Quick Tip: Some types of pain do not respond well to opioids and require adjuvant analgesics
These drugs are safe, effective and appropriate in palliative care provided that clinicians:
The place for opioids in pain management may be guided by a step-wise approach (such as the traditional WHO “analgesic ladder”), moving up the steps if pain control is not achieved.
Non-opioid (Paracetamol and/or NSAID) +/- adjuvant
Opioid for mild to moderate pain* +/- non-opioid (Paracetamol and/or NSAID) +/- adjuvant
(* e.g. codeine, dihydrocodeine, tramadol)
Opioid for moderate to severe pain* +/- non-opioid (Paracetamol and/or NSAID) +/- adjuvant
(* e.g. morphine, oxycodone, fentanyl)
Quick Tip: Morphine is the first line strong opioid of choice
Alfentanil: Please seek specialist advice about the use of alfentanil
Synthetic injectable highly potent opioid. Thirty times as potent as oral morphine (1mg SC alfentanil is approximately equivalent to 30mg PO morphine). Used in preference to other SC opioids in renal failure because there is no accumulation of neurotoxic metabolites. Single SC doses (as required doses) are very short-lasting (<2hours) and this may make alfentanil unsuitable as an opioid for breakthrough analgesia even in the context of renal impairment. Reduce dose in liver failure. Opioid withdrawal symptoms (like ‘gastric ‘flu’) may occur (rarely) when switching from other opioids. If so, give ‘as required’ dose of previous opioid for a few days.
Strong opioid used as sublingual tablets and transdermal patches (7-day range and 3-4 day range). Stable dose achieved 12-24 hours after applying patch. Safe in renal failure and moderate liver failure.
Di-acetylmorphine (diamorphine) is rapidly metabolised to morphine. It has no clinical advantage over morphine but is much more soluble, therefore recommended for use where opioid dose requirement exceeds morphine 360mg/24hours by SC infusion.
Highly potent synthetic opioid. At least 100 times as potent as oral morphine. Potency often unappreciated resulting in serious adverse events. See MHRA warnings on accidental exposure. Available as transdermal patches, injection, and transmucosal (buccal, sublingual and intranasal) formulations. A practical choice of opioid for use by transdermal or transmucosal route in severe and end stage renal failure. May be less constipating than morphine.
Transmucosal formulations: rapid onset, short acting. Useful for procedure and movement related pain, and short pain episodes and as breakthrough medication.
Transdermal formulation (patches): useful when oral route not possible or in those with compliance/concordance problems. Not well suited to titration in unstable pain as takes 24 hours to achieve steady state after dose adjustment (increase OR decrease).
Semi-synthetic opioid. Oral and injectable preparation. Considered to be 5 to 7.5 times more potent than morphine. Less often used due to limited Immediate release (IR) preparations. Despite its active metabolites being renally excreted, it is sometimes used as a preferred strong opioid in renal impairment.
First line strong opioid for use by mouth and injection/infusion. When used by SC infusion, doses greater than 360mg/24hours are difficult to deliver because of the volume of the corresponding breakthrough dose. A morphine rescue dose greater than 60mg (i.e. 1/6th of 360mg/24hours) is 2mls in volume and will be a painful SC injection. In this situation seek specialist advice.
Semi-synthetic oral and injectable opioid. Alternative opioid if morphine not tolerated or toxicity occurs. Considered to be 1.5 to 2 times as potent as morphine. When switching either way between morphine and oxycodone, start the new drug at the lowest dose based on the ratios and re-titrate as needed. Be careful not to confuse the MR formulation (usually tablets) with the IR form (usually capsules, liquid or injection).
Quick Tip: Guidance varies depending on whether the oral opioid is Immediate Release (IR) or Modified Release
Oral to subcutaneous infusion
From IR opioid: start syringe driver immediately.
From 12-hrly MR opioid: start syringe driver 2 hours before next oral dose would have been due.
