equivalence of 2 (13).
Not available
0.3 - 0.4
Manufacturer states that direct opioid
conversion has not been studied so potency
equivalence has been calculated indirectly (20).
Switching from another µ agonist (e.g.
morphine) may cause low-grade opioid
withdrawal. Role of tapentadol in palliative care
is unclear (4).
4-9
0.1 - 0.25
Manufacturer advises a potency equivalence of
0.1 - 0.17 (21).
Tapentadol (4,20)
Tramadol
(4,7,8,9,19,21)
Codeine is partly metabolised to morphine (4).
Some sources suggest a potency equivalence
of 5 when converting from morphine to
hydromorphone, but only 3.5-4 if switching from
hydromorphone to morphine (4,16,18). The
manufacturer states an approximate potency
equivalence of 5-10 (11).
Equivalent potencies are only approximate and can be unpredictable. When converting from one
opioid to another, it is often appropriate to use a lower dose than the suggested equivalence
above. Close monitoring for side effects and efficacy is mandatory, especially at higher doses.
3
From the National Electronic Library for Medicines. www.nelm.nhs.uk
Medicines Q&As
Example conversion:
Converting from morphine m/r 15mg bd to oral oxycodone:
 Total daily dose of morphine is 30mg.
 From Table 1, oxycodone potency equivalence = 1.3 – 2.
 Divide 30mg/1.3 = 23mg and 30mg/2 = 15mg.
 Therefore the approximate equivalent total daily dose of oral oxycodone is 15 - 23mg in
divided doses. See notes above on how this should be used in practice.
Limitations







