Medicines Q&As
Q&A 302. 3
How should conversion from oral morphine to fentanyl patches
be carried out?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Date prepared: 30th July 2012 (partial revision 17th December 2012)
Background
Fentanyl patches are an effective alternative to oral morphine and a common question is how to
change a patient from oral morphine to a fentanyl patch (1). Fentanyl patches are indicated in
patients with stable pain who have difficulty swallowing, unacceptable side effects with oral
morphine or other opiates e.g. oxycodone, hydromorphone; renal failure, persistent nausea and
vomiting, gastrointestinal obstruction or poor compliance with oral medication (2,3). Each new
patch is applied for 72 hours and provides continuous delivery of fentanyl (2). Fentanyl patches
are not suitable for acute pain or for patients who have rapidly changing analgesic requirements
because the long time to steady state prevents rapid titration of the dose (4).
The National Patient Safety Agency issued a rapid response report in July 2008 aimed at reducing
dosing errors with opioid medicines (5). This highlights dose conversion as one of the areas where
prescribing errors can occur (5). It states: “where a change in formulation or medicine is required,
practitioners inexperienced in the use of opioids should use references for dose conversion to aid
calculation of a safe dose” (5).
Answer
Advice on equivalent potencies of oral morphine and transdermal fentanyl
Manufacturers list a wide range of oral morphine doses corresponding to each fentanyl patch
strength, with a resultant wide range in conversion ratios of oral morphine to transdermal fentanyl
(approximately 75:1 to 223:1) (2,6,7,8,9,10,11,12). Studies confirm the wide range in conversion
ratios and note that ratios that are conservative in one direction may be excessive in the reverse
(2,13). Direct conversion from oral morphine to transdermal fentanyl with a ratio of oral morphine
to transdermal fentanyl of 100:1 was examined in 98 patients with cancer pain (14). Regression
analysis at the end of the study revealed a mean oral morphine to transdermal fentanyl ratio of
70:1 (14). However, the authors concluded that a calculation table for the conversion of oral
morphine to transdermal fentanyl with a ratio of 100:1 is safe and effective (14). Although this is
lower than the true ratio determined in the study, it implies a sufficient margin for safety and may
avoid overdoses caused by inter-individual differences in response to different opioids (14). A
conversion ratio of 100:1 is also endorsed by the Palliative Care Formulary (PCF), a resource
about the use of medicines in palliative care and the British National Formulary (BNF) (3,4).
However, manufacturers guidance and some local guidelines advocate a range of conversion
ratios to avoid overdosing patients (6,7,8,9,10,11,12,15). NICE advise to “Use caution when
calculating opioid equivalence for transdermal patches: A transdermal fentanyl 12 microgram
patch equates to approximately 45 mg oral morphine daily” (16).
Comparative doses of oral morphine to transdermal fentanyl are given in Table 1. The dose
conversion used in this table of oral morphine: transdermal fentanyl demonstrates the ratio
advocated in practice of 100:1 (recommended by the BNF and PCF). The Summary of Product
Characteristics (SPC) for the specific fentanyl patch being used should also be consulted. The
dose conversions advised vary between SPCs and may be up to 223:1. This is an approximate
guide only as comprehensive data are lacking and there is inter-individual variation. Patients who
are taking a daily dose of morphine that falls between fentanyl patch strengths will need to be
changed to a patch which is either slightly less or slightly more potent than the morphine dose (3).
This will be a clinical decision. In practice, many clinicians start at a lower dose and titrate with
oral morphine (15). It is advisable to establish the exact analgesic requirement before initiating or
changing the patch strength (15). If switching because of possible opioid-induced hyperalgesia,
reduce the calculated equivalence by 25-50% (3).
From the NHS Evidence website www.evidence.nhs.uk
Medicines Q&As
Patients will require frequent reassessment of efficacy and adverse effects and dose titration after
patch initiation or dose change as well as a short acting opioid for breakthrough pain (2). Steady
state concentrations of fentanyl are reported as being achieved after approximately 36 to 72 hours
(3,17). The patient should use breakthrough analgesia as needed for the first 3 days particularly
the first 24 hours (3). Appropriate “when required” doses of morphine are given in Table 1.
