Considerations when switching routes of administration or formulations of opioids in palliative care

The oral route of drug administration is preferred in palliative care; however, other routes of administration (eg subcutaneous, intravenous, transdermal, transmucosal) may need to be considered in a patient because of:

an inability to swallow
impaired absorption (eg bowel obstruction)
urgent need (parenteral opioids have a faster onset of action compared to transdermal and oral administration)
excessive tablet burden
poor adherence.

In these situations, consider switching the route of administration using either the same opioid (eg changing oral morphine to a continuous subcutaneous morphine infusion) or a different opioid (eg changing oral morphine to transdermal fentanyl). If the same opioid is used, a dose reduction is not required. If using a different opioid, see Overview of switching opioids in palliative care for information on calculating an equivalent dose.

Switching routes of administration requires consideration of the time of onset and offset of action for both the new and old opioid formulation—see Suggestions for how to time the switch between opioid formulations and/or routes of administration in palliative care for suggestions on how to time the switch between different opioid formulations and/or routes of administration.

For general information about the route of drug administration in palliative care, see Choice of route of drug administration in palliative care.

Example dose calculation when switching from an oral opioid to a continuous subcutaneous opioid infusion in palliative care gives an example of how to calculate an approximate equianalgesic dose when changing the route of administration of an opioid.

The pharmacokinetic properties of modified-release opioid formulations can differ significantly—do not use modified-release opioid formulations interchangeably.

Be particularly cautious when changing from an oral opioid to a transdermal patch because of their different pharmacokinetic properties. Principles of switching from an oral opioid to transdermal fentanyl in palliative care describes how to change from an oral opioid to transdermal fentanyl. The equianalgesic ratios used in fentanyl patch product information have been shown to be sufficiently conservative that a reduction of the calculated equianalgesic dose is not required. Example dose calculation when switching from an oral opioid to transdermal fentanyl in palliative care gives an example dose calculation when switching from an oral opioid to transdermal fentanyl in palliative care.

Use caution when calculating equianalgesic doses for patients who are cachectic or on high doses of transdermal fentanyl; often significantly lower doses of non-fentanyl opioids are needed than conversion charts suggest—seek specialist advice. Transdermal fentanyl absorption can be variable in cachectic cancer patients and has nonlinear pharmacokinetics at high doses.