Subcutaneous infusion to oral
Switching to either IR or MR opioid, stop the syringe driver and give first oral dose at the same time.
Oral to patch
From IR opioid: apply patch when convenient and use oral IR opioid as required.
From twice daily MR opioid: apply patch at same time as last dose of MR oral opioid.
(From once daily MR opioid: apply patch 12 hours after last dose of MR opioid).
Patch to oral
Remove patch 6 hours before giving first dose of oral MR opioid.
For first 24 hours (i.e. first two doses) give HALF the calculated equivalent dose since the transdermal opioid will take time to be cleared from plasma and subcutaneous reservoir.
After 24 hours, increase to the calculated equivalent dose if clinically indicated by pain.
Patch to subcutaneous infusion
If the patient is thought to be in the last hours to days of life, leave the patch in place and continue to change it at the right time intervals, and add a syringe driver with injectable medication alongside to make up the additional opioid treatment needed.
In other situations where a change from patch is required, remove patch and start syringe driver 6 hours later using HALF the calculated opioid equivalent dose for the first 24 hours then adjust according to symptom control and the need for breakthrough analgesia.
Subcutaneous infusion to patch
Apply patch. Continue subcutaneous infusion for a further 6 hours then discontinue syringe driver.
Quick Tip: Morphine is the first line WHO step 3 opioid of choice
Breakthrough doses of opioids
Quick Tip: If the opioid switch is because of opioid toxicity, check the eGFR and seek specialist advice on opioid choice and dose. Breakthrough doses may be needed to cover transition periods.
Moving from an opioid for moderate pain to an opioid for severe pain
Quick tip: Addiction is a common concern for a lot of patients and families
Opioids and addiction - Psychological dependence is rare in patients with severe pain in whom opioids are titrated carefully. When caring for patients with history of substance misuse, liaise with that specialist team and do not withhold pain relief when there is clinical need. Physiological dependence will not prevent dose reduction/gradual withdrawal when pain has been addressed by other measures. Increasing doses without benefit may indicate tolerance or a pain that is poorly responsive to opioids requiring adjuvant analgesia– seek specialist advice.
Opioids and respiratory depression – Opioids may cause respiratory depression but this is usually counteracted by pain. Dose titration, clinical judgement and regular review allow safe use even in patients with cardio-respiratory disease.
Opioids and renal impairment – In acute kidney injury, and chronic and end-stage renal failure, opioids must be used cautiously because some have active metabolites that accumulate if renal clearance is reduced. Opioids differ in their potential to cause toxicity and this influences the choice. Some opioids are cleared by dialysis which may result in pain flare afterwards.
Mild-moderate renal impairment - reduce dose, lengthen dose interval and review regularly. Be cautious with codeine, dihydrocodeine, morphine and oxycodone.
Severe renal impairment (eGFR < 30ml/min) - Avoid regular codeine, morphine and oxycodone; low dose immediate release (IR) oxycodone with increased dose intervals may be appropriate in some clinical situations. Consider fentanyl, buprenorphine or alfentanil depending on type of pain and preferred route of administration. You are strongly advised to seek specialist advice on use of alfentanil. Tramadol may be used cautiously and at reduced dose or increased dose interval in the short term. Methadone for pain may be continued under specialist supervision.
BNF: ‘prescribing in renal impairment’
‘The renal drug handbook’ (Ashley & Dunleavy (eds) 4th edition; 2014; Radcliffe
Quick Tip: Side effects are different from opioid toxicity. Constipation and dry mouth are lasting side effects of morphine, whereas nausea and vomiting and sedation often settle within days.
Opioid toxicity (for Emergency Treatment see Emergencies)
Features: myoclonic jerks, pin-point pupils, hallucination, confusion, reduced respiratory rate. Reduce opioid dose by 30-50%. Check renal function. Seek specialist advice on alternative analgesics or opioid switch.