If the patient requires two or more rescue doses of morphine per day after 48 hours, the strength
of the next patch to be applied (after 72 hours) should be increased by the equivalent patch
strength (usually 12-25 micrograms/hour) (3,15). Dose adjustment is not recommended more
frequently than every 72 hours and dose titration should be limited to increments of 12 or 25
micrograms/hour as appropriate (3,13).
Table 1: Conversion doses from oral morphine to transdermal fentanyl based on the dose
ratios 100:1 (adapted from the PCF and the BNF) (3,4)
Note: this table should be used in conjunction with Summary of Product Characteristics for the
fentanyl patch being used
Oral 24-hour morphine
(milligrams/day)
Transdermal fentanyl
When required
dose of
morphine
(milligrams)
advised in PCFa
30
60
(micrograms/hour)
12
25
milligrams/24hours
0.3
0.6
5
10
120
50
1.2
20
180
75
1.8
30
240
100
2.4
40
a. using traditional 1/6 of total daily dose as when required dose
More than one fentanyl patch may be used for dose adjustments and for doses greater than
100micrograms/hour (4,11). However, they should be applied at the same time to avoid confusion
(4).
When should the regular oral morphine be stopped following the initiation of fentanyl
patches?
Effective systemic analgesic concentrations of fentanyl are usually reached less than 12 hours
after applying the patch (3). When converting oral morphine to transdermal fentanyl:
 if taking 4 hourly oral morphine, continue giving regular doses for 12 hours after applying
the fentanyl patch
 if taking 12 hourly modified release morphine, give the last dose and apply the first
fentanyl patch at the same time
 if taking 24 hourly modified release morphine, apply the first fentanyl patch 12 hours after
the final modified release dose (2,3).
From the NHS Evidence website www.evidence.nhs.uk
Medicines Q&As
Are there any other factors to consider when switching from oral morphine to fentanyl
patches?
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Fentanyl is less constipating than morphine (3,14). Therefore, when patients are
converted from morphine to fentanyl, the dose of laxative(s) may need to be reduced and
subsequently adjusted according to need (3,15).
Patients may suffer from withdrawal symptoms (e.g. restlessness, diarrhoea, colic,
nausea, sweating) despite satisfactory pain relief (3,11). These symptoms can be treated
with rescue doses of morphine until they resolve after a few days (3).
Since peak fentanyl levels occur after 12 to 24 hours of treatment, monitoring of the
patient for adverse events, which may include hypoventilation is recommended for at least
48 hours after initiation of transdermal fentanyl or up-titration of the dose (11).
Healthcare professionals should ensure patients and caregivers are aware of signs and
symptoms of fentanyl overdose –i.e. trouble breathing or shallow breathing; tiredness;
extreme sleepiness or sedation; inability to think, walk or talk normally; and feeling faint,
dizzy or confused. Patients and caregivers should be advised to seek medical attention
immediately if overdose is suspected (18). Fentanyl toxicity may be more subtle than
morphine toxicity due to a lack of hallucinations, myoclonus etc. and can present as
vagueness, drowsiness or ‘not feeling well’ (17).
When a fentanyl patch is removed a subcutaneous depot remains (2). Serum
concentrations fall gradually, decreasing by 50% in 16 hours (range 13 to 22 hours) (2).
Patients who experience serious adverse effects should have patches removed
immediately and should be monitored for up to 24 hours after the patch is removed (18).
Increased body temperature, exposure of patches to external heat sources, and
concomitant use of CYP3A4 inhibitors may lead to potentially dangerous increases in
serum fentanyl levels. Concomitant use of other CNS depressants might also potentiate
fentanyl adverse effects (18)
There are two different formulations of fentanyl patch – reservoir and matrix which can be
supplied against a direction for fentanyl patch. Where possible patients should be
maintained on the same formulation (15).