Table 1. Suggestions for how to time the switch between opioid formulations and/or routes of administration in palliative care
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Note: Note: The advice in this table is guidance only—individuals vary markedly in their response to different opioids, and different routes of administration have different bioavailability; frequent review is necessary. Seek expert advice when switching opioids in patients taking more than 100 mg oral morphine (or equivalent) in 24 hours. Ensure all patients have adequate immediate-release opioids available as required for breakthrough symptoms.
Click on the opioid that is being stopped (ie the opioid you are changing from): transdermal buprenorphine transdermal fentanyl twice-daily modified-release opioid once-daily modified-release opioid continuous subcutaneous opioid infusion
Changing from TRANSDERMAL BUPRENORPHINE to:
transdermal fentanyl	Apply fentanyl patch 24 hours after removing buprenorphine patch
twice-daily modified-release opioid	Give first dose 24 hours after removing patch
once-daily modified-release opioid	Give first dose 24 hours after removing patch
continuous subcutaneous opioid infusion	Start infusion 12 to 18 hours after removing patch [NB1]
Changing from TRANSDERMAL FENTANYL to:
transdermal buprenorphine	[NB2]
twice-daily modified-release opioid	Give first dose 8 to 12 hours after removing patch
once-daily modified-release opioid	Give first dose 4 to 8 hours after removing patch
continuous subcutaneous opioid infusion	Start infusion 6 to 8 hours after removing patch [NB1]
Changing from TWICE-DAILY MODIFIED-RELEASE OPIOID to:
transdermal buprenorphine	[NB2]
transdermal fentanyl	Apply patch at the same time as last dose
twice-daily modified-release opioid [NB3]	Give first dose 12 hours after last dose
once-daily modified-release opioid	Give first dose 12 hours after last dose
continuous subcutaneous opioid infusion	If pain is well controlled, start infusion 2 to 4 hours before the next opioid dose would have been given If pain is not controlled, infusion may need to be started earlier; seek specialist palliative care advice
Changing from ONCE-DAILY MODIFIED-RELEASE OPIOID to:
transdermal buprenorphine	[NB2]
transdermal fentanyl	Apply patch 18 hours after last dose
twice-daily modified-release opioid	Give first dose 24 hours after last dose
once-daily modified-release opioid [NB3]	Give first dose 24 hours after last dose
continuous subcutaneous opioid infusion	If pain is well controlled, start infusion 2 to 4 hours before the next opioid dose would have been given If pain is not controlled, infusion may need to be started earlier; seek specialist palliative care advice
Changing from CONTINUOUS SUBCUTANEOUS OPIOID INFUSION to:
transdermal buprenorphine	Apply patch and stop infusion 12 to 18 hours later [NB4]
transdermal fentanyl	Apply patch and stop infusion 6 to 8 hours later
twice-daily modified-release opioid	Give first oral dose and stop infusion 2 to 4 hours later
once-daily modified-release opioid	Give first oral dose and stop infusion 4 to 6 hours later
Note: NB1: In the last days of life, to avoid potentially inaccurate dose conversion, continue transdermal patches; additional analgesic therapy can be administered subcutaneously, as required. NB2: Advice not given because in practice this change is unlikely. Seek specialist palliative care advice. NB3: This advice is for changing to a different opioid or a different brand of the same opioid. NB4: It takes up to 3 days for buprenorphine to reach steady-state concentration.

Table 2. Example dose calculation when switching from an oral opioid to a continuous subcutaneous opioid infusion in palliative care
Original dose
A patient taking morphine modified-release 50 mg orally once daily has been deteriorating; their ability to swallow is declining, increasing the risk of aspiration pneumonia. Two as-required doses of morphine immediate-release 5 mg orally are needed daily and are effective for breakthrough pain. The patient is approaching the end of life and would like to remain at home. A change to a continuous subcutaneous infusion of morphine is suggested.
Calculation [NB1]
morphine modified-release 50 mg orally once daily plus 2 breakthrough doses of morphine immediate-release 5 mg orally gives a total of morphine 60 mg orally in 24 hours morphine 60 mg orally in 24 hours is approximately equivalent to morphine 20 mg subcutaneously in 24 hours (see Approximate equianalgesic doses of opioids in palliative care for approximate equianalgesic doses of opioids given via different routes)—use this amount for the continuous subcutaneous morphine infusion dose use one-twelfth to one-sixth of the 24-hour subcutaneous morphine amount for a breakthrough pain dose: morphine 1.7 to 3.3 mg subcutaneously, rounded up to 2.5 to 5 mg [NB2]
New dose
For the continuous subcutaneous morphine infusion morphine 20 mg/24 hours by continuous subcutaneous infusion, starting 2 to 4 hours before when the next dose of the oral once-daily morphine would have been given [NB3] For the breakthrough subcutaneous morphine dose morphine 2.5 to 5 mg subcutaneously, 1-hourly as required
Note: NB1: Confirm manual calculations using a digital opioid conversion calculator (eg eviQ calculator or the Australian and New Zealand College of Anaesthetists (ANZCA) Faculty of Pain Medicine opioid calculator and application), or check them with a palliative care specialist, pharmacist or colleague. NB2: Round up the dose for convenience, depending on the volume of available morphine ampoules. NB3: If pain was not controlled with the oral opioid, the infusion may need to be started earlier—seek specialist palliative care advice. See Suggestions for how to time the switch between opioid formulations and/or routes of administration in palliative care for how to time the switch between different opioid formulations and routes of administration.

Figure 1. Principles of switching from an oral opioid to transdermal fentanyl in palliative care

Establish the total amount of oral opioid taken in the previous 24 hours:

include the regular dose and doses taken for breakthrough pain
do not include doses taken for incident pain.