Evidence for the effectiveness of switching opioids when managing cancer pain or chronic noncancer pain is limited (14,15,22). There are currently no evidence-based guidelines for opioid choices
when considering opioid conversion (22).
Much of the dose equivalence information was derived from single dose studies and therefore may
have limitations in applicability to repetitive administration (16). Also, some studies were not designed
for the detection of relative opioid potencies and in some cases opioid equianalgesic conversion
dosing recommendations may have emerged as secondary observations (3).
The studies that are available have differing patient populations, study methods and small sample
sizes. The duration of opioid exposure and the issue of tolerance are also factors in the interpretation
of data (17).
It has been suggested that the directional quality of cross tolerance may not be equal and has not
been fully explored. Ratios may change according to the direction of an opioid switch; however the
clinical relevance of this is not clear (17,18). Although it is unlikely to have a major impact when
switching at lower doses, it is possible that failure to recognise the directional difference may result in
negative consequences when switching at higher doses (18).
Dose conversion tables are not meant to provide recommended initiation doses for a given opioid or
patient (16).
Randomised trials are needed to standardise conversion ratios when switching from one opioid to
another (15,22).
The data presented are derived from adults and so may not be applicable to children.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
 Q&As are believed to accurately reflect the medical literature at the time of writing.
 The authors of Medicines Q&As are not responsible for the content of external websites and
links are made available solely to indicate their potential usefulness to users of NeLM. You must use
your judgement to determine the accuracy and relevance of the information they contain.
 This document is intended for use by NHS healthcare professionals and cannot be used for
commercial or marketing purposes.
 See NeLM for full disclaimer.
References
1. National Prescribing Centre. The Use of Strong Opioids in Palliative Care. MeReC Briefing. 2003;
Issue 22. http://www.npc.nhs.uk/merec/pain/otherback/resources/merec_briefing_no22.pdf
2. Cherny N, Ripamonti C, Pereira J, et al. Strategies to Manage the Adverse Effects of Oral Morphine:
An evidence-based report. J Clin Oncol 2001;19:2542-2554.
3. Gammaitoni AR, Fine P, Alvarez N et al. Clinical application of opioid equianalgesic data. Clin J Pain
2003;19:286-297.
4
From the National Electronic Library for Medicines. www.nelm.nhs.uk
Medicines Q&As
4. Twycross R, Wilcock A (eds). Palliative Care Formulary. 4th Edition. Palliativedrugs.com Ltd.
Nottingham. 2011.pp 331-335,354-5,362,341,347,383-4,414,424-5,625-7.
5. Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin
Oncol 2002;20:348-352.
6. Williams J. Palliative Care Prescribing. Drug Information Letter No.117. 2001:7-19.
7. Fukshansky M, Are M, Burton AW. The role of opioids in cancer pain management. Pain Practice
2005;5:43-54.
8. Wessex and ASWCS Palliative Physicians. The Palliative Care Handbook. Advice on clinical
management. 7th Edition. Countess Mountbatten House. Southampton University Hospitals. October
2010:10.
9. Regnard C, Dean M (eds). A Guide to Symptom Relief in Palliative Care 6th edition. Radcliffe
Publishing. Oxford; 2010:67.
10. Personal communication, Reckitt Benckiser Medical Information department. 28th September 2011.
11. SPC Palladone (hydromorphone) capsules. Napp Pharmaceuticals Ltd. Accessed via
http://www.medicines.org.uk/emc/ on 26th September 2011 (SPC last updated on the eMC: 25th
September 2009).
12. Prescribing in Palliative Care: Pain. Joint Formulary Committee. British National Formulary. No 62.
London: BMJ Group and Pharmaceutical Press; September 2011. Accessed via http://bnf.org on 29th
September 2011.
13. SPC OxyNorm (oxycodone) 5, 10, 20mg capsules. Napp Pharmaceuticals Ltd. Accessed via
http://www.medicines.org.uk/emc/ on 27th September 2011 (SPC last updated on the eMC: 27th
November 2008).
14. Quigley C. The role of opioids in cancer pain. BMJ 2005;331:825-829.
15. Quigley C. Opioid switching to improve pain relief and drug tolerability. Cochrane Database of
Systematic Reviews 2004, Issue 3. Art No:CD004847. DOI: 10.1002/14651858.CD004847. Published
in Issue 11. November 2010.
16. Anderson R, Saiers JH, Abram S et al. Accuracy in equianalgesic dosing: conversion dilemmas. J
Pain Symptom Manage 2001;21:397-406.
17. Berdine HJ, Nesbit SA. Equianalgesic dosing of opioids. J Pain Palliat Care Pharmacother
2006;20:79-84.
18. Pereira J, Lawlor P, Vigano A et al. Equianalgesic dose ratios for opioids: a critical review and
proposals for long-term dosing. J Pain Symptom Manage 2001;22:672-687.
19. Droney J, Riley J. Recent advances in the use of opioids for cancer pain. Journal of Pain Research
2009;2:135-155.
20. Personal communication, Grünenthal Ltd Medical Information department. 23rd September 2011.
21. SPC Zydol (tramadol) 50mg capsules. Grünenthal Ltd. Accessed via
http://www.medicines.org.uk/emc/ on 27th September 2011 (SPC last updated on the eMC: 27th
January 2011).
22. Vissers KCP, Besse K, Hans G et al. Opioid rotation in the management of chronic pain: where is the
evidence? Pain Practice 2010;10(2):85-93.
23. Mercadante S, Caraceni A. Conversion ratios for opioid switching in the treatment of cancer pain: a
systematic review. Palliative Medicine 2011;25(5):504-515.
5
From the National Electronic Library for Medicines. www.nelm.nhs.uk
Medicines Q&As
Quality Assurance
Prepared by
Kate Pickett, Medicines Q&A Pharmacist (based on earlier work by Louisa Rowlands & Anne Cole),
Wessex Drug and Medicines Information Centre, University Hospital Southampton NHS Foundation
Trust.
Date Prepared
20th September 2011
Checked by
Sue Gough (based on the Q&A checked by Dr Simon Wills), Critical Evaluation Pharmacist, Wessex Drug
and Medicines Information Centre, University Hospital Southampton NHS Foundation Trust.
Date of check
27th April 2012
Search strategy
 Embase - search strategy: “opioid.af AND equivalence.af”
“(exp opiate agonist/ OR exp narcotic analgesic agent/ OR exp narcotic
agent/) AND equivalence.af (limited to H=Y and LG=EN)”
“(exp opiate agonist/ OR exp narcotic analgesic agent/ OR exp narcotic
agent/) AND exp bioequivalence/ (limited to H=Y and LG=EN)”

Medline - search strategy: “opioid.af AND equivalence.af”
“(exp analgesics, opioid/ OR exp narcotics/) AND exp therapeuticequivalency/ (limited to H=Y and LG=EN)”





Electronic Medicines Compendium. Accessed via / http://www.medicines.org.uk/emc/
Cochrane Library. Accessed via http://www.thecochranelibrary.com/
National Prescribing Centre website. Accessed via http://www.npc.nhs.uk/
SIGN Guidelines. Accessed via http://www.sign.ac.uk
Specialist textbooks
6
From the National Electronic Library for Medicines. www.nelm.nhs.uk