Abuse potential of reservoir patches should be a consideration in areas of high drug
diversion (15).
NICE Guidance states: “Consider initiating transdermal patches with the lowest acquisition
cost for patients in whom oral opioids are not suitable and analgesic requirements are
stable, supported by specialist advice where needed” (16).
Summary
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Data from a small study has shown that conversion of oral morphine to transdermal
fentanyl with a ratio of 100:1 is safe and effective. This ratio is also endorsed by the
Palliative Care Formulary and the British National Formulary. This differs from ratios
recommended in some UK Summary of Products Characteristics . The decision regarding
which conversion ratio to use should be based on patient specific factors, the level of
patient monitoring which can be offered and the clinical setting.
Comparative doses of oral morphine and transdermal fentanyl are given in Table 1. This
should be used in conjunction with the Summary of Product Characteristics for the fentanyl
patch being used.
Patients who are taking a daily dose of morphine that is not exactly equivalent to a
particular fentanyl patch strength, will need to be changed to a patch which is either
slightly less or slightly more potent than the morphine dose. This will be a clinical decision
based on patient specific factors and patients should be monitored.
Effective systemic analgesic concentrations of fentanyl are reached less than 12 hours
after applying the patch. Guidance is given above regarding the discontinuation of the
regular morphine dose.
From the NHS Evidence website www.evidence.nhs.uk
Medicines Q&As
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Patients will require frequent reassessment of efficacy and adverse effects and dose
titration after patch initiation or dose change as well as a short acting opioid for
breakthrough pain.
Steady state concentrations of fentanyl are reported as being achieved after
approximately 36 to 72 hours. The patient should use breakthrough analgesia as required
for the first 3 days particularly the first 24 hours.
The dose of laxative(s) may need to be reduced and subsequently adjusted according to
need as fentanyl is less constipating than morphine.
Limitations
Caution is needed when converting patients between oral morphine and transdermal fentanyl. The
conversion ratios given are an approximate guide only because of:
 wide inter-individual variation in opioid pharmacokinetics (3)
 variables such as concurrent medication and nutritional status (3)
 interproduct variability and generic prescribing of fentanyl products
 a lack of comprehensive trial data
The data presented are derived from adults and may not be applicable to children. The information
in this Q&A should be used in conjunction with the relevant Summary of Product Characteristics.
Disclaimer
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 Each Q&A relates only to the clinical scenario described.
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References
1. National Prescribing Centre. The Use of Strong Opioids in Palliative Care. MeReC
Briefing. 2003; Issue 22. Accessed online at
http://www.npc.nhs.uk/merec/pain/otherback/resources/merec_briefing_no22.pdf on
25/6/2012
2. Scottish Intercollegiate Guidelines Network. Guideline 106: Control of Pain in Adults with
Cancer. November 2008. Accessed online at
http://www.sign.ac.uk/guidelines/fulltext/106/index.html on 25/6/2012
3. Twycross R, Wilcock A (eds). Palliative Care Formulary. 4th Edition.
Nottingham:Palliativedrugs.com Ltd : 2011 pp391-399.
4. Martin J (editor). British National Formulary December 2012 4. Accessed online via:
www.bnf.org on 17/12/2012
5. National Patient Safety Agency. Rapid Response Report: NPSA/2008/RRR05. Reducing
dosing errors with Opioid Medicines. July 2008. Accessed online via
http://www.nrls.npsa.nhs.uk/resources/?entryid45=59888&p=2&char=R on 23/05/2012
6. Summary of Product Characteristics - Osmanil 100 micrograms/hr transdermal patch.
Zentiva. Accessed online at http://www.medicines.org.uk/emc/medicine/25661/SPC/ on
23/05/12 [date of revision of the text 24/08/2011]
7. Summary of Product Characteristics –Mezolar Matrix Transdermal Patches. Accessed
online at http://www.medicines.org.uk/emc/medicine/21734/SPC/on 11/06/12 [date of
revision of the text 11/2010]
From the NHS Evidence website www.evidence.nhs.uk
Medicines Q&As
8. Summary of Product Characteristics –Durogesic DTrans 12/25/50/75/100mcg/hr
Transdermal Patch. Accessed online at
http://www.medicines.org.uk/emc/medicine/17086/SPC/ on 12/06/12 [date of revision of
the text 20th January 2012]