Calculate the equivalent dose of a transdermal fentanyl patch, using one of the following:

tables giving suggested starting doses in the fentanyl patch product information [NB1]
equianalgesic doses given in Approximate equianalgesic doses of opioids in palliative care, if the oral opioid dose is equivalent to oral morphine 90 mg or less daily.
an online dose calculator, such as the eviQ calculator or the Australian and New Zealand College of Anaesthetists (ANZCA) Faculty of Pain Medicine opioid calculator and application.

Confirm with a specialist that the calculated equivalent strength of transdermal fentanyl patch is correct.

Apply the patch according to the time suggested in Suggestions for how to time the switch between opioid formulations and/or routes of administration in palliative care.

Always prescribe an immediate-release opioid for breakthrough pain. Consider the patient’s ability to swallow when choosing an opioid and formulation [NB2].

There is significant inter- and intrapatient variability in the response to different opioids and doses used—after any change, monitor the patient for response and adverse effects.

Note:

NB1: The equianalgesic ratios used in fentanyl patch product information have been shown to be sufficiently conservative that a reduction of the calculated equianalgesic dose is not required.

NB2: If liquid oral morphine is appropriate for breakthrough pain, calculate the breakthrough dose of liquid oral morphine using one-twelfth to one-sixth of the total amount of morphine taken in the previous 24 hours. In the event of Ordine (immediate-release morphine) oral liquid discontinuation, alternative products may be accessed under the Therapeutic Goods Administration (TGA) Section 19A. For more information, see the TGA website.

Table 3. Example dose calculation when switching from an oral opioid to transdermal fentanyl in palliative care
Original dose
A patient taking morphine modified-release 25 mg orally twice daily for 4 months with good pain control is starting to have difficulty swallowing. A change to a transdermal fentanyl patch is requested [NB1].
Calculation [NB2]
Morphine modified-release 25 mg orally twice daily gives a total of oral morphine 50 mg in 24 hours Oral morphine 50 mg in 24 hours is approximately equivalent to transdermal fentanyl 16.7 micrograms/hour (see Approximate equianalgesic doses of opioids in palliative care for approximate equianalgesic doses of different opioids) [NB3] Use the closest transdermal fentanyl patch dose for the regular transdermal fentanyl dose: 12 micrograms/hour fentanyl patch Use one-twelfth to one-sixth of the 24-hour oral morphine dose in oral liquid immediate-release morphine for breakthrough pain [NB6]
New dose
For the regular transdermal fentanyl dose Apply the fentanyl 12 microgram/hour patch at the same time as the final oral modified-release morphine dose is taken [NB4] For the breakthrough immediate-release opioid dose Use oral liquid immediate-release morphine 5 to 10 mg, 1-hourly as required [NB6] If the patient is completely unable to swallow, seek expert advice for consideration of transmucosal fentanyl [NB5]
Note: NB1: For principles of switching from an oral opioid to transdermal fentanyl, see Principles of switching from an oral opioid to transdermal fentanyl in palliative care. NB2: Confirm manual calculations using a digital opioid conversion calculator (eg eviQ calculator or the Australian and New Zealand College of Anaesthetists (ANZCA) Faculty of Pain Medicine opioid calculator and application), or check them with a palliative care specialist, pharmacist or colleague. NB3: The equianalgesic ratios used in fentanyl patch product information have been shown to be sufficiently conservative that a reduction of the calculated equianalgesic dose is not required. NB4: See Suggestions for how to time the switch between opioid formulations and/or routes of administration in palliative care for how to time the switch between different opioid formulations and routes of administration. NB5: Dose equivalence between transmucosal fentanyl and other opioid formulations has not been established. NB6: In the event of Ordine (immediate-release morphine) oral liquid discontinuation, alternative products may be accessed under the Therapeutic Goods Administration (TGA) Section 19A. For more information, see the TGA website.