9. Summary of Product Characteristics – Fencino 75 micrograms/hour Transdermal Patch.
Accessed online at http://www.medicines.org.uk/emc/medicine/25010/SPC/ on 19/06/2012
[date of revision of the text August 2011]
10. Summary of Product Characteristics - Fentalis Reservoir Transdermal patches. Accessed
online at http://www.medicines.org.uk/emc/medicine/21735/SPC/ on 25/06/2012 [date of
revision of the text September 2007].
11. Summary of Product Characteristics - Matrifen. Accessed online at
http://www.medicines.org.uk/emc/medicine/19278/SPC/ on 19/6/2012 [date of revision of
the text 03/01/2012]
12. Summary of Product Characteristics– Victanyl 100 micrograms/hour Transdermal Patch
(Actavis UK Ltd). Accessed online at
http://www.medicines.org.uk/emc/medicine/21568/SPC on 19/06/2012 [date of revision of
the text 21/11/2011]
13. Patanwala A, Duby J, Waters D et al. Opioid Conversions in Acute Care. Ann
Pharmacother 2007; 41: 255-267.
14. Donner B, Zenz M, Tryba, M et al. Direct conversion from oral morphine to transdermal
fentanyl: a multicenter study in patients with cancer pain. Pain 1996;64:527-534.
15. Specialist palliative care pharmacist, The Royal Marsden NHS Foundation Trust formally
working at St Peters Hospice. Personal communication19/3/2010 and 19/7/2012
16. National Institute for Health and Clinical Excellence. Opioids in palliative care: safe and
effective prescribing of strong opioids for pain in palliative care of adults. NICE Clinical
Guideline 140. Issue date: May 2012. Accessed online via www.nice.org.uk on 23/7/ 2012
17. Bank, I. Fentanyl, Palliative Care Guidelines Plus. Accessed online at
http://book.pallcare.info on 26/03/2012
18. MHRA.Drug Safety Update. Volume 2, Issue 2, September 2008. Accessed online at
http://www.mhra.gov.uk/Publications/Safetyguidance/%20DrugSafetyUpdate/CON025631
on 20/6/2012
Quality Assurance
Prepared by
Emma Templeman, South West Medicines Information & Training, Bristol
Date Prepared
30th July 2012 (partial revision 17th December 2012)
Checked by
Julia Kuczynska, South West Medicines Information & Training, Bristol
Date of check
1st August 2012 (partial revision checked 20th December 2012)
From the NHS Evidence website www.evidence.nhs.uk
Medicines Q&As
Search strategy
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BNF December 2012. http://bnf.org/bnf/
Electronic Medicines Compendium. Accessed via http://www.medicines.org.uk/emc/
Martindale, The Complete Drug Reference. Pharmaceutical Press. Accessed via
www.medicinescomplete.com,
MICROMEDEX Accessed via http://www.thomsonhc.com/home/dispatch
National Electronic Library for Medicine. Accessed via www.nelm.nhs.uk
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National Institute for Health and Clinical Excellence. Accessed via www.nice.org.uk
Clinical Knowledge Summaries. Accessed via www.cks.nhs.uk
Cochrane Library. Accessed via www.thecochranelibrary.com
National Prescribing Centre website. Accessed via http://www.npc.co.uk
SIGN Guidelines. Accessed via http://www.sign.ac.uk
Specialist palliative care textbooks and websites
Embase (exp “fentanyl” AND exp “morphine” AND exp “transdermal drug administration”)
Medline (exp “fentanyl” AND exp “morphine” AND exp “administration, cutaneous”)
Specialist palliative care pharmacist, The Royal Marsden, London.
From the NHS Evidence website www.evidence.nhs.uk